Functions - Director of UMR U557 Inserm/Inra/Cnam « Epidémiologie Nutritionnelle »: since 2001 - Responsible of the’Unité de Surveillance et d’Epidémiologie Nutritionnelle (USEN, Institut de Veille Sanitaire/Cnam) : depuis 2000 - Director of thr Centre de Recherche en Nutrition Humaine (CRNH) Ile-de-France (GIS AP-HP/Paris 13/ Paris 6/Inserm/Inra/InaPG/Cnam/InVS) : since march 2005
International exchanges • Post-doc : Kansas University Medical Center, (march–august 1984) • Invited researcher : Epidémiologie de la Nutrition à l'Université de Sherbrooke (Canada) (3 months in 1992 and in 1994). • Invited member of the Comité d’Evaluation de l’Etude Santé-Quebec (Canada), (1996). • Invited researcher to the Fred Hutchinson Cancer Research Center, Seattle, USA (july-august 2000) • Invited researcher to the Dept of Nutritional Sciences, Univ of Berkeley, Calfornia, USA (july 2001 and july 2002) • Invited researcher to Fred Hutchinson Cancer Research Center, Seattle, USA (july-august 2003 and 2004) • Invited researcher to the Institut du Cancer, Université de Laval Québec, Canada (july 2005) • Invited researcher to the Imperial College, Depart of Public Health, London, UK (july 2007)
Public health activities • Chairman (1998-1999) of the expert group in charge of the report “ Une politique nutritionnelle pour la France ”. • member of the Expert Group of the Haut Comité pour la Santé Publique (HCSP) : “Impact sur la santé de l’évolution des habitudes nutritionnelles” 1999-2000. Writer of the repor: “ Pour une politique nutritionnelle de Santé Publique en France : enjeux et propositions ” (september 2000). • Vice-Chairman of the Sterering Comitee of the Programme National Nutrition Santé, PNNS (2001-2006) • Chargé de mission (march 2003) for the national program « Alimentation et Insertion » • Member of the Steering Comitee of the Program « Bien Vieillir » • Chairman of the Sterering Comitee of the Programme National Nutrition Santé n°2, PNNS2 (from 2007)
Expertise • Member of the Comité d’Experts Spécialisés en Nutrition Humaine (AFSSA) since 2000. • Member of the Conseil National de l’Alimentation (CNA) since 2 001 • Chairman of the Working Group on the reduction of salt in France (AFSSA) (may 2001 – january 2002). • Member of the Expert Group (1999-2001) of t he Program RARE, Ministère de la Recherche. • Member of the working group of the “ATC Nutrition” INSERM (2001,2002). • Member of the group in charge to devenlop a Public Health Network (INSERM) • Member of the INSERM Commitee on cohorts (2003). • Member of the Expert Commitees of the National Institute for Prevention and Health Education (INPES) in charge of the development of national mediatic campaigns of nutrition of PNNS • Member of the working groups of AFSSA in charge of the redaction of PNNS Guides « La Santé Vient en Mangeant : le Guide Alimentaire pour Tous » ; « la Santé Vient en Bougeant » ; le Guide Alimentaire Enfant ; le Guide Alimentaire Sujet Agé. • Expert for WHO
Member of scientific societies: ADELF ( Association of French speaking Epidemiologists), AFN (French Association for Nutrition), SNDLF (French speaking Society on Nutrition), GEN (Group of European Nutritionists), INACG (International Nutritional Anaemia Consultative Group)
Distinction: 1997 Research Price accorded by the French Institute for Nutrition Doctor Honoris Causa, Faculty of Agronomical Science of Gembloux (Belgium), May 9th, 2007
Abstract: Increased fruit and vegetable consumption has become a health priority in many countries. Therefore, data investigating the influence of different types of fruits and vegetables on serum antioxidant levels would be useful. The objective of the study was to assess the relationship between fruit and vegetable consumption and vitamin serum antioxidant concentrations. Specific fruit and vegetable groups are evaluated. A total of 3521 subjects (1487 men and 2034 women), aged 35-60 years, participating in the SU.VI.MAX cohort were included in this study. Blood samples of participants were analysed for beta-carotene, vitamin C and alpha-tocopherol. Each subject had completed at least six dietary records during the first 2 years of the study. It was found that women had higher mean beta-carotene and vitamin C serum concentrations than men, but lower alpha-tocopherol serum concentrations. Serum beta-carotene and vitamin C concentrations were positively correlated with consumption of both fruit and vegetables, as well as with most of the fruit and vegetable groups tested. These relationships persisted after adjustment for confounding factors. Regression analysis showed a linear dose-response relationship. Root vegetables and citrus fruits were particularly associated with beta-carotene serum status as were citrus fruits for vitamin C. Fruit and vegetable consumption was either not or weakly associated with alpha-tocopherol serum concentrations. These results describe antioxidant serum concentrations according to fruit and vegetable consumption in a large sample and support the findings of previous studies involving a more limited number of subjects.
Abstract: BACKGROUND: PBX1 is a biological candidate gene for type 2 diabetes at the 1q21-q24 susceptibility locus. The aim of this study was to evaluate the association of common PBX1 variants with type 2 diabetes in French Caucasian subjects. METHODS: Employing a case-control design, we genotyped 39 SNPs spanning the PBX1 locus in 3,093 subjects to test for association with type 2 diabetes. RESULTS: Several PBX1 SNPs, including the G21S coding SNP rs2275558, were nominally associated with type 2 diabetes but the strongest result was obtained with the intron 2 SNP rs2792248 (P = 0.004, OR 1.20 [95% CI 1.06-1.37]). The SNPSpD multiple testing correction method gave a significance threshold of P = 0.002 for the 39 SNPs genotyped, indicating that the rs2792248 association did not survive multiple testing adjustment. SNP rs2792248 did not show evidence of association with the French 1q linkage signal (P = 0.31; weighted NPL score 2.16). None of the PBX1 SNPs nominally associated with type 2 diabetes were associated with a range of quantitative metabolic traits in the normoglycemic control subjects CONCLUSION: The available data does not support a major influence of common PBX1 variants on type 2 diabetes susceptibility or quantitative metabolic traits. In order to make progress in identifying the elusive susceptibility variants in the 1q region it will be necessary to carry out further large association studies, meta-analyses of existing data from individual studies, and deep resequencing of the 1q region.
Abstract: This study aimed to seek whether habitual fish and seafood or n-3 long-chain PUFA intake could influence the occurrence of depressive episodes. In a subsample from the French SU.VI.MAX cohort, dietary habits have been assessed during the first 2 years of the follow-up (six 24-h records) and declarations of antidepressant prescription, taken as markers of depressive episodes, have been recorded during the 8-year follow-up. Subjects consuming fatty fish or with an intake of long-chain n-3 PUFA higher than 0.10% of energy intake had a significantly lesser risk of any depressive episode and of recurrent depressive episodes, but not of single depressive episode. These associations were stronger in men and in non-smokers. In contrast, smokers eating fatty fish had an increased risk of recurrent depression. These results suggest that a usual intake of fatty fish or long-chain n-3 PUFA may decrease the risk of recurrent depression in non-smokers.
Abstract: Left-and right-handers have coexisted since the Palaeolithic age. Hand preference is heritable. Moreover, there is extensive evidence of an association between left-handedness and several fitness costs. In this context, the persistence of the polymorphism is interesting. Here, we explore the associations between socio-economic status and handedness, analysing data from two large cohorts of adult men and women. Such associations are relevant to an evolutionary approach, as the socio-economic and the reproductive value are related. Our results partly support the hypothesis that left-handers have a socio-economic status advantage, countervailing the health issues. Although the models explain a small proportion of the variance observed, the frequency of left-handedness is significantly higher: (1) among women of higher educational level; (2) among categories of higher income; and (3) among individuals who have a higher position in the company. The importance of these findings for the evolution of the polymorphism of handedness is discussed.
Abstract: BACKGROUND: Despite the increasing use of indoor tanning facilities, little is known regarding the behaviour of adults with respect to artificial and natural ultraviolet (UV) radiation exposure and the relationship between the two forms of exposure. OBJECTIVES: To describe the beliefs and behaviour of French middle-aged volunteers regarding artificial and natural UV exposure. METHODS: Cross-sectional study of a French national cohort using a self-completed questionnaire. RESULTS: Participants were identified as 'indoor UV tanners' (n= 1076) and as 'non-users' (n= 6124). Predictor factors associated with indoor tanning were gender, age, smoking, phototype, region of residence, sun exposure during hobbies, voluntary sun exposure in particular during the hottest hours of the day, nudism practice, facial sunscreen habits, sunglass use, importance for lying in the sun and the claim 'ever heard of melanoma'. LIMITATIONS: The quality of information may be limited by the data collection method. CONCLUSION: Whereas indoor tanning should be discouraged, it seems that indoor tanners are also regular sunbathers unconcerned about the risk of photoageing and skin cancer occurrence. Moreover, indoor tanners seem to have more behavioural risk factors for cancer, such as smoking.
Abstract: To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.
Abstract: Objective:Estimation of dietary intake of polyphenols is difficult, due to limited availability of food composition data and bias inherent to dietary assessment methods. The aim of the present study was to evaluate whether we could detect polyphenols and their metabolites in a spot urine sample in a free-living human population and whether it was related to those observed in 24-h urine samples, for potential use as a biomarkers of polyphenol intake.Subjects:Four 24-h urine samples and two spot urine samples were collected from 154 participants of the SU.VI.MAX cohort (a randomized primary-prevention trial evaluating the effect of daily antioxidant supplementation on chronic diseases) in two separate studies over, respectively, a 7- and 2-day periods. Thirteen polyphenols and metabolites (chlorogenic acid (CGA), caffeic acid (CA), m-coumaric acid (mCOU), gallic acid (GA), 4-O-methylgallic acid (MeGA), quercetin (Q), isorhamnetin (MeQ), kaempferol (K), hesperetin (HESP), naringenin (NAR), phloretin (PHLOR), enterolactone (ENL) and enterodiol (END) were measured using HPLC-ESI-MS-MS.Results:Correlations between the urinary excretion levels were observed. The most significant were explained by metabolic filiations (CGA/CA, CA/mCOU, GA/MeGA, Q/MeQ, NAR/PHLOR, ENL/END) or co-occurrence in a same food source (NAR/HESP). Concentrations in spot samples correlated with those in 24-h urine sample (P<0.02, except for CA and for MeQ). Intra-individual variations were smaller than inter-individual variations for all polyphenols (P<0.01) except for MeGA and for PHLOR.Conclusion:These results show that these polyphenols and metabolites are useful biomarkers for polyphenol intake.European Journal of Clinical Nutrition (2008) 62, 519-525; doi:10.1038/sj.ejcn.1602744; published online 4 April 2007.
Abstract: AIMS/HYPOTHESIS: In the present study, we sought to examine the evidence that LMNA variants are associated with type 2 diabetes and quantitative metabolic traits in French Europid individuals. METHODS: We genotyped 24 single nucleotide polymorphisms (SNPs) spanning the LMNA gene in 3,093 case-control participants. The association between LMNA SNPs and quantitative metabolic traits was also examined in the 1,674 normoglycaemic adults who made up the control cohort. RESULTS: SNP rs505058, a synonymous SNP (D446D) in exon 7, showed nominal evidence of association with type 2 diabetes [p = 0.003, odds ratio (OR) 1.30 (95% CI 1.09-1.56)] in French Europids. A meta-analysis of available rs505058 genotype data from 7,819 participants provided support for a modest association of rs505058 with type 2 diabetes [p = 0.003, OR 1.19 (95% CI 1.06-1.35)]. We found no evidence (p = 0.91) that the tag SNP rs4641 is associated with type 2 diabetes. However, a meta-analysis of all available rs4641 genotype data in a total of 15,591 participants produced borderline evidence of association [p = 0.054, OR 1.05 (95% CI 1.00-1.11)]. SNP rs6669212, in the 3' untranslated region of LMNA, exhibited suggestive associations with WHR (p = 0.013), fasting serum levels of total cholesterol (p = 0.023) and triacylglycerol (p = 0.015). We emphasise that these quantitative trait associations are not corrected for multiple testing. CONCLUSIONS/INTERPRETATION: The available data do not support a major effect of common LMNA variation on type 2 diabetes susceptibility in northern Europeans. Further large-scale studies are required to conclusively establish the extent to which LMNA variants have an impact on quantitative metabolic traits.
Abstract: AIMS/HYPOTHESIS: Genome-wide association studies (GWASs) recently identified common variants in the CDKN2A/CDKN2B region on chromosome 9p as being strongly associated with type 2 diabetes. Since these association signals were not picked up by the French-Canadian GWAS, we sought to replicate these findings in the French Europid population and to further characterise the susceptibility variants at this novel locus. METHODS: We genotyped 20 single nucleotide polymorphisms (SNPs) spanning the CDKN2A/CDKN2B locus in our type 2 diabetes case-control cohort. The association between CDKN2A/CDKN2B SNPs and quantitative metabolic traits was also examined in the normoglycaemic participants comprising the control cohort. RESULTS: We report replication of the strong association of rs10811661 with type 2 diabetes found in the GWASs ([Formula: see text]; OR 1.43 [95% CI 1.24-1.64]). The other CDKN2A/CDKN2B susceptibility variant, rs564398, did not attain statistical significance (p = 0.053; OR 1.11 [95% CI 1.00-1.24]) in the present study. We also obtained several additional nominal association signals (p < 0.05) at the CDKN2A/CDKN2B locus; however, only the rs3218018 result (p = 0.002) survived Bonferroni correction for multiple testing (adjusted p = 0.04). CONCLUSIONS/INTERPRETATION: Our comprehensive association study of common variation spanning the CDKN2A/CDKN2B locus confirms the strong association between the distal susceptibility variant rs10811661 and type 2 diabetes in the French population. Further genetic and functional studies are required to identify the aetiological variants at this locus and determine the cellular and physiological mechanisms by which they act to modulate type 2 diabetes susceptibility.
Abstract: OBJECTIVE: Weight gain is a risk factor for metabolic syndrome (MS). However, it is not known whether weight fluctuations (WF) have a deleterious effect upon MS risk. In the present study, we investigated this association in subjects participating in the SU.VI.MAX cohort. METHODS: MS status was assessed at baseline (1994/1995) and at the end of follow-up (2001/2002) using the National Cholesterol Education Program-Adult Treatment Panel III criteria. WF were estimated with four weight measures during follow-up. Odds ratio (OR, 95% confidence interval (CI)) for incident MS cases was evaluated according to four WF groups (no WF and tertiles of WF) in 3553 middle-aged subjects. RESULTS: The OR (95% CI) for MS was 2.06 (1.20-3.52) for the third WF tertile compared to the first tertile. This association was independent of confounding variables, especially relative weight change during follow-up. Subjects without WF had a 2.72-fold increase (1.64-4.53) for MS risk compared to the first tertile of WF. For MS components taken separately, similar associations were found for raised blood pressure, low high-density lipoprotein-cholesterol and increased waist circumference. CONCLUSION: Our results showed that WF was an independent risk factor for MS after 7 years of follow-up. Moreover, subjects without WF were also at risk for MS, due to the highest weight gain during follow-up. These results support the benefits of weight stability and emphasize the importance of weight gain prevention starting from early adulthood.
Abstract: OBJECTIVE: To evaluate the ability of the Framingham risk function to predict the 10-year coronary heart disease (CHD) risk in French men. METHODS: 3440 men, aged 45 to 60years, free of CHD at baseline, were selected from the SU.VI.MAX cohort. The expected number of event, obtained from applying the Framingham risk score to the baseline SU.VI.MAX biological and clinical data of 1994/1996, were compared to the actual risks observed in the cohort. The accuracy of the Framingham risk function was assessed using the area under the receiver operating characteristic (ROC) curve. RESULTS: The overall Framingham risk function predicted twice as many CHD events than observed. The area under the ROC curve for Framingham risk score was 74%. CONCLUSION: The Framingham risk function may discriminate between high risk from low risk subjects, but it is not valid for estimating absolute 10-year CHD risk in this French population.
Abstract: Plasma aldosterone and renin levels have been associated with blood pressure increase and 3-4 year incidence of hypertension in a middle-aged North American community in Framingham. To confirm these findings in a different population, a nested case-control study was performed in a national sample of 1984 French non-hypertensive volunteers aged 45-64 year and followed for 5 years. Cases and controls (individuals becoming hypertensive or remaining non-hypertensive on follow-up) were individually matched on sex, diastolic and systolic pressures at baseline. Multivariable regression models show that plasma aldosterone and renin are respectively positively and negatively associated with the increase in systolic pressure (P=0.01 and 0.001) and the risk of hypertension (22% increase and 16% decrease per s.d. increment in the log, P=0.04 and 0.07). These associations are mostly observed in the lowest tertiles of dietary sodium and potassium intakes where plasma aldosterone is positively associated with the increase in systolic pressure (P=0.01 and 0.08) and the risk of hypertension (59 and 69% increase per s.d. increment in the log, P=0.02 and 0.01), whereas plasma renin is negatively associated with the increase in systolic pressure (P=0.0004 and 0.004) and the risk of hypertension (31 and 28% decrease per s.d. increment in the log, P=0.03 and 0.05). These results reinforce the hypothesis that high plasma aldosterone and low plasma renin levels precede blood pressure increase and the occurrence of hypertension in middle-aged Caucasian populations.Journal of Human Hypertension advance online publication, 1 May 2008; doi:10.1038/jhh.2008.27.
Abstract: Objective: We performed a comprehensive genetic association study of common variation spanning the IGF2BP2 locus, in order to replicate the association of the 'confirmed' type 2 diabetes susceptibility variants rs4402960 and rs1470579 in the French Caucasian population, and to further characterise the susceptibility variants at this novel locus. Research Design and Methods: We genotyped a total of 21 tagging SNPs spanning the IGF2BP2 locus in our type 2 diabetes case-control cohort comprising in 3,093 French Caucasian subjects. Results: IGF2BP2 variants rs4402960 and rs1470579 were not associated with type 2 diabetes in the present study (P = 0.632 and P = 0.896, respectively). Meta-analysis of genotype data from over 34,000 subjects demonstrated that our inability to replicate rs4402960/rs1470579 was consistent with the findings from several previous GWAS datasets that were under-powered to detect this modest association signal (OR 1.14). We obtained novel evidence that rs9826022, a borderline rare variant (5% MAF) in the 3' downstream region, was associated with type 2 diabetes (P = 0.0002; OR 1.53 [95% CI 1.22-1.91]). This result was corroborated by the meta-analysis of 10,542 genotypes from the current study and GWAS datasets using both fixed (P = 9.47 x 10(-6); OR 1.30 [95% CI 1.16-1.46]) and random effects (P = 0.001; 1.30 [95 %CI 1.11-1.52)] calculations. Conclusions: We were unable to replicate the confirmed rs4402960/rs1470579 susceptibility variants, but found novel evidence for a rare variant in the 3' downstream region of IGF2BP2. Further genetic and functional studies are required to identify the aetiological IGF2BP2 variants.
Abstract: We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses.
Abstract: The aim was to estimate the association between dairy products (total and their subgroups), calcium intake and the risk of breast cancer. As few studies have considered menopausal status, we also investigated stratified analyses. This analysis included 3,627 women from the French SU.VI.MAX study, among whom 92 developed breast cancer during the follow-up period. Food consumption was assessed based on five 24-hour records completed during the previous 18 months to follow-up. Calcium intake was calculated using an ad-hoc food composition database. Cox proportional hazards models were used to estimate relative risk (RR), comparing 4th quartile vs. 1st quartile, and 95% confidence intervals (95% CI). A lower risk of breast cancer was observed with high total dairy product consumption in the whole population (RR = 0.55, 95% CI = 0.29-1.03, p(trend) = 0.03) and among premenopausal women with a RR of 0.35 (95% CI = 0.12-0.95, p(trend) = 0.01). None of these associations remained after control for calcium intake. Increasing calcium intake was inversely associated with breast cancer risk considering the whole population (RR = 0.50, 95% CI = 0.27-0.91, p(trend) = 0.04) and among the subgroup of premenopausal women (RR = 0.26, 95% CI = 0.10-0.71, p(trend) = 0.01) respectively. Our data support the hypothesis that dairy products, through calcium content or a correlated component, might have a negative association with the risk of breast cancer, particularly among premenopausal women.
Abstract: Objective:To measure the correlations between habitual intakes of individual n-6 and n-3 polyunsaturated fatty acids (PUFA) and their percentages in total plasma fatty acids in a population of adult men and women.Subjects/Methods:Two hundred and seventy-six men and 257 women aged 45-60 (men) or 35-60 (women) at baseline, volunteers of the French SU.VI.MAX cohort. Fifteen 24-h record questionnaires were used to estimate the habitual intake of energy, total fat and linoleic, alpha-linolenic acid, arachidonic, eicosapentaenoic (EPA), n-3 docosapentaenoic (DPA) and docosahexaenoic (DHA) acids. Fatty acid composition of fasting plasma total lipids has been determined at baseline.Results:Dietary intakes of linoleic acid, arachidonic acid, EPA and DHA were weakly but significantly correlated (0.16<r<0.28, P<0.01) with their respective percentages in plasma total fatty acids in both men and women. No correlation was observed between the plasma levels of alpha-linolenic acid and its dietary intake, and between the plasma levels of arachidonic acid and long-chain n-3 PUFA and the intakes of their 18-carbon precursors, linoleic and alpha-linolenic acid, respectively.Conclusions:The percentages of linoleic acid, arachidonic acid, EPA and DHA in plasma total fatty acids, but not that of alpha-linolenic acid, are acceptable markers of their habitual levels of intake. The plasma levels of long-chain n-6 and n-3 PUFA are not influenced by the intake levels of their precursors, linoleic and alpha-linolenic acids.European Journal of Clinical Nutrition advance online publication, 11 July 2007; doi:10.1038/sj.ejcn.1602836.
Abstract: CONTEXT: The melanin-concentrating hormone receptor 2 (MCHR2) is a G protein-coupled receptor for melanin-concentrating hormone, a neuropeptide that plays an important role in feeding behaviors. MCHR2 maps on chromosome 6q16.3, in a susceptibility locus for childhood obesity. OBJECTIVE: The aim of this study was to investigate the association between MCHR2 variation and human obesity. DESIGN: Case control and family-based studies were performed. PARTICIPANTS: A total of 141 obese children and 24 nonobese adult subjects was sequenced, and case-control analyses were conducted using 628 severely obese children and 1,401 controls. RESULTS: There were 11 single nucleotide polymorphisms (SNPs) identified. We showed nominal association among -38,245 ATG A/G SNP (P = 0.03; 95% confidence interval 1.02-1.34; odds ratio 1.17), A76A T/C SNP (P = 0.03; 95% confidence interval 0.58-0.97; odds ratio 0.75), and childhood obesity. Analysis of 645 trios with childhood obesity supported further the A76A T/C association, showing an overtransmission to obese children of the at risk T allele (59.0%; P = 0.01), especially in children with most severe forms of obesity (Z score of body mass index > 4) (67.0%; P = 0.003). The A76A at risk T allele was also associated with overeating during meals (P = 0.02) in an additional group of 102 nonobese children. None of the MCHR2 variants, including the A76A SNP, showed association with adult severe obesity, although a trend for association of the T allele of this variant with food disinhibition (P = 0.06) and higher hunger (P = 0.09) was found. This variant was not associated with childhood obesity in an independent case-control study, including 1,573 subjects (P = 0.98). Moreover, the A76A SNP did not explain the linkage on the 6q locus. CONCLUSION: Our results altogether suggest that MCHR2 is not a major contributor to polygenic obesity and support a modest effect of the A76A SNP on food intake abnormalities in childhood.
Abstract: BACKGROUND: Travel health information includes warning on sun exposure, particularly for fair-skinned individuals travelling to tropical countries. METHOD: A self-completed questionnaire on sun exposure behaviour was sent to the 12,741 French adults enrolled in the SU.VI.MAX cohort. Among the 7822 participants, 196 (110 women and 86 men) declared at least one visit to a high UV-index country over the past year for more than 1 month, subsequently referred to as long-term travellers. The remaining 7626 participants (non-travellers) accounted for 4862 women and 2764 men. RESULTS: Women travellers declared more frequently skin exposure to the sun over the past year, practised tanning in high UV-index areas more than 2h daily, experienced intensive sun exposure than non-travellers. Moreover, they asserted that basking in the sun is very important. Comparable results were found in men. The use of sun protection products was similar in travellers and non-travellers, but women tended to use sunscreen products more often, more regularly and with a higher sun protection factor (SPF) than men. CONCLUSIONS: Specific health education campaigns and pre-travel advice aiming to reduce sun exposure and to improve protective measures against ultraviolet (UV) radiation should be addressed to travellers to countries with high UV-index.
Abstract: BACKGROUND: Although short-term effects of the Dietary Approaches to Stop Hypertension (DASH) diet on blood pressure have been shown in intervention studies, less is known about the long-term effects. OBJECTIVE: The aim was to study the relation between dietary patterns based on DASH diet characteristics and blood pressure (BP) and BP change in a clinical trial of antioxidants conducted in France from 1994 to 2002. DESIGN: Repeated 24-h dietary records were collected during the first year of follow-up. Dietary variables studied included fruit and vegetables, dairy products and fat (defined by Keys score), and two hypothesis-oriented scores based on the DASH diet. We performed a cross-sectional analysis of BP measured at the first clinical examination (1995-1996) in 4652 participants aged 35-63 y and a longitudinal analysis of BP change over a median follow-up of 5.4 y (n = 2341). RESULTS: The mean increases in systolic (SBP) and diastolic (DBP) BPs were 9.3 and 4.5 mm Hg, respectively. After adjustment for potential confounders, higher fruit and vegetable consumption was associated with lower SBP and DBP at first clinical examination (P for trend < 0.02 for both) and a lower 5-y increase in SBP (-2.1 mm Hg in the 4th compared with the 1st quartile; P for trend < 0.004) and DBP (-0.7 mm Hg in the 4th compared with the 1st quartile; P for trend < 0.03). The 2 DASH scores also were significantly associated with a lower BP at the first clinical examination and a lower BP increase. No significant relations were observed with dairy products or Keys score in either analyses. CONCLUSION: These results suggest that high fruit and vegetable intakes may be associated with a lower increase in BP with aging.
Abstract: BACKGROUND: Overexposure to sunlight during long stays in tropical countries can reveal short- and long-term harmful effects on the skin of Caucasian residents, especially for fair-skinned subjects. The aim of this study was to describe sun exposure and sun protection behaviors during lifetime among French adults who declared having experienced at least one expatriation period in tropical or high-sun index areas for a duration of more than three consecutive months. METHODS: A self-reported questionnaire on sun exposure behavior was addressed two times, in 1997 and 2001, to the 12,741 French adult volunteers enrolled in the SU.VI.MAX cohort. A total of 8,084 subjects answered to the first survey and 1,332 additional responders answered to the second. Among the 9,416 individuals, 1,594 (652 women and 942 men) corresponded to expatriates and the remaining 7,822 to nonexpatriates (4,972 women and 2,850 men). A descriptive analysis of sun exposure and sun protection behaviors during lifetime of expatriates and nonexpatriates was performed by gender. RESULTS: Among women, 39% of expatriates belonged to the 50 to 60 class of age at inclusion, versus 33% in nonexpatriates (72 and 55% in men, respectively). In women, expatriates declared more frequently having during lifetime exposed voluntarily their skin to the sun, practiced tanning between 11 a.m. and 4 p.m., less gradually exposed their skin, experienced intensive sun exposure, and exposed their skin during nautical sports and practiced naturism. In men, expatriates declared more frequently having experienced intensive sun exposure and exposed their skin during outdoor occupations and during nautical and mountain sports. CONCLUSIONS: Although expatriates are aware of travel health advices concerning the countries where they planned to stay, they are usually poorly informed about sun exposure risk factors. Such individuals who planned to expatriate in countries with a high ultraviolet index should benefit from a visit to a travel clinic including specific health care information for risk related to sun exposure, ie, skin cancers and photoaging.
Abstract: Candidate gene analyses are often inconclusive owing to genetic or phenotypic heterogeneity, low statistical power, selection of nonfunctional SNPs, and inadequate statistical analysis of the genetic architecture. Angiotensin-converting enzyme (ACE) is involved in adipocyte growth and function and the ACE-processed angiotensin II inhibits adipocyte differentiation. Associations between body mass index (BMI) and ACE polymorphisms have been reported in general populations, but the contribution to severe obesity of this gene, which is located under an obesity genome-scan linkage peak on 17q23, is unknown. ACE is one of the most studied genes and markers responsible for variation in circulating ACE enzyme levels have been extensively characterised. Eight of these variants were genotyped in 1054 severely obese cases and 918 nonobese controls, as well as 116 nuclear families from the genome scan (n=447), enabling the known clades to be inferred. Qualitative analysis of individual single-nucleotide polymorphisms (SNPs), haplotypes, clades, and diploclades demonstrated no significant associations (P<0.05) after minimal correction for multiple testing. Quantitative analysis of clades and diploclades for BMI, waist-to-hip ratio, or ZBMI in children were also not significant. This rigorous, large-scale study of common, well-defined, severe polygenic obesity provides strong evidence that functionally relevant sequence variation in ACE, whether it is defined at the level of SNPs, haplotypes, or clades, is not associated with severe obesity in French Caucasians. Such a study design exemplifies the strategy needed to clearly define the contribution of the ACE gene to the plethora of complex genetic diseases where weak associations have been previously reported.
Abstract: BACKGROUND: Few studies suggest that the combined increase in plasma triglycerides (TG) and in waist circumference (WC), termed 'hypertriglyceridemic waist' (HTGW), is an interesting marker of risk for cardiovascular disease (CVD). OBJECTIVE: Using cutoffs used for defining HTGW, we examined the prospective association of HTGW with CVD risk in a French cohort of men. DESIGN: Men were participants in the SU.VI.MAX study, an intervention trial testing the impact of an antioxidant supplementation on chronic diseases. Data were collected in 1994-1996 in 3430 men followed up for 7.5 years. Cutoffs used for defining HTGW were WC > or =90 cm and TG > or =2 mmol/l. We assessed the relative risk (RR) (95% confidence interval (CI)) of CVD in groups defined according to both WC and TG levels. RESULTS: In this population, 41.2% of the subjects were classified as low WC/low TG, 43.2% as high WC/low TG, 3.5% as low WC/high TG and 12.1% as HTGW. During follow-up, 122 subjects had a CVD event. In this group, HTGW prevalence was 26.2%. After adjustment for age, RR (95% CI) for CVD for the HTGW group showed the highest association with CVD risk: 2.13 (1.21-3.76), using low WC/ low TG as the reference group. CONCLUSION: HTGW was associated with the risk of CVD after 7.5 years of follow-up in a low-risk middle-aged men population. This marker may be used as a useful clinical tool to screen for men at risk of CVD.
Abstract: AIMS/HYPOTHESIS: Genetic variants of genes for peptide YY (PYY), neuropeptide Y2 receptor (NPY2R) and pancreatic polypeptide (PPY) were investigated for association with severe obesity. SUBJECTS AND METHODS: The initial screening of the genes for variants was performed by sequencing in a group of severely obese subjects (n=161). Case-control analysis of the common variants was then carried out in 557 severely obese adults, 515 severely obese children and 1,163 non-obese/non-diabetic control subjects. Rare variants were genotyped in 700 obese children and the non-obese/non-diabetic control subjects (n=1,163). RESULTS: Significant association was found for a 5' variant (rs6857715) in the NPY2R gene with both severe adult obesity (p=0.002) and childhood obesity (p=0.02). This significant association was further supported by a pooled allelic analysis of all obese cases (adults and children, n=928) vs the control subjects (n=938) (p=0.0004, odds ratio=1.3, 95% CI 1.1-1.5). Quantitative trait analysis of BMI and WHR was performed and significant association was observed for SNP rs1047214 in NPY2R with an increase in WHR in the severely obese children (co-dominant model p=0.005, recessive model p=0.001). Association was also observed for an intron 3 variant (rs162430) in the PYY gene with childhood obesity (p=0.04). No significant associations were observed for PPY variants. Only one rare variant in the NPY2R gene (C-5641T) was not found in lean individuals and this was found to co-segregate with obesity in one family. CONCLUSIONS/INTERPRETATION: These results provide evidence of association for NPY2R and PYY gene variants with obesity and none for PPY variants. A rare variant of the NPY2R gene showed evidence of co-segregation with obesity and its contribution to obesity should be investigated further.
Abstract: OBJECTIVE: A number of potential health effects have lately been accorded to tea consumption. It is, however, not clear whether an increase in tea consumption increases the risk of iron depletion in a normal apparently healthy adult population. We have therefore evaluated this. DESIGN: Cross-sectional study. SUBJECTS: A total of 954 men (aged 52-68 years) and 1639 women (aged 42-68 years), who were participants of SU.VI.MAX Study, completed a detailed questionnaire on tea consumption. To determine the iron status of the participants, a venous blood sample was drawn and serum-ferritin was measured. Iron depletion was defined as a serum ferritin concentration <16 microg/l. Three 1-day food records were used to estimate the intake of other dietary enhancing or inhibiting factors of iron absorption, which were included in the logistic regression models. RESULTS: The mean serum-ferritin concentration was not related to black, green and herbal tea consumption in men, pre- or postmenopausal women. Also the risk of iron depletion was in the multivariate model not related to any kind of tea drinking or to the strength of tea, the infusion time or the time of tea drinking. CONCLUSIONS: The data suggest that normal apparently healthy adults are not at risk of iron depletion owing to any kind of tea drinking.
Abstract: Cognitive impairment can be influenced by a number of factors. The potential effect of nutrition has become a topic of increasing scientific and public interest. In particular, there are arguments that nutrients (food and/or supplements) such as vitamins, trace minerals, lipids, can affect the risk of cognitive decline and dementia, especially in frail elderly people at risk of deficiencies. Our objective in this paper is to review data relating diet to risk of cognitive decline and dementia, especially Alzheimer's disease (AD). We chose to focus our statements on homocysteine-related vitamins (B-vitamins), antioxidant nutrients (vitamins E and C, carotenoids, flavonoids, enzymatic cofactors) and dietary lipids. Results of epidemiological studies may sometimes appeared conflicting; however, certain associations are frequently found. High intake of saturated and trans-unsaturated (hydrogenated) fats were positively associated with increased risk of AD, whereas intake of polyunsaturated and monounsaturated fats were protective against cognitive decline in the elderly in prospective studies. Fish consumption has been associated with lower risk of AD in longitudinal cohort studies. Moreover, epidemiologic data suggest a protective role of the B-vitamins, especially vitamins B9 and B12, on cognitive decline and dementia. Finally, the results on antioxidant nutrients may suggest the importance of having a balanced combination of several antioxidant nutrients to exert a significant effect on the prevention of cognitive decline and dementia, while taking into account the potential adverse effects of these nutrients. There is no lack of attractive hypotheses to support research on the relationships between nutrition and cognitive decline. It is important to stress the need to develop further prospective studies of sufficiently long duration, including subjects whose diet is monitored at a sufficiently early stage or at least before disease or cognitive decline exist. Meta analyses should be developed, and on the basis of their results the most appropriate interventional studies can be planned. These studies must control for the greatest number of known confounding factors and take into account the impact of the standard social determinants of food habits, such as the regional cultures, social status, and educational level.
Abstract: This research aimed to test whether supplementation with a combination of antioxidant vitamins and minerals could reduce the risk of skin cancers (SC). It was performed within the framework of the Supplementation in Vitamins and Mineral Antioxidants study, a randomized, double-blinded, placebo-controlled, primary prevention trial testing the efficacy of nutritional doses of antioxidants in reducing incidence of cancer and ischemic heart disease in the general population. French adults (7876 women and 5141 men) were randomized to take an oral daily capsule of antioxidants (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 microg selenium, and 20 mg zinc) or a matching placebo. The median time of follow-up was 7.5 y. A total of 157 cases of all types of SC were reported, from which 25 were melanomas. Because the effect of antioxidants on SC incidence varied according to gender, men and women were analyzed separately. In women, the incidence of SC was higher in the antioxidant group [adjusted hazard ratio (adjusted HR) = 1.68; P = 0.03]. Conversely, in men, incidence did not differ between the 2 treatment groups (adjusted HR = 0.69; P = 0.11). Despite the small number of events, the incidence of melanoma was also higher in the antioxidant group for women (adjusted HR = 4.31; P = 0.02). The incidence of nonmelanoma SC did not differ between the antioxidant and placebo groups (adjusted HR = 1.37; P = 0.22 for women and adjusted HR = 0.72; P = 0.19 for men). Our findings suggest that antioxidant supplementation affects the incidence of SC differentially in men and women.
Abstract: A low folate intake or a low folate status have been found to be associated with a higher frequency of depression in populations, but the existence and the direction of a causal link between folate intake or status and depression is still uncertain. The aim of this study was to seek the relation between the habitual folate intake in middle-aged men and women and the occurrence of depressive episodes. In a subsample of 1864 subjects (809 men and 1055 women) from the French SU.VI.MAX cohort, dietary habits have been measured at the beginning of the follow-up (six 24 h records) and declarations of antidepressant prescription, taken as markers of depressive episodes, have been recorded during the 8-year follow-up. No significant association was observed between folate intake and the risk of any depressive episode or of a single depressive episode during the follow-up, in both men and women. In contrast, the risk of experiencing recurrent depressive episodes (two or more) during the follow-up was strongly reduced in men with high folate intake (OR 0.25 (95 % CI 0.06, 0.98) for the highest tertile v. the lowest, P for trend 0.046). This association was not observed in women. These results suggest that a low folate intake may increase the risk of recurrent depression in men.
Abstract: Significant differences in serum selenium concentration according to contraceptive treatment and age have been evidenced in women of the SU.VI.M.AX cohort. This study aimed at verifying the physiopathological hypothesis that the observed increase in serum selenium concentration could be related to serum lipid increase and/or bleeding decrease. Women were divided into six groups: menopausal with or without hormonal replacement therapy; non-menopausal using contraceptive pills; intrauterine device; other contraceptive treatment or no contraceptive treatment. Adjusted linear regression indicated positive associations between selenium and apolipoprotein A1 (r(2) from 0.038 to 0.074, p<0.07 depending on groups) or ferritin in serum (r(2) from 0.032 to 0.075, p<0.07 depending on groups). These relationships could explain the differences observed according to hormonal treatment and age in the SU.VI.MAX study.
Abstract: Objective To examine a possible relationship between alcohol consumption and thyroid volume and function. Subjects 1493 subjects, 599 males (45-60 years old) and 894 females (35-60 years old) with no known thyroid disorders and who were participating in the SU.VI.MAX study. Measures Daily dietary intakes and alcohol consumption in grams per day were based on five 24-h dietary records. Thyroid volume and structure were measured by ultrasonography. At baseline, TSH and free T(4) were measured. Results Male and female drinkers consumed (mean +/-SD), respectively, 30.6 g (+/-23.3) and 14.2 g (+/-13.4) of ethanol per day. There was a decrease in carbohydrate intake with higher alcohol consumption among male (P= 0.0001) and female drinkers (P= 0.06). Alcohol intake was associated with higher thyroid volume in males and females independently of iodine status. Multivariate odds ratios (ORs, 95% CI) of thyroid enlargement (sex-specific 85th percentile values of >/=20 ml for males, >/=14 ml for females) in males and females who drank >/=45 g/day and >/=20 g/day, respectively, were 2.22 (1.10-4.47) and 2.1 (1.15-3.90) compared with low drinkers, and 11.75 (2.15-64.12) and 2.03 (1.04-3.96) compared with abstainers. ORs were slightly increased when smokers were excluded. Alcohol intake was associated with low free T(4) levels in male drinkers independently of TSH. Conclusions An increasing dose-response relationship was found between alcohol intake levels and ORs for thyroid enlargement in both males and females. Alcohol consumption was strongly associated with a higher risk in females.
Abstract: BACKGROUND: Prevalence of clinically manifest orofacial herpes in the general population is poorly characterized. Objectives To establish the lifetime prevalence of clinically manifest orofacial herpes and its relationship with herpes simplex virus (HSV) serotype in the French general population. PATIENTS/METHODS: Subjects (N = 2796) were serotyped for HSV1 and HSV2 and provided data on herpetic symptoms by questionnaire. Subjects reporting at least one episode of orobuccal ulcerative mucosal lesions were classified as clinically manifest orofacial herpes. RESULTS: Lifetime prevalence of clinically manifest orofacial herpes was 38.3% (42.1% in women, 32.4% in men). Prevalence in subjects seropositive for HSV1 was 50.3%. This prevalence rate was independent of HSV2 serotype. Prevalence in subjects infected with HSV2 alone was similar to that in subjects seronegative for HSV. LIMITATIONS: Lack of case ascertainment limits precision of the data. CONCLUSIONS: Clinically manifest orofacial herpes was reported in one third of the sample, principally associated with HSV1 infection. HSV2 infection did not produce orofacial lesions nor influence clinical manifestations of HSV1 infection.
Abstract: AIM: Few studies have investigated the relationship between iron stores and measures of atherosclerosis. Most of these studies were cross-sectional and yielded conflicting results. We aimed to assess the relationship between serum ferritin concentrations and dietary iron intake measured at baseline and 7.5 year pulse wave velocity (PWV), intima-media thickness (IMT) and plaques in a group of 824 men and women without known CVD, cancer or hemochromatosis. METHODS: The SUVIMAX study is a randomized double-blind, placebo-controlled primary prevention trial designed to test the effect of antioxidant supplementation in reducing ischemic cardiovascular diseases and cancer. RESULTS: In multivariate analyses, no association was found between baseline serum ferritin levels and IMT 7 years later (beta (95% CI)=0.003 (-0.005;0.011) in men; -0.005 (-0.013;0.004) and -0.001 (-0.011;0.009) in women, before and after menopause, respectively), plaques (OR (95% CI)=1.09 (0.88;1.34) in men; 0.93 (0.66;1.31) and 0.95 (0.70;1.29) in women, before and after menopause, respectively) or PWV (beta (95% CI)=0.078 (-0.154;0.310) in men; -0.018 (-0266;0.231) in women before and after menopause). Results for dietary iron intake were similar. CONCLUSION: Our results do not support the hypothesis that dietary iron intake and body iron stores are deleterious to the structure and function of large arteries in subjects free of CVD, cancer or hemochromatosis.
Abstract: OBJECTIVE: This trial evaluated the effect of antioxidant supplementation on the urinary excretion of 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio, a marker of the pathogenesis of thrombosis and arteriosclerosis. METHODS: This study was a randomised, double-blind, placebo-controlled trial involving 186 presumably healthy volunteers. One hundred received a multi-antioxidant supplementation and 86 a placebo for two years. Blood zinc, selenium, beta-carotene, vitamin C and E and urinary excretion of 11-dehydro TXB(2) and 2,3 dinor 6 keto PGF(1alpha) were measured. RESULTS: Baseline subject characteristics did not differ between the two groups. Blood zinc, selenium, and beta-carotene concentrations significantly increased between baseline and two years in the multi-antioxidant supplementation group supporting subject compliance (p < 0.05). At two years, the median urinary 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio was significantly lower in the multi-antioxidant supplementation group (3.4 versus 2.78, p = 0.015). Serum selenium concentration was the only antioxidant studied that was significantly related to the urinary 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio. CONCLUSIONS: These results support the hypothesis that a low-dose multi-antioxidant supplementation may contributes to a reduction in platelet activation which is beneficial for cardiovascular function.
Abstract: Iron deficiency has been suspected to represent one of the possible causes of excessive hair loss in women. The aim of our study was to assess this relationship in a very large population of 5110 women aged between 35 and 60 years. Hair loss was evaluated using a standardized questionnaire sent to all volunteers. The iron status was assessed by a serum ferritin assay carried out in each volunteer. Multivariate analysis allowed us to identify three categories: "absence of hair loss" (43%), "moderate hair loss" (48%) and "excessive hair loss" (9%). Among the women affected by excessive hair loss, a larger proportion of women (59%) had low iron stores (< 40 microg/L) compared to the remainder of the population (48%). Analysis of variance and logistic regression show that a low iron store represents a risk factor for hair loss in non-menopausal women.
Abstract: OBJECTIVES/HYPOTHESIS: To evaluate, by a prospective questionnaire study, the incidence of spontaneous nasal pathology in mature women over a 12-month period, in particular nasal bleeding and the relationships of these symptoms with various factors. METHODS: Participants were drawn from a sample of 12,735 adult French volunteers participating in a study of antioxidant nutrients ("SU.VI.MAX"); 3500 women aged 50-64 years were randomly selected from good responders in the SU.Vl.MAX population. The responses of 2197 women were analysed. RESULTS: Nearly 70% of subjects reported at least one episode of rhinitis, with a mean (SD) of 1.88 (2.17) episodes per subject. Rhinitis was related to passive exposure to tobacco smoke (adjusted odds ratio [OR] 1.31, 95% CI 1.05-1.63), menopause (OR 1.47, 95% CI 1.16-1.88), and occupational exposure to vapours or dusts (OR 1.55, 95% CI 1.01-2.37). Nasal bleeding was reported as traces of blood by 16.5% of subjects, and as epistaxis (significant nasal bleeding) by 7.6%. Both symptoms were related to passive exposure to tobacco smoke (OR 1.63, 95% CI 1.22-2.19; OR 1.56, 95% CI 1.05-2.32, respectively) but not to use of systemic or topical medication. CONCLUSION: A substantial number of mature women experience nasal symptoms during the course of a year. Rhinitis and nasal bleeding were correlated with passive exposure to tobacco smoke.
Abstract: CONTEXT: Heterozygous mutations in the melanocortin-4 receptor (MC4R) gene are the most common monogenic form of severe obesity in children. There are conflicting reports regarding the prevalence, nature, and pathogenic effects of MC4R mutations in adults with severe late-onset obesity. OBJECTIVE: Our objective was to determine the prevalence of MC4R mutations in a cohort of severely obese adults and to determine the clinical phenotype and the phenotype-genotype relationship within adult MC4R mutation carriers. DESIGN AND SETTING: We conducted an observational study at a referral center. PATIENTS OR OTHER PARTICIPANTS: Participants included 769 adult patients with body mass index of at least 35 kg/m(2) and 444 nonobese control individuals. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: We assessed the prevalence of pathogenic MC4R mutations, functional characteristics of the detected mutations, phenotype, and phenotype-genotype relationship within mutation carriers. RESULTS: The global prevalence of obesity-specific MC4R mutations was 2.6%, and the 95% confidence interval (CI(95)) was 1.5-3.7. The prevalence of MC4R mutations was similar in patients developing obesity in childhood (2.83%; CI(95), 0.9-4.8) and in patients with a later onset of the disease (2.35%; CI(95), 0.9-3.8). Adult obese MC4R mutation carriers did not present with binge eating or with any specific clinical phenotype. The severity of the functional alterations of the mutated MC4Rs and in particular the intracellular retention of the receptor correlates both with the severity and the onset of the obesity in the mutation carriers. CONCLUSIONS: Obese adult carriers of functionally relevant MC4R mutations do not specifically present with binge-eating disorder or a history of early-onset obesity. The onset and severity of the obesity in the carriers is related to the functional severity of the MC4R mutations.
Abstract: Estimation of dietary intake of polyphenols is difficult, due to limited availability of food composition data and bias inherent to dietary assessment methods. The aim of the present study was to evaluate the associations between the intake of polyphenol-rich foods and the urinary excretion of several phenolic compounds and therefore explore whether these phenolic compounds could be used as a biomarker of intake. Fifty-three participants of the SU.VI.MAX study (a randomised primary-prevention trial evaluating the effect of daily antioxidant supplementation on chronic diseases) collected a 24 h urine and a spot urine sample and filled a dietary record during a 2 d period. Thirteen polyphenols and metabolites, chlorogenic acid, caffeic acid, m-coumaric acid, gallic acid, 4-O-methylgallic acid, quercetin, isorhamnetin, kaempferol, hesperetin, naringenin, phloretin, enterolactone and enterodiol, were measured using HPLC-electrospray ionisation-MS-MS. In spot samples apple consumption was positively correlated to phloretin, grapefruit consumption to naringenin, orange to hesperetin, citrus fruit consumption to both naringenin and hesperetin, with r coefficients ranging from 0.31 to 0.57 (P < 0.05). The combination of fruits and/or fruit juices was positively correlated to gallic acid and 4-O-methylgallic acid, isorhamnetin, kaempferol, hesperetin, naringenin and phloretin (r 0.24-0.44, P < 0.05). Coffee consumption was positively correlated to caffeic and chlorogenic acids (r 0.29 and 0.63, P < 0.05 respectively). Black tea and wine consumption were positively correlated with gallic and 4-O-methylgallic acids (r 0.37-0.54, P < 0.001). The present results suggest that several polyphenols measured in a spot urine sample can be used as biomarkers of polyphenol-rich food intake.
Abstract: BACKGROUND: To study the association between the total plasma homocysteine (tHcy) concentration and the carotid artery intima-medial wall thickness (IMT), pulse wave velocity (PWV) and the presence of arterial plaques in a French population. METHODS: Cross-sectional analysis of data from 556 male and 559 female middle-aged participants (mean (+/-SD) age 59.6+/-4.7 years) provided by an ongoing intervention trial. RESULTS: Mean geometric tHcy concentration was higher for men than for women (10.6 vs. 8.5 micromol/L, p<0.001) and was associated in the expected direction with known determinants. The mean IMT was 0.71+/-0.1 mm for men and 0.69+/-0.1 mm for women (p<0.001), the mean PWV was, respectively, 12.0+/-2.8 and 10.9+/-2.2 m/sec (p<0.001), and the percentages of subjects with plaques were, respectively, 40.8% and 22.7% (p<0.001). In men only, the age-adjusted mean IMT and PWV increased with an increasing tHcy concentration: the IMT was 0.71 mm in the first tHcy-quartile and 0.73 mm in the fourth tHcy-quartile (p for linear trend=0.03), the PWV values were, respectively, 11.6 and 12.4 m/sec (p for linear trend=0.01). These associations disappeared after adjustment for conventional cardiovascular disease risk factors. CONCLUSION: In this population, the tHcy concentration was not associated with measures of arterial thickness and stiffness.
Abstract: BACKGROUND: Imported malaria remains an important, but often unrecognised, health problem in Europe. Little information exists on the incidence of imported malaria with respect to exposure. This study aimed to estimate the incidence of malaria in a cohort of travellers with respect to protection measures. METHOD: In all 13,017 participants enrolled in a French general population cohort (SU.VI.MAX cohort) and followed-up over 8 years were investigated. All participants received a retrospective questionnaire about travel to malaria-endemic countries relating to countries visited, duration of stay, use of protection measures and chemoprophylaxis. Malaria cases was confirmed from medical records. RESULTS: Data were obtained for 752 individuals who made 1,393 trips to malaria-endemic areas. This sample was predominantly middle-class and high-risk groups such as migrants were not represented. Mechanical protection was used in 589 trips (42.3%) and chemoprophylaxis in 1,017 trips (73.0%). This was appropriate for the zone in 615 trips (44.0%) and adequate compliance was reported in the case of 497 trips (35.6%). Appropriate chemoprophylaxis and physical protection measures were used in 21.7% of the trips. Six laboratory-confirmed cases of imported malaria yielded an estimated incidence density of 148 cases/month of exposure/10,000 travellers. In five cases, appropriate protection measures had not been taken. CONCLUSION: Appropriate chemoprophylaxis and physical protection measures against malaria infection are used by less than one-quarter of a sample of predominantly middle-class travellers from France to endemic areas. More intense education measures need to be implemented to reduce the risk of imported malaria.
Abstract: BACKGROUND: Longitudinal administration of health-related quality of life instruments to a general, initially healthy population allows for changes to be assessed as they occur, rather than afterwards. The aim here was to investigate the impact of coronary artery disease occurrence on health-related quality of life. RESULTS: The 36-item Short-Form questionnaire was applied to the French SU.VI.MAX cohort in 1996 and 2001. Findings in 62 patients who developed coronary artery disease between the two measures were compared with those in 310 age- and sex-matched cardiovascular-free controls. The mean interval between the initial health-related quality of life assessment and coronary artery disease diagnosis was 34.5 (+/-19.6) months. Between the two health-related quality of life assessments, some dimensions decreased in the coronary artery disease group but not among controls. After adjustment (for body mass index, tobacco habits, diabetes and levels of circulating apolipoprotein A1 and B), the degree of change in health-related quality of life between the two groups differed by: -10.0 points (p=0.02) for the role-physical dimension, -10.6 points (p=0.02) for role-emotional, -4.7 points (p=0.03) for vitality and -8.8 points (p<0.0001) for general health. CONCLUSION: At an average of 2.5 years post-coronary artery disease diagnosis, aspects most likely to be affected were those with a component related to emotional and physical functioning, and vitality and general health. Close examination of the scores for each domain of the SF-36 reveals the most impaired aspects of health-related quality of life in subjects with coronary problems, thereby enabling practitioners to tailor their interventions.
Abstract: BACKGROUND: While a relationship between alcohol and cardiovascular risk factors is well established, data suggest that the type of alcoholic beverage could modulate this relationship.AIM OF THE STUDY: To determine whether drinking patterns modulate the relationship between alcohol and cardiovascular risk factors.METHODS: We tested the relationship between preference of alcoholic beverages and atherosclerotic risk factors in a cross-sectional study of 2,126 men. A hierarchical clustering method determined six drinking patterns, 'low drinkers', 'high quality wines', 'beer and cider', 'digestives', 'local wines', and 'table wines', according to the preferential intake of alcoholic beverages. Logistic models estimated the relative risk of abnormal markers in the drinking patterns compared with low drinkers. Unadjusted estimates investigated the relationship with the cluster as a group, while adjustment on alcohol, nutritional and socio-demographic factors investigated the relationship with the preference of alcoholic beverage in itself.RESULTS: Abstainers had high total plasma homocysteine (tHcy), even after full adjustment (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.8). Drinkers of high quality wine had low lipoprotein( a), high tHcy and high body mass index; beer and cider drinkers had high tHcy and waist circumference. Drinkers of digestives had high triacylglycerol; after adjustment they were at risk of low apolipoprotein A-I (OR = 3.1, 95% CI: 1.2, 7.3), and high tHcy (OR = 4.9, 95% CI: 1.2, 33.3). Local wines drinkers were similar to low drinkers. Table wine drinkers had high apolipoprotein B, high triacylglycerol, and high waist-to-hip ratio.CONCLUSION: Our data suggest that preference of alcoholic beverage could indicate groups at specific risks of atherosclerotic disease.
Abstract: Adiponectin is a metabolic link between adipose tissue and insulin action, mediating part of obesity-associated insulin resistance and type 2 diabetes. Two adiponectin receptors have been identified, and we investigated whether sequence variations in adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2) genes could contribute to the genetic risk for type 2 diabetes in a case-control study of 1,498 Caucasian subjects. We sequenced the putative functional regions of the two genes in 48 subjects and selected single nucleotide polymorphisms (SNPs) from the public database. Five SNPs in ADIPOR1 and 12 in ADIPOR2 were tested for association with type 2 diabetes. No SNP of ADIPOR1 showed association in any of the samples from the French population. In contrast, three SNPs of ADIPOR2 showed nominal evidence for association with type 2 diabetes before correction for multiple testing (odds ratio [OR] 1.29-1.37, P = 0.034-0.014); only rs767870, located in intron 6, was replicated in an additional diabetes dataset (n = 636, OR 1.29, P = 0.020) with significant allelic association from the overall meta-analysis of 2,876 subjects (adjusted OR 1.25 [95% CI 1.07-1.45], P = 0.0051). In conclusion, our data suggest a modest contribution of ADIPOR2 variants in diabetes risk in the French population.
Abstract: BACKGROUND: In intervention studies (DASH), high fruits and vegetables intake lower blood pressure (BP). Less is known on long-term effects of fruits and vegetables intake on BP, especially in European population. OBJECTIVE: To study the relation between fruits and vegetables intake and BP change in the SU.VI.MAX study. METHOD: In the SU.VI.MAX study (1994-2002), BP was measured and information on medical treatment was collected during two clinical examination session in 1995-1996 and 2001-2002. Dietary information came from 24 h dietary records completed every two months, by each volunteer during the first two years of follow-up. We performed a transversal analysis of BP measured at the first clinical examination in 6 427 subjects aged 36-62 years. A longitudinal analysis including subjects without hypertension at baseline was performed on BP change between the two examination (n=2958). RESULTS: At first examination, after adjusting for main confounding factors, subjects reporting high vegetables intake (last quintile) had a lower (-1.6 mmHg, p trend <0.01) systolic BP (SBP) than subjects reporting lower intake (first quintile). High fruits intake was slightly associated with lower SBP (1.1 mmHg, NS). At the end of the follow-up, the mean increase of SBP was of 9.5 mmHg. This increase was 2.2 mmHg lower (p < 0.003) in the last quintile of vegetables intake. No similar relation was observed with fruits intake. CONCLUSION: These results suggest that vegetables intake may be associated with lower BP and a lower increase of BP over years. This last association may have implications for the prevention of hypertension which appears with aging.
Abstract: The SU.VI.MAX study is a double blind, randomized, placebo-controlled trial testing, for 7,5 years, the effect of a combination of antioxidant vitamins and minerals, at doses considered to be nutritional (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 microg selenium and 20 mg zinc) in reducing cancer and ischemic vascular disease incidence in a general population (12.741 middle-aged). After 7.5 years, low-dose antioxidant supplementation had no effect on vascular disease incidence. This dose lowered, however, total cancer incidence in men, but not in women. With regard to contradictory results of observational and interventional studies published for the last decades, we can consider that the effect of antioxidants on cancer may depend on the doses (nutritional versus pharmacological), baseline antioxidant status (different between gender and/or nutritional status) and health status of subjects (healthy versus cancer high-risk subjects). Antioxidant supplementation may have a beneficial effect on cancer incidence only in healthy subjects who are not exposed to cancer risk, and with a particularly low baseline status. Finally, antioxidants as well as free radicals appear to be ambiguous nutrients with a wide range of benefits and toxicity. High doses of antioxidant supplements may be deleterious in high-risk subjects without any clinical symptoms in whom the initial phase of cancer development has already started.
Abstract: BACKGROUND AND PURPOSE: We examined the associations of parental longevity with carotid intima-media thickness, carotid plaques, and aortic arterial stiffness in adult offspring. METHODS: A population of 1117 volunteers who participated in the SUVIMAX Vascular Study (mean age, 59.7 years; 49.0% women) were included. Carotid-femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid B-mode ultrasound examination included measurements (at sites free of plaque) of intima-media thickness at the common carotid arteries and assessment of atherosclerotic plaques in the extracranial carotid arteries. RESULTS: The prevalence of carotid plaques in subjects whose fathers had died at <65 years, in those whose fathers were alive at 65 years but who had died by 80 years, and in those whose fathers were alive at 80 years was 40.4%, 30.4%, and 28.9%, respectively (P<0.001). The multivariate odds ratios of carotid plaques in the 3 groups of paternal longevity, adjusted for conventional cardiovascular risk factors, were 1, 0.68 (95% CI, 0.48 to 0.96), and 0.69 (95% CI, 0.49 to 0.98), respectively. The mean common carotid arteries intima-media thickness was higher in subjects with premature paternal death in univariate (P<0.007) but not in multivariate (P=0.39) analyses. Mean PWV decreased with increasing paternal longevity in both univariate and multivariate analyses. The multivariate-adjusted means of PWV in the 3 groups of paternal longevity were 11.9+/-0.14, 11.7+/-0.12, and 11.0+/-0.12 m/s (P<0.0001), respectively. In contrast, neither B-mode ultrasound measurements nor PWV measurements were associated with maternal longevity. CONCLUSIONS: These results may indicate that there are modifications of structure and function of large arteries according to paternal longevity.
Abstract: The object of this work was to determine the risk of hypertension after 6.5 years'- follow-up of supplementation in vitamins and antioxidant minerals at nutritional doses in the SU.VI.MAX trial. The authors also studied the association with plasma concentrations of antioxidants at inclusion and at long term. This was a randomised nutritional primary prevention study including 5086 adults of the SU.VI.MAX trial. After 6.5 years' follow-up, no effect of supplementation on the risk of developing hypertension could be shown compared with the placebo group: odds ratios (OR IC 95%): 1.04 (0.87-1.23) in men and 1.10 (0.95-1.29) in women. Besides, in the male 2nd and 3rd tertiles of serum beta-carotene levels at inclusion the risk of hypertension was lower [multivariate OR: 0.70 (0.44-1.12) and 0.53 (0.33-0.86) for placebo, and 0.59 (0.37-0.94) and 0.67 (0.42-1.07) for the supplemented groups]. The authors conclude that, despite a reverse relationship in men between the plasma concentrations of beta-carotene and the risk of hypertension, supplementation in antioxidants at nutritional doses had no effect on the risk of developing hypertension after 6.5 years' follow-up.
Abstract: A voluminous body of epidemiological research concerning the potential role of antioxidant nutrients in the prevention of cancers has accumulated over the past few decades. However, results of large recent intervention trials do not support a preventive effect against cancer for supplementation with antioxidant nutrients. Seemingly contradictory results between observational studies and randomised trials can be explained by the fact that doses used in clinical trials were much higher than the highest levels attained by the usual dietary intake which, in observational studies, were found to be associated with the lowest risk of cancer. Recently, the Supplementation en Vitamines et Mine raux Antioxydants (SU.VI.MAX) study, a randomised, double-blind, placebo-controlled primary prevention trial, tested the efficacy of supplementation with a combination of antioxidant vitamins and minerals, at nutritional doses, in reducing the cancer incidence in a general population not selected for risk factors. After 7.5 years, low-dose antioxidant supplementation lowered the total cancer incidence in men only. This may be explained by a lower baseline status of certain antioxidants in men compared to women. Finally, the effect of antioxidant supplementation on the incidence of cancer could depend on baseline antioxidant status (which differs from gender and/or nutritional status) and the health status of subjects (healthy v. cancer high-risk subjects). Antioxidant supplementation may have a beneficial effect upon cancer incidence only in healthy subjects who are not exposed to cancer risk and who have a particularly low baseline status. High doses of antioxidant supplementation may be deleterious in subjects in whom the initial phase of cancer development has already started, and they could be ineffective in well-nourished subjects with adequate antioxidant status.
Abstract: The consumption of fruit and vegetables is associated with a reduced rate of coronary heart disease (CHD) in observational cohorts. The purpose of this study was to assess the strength of this association in a meta-analysis. Cohort studies were selected if they reported relative risks (RRs) and 95% CI for coronary heart disease or mortality and if they presented a quantitative assessment of fruit and vegetable intake. The pooled RRs were calculated for each additional portion of fruit and/or vegetables consumed per day, and the linearity of the associations were examined. Nine studies were eligible for inclusion in the meta-analysis that consisted of 91,379 men, 129,701 women, and 5,007 CHD events. The risk of CHD was decreased by 4% [RR (95% CI): 0.96 (0.93-0.99), P = 0.0027] for each additional portion per day of fruit and vegetable intake and by 7% [0.93 (0.89-0.96), P < 0.0001] for fruit intake. The association between vegetable intake and CHD risk was heterogeneous (P = 0.0043), more marked for cardiovascular mortality [0.74 (0.75-0.84), P < 0.0001] than for fatal and nonfatal myocardial infarction [0.95 (0.92-0.99), P = 0.0058]. Visual inspection of the funnel plot suggested a publication bias, although not statistically significant. Therefore, the reported RRs are probably overestimated. This meta-analysis of cohort studies shows that fruit and vegetable consumption is inversely associated with the risk of CHD. The causal mechanism of this association, however, remains to be demonstrated.
Abstract: OBJECTIVE: Alcohol consumption may play a role in the development of obesity but the relationship between alcohol and weight is still unclear. The aim of our study was to assess the cross-sectional association of intakes of total alcohol and of specific alcoholic beverages (wine, beer and spirits) with waist-to-hip ratio (WHR) and body mass index (BMI) in a large sample of adults from all over France. DESIGN: Cross-sectional. SETTING: Participants were free-living healthy volunteers of the SU.VI.MAX study (an intervention study on the effects of antioxidant supplementation on chronic diseases). SUBJECTS: For 1481 women aged 35-60 years and 1210 men aged 45-60 years, intakes of total alcohol and specific alcoholic beverages were assessed by six 24-hour dietary records. BMI and WHR were measured during a clinical examination the year after. RESULTS: A J-shaped relationship was found between total alcohol consumption and WHR in both sexes and between total alcohol consumption and BMI in men only (P<0.05). The same relationships were observed with wine (P<0.05); men and women consuming less than 100 g day(-1) had a lower BMI (men only) and WHR than non-drinkers or those consuming more. Spirits consumption was positively associated with BMI (linear regression coefficient beta=0.21, 95% confidence interval (CI): 0.09-0.34 and beta=0.22, 95% CI: 0.06-0.39 for men and women, respectively) and WHR (beta=0.003, 95% CI: 0.001-0.005 and beta=0.003, 95%CI: 0.0002-0.006) in both sexes in a linear fashion. No relationship between beer consumption and BMI or WHR was found. CONCLUSION: If confirmed in longitudinal studies, our results indicate that consumption of alcoholic beverages may be a risk factor for obesity.
Abstract: OBJECTIVE: To investigate associations of body composition assessed by bioimpedance analysis and anthropometric indicators of fat repartition with carotid structure and function. DESIGN: Cross-sectional epidemiological study. SUBJECTS: A total of 1014 middle-aged apparently healthy adults participating in the SU.VI.MAX study. MEASUREMENTS: Body composition (fat mass, fat-free mass) was assessed by bioimpedance analysis and anthropometric indicators of fat repartition (waist circumference (WC); waist-hip-ratio (WHR)) were simultaneously collected. Carotid ultrasound examination included measurements of intima-media thickness (IMT) at the common carotid arteries (CCA) and assessment of atherosclerotic plaques in extracranial carotid arteries. Carotid-femoral pulse-wave velocity (PWV) was used as a marker of aortic stiffness.RESULTS:In multivariate analyses adjusted for major known cardiovascular risk factors in addition to age, gender and height, fat-free mass, fat mass (FM), and WC were positively associated with CCA-IMT and lumen diameter. No significant association was found with occurrence of carotid plaques. PWV was only associated with WC. Associations of CCA-IMT and PWV with WC were not significant anymore after further adjustment on body mass index (BMI) or FM. CONCLUSION: WC was the only measurement positively associated with both early atherosclerosis markers such as CCA-IMT and arterial stiffness. Although this association depends on overall adiposity, as assessed by the BMI, it emphasizes the importance of WC in clinical practice and prevention programs as a screening tool for individuals at risk for cardiovascular disease.
Abstract: BACKGROUND: There are few data on the relationship between health-related quality of life (HRQoL) and leisure time physical activity (LTPA) in the general population. We investigated the relationships of meeting public health recommendations (PHR) for moderate and vigorous physical activity with HRQoL in French adult subjects. METHODS: LTPA and HRQoL were assessed in 1998 in 2333 men and 3321 women from the SU.VI.MAX. cohort using the French versions of the Modifiable Activity Questionnaire (MAQ) and the SF-36 questionnaire, respectively. Relationship between LTPA and HRQoL was assessed using analysis of variance. RESULTS: Results from multivariate analysis showed that meeting physical activity recommended levels was associated with higher HRQoL scores (except in Bodily pain dimension for women): differences in mean HRQoL scores between subjects meeting or not PHR ranged from 2.4 (Mental health) to 4.5 (Vitality) and from 2.2 (Bodily pain) to 5.7 (Vitality) for women and men, respectively. CONCLUSIONS: Subjects meeting PHR for physical activity had better HRQoL than those who did not. Our data suggest that 30' of moderate LTPA per day on a regular basis may be beneficial on HRQoL. Higher intensity LTPA is associated with greater HRQoL. This emphasizes the importance to promote at least moderate physical activity.
Abstract: OBJECTIVE: To study the relationships of time spent in sedentary occupations with the National Cholesterol Education Program-defined metabolic syndrome (MS), taking into account the habitual level of physical activity (PA). RESEARCH METHODS AND PROCEDURES: This was a cross-sectional analysis in 1902 men and 1932 women 50 to 69 years of age participating in the French Supplementation with Antioxidant Vitamins and Minerals study. We assessed past-year PA, television watching or computer use, and reading during leisure with the Modifiable Activity Questionnaire. Subjects who performed at least 150 min/wk of moderate-intensity PA (3 to 6 metabolic equivalent tasks) or 60 min/wk of vigorous PA (>6 metabolic equivalent tasks) were considered as meeting recommended levels. RESULTS: The frequency of most MS components increased with time spent in front of a screen and decreased with increasing PA levels. The likelihood to have MS, adjusted for age, education, and smoking, was decreased by one-third in subjects meeting moderate PA guidelines and by two-thirds in subjects meeting vigorous PA recommendations [odds ratio (95% CI), 0.34 (0.17 to 0.66) in women, 0.44 (0.28 to 0.68) in men] compared with those with insufficient PA. Independently of PA levels, time spent in front of a screen was positively associated with the likelihood to have the MS in women [odds ratio (95% CI), 3.30 (2.04 to 5.34)], whereas in both sexes, no association was found with time spent reading. DISCUSSION: The relationship of the MS with a sedentary lifestyle differs according to sex and type of sedentary occupation. These results suggest the need to assess selected indicators of sedentary behavior in preventive programs.
Abstract: Antioxidant micronutrients have been reported to be associated with an improvement in the blood profile, but the results are not consistent. The aim of the present study was to assess the effects of antioxidant supplementation on changes in the serum lipid profile of adult participants in the SU.VI.MAX study. French adults (n = 12,741: 7,713 females aged 35-60 yr, and 5,028 males aged 45-60 yr) received daily antioxidant supplementation (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 microg selenium, and 20 mg zinc) or a matching placebo. Median follow-up time was 7.5 yr. After 7.5 yr, no effect of supplementation on total cholesterol was observed in men or women after adjusting for baseline total cholesterol levels and lipid-lowering medications. The prevalence of hypercholesterolemia (> or =6.5 mmol/L) showed a trend toward being higher in women who received supplements compared with those who received the placebo (P= 0.06). In both sexes, the group receiving supplements exhibited higher mean serum TG concentrations than did the placebo group (P= 0.06 in men; P= 0.05 in women). The prevalence of hypertriglyceridemia (> or =2.3 mmol/L) was also significantly higher in men who received supplements (P= 0.03), but not in women. Our results suggest than long-term daily supplementation with low doses of beta-carotene, vitamins C and E, selenium, and zinc does not result in an improved lipid profile and could even adversely affect some blood lipids, possibly with a higher risk of hyperlipidemia in women.
Abstract: OBJECTIVE: To assess relationships between energy, nutrient and food intakes, alcohol consumption, smoking status and body mass index (BMI), and serum concentrations of beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc. METHODS: Data on health status, alcohol consumption, smoking habits, anthropometric data and biochemical measurements were obtained in 1821 women aged 35-60 y and 1307 men aged 45-60 y, participant to the SU.VI.MAX Study. Data on dietary intake were available on a subsample who reported six 24-h dietary records during the first 18 months of the study. RESULTS: Women had higher baseline serum beta-carotene and vitamin C concentrations and lower concentration for serum vitamin E, zinc and selenium than men. In women, younger age was associated with lowered mean concentration of serum beta-carotene, vitamin E and selenium. In men, only differences were observed for serum zinc, which was lower in older men. Current smokers of both sexes had significantly lower concentrations of serum beta-carotene, vitamin C and selenium, and, only in women, of vitamin E, than nonsmokers. Alcohol consumers had lower concentrations of serum beta-carotene and higher selenium concentrations. Serum beta-carotene and vitamin C concentrations were lower in obese subjects. There were positive associations of dietary beta-carotene, vitamin C and E with their serum concentrations. Age, nutrient and alcohol intakes, serum cholesterol, BMI and smoking status explained 15.2% of the variance of serum beta-carotene in men and 13.9% in women, and 10.8 and 10.0% for serum vitamin C, and 26.3 and 28.6% for serum vitamin E, respectively. CONCLUSION: Serum antioxidant nutrient concentrations are primarily influenced by sex, age, obesity, tobacco smoking, alcohol consumption and especially dietary intake of those antioxidant nutrients.
Abstract: We identified a locus on chromosome 6q16.3-q24.2 (ref. 1) associated with childhood obesity that includes 2.4 Mb common to eight genome scans for type 2 diabetes (T2D) or obesity. Analysis of the gene ENPP1 (also called PC-1), a candidate for insulin resistance, in 6,147 subjects showed association between a three-allele risk haplotype (K121Q, IVS20delT-11 and A-->G+1044TGA; QdelTG) and childhood obesity (odds ratio (OR) = 1.69, P = 0.0006), morbid or moderate obesity in adults (OR = 1.50, P = 0.006 or OR = 1.37, P = 0.02, respectively) and T2D (OR = 1.56, P = 0.00002). The Genotype IBD Sharing Test suggested that this obesity-associated ENPP1 risk haplotype contributes to the observed chromosome 6q linkage with childhood obesity. The haplotype confers a higher risk of glucose intolerance and T2D to obese children and their parents and associates with increased serum levels of soluble ENPP1 protein in children. Expression of a long ENPP1 mRNA isoform, which includes the obesity-associated A-->G+1044TGA SNP, was specific for pancreatic islet beta cells, adipocytes and liver. These findings suggest that several variants of ENPP1 have a primary role in mediating insulin resistance and in the development of both obesity and T2D, suggesting that an underlying molecular mechanism is common to both conditions.
Abstract: Randomized trials have shown, unexpectedly, that supplementation with selenium or vitamin E is associated with a reduction of prostate cancer risk. We assess whether a supplementation with low doses of antioxidant vitamins and minerals could reduce the occurrence of prostate cancer and influence biochemical markers. The SU.VI.MAX trial comprised 5,141 men randomized to take either a placebo or a supplementation with nutritional doses of vitamin C, vitamin E, beta-carotene, selenium and zinc daily for 8 years. Biochemical markers of prostate cancer risk such as prostate-specific antigen (PSA) and insulin-like growth factors (IGFs) were measured on plasma samples collected at enrollment and at the end of follow-up from 3,616 men. Cox regression models were used to estimate the hazard ratio and related 95% confidence interval of prostate cancer associated with the supplementation and to examine whether the effect differed among predetermined susceptible subgroups. During the follow-up, 103 cases of prostate cancer were diagnosed. Overall, there was a moderate nonsignificant reduction in prostate cancer rate associated with the supplementation (hazard ratio = 0.88; 95% CI = 0.60-1.29). However, the effect differed significantly between men with normal baseline PSA (< 3 microg/L) and those with elevated PSA (p = 0.009). Among men with normal PSA, there was a marked statistically significant reduction in the rate of prostate cancer for men receiving the supplements (hazard ratio = 0.52; 95% CI = 0.29-0.92). In men with elevated PSA at baseline, the supplementation was associated with an increased incidence of prostate cancer of borderline statistical significance (hazard ratio = 1.54; 95% CI = 0.87-2.72). The supplementation had no effect on PSA or IGF levels. Our findings support the hypothesis that chemoprevention of prostate cancer can be achieved with nutritional doses of antioxidant vitamins and minerals.
Abstract: BACKGROUND: Although it is well admitted that alcohol displays a U-shaped relationship with atherosclerotic vascular disease, individual relationships between alcohol and atherosclerosis risk factors may be different and have not been determined precisely for several of them. METHODS: A cross-sectional study within the SU.VI.MAX French cohort study was performed to assess the curve of potential relationships between alcohol and atherosclerosis risk factors in 2126 healthy men. Mean daily alcohol intake was derived from 37 alcoholic beverages in twelve 24-hr dietary recalls. Logistic models were adjusted for age. RESULTS: Apolipoprotein B (ApoB), fasting glucose, body mass index, waist-to-hip ratio, and waist circumference displayed a linear relationship with alcohol. The odds ratios and 95% confidence intervals associated with abnormal values of the markers for the highest quintile of alcohol intake were 1.45 (1.06-1.97) for ApoB, 1.98 (1.40-2.80) for fasting glucose, and 1.74 (1.30-2.34) for body mass index. An inverse J-shaped relationship was assumed for ApoA1 and ApoB/ApoA1 ratio, whereas a U-shaped relationship was observed for serum triglycerides and mixed hyperlipidemia. Only the highest quintile of alcohol was associated with hypertension, although the test for linearity was also significant. No association was observed for Lp(a) or homocysteine. Associations were unmodified by further adjustment for carbohydrates, fiber, lipids, tobacco, or exercise. CONCLUSIONS: The aggregate of the disparate alcohol risk factor relationships suggests probable net benefit at 15 to 25 g of alcohol/day.
Abstract: An important question being raised by nutritionists today is whether available scientific data support an important role for polyphenols in the prevention of pathologic conditions that represent an important public health burden, such as cardiovascular diseases, cancers, and osteoporosis. More broadly, when can we consider scientific knowledge sufficient to allow specific public health implications and recommendations? The history of the relationship between beta-carotene and cancer illustrates the complexity of the research process leading to the demonstration of a causal relationship between nutritional factors and the prevention of disease. The beta-carotene story, which has developed in the past 30 y, is particularly significant and illustrative because of apparent controversies that are far from resolved. This is an extremely interesting example from which many lessons can be learned. For beta-carotene, we need to collect sufficient information from experimental, clinical, and epidemiologic research before we support any specific public health recommendations. The same principles must be applied to recommendations regarding polyphenols (in particular, which polyphenols, at which doses, to achieve which benefits for which populations). If these questions are not answered, then we run the risk of needing to renounce recommendations regarding polyphenols in the future, damaging the credibility of nutritional recommendations for public health.
Abstract: OBJECTIVE: To assess longitudinally the impact of new onset musculoskeletal (MSK) disorders on quality of life (QoL). METHODS: An inception cohort of 1202 subjects in France aged 45-60 years was determined to be free of MSK problems at baseline. Over 28 months of follow up between 1996 and 1998, 310 were diagnosed with MSK disorders and matched for age and sex with 620 healthy controls. The impact of the MSK disorder onset on QoL was assessed by the change in SF-36 dimension scores over time, using a linear mixed ANOVA model to compare the groups. RESULTS: The incidence of MSK disorder was 13.6% per person-year in the spine, 4.2% per person-year in a joint, and 4.6% per person-year at an extra-articular site. The greatest change in QoL was a 10 point drop in the 100 point SF-36 bodily pain dimension scale in the MSK group. Compared with controls, subjects with an MSK disorder had significantly greater reductions in the following dimensions: bodily pain (a -7.4 point difference in change), vitality (-2.7), general health (-1.8), and physical functioning (-1.3). Within the MSK group, chronic disorders had a greater impact than acute ones on the physical functioning (-2.1), role emotional (-8.4), and social functioning (-5.9) dimensions. CONCLUSION: New onset MSK disorders have a marked deleterious effect on QoL in the physical domain, with lesser effects on social and mental functioning. This evidence of an early significant impact on their QoL reinforces recent recommendations for early treatment and primary prevention.
Abstract: KLF11 (TIEG2) is a pancreas-enriched transcription factor that has elicited significant attention because of its role as negative regulator of exocrine cell growth in vitro and in vivo. However, its functional role in the endocrine pancreas remains to be established. Here, we report, for the first time, to our knowledge, the characterization of KLF11 as a glucose-inducible regulator of the insulin gene. A combination of random oligonucleotide binding, EMSA, luciferase reporter, and chromatin immunoprecipitation assays shows that KLF11 binds to the insulin promoter and regulates its activity in beta cells. Genetic analysis of the KLF11 gene revealed two rare variants (Ala347Ser and Thr220Met) that segregate with diabetes in families with early-onset type 2 diabetes, and significantly impair its transcriptional activity. In addition, analysis of 1,696 type 2 diabetes mellitus and 1,776 normoglycemic subjects show a frequent polymorphic Gln62Arg variant that significantly associates with type 2 diabetes mellitus in North European populations (OR = 1.29, P = 0.00033). Moreover, this variant alters the corepressor mSin3A-binding activity of KLF11, impairs the activation of the insulin promoter and shows lower levels of insulin expression in pancreatic beta cells. In addition, subjects carrying the Gln62Arg allele show decreased plasma insulin after an oral glucose challenge. Interestingly, all three nonsynonymous KLF11 variants show increased repression of the catalase 1 promoter, suggesting a role in free radical clearance that may render beta cells more sensitive to oxidative stress. Thus, both functional and genetic analyses reveal that KLF11 plays a role in the regulation of pancreatic beta cell physiology, and its variants may contribute to the development of diabetes.
Abstract: BACKGROUND: Cocaine and amphetamine regulated transcript (CART) is an anorectic neuropeptide located principally in hypothalamus. CART has been shown to be involved in control of feeding behavior, but a direct relationship with obesity has not been established. The aim of this study was to evaluate the effect of polymorphisms within the CART gene with regards to a possible association with obesity in a Caucasian population. RESULTS: Screening of the entire gene as well as a 3.7 kb region of 5' upstream sequence revealed 31 SNPs and 3 rare variants; 14 of which were subsequently genotyped in 292 French morbidly obese subjects and 368 controls. Haplotype analysis suggested an association with obesity which was found to be mainly due to SNP-3608T>C (rs7379701) (p = 0.009). Genotyping additional cases and controls also of European Caucasian origin supported further this possible association between the CART SNP -3608T>C T allele and obesity (global p-value = 0.0005). Functional studies also suggested that the SNP -3608T>C could modulate nuclear protein binding. CONCLUSION: CART SNP -3608T>C may possibly contribute to the genetic risk for obesity in the Caucasian population. However confirmation of the importance of the role of the CART gene in energy homeostasis and obesity will require investigation and replication in further populations.
Abstract: OBJECTIVE: The objective of this study was to provide information on the prevalence of herpes simplex infections in the general population in Europe. GOALS: The goals of this study were to determine the prevalence of clinically probable genital herpes and the relationship between serotype and clinical expression in a French community-based sample. STUDY: A total of 4410 subjects chosen at random were serotyped for herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). Data on symptoms were obtained by questionnaire allowing retrospective diagnosis of clinically probable genital herpes. RESULTS: Questionnaire data and serotype were available for 3192 subjects. Seroprevalences of HSV-1 and HSV-2 were 65.6% and 15.5%, respectively. Prevalence of clinically probable genital herpes was 11.8%, identified in 11.1% of HSV-1-positive subjects and 26.8% of HSV-2-positive subjects, with a lower prevalence in those coinfected with both virus types. CONCLUSIONS: Clinically probable genital herpes was observed in one fourth of subjects with HSV-2 infections and in some subjects with HSV-1 infection. Coinfection with HSV-1 appeared to protect against symptom expression in subjects infected with HSV-2.
Abstract: Although there is a high degree of proof relating plasma homocysteine levels to cardiovascular risk, the role of homocysteine as a causal cardiovascular risk factor remains controversial. Prospective long-term clinical trials in high cardiovascular risk populations usually show a positive relationship between plasma homocysteine and the degree of cardiovascular risk. However, shorter term studies and/or those carried out in populations with lower cardiovascular risk show either a weaker correlation or no relationship at all. To date no study has shown proof of the reversibility of cardiovascular risk due to hyperhomocysteinaemia; nevertheless, a number of studies using intermediate criteria support the hypothesis of a benefit due to reduction of plasma homocysteine levels. A number of therapeutic trials published with clinical criteria have not shown convincing results in either direction. A number of interventional trials are underway: notably the SUFOLOM 3 trial in France, and the question of a benefit on cardiovascular risk by reducing homocysteine levels should be answered in the next few years. In the meantime, with the exception of homocysteinuria in which therapeutic strategies have shown their efficacy in the reduction of atherothrombotic risk with high levels of proof, the authors do not recommend the treatment of mild hyperhomocysteinaemia in any clinical setting other than "clinical trials" and certain "compassionate" indications such as early and/or recurrent vascular events associated with hyperhomocysteinaemia in the absence of conventional risk factors.
Abstract: BACKGROUND: Blood lipid profile of French men and women obtained from the general population is not well known. Furthermore, the association between these lipids, as a function of other potential risk factors for cardiovascular disease, and sociodemographic factors such as age, educational level, and region of residence is not well studied in large samples in Europe. METHODS: Data on French healthy volunteers, aged between 40 and 65 years for men (n = 5141) and 35 and 65 years for women (n = 7876) were obtained from the "Supplementation en Vitamines et Mineraux Antioxydants" (SU.VI.MAX) study, a primary prevention trial. Baseline blood samples were collected in 1994-1995 and analyzed for cholesterol, triglyceride, apolipoproteins (apo)-B and -A1. The results were analyzed separately for men and women as a function of age, educational level, and area of residence. RESULTS: Overall, blood lipid levels for men and women did not differ significantly from those reported in other Western industrialized countries. Except for triglyceride in men, all blood lipids were statistically different among ages. In women, cholesterol, apo-A1, and apo-B showed a significant decrease with educational level. Statistical differences were found in both genders between blood lipids and lipoproteins among regions of residence. CONCLUSIONS: Even if differences between region of residence were found in blood lipid levels, this cannot explain the North-East to South gradient in the prevalence of cardiovascular disease in France nor differences between France and other industrialized Western countries.
Abstract: The aim of the present study was to evaluate the relation between iron status and cancer in a population of middle-aged adults living in France where iron supplementation and iron-fortified foods are rarely used. The SU.VI.MAX study is a randomized, double-blind, placebo-controlled primary prevention trial evaluating the effect of antioxidant supplementation on chronic diseases in women aged 35-60 and men aged 45-60 y. At baseline, concentrations of hemoglobin, serum transferrin and serum ferritin were measured in 10,197 subjects. Data on dietary intake were estimated from six 24-h dietary records completed during the first 2 study years and available for 5287 subjects. All cancer cases that occurred during the 7.5-y follow-up were validated. In men, baseline serum transferrin and serum ferritin concentrations did not differ between subjects with cancers (n = 467) and those without. In women, serum ferritin was higher (P < 0.0001) and serum transferrin tended to be lower (P < 0.08) in cancer cases. Iron status was not related to cancer risk in men, but women with serum ferritin concentrations > 160 microg/L had an increased risk of cancer (odds ratio = 1.88, 95% CI: 1.05,3.35). No relation was found between dietary iron intake and risk of all cancer sites combined for either men or women. Our results suggest that iron status is not a predictor of cancer risk in men, whereas a serum ferritin concentration > 160 microg/L may be associated with an increase in cancer risk in women.
Abstract: OBJECTIVE: To assess the effects of supplementation with a combination of antioxidant vitamins and trace elements, at nutritional doses, upon the 6.5-year risk of hypertension in the SU.VI.MAX trial. To describe the association between baseline plasma antioxidant levels and the same long-term risk using observational data from the study. SETTING: A total of 5086 adults from the SU.VI.MAX trial, a randomized primary prevention trial. RESULTS: Compared with the placebo group, no effect of supplementation upon the 6.5-year risk of hypertension could be detected (odds ratio, 1.04 and 95% confidence interval, 0.87-1.23 in men; and odds ratio, 1.10 and 95% confidence interval, 0.95-1.29 in women). Furthermore, compared with men in the first tertile, those in the second and third tertiles of serum baseline levels of beta-carotene presented a lower risk of hypertension in both the placebo and supplementation groups. Multivariate-adjusted odds ratios (95% confidence interval) were 0.70 (0.44-1.12) and 0.53 (0.33-0.86) in the placebo group, and were 0.59 (0.37-0.94) and 0.67 (0.42-1.07) in the supplementation group. In women, a decreasing trend was observed with vitamin C levels and risk of hypertension in the intervention group. No association could be shown between vitamin E and trace element plasma levels and the risk of hypertension. CONCLUSIONS: Despite an inverse association between baseline plasma levels of beta-carotene in men and the risk of developing hypertension, we could not demonstrate any beneficial effect of low-dose antioxidant supplementation upon the 6.5-year risk of hypertension in the randomized analysis.
Abstract: Although iron is one of the most abundant metals in the Earth's crust, humans are often deficient in this element. This is mainly due to inefficient absorption of ferric ions, the main naturally occurring form. The risk of deficiency is lower in industrialized countries, yet a large proportion of these populations, and especially infants, pregnant women and young women, have poor ferritin status. The consequences of non anemic iron deficiency are unclear Conversely, excessive iron stores can be harmful, owing to the pro-oxidant imbalance they create.
Abstract: alpha2-Heremans-Schmid glycoprotein (AHSG) is an abundant plasma protein synthesized predominantly in the liver. The AHSG gene, consisting of seven exons and spanning 8.2 kb of genomic DNA, is located at chromosome 3q27, a susceptibility locus for type 2 diabetes and the metabolic syndrome. AHSG is a natural inhibitor of the insulin receptor tyrosine kinase, and AHSG-null mice exhibit significantly enhanced insulin sensitivity. These observations suggested that the AHSG gene is a strong positional and biological candidate for type 2 diabetes susceptibility. Direct sequencing of the AHSG promoter region and exons identified nine common single nucleotide polymorphisms (SNPs) with a minor allele frequency > or =5%. We carried out a detailed genetic association study of the contribution of these common AHSG SNPs to genetic susceptibility of type 2 diabetes in French Caucasians. The major allele of a synonymous coding SNP in exon 7 (rs1071592) presented significant evidence of association with type 2 diabetes (P = 0.008, odds ratio 1.27 [95% CI 1.06-1.52]). Two other SNPs (rs2248690 and rs4918) in strong linkage disequilibrium with rs1071592 showed evidence approaching significance. A haplotype carrying the minor allele of SNP rs1071592 was protective against type 2 diabetes (P = 0.014). However, our analyses indicated that rs1071592 is not associated with the evidence for linkage of type 2 diabetes to 3q27.
Abstract: Upstream transcription factor 1 (USF1) is a ubiquitously expressed transcription factor of the basic helix-loop-helix leucine zipper family that has been shown to regulate the expression of a raft of key genes involved in glucose and lipid metabolism. The USF1 gene is located at chromosome 1q22-q23, within the most consistently replicated type 2 diabetes susceptibility locus in the human genome. In this study, we have examined the contribution of eight common USF1 single nucleotide polymorphisms (SNPs) to type 2 diabetes susceptibility in the French Caucasian population. None of the USF1 SNPs genotyped, including two SNPs previously associated with familial combined hyperlipidemia (rs2073658 and rs3737787), showed evidence of association with type 2 diabetes. In addition, USF1 SNPs were not associated with plasma levels of glucose, triglycerides, total cholesterol, or apolipoproteins A1 or B in normoglycemic subjects. A total of four common USF1 haplotypes were identified, accounting for >99% of chromosomes. There was no significant difference in the USF1 haplotype distribution of the case and control subjects. In conclusion, we report here that we were unable to find any evidence to support the hypothesis that genetic variation in the USF1 gene makes a significant contribution to type 2 diabetes susceptibility in the French Caucasian population.
Abstract: BACKGROUND: Increased consumption of dietary fiber is widely recommended to maintain or improve health, but knowledge of the relation between dietary fiber sources and cardiovascular disease risk factors is limited. OBJECTIVE: We examined the relation between the source or type of dietary fiber intake and cardiovascular disease risk factors in a cohort of adult men and women. DESIGN: In a cross-sectional study, quintiles of fiber intake were determined from dietary records, separately for 2532 men and 3429 women. Age- and multivariate-controlled logistic models investigated the odds ratios of abnormal markers for quintiles 2-5 of fiber intake compared with the lowest quintile. RESULTS: The highest total dietary fiber and nonsoluble dietary fiber intakes were associated with a significantly (P < 0.05) lower risk of overweight and elevated waist-to-hip ratio, blood pressure, plasma apolipoprotein (apo) B, apo B:apo A-I, cholesterol, triacylglycerols, and homocysteine. Soluble dietary fiber was less effective. Fiber from cereals was associated with a lower body mass index, blood pressure, and homocysteine concentration; fiber from vegetables with a lower blood pressure and homocysteine concentration; and fiber from fruit with a lower waist-to-hip ratio and blood pressure. Fiber from dried fruit or nuts and seeds was associated with a lower body mass index, waist-to-hip ratio, and fasting apo B and glucose concentrations. Fiber from pulses had no specific effect. CONCLUSION: Dietary fiber intake is inversely correlated with several cardiovascular disease risk factors in both sexes, which supports its protective role against cardiovascular disease and recommendations for its increased consumption.
Abstract: The SUpplementation en VItamines et Mineraux AntioXydants (SU.VI.MAX) study, a randomised double-blind, primary-prevention trial showed that after 7.5 years, low-dose antioxidant supplementation lowered the total cancer incidence in men, but not in women. To explain this difference in the impact of antioxidant supplementation in men and women, we hypothesised that the effect of supplementation is dependent on initial antioxidant status; 12 741 French adults (7713 females aged 35--60 years; 5028 males aged 45--60 years) received daily antioxidant supplementation (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 microg Se, 20 mg Zn daily) or a matching placebo. Cut-off limits for baseline serum concentrations of the different antioxidant vitamins and minerals were defined as follows for both men and women: 0.3 micromol/l for beta-carotene, 11.4 micromol/l for vitamin C, 15 micromol/l for vitamin E, 0.75 micromol/l for Se and 10.7 micromol/l for Zn. The percentage of men with serum concentrations under cut-off limits was higher for vitamins C and E and beta-carotene in those who developed a cancer than in those who did not. The risk of cancer was higher in men with baseline concentrations of serum vitamin C or vitamin E under cut-off limits, but not in women. The effect of supplementation was greater in men with baseline serum concentrations of vitamin C, vitamin E and beta-carotene below the cut-off limits compared with those above it. This effect was maintained only for vitamin E after adjustment for age, tobacco, and alcohol consumption and BMI. No effect of supplementation could be seen in women. Baseline antioxidant status is related to the risk of cancer in men but not in women and therefore does not entirely explain the differences observed in the effect of antioxidant supplementation on cancer risk between sexes in the SU.VI.MAX study.
Abstract: The number of pregnancies affected by neural tube defects has been estimated to be 4000/year in Europe, with a higher prevalence in Celtic populations and in women of low socioeconomic status. Since the 1980s, it has been shown that supplementation with folic acid during the periconceptual period reduces the risk of neural tube defects in the fetus. However, in view of the period during which supplementation should be taken (< 4 weeks before conception until 8-10 weeks after) and the fact that in some countries 30-50% of pregnancies are unplanned, a public health initiative based solely on increasing dietary folate intake or recommendations on use of folic acid supplements is likely to be insufficient. Mandatory fortification has been started in 38 countries throughout the world. Several European countries have advocated mandatory flour folic acid fortification over the last 6 years, but none has introduced it. A recent public health decision in Hungary stimulated flour fortification on a voluntary basis, but it remains the only European country to take this action. Many European countries have deferred a decision to introduce fortification because of concerns about possible masking of vitamin B (12) deficiency. This review advocates a proposal for combined fortification of folic acid and vitamin B (12) to address possible hazards of fortification with folic acid alone.
Abstract: Several epidemiologic studies have examined with diverging results the relationships between circulating levels of insulin-like growth factors (IGF) and of IGF-binding proteins (IGFBP) and prostate cancer risk. We assessed the association of prediagnostic plasma levels of IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and subsequent occurrence of prostate cancer in a case-control study nested in the SU.VI.MAX trial. The SU.VI.MAX study was a primary prevention trial testing a daily supplementation with low-dose antioxidant vitamins and minerals in male and female middle-aged volunteers in France. One hundred prostate cancer cases were diagnosed among 4,855 SU.VI.MAX participants over a 9-year follow-up period. For each case, four age-matched controls were selected randomly. Frozen baseline plasma samples were used to measure IGF-I, IGF-II, IGFBP-2, and IGFBP-3. Conditional logistic regression was used to assess the association between these four biochemical markers and prostate cancer risk. After controlling for the intervention group in the trial and the other IGF axis variables, the odds ratios and 95% confidence interval (95% CI) comparing the upper quartile to the baseline quartile were 1.83 (95% CI, 0.85-3.95), 1.05 (95% CI, 0.35-3.18), 0.79 (95% CI, 0.39-1.58), and 0.42 (95% CI, 0.12-1.52) for IGF-I, IGF-II, IGFBP-2, and IGFBP-3, respectively. More suggestive associations for IGF-I and IGFBP-3 were observed with advanced and aggressive cancers. Our results are consistent with those of some previous prospective studies and suggest that IGF axis variables are not long-term predictors of the occurrence of prostate cancer.
Abstract: Magnesium (Mg) is the second most common intracellular electrolyte; in the body. Few data are available in general population studies on the assessment of Mg status and its relationship to dietary intake. We explored the relationship between several biological Mg surrogates (serum, red cell, and urinary), Mg intake, age, alcohol intake, and mean energy intake in a large sample of French adults issued from the SUVIMAX study. Serum Mg was positively correlated with red cell Mg in men and women (r = 0.17; p < 0.001) whereas no association was found between urinary Mg and red cell Mg nor between urinary Mg and serum Mg. Age was positively correlated with serum and red cell Mg in women (p < 0.001) and negatively correlated with urinary Mg in both genders (p < 0.001). Finally, a negative correlation was found between dietary intake and red cell Mg in women (r = -0.06; p < 0.05). Among the biological Mg surrogates, an association was found between serum Mg and red cell Mg. Further investigations should be conducted in order to determine the role played by dietary Mg intake in the relationship between health status and several biological Mg measurements.
Abstract: OBJECTIVES: To assess the relationship between type of ventilation in the workplace, health services attendance, and sickness absence among middle-aged women. METHODS: In a national sample of 920 professionally active women aged 49-65 yr from the SU.VI.MAX cohort, recruited from the general population in France, health services attendance and sickness absence were assessed prospectively during 1999. RESULTS: Being exposed to heating, ventilation, and air-conditioning (HVAC) systems in the workplace proved to be a risk factor for attendance at global and several specialist medical services. The adjusted odds ratio for otorhinolaryngologist attendance was 2.33 (95% CI = 1.35-4.04) in the HVAC group compared with the natural ventilation group, and 1.70 (1.13-2.58) for sickness absence. Dermatologist and global medical services attendance rates may also be higher in this group (P = 0.06 in both cases). CONCLUSIONS: Exposure to HVAC systems was a strong and significant risk factor for otorhinolaryngologist attendance and sickness absence. HVAC systems are prevalent in recent office buildings and have been shown to be associated with several adverse health effects in terms of morbidity and mortality. From a public-health perspective, our results outline the need for a quantitative assessment of the health impact of ventilation systems, taking into account the possible loss of production that exists in addition to the direct costs of medical services use.
Abstract: OBJECTIVE: We evaluated the characteristics of French subjects meeting current public health recommendations for physical activity. METHODS: We assessed leisure-time physical activity cross-sectionally in 7404 adults aged 45 to 68 years with applied logistic regression models. RESULTS: Meeting the recommended physical activity levels was more likely in subjects aged 60 years and older and in women with higher education levels or living in rural areas and was less likely in smokers. No association was found with time spent watching television. The contribution of vigorous activity to total time spent being active was approximately 2 times higher in subjects meeting recommendations. CONCLUSIONS: Participation in some vigorous activity may be viewed as a "facilitator" to attain physical activity recommendations. Relationships with physical environment variables in Europe need further investigation.
Abstract: OBJECTIVES: Abdominal fat accumulation is a risk factor for type 2 diabetes and cardiovascular disease. Identifying the demographic and lifestyle correlates of abdominal adiposity is an important step to target at-risk populations in prevention programs. There are few data of this kind in France. METHODS: Anthropometric indicators of overall (body mass index, BMI) and abdominal (waist hip ratio, WHR; waist circumference, WC) adiposity, educational level, smoking status, and physical activity were assessed in 6,705 middle-aged men and women participating in the SU.VI.MAX study. RESULTS: The likelihood of being obese was increased more than twice in physically inactive subjects of both genders after adjustment for age, smoking status and educational level (OR=2.22, CI95%: 1.74-2.83 in men; OR=2.38, CI95%: 1.84-3.09 in women). Having a high WHR (>=0.95 in men, >=0.80 in women) was more likely in subjects >=50 y, in current smokers, and less likely in men with higher education. The likelihood of having a high WHR was also increased in physically inactive subjects of both genders after adjustment for age, BMI, smoking status and educational level (OR=1.33, CI95%: 1.10-1.60 in men; OR=1.46, CI95%: 1.22-1.74 in women). Having a high WC (>=102 cm in men, >=88 cm in women) was positively associated with age and also with physical inactivity (OR=1.63, CI95%: 1.20-2.22 in women). CONCLUSIONS: These cross-sectional data suggest significant positive associations of physical inactivity with both the WHR and WC, independently of overall adiposity as assessed by the BMI.
Abstract: BACKGROUND: It has been suggested that a low dietary intake of antioxidant vitamins and minerals increases the incidence rate of cardiovascular disease and cancer. To date, however, the published results of randomized, placebo-controlled trials of supplements containing antioxidant nutrients have not provided clear evidence of a beneficial effect. We tested the efficacy of nutritional doses of supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and ischemic cardiovascular disease in the general population. METHODS: The Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study is a randomized, double-blind, placebo-controlled primary prevention trial. A total of 13 017 French adults (7876 women aged 35-60 years and 5141 men aged 45-60 years) were included. All participants took a single daily capsule of a combination of 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 mug of selenium, and 20 mg of zinc, or a placebo. Median follow-up time was 7.5 years. RESULTS: No major differences were detected between the groups in total cancer incidence (267 [4.1%] for the study group vs 295 [4.5%] for the placebo group), ischemic cardiovascular disease incidence (134 [2.1%] vs 137[2.1%]), or all-cause mortality (76 [1.2%] vs 98 [1.5%]). However, a significant interaction between sex and group effects on cancer incidence was found (P = .004). Sex-stratified analysis showed a protective effect of antioxidants in men (relative risk, 0.69 [95% confidence interval [CI], 0.53-0.91]) but not in women (relative risk, 1.04 [95% CI, 0.85-1.29]). A similar trend was observed for all-cause mortality (relative risk, 0.63 [95% CI, 0.42-0.93] in men vs 1.03 [95% CI, 0.64-1.63] in women; P = .11 for interaction). CONCLUSIONS: After 7.5 years, low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women. Supplementation may be effective in men only because of their lower baseline status of certain antioxidants, especially of beta carotene.
Abstract: The results of dietary intervention trials favor the hypothesis that higher intakes of B-vitamins (folate, vitamin B(6) and B(12)), and subsequently lower total homocysteine (tHcy) concentrations, are causally associated with a decreased risk of vascular disease in patients with cardiovascular diseases (CVD). The same is true for a higher intake of omega-3 fish fatty acids. Yet, the lack of hard end points and/or appropriate study designs precludes a definitive conclusion about causality. In the future, intervention trials with hard end points and randomized double-blind placebo-controlled designs should be able to elucidate the causality problem. There are several pathways by which B-vitamins and omega-3 fatty acids may exert their protective effect on CVD, a common pathway is a beneficial effect on the endothelial function and hemostasis. With respect to synergy between B-vitamins and omega-3 fatty acids, there is no evidence that fish oils have a tHcy-lowering effect beyond the effect of the B-vitamins. Nevertheless, animal studies clearly illustrate that vitamin B(6)- as well as folate-metabolism are linked with those of long-chain omega-3 fatty acids. Furthermore, a human study indicated synergistic effects of folic acid (synthetic form of folate) and vitamin B(6) together with omega-3 fatty acids on the atherogenic index and the fibrinogen concentration. Although these results are promising, they were produced in very small selective study populations. Thus, confirmation in large well-designed intervention trials is warranted.
Abstract: BACKGROUND: Investigations focusing and implementing on the impact of cancer on health-related quality of life (HRQoL) by the way of a mean comparison between cancer patients and subjects from the general population, are scarce and usually cross-sectional. Longitudinal application of HRQoL instruments to a general, initially healthy population allows for change to be assessed as an event occurs, rather than afterwards. The objective of the present study was to investigate the impact of new cancer on HRQoL. METHODS: The 36-item Short Form (SF-36) and 12-item General Health Questionnaire (GHQ-12) were applied to the French SU.VI.MAX cohort in 1996 and 1998. A controlled longitudinal study was used to determine the impact on HRQoL of newly diagnosed cancer: 84 patients with cancer that occurred between the 2 HRQoL measures were compared with 420 age- and sex-matched cancer-free controls. RESULTS: Initial HRQoL level was similar in the two groups. A new cancer had a particularly marked effect on the SF-36 Physical functioning, Role-physical and General health dimensions (more than 6.6-point difference in change in HRQoL evolution on a 0-100 scale). The Bodily pain and Vitality dimensions were less severely affected (difference in change varying from 4.4 to 6.3 points), and there was no effect on either the GHQ-12 score or the SF-36 Mental health, Role-emotional and Social functioning dimensions. CONCLUSIONS: The negative impact of cancer on the lives of patients was assessed in terms of HRQoL. The aspects most likely to be affected were those with a physical component, and general health perceptions. These results can thus help quantify the impact of a new cancer on HRQoL evolution and potentially facilitate early intervention by identifying the most affected HRQoL domains.
Abstract: Synthesis of free radicals might play a role in the cellular process of atherosclerosis. This process can be stopped by antioxidants such as beta-carotene, vitamin C, or vitamin E, which will inactivate the effects of free radicals. Although antioxidant vitamins have not been proven to prevent cardiovascular diseases through the modulation of lipid peroxidation, it has been suggested that peroxidation might be a pathway to such prevention, mediated through the effects of antioxidants on blood pressure (BP) and arterial stiffness. Several observational epidemiologic studies and some clinical trials have suggested an inverse association between dietary intake of fruits and vegetables, and BP. An inverse link between serum levels of vitamin C and BP has also been determined in observational epidemiologic settings. Some relations between other antioxidant vitamins (retinol and beta-carotene) and BP are reported; they confer the same inverse association. However, results from clinical trials testing the effect of a single, or a combination of antioxidants at high pharmacologic doses have revealed inconsistent BP findings. So far, no evidence confirms that oral antioxidant supplementation is effective in preventing or treating high BP. Additional large studies should be conducted to determine the effect on BP of antioxidant supplementation at nutritional doses.
Abstract: A high consumption of flavonoids may lower cardiovascular risk through their antioxidant capacity. This study evaluated the relation between consumption of foods rich in flavonoids and estimated cardiovascular risk. A cross-sectional analysis was performed in 1286 women and 1005 men of the SU.VI.MAX Study (an 8-y trial evaluating the effect of antioxidant supplementation on the incidence of major chronic diseases). Dietary intakes were estimated using six 24-h dietary records collected during the year between the clinical measurement of blood pressure, weight and height and the biological measurement of total serum cholesterol and fasting plasma glucose. The relation between flavonoid rich food consumption and cardiovascular risk factors was evaluated with analyses of covariance and the effect on cardiovascular risk with logistic regression analyses. In women, flavonoid-rich food consumption was inversely related to systolic blood pressure (P = 0.005). No relation between risk factors and flavonoid-rich food consumption was seen in men. Women in the highest tertile of flavonoid-rich food consumption were at lower risk for cardiovascular disease [odds ratio (OR): 0.31; 95%CI: 0.14, 0.68], whereas a positive tendency was seen in men (OR: 1.38; 95%CI: 0.96, 2.00). These results indicate that in women, a high consumption of flavonoid-rich foods may prevent cardiovascular disease.
Abstract: BACKGROUND: Establishing patterns of alcohol consumption may be useful for investigating the relationship between alcohol and diseases. METHODS: We used a hierarchical agglomerative clustering method to describe the intake of eight types of alcoholic beverages and to determine drinking patterns in a cohort of 1797 men enrolled in a French 8-year intervention study involving nutritional doses of vitamins and minerals, the SU.VI.MAX study. RESULTS: Cluster 1, referred to as 'abstainers', was defined a priori and included 329 men who drank less than 5 g of alcohol per day. Six drinking patterns were defined in alcohol drinkers, with increasing mean alcohol intake: cluster 2, 'low drinkers', included 670 subjects, who drank little of any type of alcoholic beverage; cluster 3, 'high quality wines', included 584 men with a high intake of champagne, high quality wines, and high-alcohol aperitifs; cluster 4, 'beer and cider', included 190 subjects with a high intake of beer and cider; cluster 5, 'digestives', included 54 men with a specifically high consumption of digestive beverages; cluster 6, 'local wines', included 238 subjects with a high intake of local wines and low-alcohol aperitifs; cluster 7, 'table wines', included 61 men with a high intake of table wines and high-alcohol aperitifs. These clusters were significantly associated with socioeconomic and lifestyle variables such as place of residence, occupation, mean caloric intake and distribution of energy intake throughout the day, body mass index, and smoking habits. CONCLUSIONS: They will be useful in future studies of the relationship between alcohol intake and medical conditions or risk factors.
Abstract: OBJECTIVE: Limited data exist from randomized trials evaluating, noninvasively, the impact of antioxidant supplementation on vascular structure and function. METHODS AND RESULTS: This is a substudy of the SU.VI.MAX Study, which is a randomized, double-blind, placebo-controlled, cardiovascular and cancer primary prevention trial. Eligible participants (free of symptomatic chronic diseases and apparently healthy) were randomly allocated to daily receive either a combination of antioxidants (120 mg vitamin C, 30 mg vitamin E, 6 mg beta carotene, 100 microg selenium, and 20 mg zinc) or placebo and followed-up over an average of 7.2+/-0.3 years. At the end-trial examination, the carotid ultrasound examination and carotid-femoral pulse-wave velocity (PWV) measurement were performed blindly in 1162 subjects aged older than 50 years and living in the Paris area. The percentage of subjects with carotid plaques was higher in the intervention group compared with the placebo group (35.2% versus 29.5%, P=0.04). Common carotid intima-media thickness (mean+/-SD) was not different between the 2 groups (0.70+/-0.08 versus 0.70+/-0.08 mm, P=0.38). Mean PWV tended to be lower (indicating less stiff aortic arteries) in the intervention group but the difference did not reach statistical significance (P=0.13). CONCLUSIONS: These results suggest no beneficial effects of long-term daily low-dose supplementation of antioxidant vitamins and minerals on carotid atherosclerosis and arterial stiffness.
Abstract: The intake of individual n-6 and n-3 PUFA has been estimated in 4,884 adult subjects (2,099 men and 2,785 women), volunteers from the French SU.VI.MAX intervention trial. The food intakes of each subject were recorded in at least ten 24-h record questionnaires completed over a period of 2.5 yr, allowing the estimation of the daily intake of energy; total fat; and linoleic, alpha-linolenic, arachidonic, eicosapentaenoic (EPA), n-3 docosapentaenoic (DPA), and docosahexaenoic (DHA) acids. The mean total fat intake corresponded to 94.1 g/d (36.3% of total energy intake) in men and 73.4 g/d (38.1% of energy) in women. The intake of linoleic acid was 10.6 g/d in men and 8.1 g/d in women, representing 4.2% of energy intake; that of alpha-linolenic acid was 0.94 g/d in men and 0.74 g/d in women, representing 0.37% of energy intake, with a mean linoleic/alpha-linolenic acid ratio of 11.3. The mean intakes of long-chain PUFA were: arachidonic acid, 204 mg/d in men and 152 mg/d in women; EPA, 150 mg/d in men and 118 mg/d in women; DPA, 75 mg/d in men and 56 mg/d in women; DHA, 273 mg/d in men and 226 mg/d in women; long-chain n-3 PUFA, 497 mg/d in men and 400 mg/d in women. Ninety-five percent of the sample consumed less than 0.5% of energy as alpha-linolenic acid, which is well below the current French recommendation for adults (0.8% of energy). In contrast, the mean intakes of long-chain n-6 and n-3 PUFA appear fairly high and fit the current French recommendations (total long-chain PUFA: 500 mg/d in men and 400 mg/d in women; DHA: 120 mg/d in men and 100 mg/d in women). The intakes of alpha-linolenic acid, and to a lesser extent of linoleic acid, were highly correlated with that of lipids. Whereas the main source of linoleic acid was vegetable oils, all food types contributed to alpha-linolenic acid intake, the main ones being animal products (meat, poultry, and dairy products). The main source of EPA and DHA (and of total long-chain n-3 PUFA) was fish and seafood, but the major source of DPA was meat, poultry, and eggs. Fish and seafood consumption showed very large interindividual variations, the low consumers being at risk of insufficient n-3 PUFA intake.
Abstract: Abnormal thyroid function has important public health consequences. However, the various degrees of thyroid dysfunction remain unsettled. The SU.VI.MAX cohort provided a unique opportunity to conduct a cross-sectional study of abnormal thyroid function in a large representative population of 11256 men and women representing the geographic distribution of the French continental adult population. Thyroid status was measured, in fasting blood samples, at baseline in 1994-1995. Serum thyrotropin (TSH) levels (abnormal < 0.4 mU/l or > or =4.0 mU/l) and free thyroxine (fT4) were both performed in duplicate on the same sample. Subjects with previous or present thyroid diseases or who were taking thyroid hormones or antithyroid drugs (n=920) were excluded (8.1%). Thus, the final study group consisted of 10346 subjects, 4121 men aged 45-60 years (mean +/-SD) (51.8+/-4.7 yrs), 2641 women aged 35-44 years (40.6+/-2.8 yrs), and 3584 women aged 45-60 years (51.4+/-4.4 yrs). Median (2.5th and 97.5th percentiles) for TSH (mU/l) were 1.52 (0.20-4.54) for men, 1.78 (0.22-5.54) for women aged 35-44 years, and 1.96 (0.22-6.80) for women aged 45-60 years. The TSH distribution of women was shifted to the right compared with men. Arithmetic mean fT4 (+/-SD) was 10.7+/-1.7 ng/l (13.8 +/-2.2 pmol/l) for men and 10.9+/-1.8 ng/l (14.0+/-2.3 pmol/l) for women. The prevalence of abnormal TSH values in men, and in women (35-44 yrs and 45-60 yrs) were TSH<0.4 mU/l 7.0%, 5.3% and 4.4%; TSH 4.0-9.9 mU/l 4.0%, 7.2% and 11.1% and TSH > or =10.0 mU/l 0.2%, 0.4% and 0.7%, respectively. Geometric mean serum TSH and arithmetic mean serum fT4 concentrations showed significant overall inter-regional differences for men and women (p<0.0001). There was also an inter-regional difference in the prevalence of thyroid dysfunction for men (p=0.003), and for the older group of women (i.e. > or =45 yrs) (p=0.04) exclusively. Over the age of 45 years, the women: men ratio for unrecognized elevated TSH levels (> or =4.0 mU/l) was 2.82, whereas it was 0.64 for low TSH levels (<0.4 mU/l). In summary, abnormal TSH values and thyroid dysfunction were more prevalent in women than men, increased with age and were significantly associated with environmental factors. A high prevalence of identified thyroid diseases in the French population was confirmed by the high number of subjects in this study with laboratory evidence of abnormal biochemical thyroid function. Further studies are needed to determine the geographical determinants of thyroid dysfunctions, especially regional differences in iodine intakes, and to assess the long-term adverse effects of biochemical thyroid dysfunction on all-cause morbidity.
Abstract: OBJECTIVE: Dietary recommendations, a pillar in the treatment of diabetes, form part of official guidelines. However, it is not known how well these recommendations are followed in the diabetic population in France. The purpose of this study was to compare the habitual diet of self-declared diabetics with non-diabetics and to evaluate whether recommendations are being followed. METHODS: The intakes of several nutrients and foods of 67 self-declared diabetic patients were compared to those of 4658 non-diabetics in the SU.VI.MAX study (a primary prevention trial evaluating the impact of antioxidant supplementation on chronic disease). All patients (aged 45 to 60 years) who had completed at least five 24-hr dietary records over the first 18 months of the SU.VI.MAX study were included. We excluded patients who had not declared a diagnosis of diabetes and those with plasma fasting glucose levels over 7 mmol/l. RESULTS: The diabetic patients who declared being diabetic reported lower carbohydrate intakes (185 +/- 10.4 vs 219 +/- 1.4 g/d for men [p=0.001], 137 +/- 9.6 vs 165 +/- 1.0 g/d for women [0.005]), with a 50% reduction in consumption of oligosaccharides. Lipid intakes were unchanged for men, but reduced for women (61 +/- 4.1 g/d vs 72 +/- 0.4 g/d [p=0.01] with a 20% reduction in saturated fatty acids. Protein consumption was higher in the diabetic than in the non-diabetic men, but comparable for the women. Energy intakes were only lower in the diabetic women (1458 +/- 81 vs 1665 +/- 9 Kcal/d for women [p=0.01]). Micronutrient intakes were similar to those of non-diabetics, but appeared to be inadequate, particularly for anti-oxidants. Diabetic men consumed more margarine and less alcohol than did the non-diabetics. CONCLUSION: Diabetic patients who declared being diabetic did modify their nutritional behaviour, as they reduced their carbohydrate intake (both men and women), increased their protein intake (men only), and decreased their lipid and energy intakes (women only). However, carbohydrate intakes were unbalanced and there was excess protein intake. So patients who declared being diabetic are not as non-compliant in nutrition as commonly thought; they try to modify their diet, but often inappropriately. This may be explained by the fact that dietary advice stems from different sources and may be contradictory. A diabetic education program requires standardised training of health professionals and the provision of unequivocal information to the mass media and the general public.
Abstract: Elevated plasma total homocysteine (tHcy) is considered as a risk factor for occlusive cardiovascular disease (CVD). This concept is based on the observations of premature vascular disease in patients with homocystinuria and on the association between tHcy and increased risk of CVD in prospective studies. However, some observations have raised questions about tHcy as a risk factor. First, low risk population based prospective studies tend to indicate a weak association or no association between tHcy and CVD. Second, several traditional risk factors for CVD are associated with tHcy and may confound the relation between tHcy and CVD. Third, the C667T transition of the methylenetetrahydrofolate reductase causes a moderate increase in tHcy but no or only minor increased CVD risk. Thus, only placebo-controlled intervention studies with tHcy-lowering B-vitamins and clinical endpoints can provide additional valid arguments for the debate over whether tHcy is a causal CVD risk factor.
Abstract: To investigate the relative contributions of meals and snacks in the daily intake of free-living humans, 54 French adults maintained food intake diaries for four 7-day periods. They recorded all food and fluid intakes mentioning whether, in their opinion, each intake event was a snack or a meal. The weekly food diaries also contained information on the circumstances of each event such as time and place, number of persons present, and affective states (hunger, satiety, etc.) before and after intake. On average, 2.7 meals and 1.3 snacks were consumed each day. Very few days included no snacking. Total daily energy and nutrient intake were not different between days with and days without snacks. Snacks differed from meals in several dimensions. Meals were about twice as large as snacks in energy and weight. Nutrient intake, in absolute values, was higher in meals. In proportions, however, snacks contained more CHO and less fat and proteins. Most foods were consumed in larger amounts in the context of meals but a few (sweets, cereal bars, biscuits, and sodas) were mostly consumed as snacks. Hunger was more intense before but less intense after meals than snacks. The satiety ratio was higher for snacks than meals. Time of day affected many intake parameters. For example, afternoon snacks exhibited a high satiety ratio for a modest intake. The present study describes the status of several potential determining factors at the time of snacks in humans, demonstrating a specific role for snacks, as opposed to meals, in the daily eating pattern of healthy adults.
Abstract: OBJECTIVE: To test the effect of a 21-day supplementation with moderate doses of antioxidant nutrients on biochemical indicators of vitamin, carotenoid and trace element levels in alcohol-dependent patients during a program of alcohol rehabilitation. DESIGN: A randomized double-blind trial was performed comparing two groups receiving daily either a combination of micronutrients (beta-carotene: 6 mg, vitamin C: 120 mg, vitamin E: 30 mg, zinc: 20 mg, selenium: 100 micro g) or a placebo. SUBJECTS: 106 alcohol-dependent patients 20 to 60 years of age without severe liver disease, hospitalized for a 21-day rehabilitation program. Measure of Outcome: Vitamin C, retinol, alpha-tocopherol, zeaxanthin/lutein, beta-cryptoxanthin, lycopene, alpha- and beta-carotene, zinc and selenium were measured in serum, initially and after supplementation. RESULTS: (1) In the placebo group, after 21 days of rehabilitation, serum concentrations of vitamin C and all five carotenoids significantly increased, whereas retinol and alpha-tocopherol concentrations decreased; zinc and selenium levels were unaffected. (2) At the end of the hospital stay, serum indicators were significantly improved in the supplement group as compared to the placebo group for vitamin C, alpha-tocopherol, beta-carotene, zinc and selenium; conversely, lycopene changes were higher in the placebo group than in supplement group. (3) Of the serum antioxidants measured at entrance, only vitamin C was significantly depleted in heavy smokers, and, after the supplementation period, vitamin C was efficiently repleted in this later group. CONCLUSION: Our results indicate that a short-term supplementation with physiological doses of antioxidant vitamins, carotenoids and trace elements during alcohol rehabilitation clearly improves micronutrient status indicators. Heavy smokers in particular seem to respond to vitamin C supplementation.
Abstract: BACKGROUND: Previous studies on the effects of alcohol consumption on total plasma homocysteine (tHcy) concentrations showed contradictory results. The conflicting results may derive in part from confounding by the type of alcoholic beverage consumed. OBJECTIVE: The objective of the study was to evaluate in a predominantly wine-drinking French population whether the relation between alcohol consumption and homocysteine concentrations is dependent on the type of alcoholic beverage consumed. DESIGN: In 1996, a cross-sectional study measuring tHcy and red blood cell folate concentrations was conducted in 1196 middle-aged women and men from the French Supplementation with Antioxidant Vitamins and Minerals Study. Intakes of alcohol, energy, coffee, and B vitamins were assessed by 6 separate 24-h dietary records from the previous year. RESULTS: tHcy concentrations were positively associated with wine intake (P = 0.01) in the women and with beer intake in the men (P = 0.002). No association with the consumption of spirits was observed. The association between beer consumption and tHcy concentrations in the men was modified by the consumption of wine; the association was positive in wine drinkers, whereas an inverse trend was seen in those who drank no wine. CONCLUSION: Wine consumption may increase tHcy concentrations, whereas beer consumption seems to have no effect (or even an inverse effect) on tHcy.
Abstract: Recent epidemiological studies have suggested that hyperhomocysteinemia is associated with increased risk of vascular disease. Homocysteine is a sulphur-containing amino acid whose metabolism stands at the intersection of two pathways: remethylation to methionine, which requires folate and vitamin B12 (or betaine in an alternative reaction); and transsulfuration to cystathionine which requires vitamin B6. The two pathways are coordinated by S-adenosylmethionine which acts as an allosteric inhibitor of the methylenetetrahydrofolate reductase (MTHFR) and as an activator of cystathionine beta-synthase (CBS). Hyperhomocysteinemia arises from disrupted homocysteine metabolism. Severe hyperhomocysteinemia is due to rare genetic defects resulting in deficiencies in CBS, MTHFR, or in enzymes involved in methyl cobalamine synthesis and homocysteine methylation. Mild hyperhomocysteinemia seen in fasting condition is due to mild impairment in the methylation pathway (i.e. folate or B12 deficiencies or MTHFR thermolability). Post-methionine-load hyperhomocysteinaemia may be due to heterozygous cystathionine-beta-synthase defect or B6 deficiency. Patients with homocystinuria and severe hyperhomocysteinemia develop arterial thrombotic events, venous thromboembolism, and more seldom premature arteriosclerosis. Experimental evidence suggests that an increased concentration of homocysteine may result in vascular changes through several mechanisms. High levels of homocysteine induce sustained injury of arterial endothelial cells, proliferation of arterial smooth muscle cells and enhance expression/activity of key participants in vascular inflammation, atherogenesis, and vulnerability of the established atherosclerotic plaque. These effects are supposed to be mediated through its oxidation and the concomitant production of reactive oxygen species. Other effects of homocysteine include: impaired generation and decreased bioavailability of endothelium-derived relaxing factor/nitric oxide; interference with many transcription factors and signal transduction; oxidation of low-density lipoproteins; lowering of endothelium-dependent vasodilatation. In fact, the effect of elevated homocysteine appears multifactorial affecting both the vascular wall structure and the blood coagulation system.
Abstract: OBJECTIVE: To investigate the relationship between selenium status, thyroid Volume and gland echostructure. DESIGN: Cross-sectional. METHODS: In 792 men (45-60 Years) and 1108 women (35-60 Years) from the SU.VI.MAX study, thyroid Volume and gland echostructure were determined ultrasonographically. At baseline, thyrotropin, free thyroxine, selenium, zinc, alpha-tocopherol, beta-carotene, retinol, urinary iodine and thiocyanate concentrations were measured. Alcohol consumption, smoking, and menopausal status were assessed by a questionnaire. A stepwise linear and a logistic regression model were used, adjusting for antioxidant vitamins, trace elements status and age. RESULTS: In women, there was an inverse association between selenium status and thyroid Volume (P=0.003). A protective effect of selenium against goiter (odds ratio (OR)=0.07, 95% confidence interval (CI)=0.008-0.6) and thyroid tIssue damage (OR=0.2, 95% CI=0.06-0.7) was observed. There was no evidence of an association between menopausal status and other antioxidant elements, thyroid Volume or thyroid hypoechogenicity. Smoking, but not alcohol consumption, was associated with an increased risk of thyroid enlargement in women (OR=3.94, 95% CI=1.64-9.48). No association between thyroid Volume, thyroid structure or selenium was found in men. CONCLUSION: Our findings suggest that selenium may protect against goiter. Selenium was related to thyroid echostructure, suggesting it may also protect against autoimmune thyroid disease.
Abstract: OBJECTIVE: To examine the consequences of single iron depletion on health in menstruating women, a common but rarely investigated situation in industrialized countries. DESIGN: We studied data issued from the SU.VI.MAX. cohort via a transversal and a longitudinal (2-y follow-up) approach. SUBJECTS AND METHODS: Iron-depleted menstruating women (ferritin &<15 micro g/l, n=472) were compared with iron-sufficient (ferritin 30-80 micro g/l, n=393) menstruating women (aged 35-51 y) in terms of health variables and quality of life (DUKE score) using logistic regression and analysis of variance. RESULTS: The risk of any infection or of specific types of infections was not increased by iron deficiency. Regarding the DUKE health profile, no specific score was significantly different between the two groups: only the scores reflecting 'physical health' (P=0.09) and 'perceived health' (P=0.12) showed a trend toward a lower level, while the best score for 'mental health' (P=0.11) was found in the group of iron-depleted women. The only significant difference between iron-depleted and iron-sufficient women concerned memory disorders, which were significantly less common in iron-depleted women, Odds ratio=0.7 (0.6-0.9; P=0.03). CONCLUSION: There is no conclusive evidence that an absence of iron stores has negative consequences; however, we must consider that in the case of a worsening of the iron balance, it may lead to a rapid decrease in the level of functional compounds. SPONSORSHIP: The laboratory Robapharm, Pierre Fabre, France.
Abstract: Cardiovascular diseases are the primary cause of mortality in France. Many epidemiological studies have shown that the total homocysteine concentration is a risk indicator for cardiovascular disease. Furthermore, it has been shown that the homocysteine concentration can be effectively lowered by supplementation with folic acid, vitamin B6 and B12. However, it is not yet known whether a reduction of the homocysteine concentration by such a supplementation indeed leads to a decreased risk of cardiovascular disease. Another possible dietary factor that may lower the risk of cardiovascular disease is fish-oil, which is rich in omega-3 fatty acids. These fatty acids lower platelet aggregation and triglyceride rich lipoproteins and may have antiarrhythmic effects. Some trials have investigated the effect of fish or fish-oil on cardiovascular mortality, and the results, although not conclusive, suggest a protective effect of a higher intake. In the SU.FOL.OM3 study we will evaluate the effect of supplementation at nutritional doses of folate (in the natural 5-methyl-tetrahydrofolate form) in combination with vitamin B6 and B12 and/or omega-3 fatty acids and/or placebo on recurrent ischemic diseases in a factorial design. The supplements will be randomly allocated to the participants in a double-blind fashion. In total 3,000 patients aged between 45 and 80 years who had a past history of myocardial infarction or unstable angina pectoris or an ischemic stroke will be included. The participants will be supplemented and followed up for a period of five years.
Abstract: The relationship between soup consumption and folic acid, beta-carotene, and vitamin E and C status was assessed in adults who regularly consumed soup compared to those who did not or who were occasional eaters. Data were obtained for 2114 men and 2874 women living in France and participating in the SU.VI.MAX cohort, who reported twelve 24-hour dietary records during a two-year follow-up period. Six-point-seven percent of women and 8.7% of men were heavy consumers of soup (i.e., they consumed soup from 9-12 days out of 12 days). Respectively, 46 and 42.5% were regular soup consumers (3-8 days out of 12), and 47.3 and 48.8% were occasional or non-soup consumers (0-2 days or less out of 12). Total energy intake did not differ between soup consumers and non-consumers. In both genders, heavy consumers of soups had significantly higher intakes of carbohydrates and lower lipid intakes. Heavy consumers of soup had higher dietary intakes of folates, beta-carotene, vitamin C and, in men, of vitamin E. In heavy consumers, soups contributed 12.5% of total dietary intake of beta-carotene in men and 13% in women. For vitamin C, vitamin E, and folates, soups contributed to 4-5% of total vitamin intake. In heavy soup consumers, mean serum vitamin C levels were higher, but not significantly, than in occasional or non-soup consumers. This trend was also observed for red blood cell folate in women only. The present data suggest that consumption of soup may be beneficial in promotional programs to increase vegetable consumption, and may contribute to a balanced diet and a healthy nutritional status, and especially vitamin status, in the overall population.
Abstract: BACKGROUND: An elevated plasma total homocysteine (tHcy) concentration seems to increase the risk of cardiovascular disease. OBJECTIVE: We evaluated the determinants of tHcy in healthy French adults. DESIGN: tHcy was measured by HPLC and fluorometric detection in 1139 women and 931 men aged 35-60 y. Subjects were participants of the Supplementation with Antioxidant Vitamins and Minerals Study, which investigates the effects of antioxidant supplementation on chronic diseases. Red blood cell folate (RBCF), plasma vitamins B-6 and B-12, and cardiovascular disease risk factors were also measured. The habitual diet was assessed in 616 subjects. Cross-sectional analyses were adjusted for age, smoking, energy intake, and concentration or intake of folate and vitamin B-6, where appropriate. RESULTS: The mean (+/-SD) tHcy concentration was 8.74 +/- 2.71 micro mol/L in women and 10.82 +/- 3.49 micro mol/L in men. In women, tHcy was positively related to age (P = 0.001), apolipoprotein B (P < 0.01), serum triacylglycerol (P < 0.01), fasting glucose (P = 0.02), and coffee and alcohol consumption (both P < 0.01) and inversely related to RBCF (P = 0.11) and plasma vitamin B-12 (P = 0.08) and vitamin B-6 (P = 0.01) intakes. In men, tHcy was positively associated with body mass index (P = 0.03), blood pressure (P < 0.02), serum triacylglycerol (P < 0.01), fasting glucose (P = 0.01), and energy intake (P < 0.01) and inversely associated with physical activity (P = 0.04), RCBF (P = 0.02), plasma vitamin B-12 (P = 0.09), and dietary fiber (P < 0.01), folate (P = 0.03), and vitamin B-6 (P = 0.09) intakes. CONCLUSION: To control tHcy, decreasing coffee and alcohol consumption may be important in women, whereas increasing physical activity, dietary fiber, and folate intake may be important in men.
Abstract: OBJECTIVE: To investigate relationships between changes in weight and changes in cardiovascular risk factors in adults, taking intentionality of weight loss into account. DESIGN: Longitudinal study in middle-aged French subjects from the SU.VI.MAX cohort. SUBJECTS: A total of 1773 men (body mass index (BMI) 25.4+/-3.1 kg/m(2), mean+/-s.d) and 2316 women (BMI 23.3+/-3.8 kg/m(2)) aged 45 y and over at baseline. MEASUREMENTS: Weight, height, blood pressure, serum total cholesterol and fasting blood glucose were measured at baseline and after a 2 y follow-up. Self-reported dieting in order to lose weight, smoking status, leisure-time physical activity, health events and current treatments were assessed through questionnaires. RESULTS: In multivariate analyses, weight change was positively associated with changes in systolic and diastolic blood pressure (P=0.0002 in women, P=0.0001 in men) and with changes in serum total cholesterol (P=0.008 in women, P=0.02 in men), after adjustment for age, baseline level of each cardiovascular risk factor and current treatments. For example, in men, a weight loss of 5 kg was associated with a decrease of 2.5 mmHg in systolic blood pressure and of 1.5 mmHg in diastolic blood pressure. Taking into account self-reported dieting did not modify these associations. CONCLUSIONS: In both genders, systolic and diastolic blood pressure and serum cholesterol increased with weight gain and decreased with weight loss, independently of the intentionality to lose weight. At the population level, modest weight loss may have a substantial impact on cardiovascular risk, and preventing even modest weight gain in adults is an important goal in terms of public health.
Abstract: BACKGROUND: In spite of the large prevalence and growing incidence of herpes simplex infection (HSV-1 and HSV-2), relatively few large serological surveys are available worldwide and it is still difficult compare frequencies of HSV contaminations in various countries. We present the results of HERPIMAX, the first epidemiological inquiry on HSV prevalence in the general French population. METHODS: Of a cohort of 12,735 presumed healthy adult volunteers included in the prospective study SU.VI.MAX, designed to assess the relation between nutritional supplementations and degenerative diseases, HERPIMAX randomly selected 4412 subjects (females 66.5%, males 33.5%). All serum samples were assessed for HSV-1 and HSV-2 IgG antibodies with a HSV type specific, enzyme immunosorbent assay (EIA). Equivocal result were retested with another HSV type specific immunoblot assay combined with a type common HSV IgG EIA in order to give a definitive interpretation. RESULTS: The mean seroprevalence was 67% for HSV-1 and 17.2% for HSV-2. For HSV-2 the seroprevalence was higher in females (17.9%) compared with males (13.7%) (p<0.001). For both HSV types, there was no significant difference in prevalence as regards age distribution in males and females, whereas prevalence increased significantly with age in females for HSV-1. Univariate analysis showed a significant association between HSV-1 prevalence and education level in males and females (p<0.001) and between HSV-2 prevalence and marital status in both sexes (p<0.001). There were geographical disparities, with a higher HSV-2 prevalence in the south of France as well as in Paris. CONCLUSION: These results confirm a high prevalence of HSV infection in France. They are also in agreement with previous results of other survey carried out in other developed countries as regards higher prevalence of HSV-2 infection in women, the stability of seroprevalence for both HSV types after 35 years of age in females and 45 years of age in males.
Abstract: Epidemiological studies performed during the last 20 years support an inverse relationship between the individual intake of fruits and vegetables and the risk of cancer. In taking into account some recent conflicting data, a working group of the Nacre network, the French Network for Food and Cancer Research, has conduced a critical analysis of epidemiological and experimental studies, including the preliminary data from the Epic cohort, the European Prospective Investigation into Cancer and Nutrition, to clarify the role of fruits and vegetables to prevent cancer. To date, a high intake of fruits and vegetables (at least, 400 g per day) is appropriate to lower the risk of cancer. Fruits and vegetables provide numerous phytochemicals which, in part, may explain their beneficial effect. Thus, studies in animal models and in cell-culture systems have furnished a lot of information about the potential mechanism by which a diet high in fruits and vegetables may reduce the risk of cancer in humans. However, more investigation in the identification of the biologically active constituents, in the knowledge of their availability and the mechanism by which they contribute to lower the risk of cancer, will increase the scientific support of a public health policy.
Abstract: OBJECTIVE: To assess the frequency of different grades of nutritional status (obesity, overweight and thinness) in French children aged 7-9 y using four current definitions based on body mass index (BMI). METHODS: Data were collected in 2000 in a randomly selected sample of French children following the protocol recommended by the European Childhood Obesity Group (ECOG). After computing the BMI (weight/height squared), four references were used to define grades of nutritional status: (1) the French references to define thinness and overweight (3rd and 97th percentiles respectively); (2) the Must et al references to define thinness, overweight and obesity (5th, 85th and 95th percentiles respectively); (3) the International Obesity Task Force cut-offs to define overweight and obesity; and (4) the Center for Disease Control 2000 references to define thinness, overweight and obesity (5th, 85th and 95th percentiles respectively). RESULTS: Age and gender standardized frequencies were estimated in 1582 children. According to the French, Must et al, IOTF and CDC references, overweight (including obesity) affected 16.3, 23.9, 18.1 and 20.6% of children, respectively; obesity affected 9.3, 3.8 and 6.4% of children according to the Must, IOTF and CDC references, respectively. Thinness was present in 3.9, 6.0 and 6.0% of children according to the French, Must and CDC references. Whatever the definition, little difference was observed between sexes. Through age classes, as a rule, overweight and obesity tended to decrease while thinness tended to increase. CONCLUSION: The present study revealed an increasing prevalence of overweight in comparison with previous French data and a trend for increasing prevalence of thinness. The IOTF-based prevalence of overweight (including obesity) in 2000 in France was similar with the prevalence recorded in the late 1980s in the USA and the prevalence of obesity in 2000 in France was similar to the prevalence of obesity in the late 1970s in the USA. Data in France are comparable to those reported in other studies conducted in Western Europe. This study provides baseline information for analysis of time trends and for geographical comparisons.
Abstract: BACKGROUND: A population of over 12,000 mature subjects participated in a longitudinal study (8 years) of nutrition and health (the Su.Vi.Max Study). In this context, a specific cross-sectional study was carried out in a randomly selected subpopulation. AIM: To identify anthropometric, nutritional and biochemical correlates of spontaneous use of 'light' foods and drinks in a free-living population. DESIGN: Men (n = 2299) and women (n = 1979), 45-60 years, reported their food intakes over six non-consecutive days. Consumers of low-fat and low-sugar foods and drinks, and artificial sweeteners, were compared with non-consumers. RESULTS: Users of low-sugar products were heavier than non-users; female consumers of low-fat products, but not males, had higher body weight and BMI than non-consumers. Users of low-sugar products had higher triacylglycerols and glycaemia than non-users while biochemical parameters were not different in users and non-users of low-fat products. Use of low-sugar products led to increased diet density of a few micronutrients, including cholesterol. Low-fat product selection was associated with increased intake of most micronutrients, both in absolute value and in density. CONCLUSIONS: In mature adults, selection of fat-reduced products was associated with improved quality of the diet, while anthropometric and biological parameters appeared less favourable in consumers of low-sugar products vs. non-consumers. The longitudinal follow-up of the cohort in future years will help determine cause-and-effect relationships among these parameters.
Abstract: Cardiovascular diseases continue to constitute a major public health problem in all industrialized countries, where they are the main causes of premature mortality. There is a large body of evidence suggesting that free radical production directly or indirectly plays a major role in cellular processes implicated in atherosclerosis. Here we present mechanistic data and results of epidemiologic studies on the relationship between antioxidant vitamin intake or biochemical status and the risk of cardiovascular diseases. Most epidemiologic data obtained on this topic have been based on observational approaches, i.e. ecological studies, case-control or prospective studies. All these studies indicate that a high dietary intake or high blood concentrations of antioxidant vitamins are associated with a reduced risk of cardiovascular diseases. Although the results of these studies are convergent, they merely suggest a relationship at the population and individual level, but do not affirm a causality link. Only intervention studies (randomized trials), by specifically changing antioxidant vitamin intake, can provide conclusive answers. The apparent discrepancies between the results of recently published trials may be explained by the type of population (general or high-risk subjects), the differing doses of supplementation (nutritional levels or higher), the number of antioxidants tested (one, two or more) and the type of administration (alone or in balanced association). It thus appears that low risk of pathologies may be related to multiple nutrients consumed, at nutritional doses, and in combination. Optimal effects may be expected with a combination of nutrients at levels similar to those found in a healthy diet. A single antioxidant vitamin given at high doses in subjects with high risk of pathologies may not have substantial benefits and could even have negative consequences.
Abstract: AIM: The impact of soup consumption on nutrient intake and nutritional indicators was assessed in adults who consumed soup compared to those who did not or who were occasional eaters. METHODS: Data were obtained for 2,188 men and 2,849 women living in France and participating in the SU.VI.MAX cohort, who reported twelve 24-h dietary records during a 2-year follow-up period (60,444 records). Subjects were divided into three groups: (1) those who ate soup 0-2 days or less out of 6 days were classified as occasional or non-consumers; (2) those who consumed soup 3-4 days out of 6 were defined as regular consumers; (3) those who consumed soup 5-6 days out of 6 were defined as heavy consumers. RESULTS: Seven per cent of women and 9% of men were heavy consumers of soup. Respectively, 46 and 42% were regular, and 47 and 49% were occasional or non-consumers. Mean energy intake was lower in heavy consumers than in occasional or non-consumers, but the difference was statistically significant only in women. In men and women, heavy consumers of soup had significantly higher intakes of carbohydrates than occasional and non-consumers (245 g J(-1) vs. 227 g J(-1) in men; 186 g J(-1) vs. 176 g J(-1) in women) and lower lipid intakes (97 g J(-1) vs. 102 g J(-1) in men; 80 g J(-1) vs. 75 g J(-1) in women). Soup consumers presented lower energy intake at dinner than light or non-consumers. In soup consumers, breakfast and lunch contained greater amounts of carbohydrates, lipids and proteins, but dinner contained significantly smaller amounts of lipids and proteins. A higher frequency of BMI > 27 kg m(-2) was found in occasional and non-soup consumers; conversely a higher frequency of BMI between 23 and 27 kg m(-2) was found in regular consumers of soup and a higher frequency of BMI < 23 kg m(-2) in heavy consumers. For women, an association was found between occasional or non- consumers and BMI > 25 kg m(-2) and between heavy consumers and BMI < 22 kg m(-2). Likewise an association was found in men only between heavy consumption of soup and lower value of serum cholesterol. CONCLUSION: The present data suggest that the consumption of soups contributes to a balanced diet. Consumption of soup may be beneficial for a healthy nutritional status in the overall population.
Abstract: Thyroid nodules were assessed by ultrasound in 3 621 presumably healthy free-living French subjects participating in the SU.VI.MAX cohort (2 160 females aged 35-60 years and 1 461 males aged 45-60 years). Urinary iodine was measured in all participants in random morning urine samples. Nodular thyroid structures ranging from 3 mm to 57 mm in diameter were found in 14.5% of the population, without significant differences between regions in the different age and sex groups. Single nodules and multiple lesions were found in, respectively, 9.7% and 3.1% of the subjects. In females, nodules increased from 12.9% to 19.2% between 35-45 years and 45-60 years, respectively (p<0.001). Thyroid nodularity was more frequent among women aged 45-60 years than among men of those ages (19.2% vs. 11.0%, p=0.001). Descriptive data provided by ultrasound differentiated the nodules into solid (43.4%), cystic (38.4%), and mixed solid-cystic (18.2%). Most solid thyroid nodules, 76.1%, were hypoechoic, while 16.6% were iso-, and 7.3% were hyperechoic. The median of iodine concentrations (n=3 276) was 8.0 microgram/100 ml, with 19.4% of the samples being<5 microgram/100 ml. Median iodine concentrations displayed wide regional variations, with values significantly higher in residents of western regions than among those living in the eastern areas (p<0.001), independently of age and sex. No relationship was found between prevalence of nodular thyroid structure and the state of borderline iodine status observed in France.
Abstract: In Europe, iron deficiency is considered to be one of the main nutritional deficiency disorders affecting large fractions of the population, particularly such physiological groups as children, menstruating women and pregnant women. Some factors such as type of contraception in women, blood donation or minor pathological blood loss (haemorrhoids, gynaecological bleeding...) considerably increase the difficulty of covering iron needs. Moreover, women, especially adolescents consuming low-energy diets, vegetarians and vegans are at high risk of iron deficiency. Although there is no evidence that an absence of iron stores has any adverse consequences, it does indicate that iron nutrition is borderline, since any further reduction in body iron is associated with a decrease in the level of functional compounds such as haemoglobin. The prevalence of iron-deficient anaemia has slightly decreased in infants and menstruating women. Some positive factors may have contributed to reducing the prevalence of iron-deficiency anaemia in some groups of population: the use of iron-fortified formulas and iron-fortified cereals; the use of oral contraceptives and increased enrichment of iron in several countries; and the use of iron supplements during pregnancy in some European countries. It is possible to prevent and control iron deficiency by counseling individuals and families about sound iron nutrition during infancy and beyond, and about iron supplementation during pregnancy, by screening persons on the basis of their risk for iron deficiency, and by treating and following up persons with presumptive iron deficiency. This may help to reduce manifestations of iron deficiency and thus improve public health. Evidence linking iron status with risk of cardiovascular disease or cancer is unconvincing and does not justify changes in food fortification or medical practice, particularly because the benefits of assuring adequate iron intake during growth and development are well established. But stronger evidence is needed before rejecting the hypothesis that greater iron stores increase the incidence of CVD or cancer. At present, currently available data do not support radical changes in dietary recommendations. They include all means for increasing the content of dietary factors enhancing iron absorption or reducing the content of factors inhibiting iron absorption. Increased knowledge and increased information about factors may be important tools in the prevention of iron deficiency in Europe.
Abstract: By integrating an agonist satiety signal, provided by alpha-melanocyte-stimulating hormone (alpha-MSH), and an antagonist signal, provided by agouti-related protein (AGRP), the melanocortin-4 receptor (MC4-R) is a key element in the hypothalamic control of food intake. Inactivation of the gene encoding this G protein-coupled receptor causes obesity in mice. In humans, frameshift mutations in MC4-R cause an early-onset dominant form of obesity in two families. In this study we find a high frequency (4%) of rare heterozygous MC4-R mutations in a large population of morbidly obese patients. No such mutations were found in controls. By analyzing the phenotypes of the probands carrying these mutations, we demonstrate that these patients display a common, nonsyndromic form of obesity. Interestingly, functional analysis of the mutant receptors indicates that obesity-associated defects in MC4-R range from loss of function to constitutive activation. Transmission of these mutations in the families of the carriers indicates a variable expressivity that is not related to the functional severity of the mutations. This variable expressivity of MC4-R-associated obesity is not due to variations in genes for alpha-MSH or AGRP. Taken together, these results demonstrate that MC4-R mutations are a frequent but heterogeneous genetic cause of morbid obesity.
Abstract: The determinants of hormone replacement therapy (HRT) were studied in a cohort of recently postmenopausal women participating, in France, in a nutritional study (SU.VI.MAX Study). Analysis was performed-analysis on 592 women aged 45 years or more, who had undergone natural menopause which appeared in the 2 previous years. No differences were observed in education level, socio-professional categories, marital status, geographic residence, smoking habits, physical activity, or past contraceptive practice. Past regular gynecologic follow-up appeared to be the strongest determinant of HRT use (odds ratio [OR]: 3.18). Women who reported having had at least one of the studied pathologies (past history of breast cancer, phlebitis, anger, uterine fibroma, hypertension, diabetes or hypercholesterolemia), past abundant menstrual blood losses, and with body mass index (BMI) > or = 25 were less likely to be taking HRT than women free of pathology, with no history of past abundant menstrual blood losses and with low BMI (OR respectively of 0.40, 0.64, 0.62). Women over 51.3 years of age were less likely to use HRT than younger women (OR: 0.92). Finally, in our population, while socio-economic level was not a major determinant of HRT use, the regularity of gynecological follow-up before menopause, overweight, and the existence of a definite or possible contra-indication were strong determinants of HRT use.
Abstract: BACKGROUND: Individual exposure to NO(2)and O(3) has been estimated in an urban population sample in southern France and the determinants identified. The present study was conducted to evaluated individual exposure to NO(2) and O(3) and to identify the environmental determinants of exposure in a larger population living in different environmental conditions. METHODS: Two hundred ninety-four volunteers were recruited from the SUVIMAX sample in Ile-de-France. The study covered 2 periods of 5 consecutive days, one in winter and the other in the fall of 1998. Passive monitors were used to estimate individual exposure and indoor concentration at the participant's dwelling. Background atmosphere concentrations were obtained for the AIRPARIF surveillance network. Single and multiple ANOVA were used for statistical analysis. RESULTS: Individual exposures were low, especially for O(3) in the considered periods of time. Mean NO(2) and O(3)concentrations were 41 microg/m(3)/h and 16 microg/m(3)/h, respectively. The NO(2) individual exposure increased with the time spent in traffic and indoor concentration. The correlation coefficient between indoor and individual levels was r=0.73, and indoor concentration explained 50% of the variance in individual exposure. The site of the dwelling with regard to high traffic street, and most strongly, the presence of a gas stove influenced indoor concentration. However, mechanical air extraction decreased the mean indoor NO(2) level of the dwellings. CONCLUSION: This study allowed identification of the environmental determinants of NO(2) exposure in an urban sample. These data, together with those obtained previously, well be used to establish an exposure matrix for NO(2).
Abstract: AIMS: The nutrient impact of ready-to-eat (RTE) cereal consumption was assessed in adults (men 45-60 years; women 35-60 years old) who regularly consumed RTE cereals anytime during the day, compared to those who did not or who were occasional eaters. METHODS: Data were obtained for 2,188 men and 2,851 women living in France and participating in the SU.VI.MAX cohort, who reported twelve 24-hour dietary records during 2 years of follow-up (60,468 records). RESULTS: In the heavy consumers group, RTE cereals provided 193 kcal/day for men and 168 kcal/day for women and contributed 8-10% of total daily energy intake; 15-17% of total daily carbohydrates intake; 4% of total daily lipids intake; 5-6% of total protein intake; and 19-23% of total fiber intake. Moreover, RTE cereals contributed 20-30% of total daily intake for vitamins B1, B2, B6 and folic acid, and 7% for vitamin B12. For minerals, they provided, respectively, for men and women, 22 and 25% of total daily intake for iron, 12 and 14% for magnesium, and 4% for calcium. In both genders, heavy consumers of RTE cereals derived a greater proportion of daily energy from carbohydrates and a lesser proportion of energy from fats. Total daily fiber intake is higher for RTE cereal consumers than for nonconsumers and increases with the frequency of consumption. Frequent consumers of RTE cereals have higher dietary intakes of calcium, magnesium, iron, vitamins B1, B2, B6, and folic acid than do nonconsumers. BMI and waist/hip ratio were significantly lower in heavy consumers of RTE cereals than in nonconsumers. CONCLUSIONS: The present data suggest that the consumption of RTE cereals contributes to a balanced diet. The strong association between cereal consumption and vitamin and mineral intakes confirm previous studies suggesting that RTE cereals make a major contribution to micronutrient intakes. The consumption of RTE cereals also appears to be associated with lower corpulence.
Abstract: OBJECTIVE: Peroxisome-proliferator-activated receptors gamma (PPAR gamma), is a key regulator of adipocyte differentiation and energy balance. Two naturally occurring mutations in the PPAR gamma gene, Pro115Gln and Pro12Ala, have recently been shown to impair the function of the PPAR gamma2 isoform of the receptor and to be associated with obesity or diabetes-related phenotypes in different populations. SUBJECTS: We studied the occurrence and possible associations of the Pro115Gln and Pro12Ala in the PPAR gamma2 gene with several clinical and metabolic phenotypes in three independent large populations of non-obese non-diabetic, type 2 diabetic, and morbidly obese French Caucasians. RESULTS: The Pro115Gln mutation was not found in any of the 1069 subjects screened including 626 obese patients. The frequency of the Pro12Ala mutation was similar in all groups (0.08, 0.11, 0.09) and was not associated with BMI or any of the clinical parameters tested. CONCLUSIONS: We conclude that the Pro115Gln mutation is not a frequent cause of morbid obesity in Caucasians and that the Pro12Ala mutation is not associated with clinically significant changes in these populations.
Abstract: OBJECTIVE: To determine and describe the extent to which European dietary data collected in disparate surveys can be meaningfully compared. DESIGN: Seven independent population-based surveys from six European countries were initially included. Differences in study designs and methodological approaches were examined. Risk factor data for 31,289 adults aged 40-59 y were harmonized and pooled in a common, centralized database. RESULTS: Direct comparisons of dietary measures across studies were not deemed appropriate due to methodological heterogeneity. Nonetheless, comparisons of intra-population contrasts by gender across sites were considered valid. Women consumed fruit and vegetables more often than men. Age-standardized gender differences in the prevalence of low fruit and vegetable consumption ranged from 7 to 18% and 5 to 15%, respectively. Data on energy intake showed good agreement across study populations. The proportion of total energy from macronutrients was similar for women and men. Gender differences for relative intakes of saturated fatty acids (percentage energy) were small and only in France were they significant. Dietary fibre density was significantly higher in women than in men. Overall, the participating Southern European populations from Italy and Spain exhibited more healthful food composition patterns. CONCLUSIONS: Contrasts in dietary patterns by gender across populations may provide the basis for health promotion campaigns. The most favourable patterns observed may serve as attainable goals for other populations. An international risk factor surveillance programme based upon locally run, good quality studies has the potential to provide the needed data. SPONSORSHIP: European Community (DG V), project 96CVVF3-446-0; Swiss Federal Office for Education and Science, OFES 96.0089.
Abstract: OBJECTIVE: To assess the impact of a daily oral iron supplementation on hematological status, cell-mediated immunity and susceptibility to infections in children living in an environment where iron deficiency, malaria and other infections are frequent. DESIGN: Randomized, double-blind iron supplementation including a placebo group. SETTING: A village in Togo, West Africa. SUBJECTS: Of the 229 6-36-month-old children of both sexes recruited, 197 with hemoglobin concentration >/=80 g/l were included and 163 completed the study. INTERVENTION: Children received daily a placebo (n=79) or a dose of 2-3 mg of elemental iron per kg of body weight (n=84) for 3 months. Hematological, nutritional and immune status were assessed at the beginning and at the end of the supplementation period, and 6 months later. Morbidity was recorded throughout the study. RESULTS: Iron supplementation had a significant and positive effect on iron status of children and no impact on the incidence of infections, especially malaria. Its probable effect on immune status was masked by interference of infections and their treatment, which contributed to improve hematological and immune status in both groups. CONCLUSION: According to the negative consequences of anemia and iron deficiency on global child development, control of iron deficiency by oral iron supplementation in young children has to be conducted, associated with prophylaxis and treatment of malaria and repeated deworming. SPONSORSHIP: Program supported by IRD. European Journal of Clinical Nutrition (2000) 54, 29-35
Abstract: STUDY OBJECTIVE: EURALIM (EURope ALIMentation), a European collaborative study, aimed to determine and describe the extent to which European data on risk factor distributions from different populations could be pooled and harmonised in a common database for international comparisons. SETTING: Seven independent population-based surveys from six European countries (France, Italy, Northern Ireland/United Kingdom, Spain, Switzerland, the Netherlands). METHODS: Data for 18 381 women and 12 908 men aged 40-59 were pooled in a common database. Central statistical analyses on major cardiovascular risk factors were conducted with careful consideration of methodological issues, including differences in study designs, data assessment tools, and analytic techniques used. MAIN RESULTS: Because of the detected variability among methods used, direct comparisons of risk factor distributions and prevalences between studies were problematic. None the less, comparisons of within population contrasts by sex, age group, and other health determinants were considered to be meaningful and apt, as illustrated here for obesity. Results were targeted and disseminated to both the general public and public health professionals and framed in the context of a European information campaign. CONCLUSIONS: International and national comparisons between existing locally run studies are feasible and useful, but harmonisation methods need improvement. Development of an international risk factor surveillance programme based on decentralised data collection is warranted. In the meantime, risk factor contrasts across populations can be used as a basis for targeting needed public health intervention programmes.
Abstract: A link between bone mineral density and skin color has been reported recently, and pigmentation has been shown to affect cutaneous vitamin D production. In the present study, we investigated the relationship between phototype, global self-assessed sun exposure, geographical location and vitamin D serum levels in 1191 French adults. When the factors were analyzed separately, individuals with lower phototypes as well as those with lower sun exposure showed significantly lower levels of vitamin D than those with darker phototypes or those with higher sun exposure. However, when factors were analyzed as a whole, the vitamin D status was no longer linked with the phototype, but with sun exposure and geographical location. Since phototypes and global self-assessments of sun exposure were positively linked, our data suggest that lower vitamin D levels in fair-skinned individuals are due to their sun exposure behavior.
Abstract: During the last years, a large number of surveys have suggested than some fractions of the French population, as in other industrialized countries, presented dietary iron intake below the recommended dietary allowances. Iron deficiency is widespread in children, menstruating women, and particularly pregnant women. Iron deficiency is enough severe to be responsible of anemia in some groups of population. Aside the classical risk of anemia (with its well-known consequences on health), the effects of iron deficiency by itself, taking into consideration the role of iron in numerous metabolic functions, needs to be more documented to assess the potential deleterious consequences upon health.
Abstract: OBJECTIVE: To study the relative importance of determinants of thyroid volume. DESIGN: Cross-sectional study on a sample of subjects issued from the SU.VI.MAX cohort. SUBJECTS: 2987 French subjects (1713 women aged 35-60 years and 1274 men aged 45-60 years). None of them had previous or present thyroid disease. MEASUREMENTS: Thyroid volume was determined by ultrasound. Serum TSH and free thyroxine (fT4) were measured in duplicate. Urinary iodine and urinary thiocyanate were assayed in random morning urine samples. RESULTS: For both sexes, thyroid volume (ml) was positively correlated with weight, height, body mass index and body surface area (P = 0.0001) and negatively with age for females (P = 0.0009). When the urinary iodine concentration was adjusted for urinary thiocyanate concentration and their interaction, the thyroid volume was negatively correlated with urinary iodine (males P = 0.02, females P = 0.006) and positively correlated with urinary thiocyanate (males P = 0.0001, females P = 0.004). Mean thyroid volume was greater among active smokers than non-smokers (males P < 0.0001, females P = 0.0004) and was greater among former smokers than among non-smokers (males P = 0.0001, females = 0.004). Free T4 and thyroid volume were positively correlated for both sexes (P = 0. 0001). TSH was negatively correlated with thyroid volume for both groups (P = 0.0001). Female users of oral contraception (aged 35-45 years) had a smaller thyroid volume than non-users (P = 0.0009). CONCLUSIONS: The state of borderline iodine deficiency observed in France, in association with a slightly goitrogenic environment, may result in sustained stimulation of the thyroid, independently of TSH level, and is of paramount importance in the formation of goitre. Smoking may affect the thyroid, inducing marked long-lasting thyroid enlargement.
Abstract: INTRODUCTION: A link between bone mineral density and skin color has been reported recently, and pigmentation has been shown to affect cutaneous vitamin D production. In the present study, we investigated the relationship between phototype, global self assessed sun exposure, geographical location and vitamin D serum levels in 1191 French adults. METHODS: Three multiple linear regression analyses were performed. The two first analyses to test separately the effect of phototype, and the effect of sun exposure on the vitamin D levels. Then, a third model was constructed, using both factors and geographical location. RESULTS: When the factors were analyzed separately, individuals with lower phototype showed significantly lower levels of vitamin D than those with darker phototype, as well as, individuals with lower sun exposure showed significantly lower levels of vitamin D than those with higher sun exposure. However in the global model, which takes into account phototype and sun exposure simultaneously together with the region of residence, the vitamin D status was no longer linked with the phototype, but with sun exposure and geographical location. CONCLUSION: Since phototype and global self-assessment of sun exposure were positively linked, our data suggest that lower vitamin D levels in fair-skinned individuals are due to their sun exposure behavior.
Abstract: The 677cytosine mutation identified in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been frequently associated with an elevated plasma homocysteine concentration. The aim of the present study was to determine the impact of this MTHFR common mutation on plasma and erythrocyte folate (RCF) and plasma total homocysteine (tHcy) concentrations in healthy French adults. A cohort of 291 subjects living in the Paris area and participating in the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study were analysed to assess the impact of MTHFR polymorphism 677C-->T on folate status and plasma tHcy concentration. The frequency of the mutant homozygote for 677C-->T polymorphism (677TT genotype) in the present cohort was 16.8%. There were significant differences in plasma tHcy between 677CC, 677CT and 677TT genotype groups. The RCF concentrations were significantly different between each genotype, the lowest levels being associated with the 677TT genotype. When segregated by gender, no differences in tHcy between homozygous 677TT, heterozygous 677CT and wild-type 677CC genotype groups in women were observed. The fasting tHcy in women was unrelated to the 677C-->T mutation. However, tHcy was significantly increased in men with the homozygous 677TT genotype. We also analysed the possible implication of a second new MTHFR polymorphism (1298A-->C) in subjects with mild hyperhomocysteinaemia (4th quartile of homocysteinaemia; tHcy >11.1 micromol/l). The polymorphism 1298A-->C did not have a notable effect on tHcy or on the RCF levels. Our observations confirm a relatively high frequency of the 677TT genotype in the French population. Women with this genotype did not show the same increase in tHcy observed in men. In the present study dietary folate intake was not measured. Thus, the interaction of dietary folate with the MTHFR genotype in the French population needs further study.
Abstract: OBJECTIVE: To examine associations between the consumption of different types of breakfasts, dietary intakes, and selected indices of nutritional status. METHODS: Dietary intakes were obtained using the dietary history method, and serum bioassays were used to assess vitamin and mineral status in a representative community-based sample of 1108 French children (ages 2 to 10 years), adolescents (ages 10 to 18 years), and adults (ages 18 to 65 years). Breakfasts were divided into three categories: low-energy (<15% of the energy RDA), medium-energy (15-25%) and high-energy (>25%). RESULTS: High-energy breakfasts were associated with the consumption of ready-to-eat (RTE) cereals. High-energy breakfasts and cereal consumption, both more common among children and adolescents than among adults, were also associated with a greater proportion of daily energy from carbohydrate and lower proportion of energy from fat. High-energy breakfasts and cereal consumption were further associated with higher intakes of vitamins and minerals as measured by percent RDAs. High-energy breakfasts and cereal consumption were associated with lower serum cholesterols and improved biochemical indices of nutritional status. Serum concentrations of vitamin B1 (in children and adolescents), vitamin B2 and beta-carotene (in adults) were significantly linked to the level of energy provided by breakfast. CONCLUSION: The consumption of breakfast cereals appears to have a positive impact on nutritional status regardless of age.
Abstract: BACKGROUND: The symptoms of venous insufficiency of the lower limbs (VILL) include a feeling of heaviness in the legs, pain, and nocturnal cramps, which may be combined with organic disorders (varicose veins). The objective of this study was to determine the prevalence of VILL in terms of both varicose veins and functional symptoms in the participants of the SUVIMAX cohort, which is representative of the French population for the age range under consideration (women: 35-60; men: 45-60). METHODS: Information on the venous status of 3065 subjects in the SUVIMAX cohort were collected from three different sources: yearly systematic clinical examination (1994-1996), monthly follow-up by a telematic network (1994-1998) and non-specific questionnaire (1997). Two mutually exclusive populations were thus defined on medically diagnosed varicose veins and venous insufficiency and reported varicose veins and venous insufficiency. RESULTS: Venous insufficiency was medically diagnosed in 192 men (14.6%) and 584 women (33.6%), and varicose veins were diagnosed in 143 men (74.5%) and 317 women (54.2%) from this group. Prevalence reported symptoms of venous insufficiency and of varicose veins was 13.6% and 7.4% respectively in men and 28.2% and 12.4% in women. Sex, age, body mass index and number of pregnancies were found to be correlated with the risk of venous insufficiency. CONCLUSIONS: VILL is a very common disease in French adults both as varicose veins and as functional symptoms. Venotonics were the main type of treatment but not enough use is made of elastic compression stockings.
Abstract: The iron status of a national sample of adults living in France and participating in the SU.VI.MAX cohort, was assessed using serum ferritin and hemoglobin concentrations. Complete data were obtained for 6648 women 35-60 y old and for 3283 men 45-60 y old. Assessment of iron dietary intakes was realized on a subsample of 3111 women and 2337 men who reported six 24 h dietary records during a one-year period; 22.7% of menstruating women and 5.3% of post-menopausal women presented a total depletion of iron stores (serum ferritin < 15 microg/l). Iron-deficient anemias were found in, respectively, 4.4% and less than 1% of these women. Three-quarters of the anemias were related to iron deficiency in menstruating women. In men, iron depletion and iron deficiency anemia were very rare. Post-menopausal women had much higher serum ferritin levels than menstruating women. In menstruating women, those using intrauterine devices had significantly lower serum ferritin levels than those without contraception, and much lower than those using oral contraception. The frequency of iron depletion reached 28.1% in women using intrauterine devices, but only 13.6% in those using oral contraceptives. The mean iron intake was 16.7 +/- 5.7 mg/d in men and 12.3 +/- 3.4 mg/d in women. Heme iron represented respectively, 11.1 and 10.4% of iron intake. Ninety-three percent of menstruating women had dietary iron intakes lower than recommended dietary allowances (RDA); 52.6% consumed less than two thirds of these RDA. In post-menopausal women and men, respectively 27.7% and 3.6% had dietary intakes lower than RDA. Serum ferritin was positively correlated with meat, fish and total iron intake, and negatively correlated with dietary products consumption, calcium and fiber intake.
Abstract: OBJECTIVE: To test the impact of supplementation with nutritional doses of antioxidant nutrients on biochemical indicators of vitamin and trace element levels. DESIGN: A randomized double-blind trial was performed comparing two groups receiving daily either a combination of vitamins (beta-carotene, 6 mg; vitamin C, 120 mg; and vitamin E, 30 mg) and trace elements (zinc, 20 mg; and selenium, 100 micrograms); or a placebo. SUBJECTS: 401 subjects (166 males aged 45 to 60 years and 235 females aged to 35 to 60 years). MEASURE OF OUTCOME: Biological markers of vitamin and trace element status and free radical parameters were measured initially, 3 months, and 6 months after supplemention. RESULTS: Mean serum concentrations of alpha-tocopherol, vitamin C, beta-carotene, zinc and selenium increased significantly after 3 months of supplementation in the group receiving multivitamins associated with minerals. At baseline, 18.2% of the men and 5.1% of the women had low concentrations of serum vitamin C (< 20 mumol/l): 2.4% of the men and 17% of the women presented low concentrations of serum retinol (< 1.4 mumol/l): 18.7% of men and 10% of women had serum beta-carotene < 0.30 mumol/l. None of the study subjects had serum alpha-tocopherol concentrations below the limit cut-off point (< 9.3 mumol/l). Low serum zinc concentrations (< 10.7 mumol/l) were found in 15.1% of men and 23.8% of women. Low serum selenium concentrations (< 0.75 mumol/l) were found in 6% of men and 6.4% of women. A significant increase in plasma and red cell GPx activity was observed in groups receiving supplementation. No modifications were observed after 6 months of supplementation for malondyaldehyde. CONCLUSION: This study demonstrates the efficacy of an intake of antioxidant vitamins and trace elements, given at nutritional doses, on biochemical indicators of vitamin and trace elements status.
Abstract: Cardiovascular diseases and cancers constitute major public health problems in all industrialized countries, where they are the main causes of premature mortality. There is a large body of evidence suggesting that free-radical production can directly or indirectly play a major role in cellular processes implicated in atherosclerosis and carcinogenesis. Here we present mechanistic data and results of epidemiologic studies on the relationship between antioxidant vitamin intake or biochemical status and the risk of cancer and cardiovascular diseases. Most epidemiologic data obtained on this topic were based on an observational approach, i.e., ecologic, case-control, or prospective studies. All these studies indicate that a high dietary intake or high blood concentrations of antioxidant vitamins are associated with a reduced risk of cardiovascular diseases and cancer at several common sites. Although the results of these studies are convergent, they merely suggest a relationship at the population and individual level but do not affirm a causality link. Only intervention studies (randomized trials), by specifically changing antioxidant vitamin intake, can provide conclusive answers. The apparent discrepancies between the results of four recently published trials may be explained by the type of population (general or high-risk subjects), the differing doses of supplementation (nutritional levels or higher), the number of antioxidants tested (one, two, or more), and the type of administration (alone or in balanced association). It thus appears that a low risk of pathologies may be related to multiple nutrients consumed at nutritional doses and in combination. Optimal effects may be expected with a combination of nutrients at levels similar to those found in a healthy diet. A single antioxidant vitamin given at high doses in subjects with high risk of pathologies (smokers, asbestos-exposed subjects) may not have substantial benefits and could even have negative consequences.
Abstract: The first ecological epidemiological studies revealed the possible preventive role of some foods which contain antioxidant compounds on cardiovascular disease and on some types of cancer. Nevertheless, later further research and the initial population-based supplementary tests at therapeutic doses have rendered contradictory results. To elucidate the cause-effect relationship of the antioxidant nutrients, the SU.VI.MAX study was considered in France. This is a prospective population-based study of randomized, double blind intervention, the prime objective of which is that of evaluating the effectiveness of a combination of antioxidant minerals and vitamins at nutritional dosages on the morbimortality by cancer and ischemic heart disease of a cohort of 12,749 volunteers of both sexes, ranging from 35 to 60 years of age, spread throughout France over an eight-year period. Likewise, an evaluation was also made of the impact of the supplement on the incidence of infectious disease, cataracts, the individual feeling of well-being and the use of health care resources, the biological markers of the vitamin and mineral status, the antioxidant activity, the immune condition and the evolution of the cardiovascular risk factors. The final points of this study are: the overall mortality, the specific mortality by cancer and/or ischemic heart disease, the incidence of cancer (of any type) and the incidence of ischemic heart disease. The assessment tools employed were: a monthly health questionnaire filled out telematically, a yearly clinical or analytical health check-up every other year, as well as the exhaustive monitoring and documentation of the adverse events and serious health problems. To ascertain the eating behavior and the evolution thereof in the individuals comprising the cohort, an eating survey was filled out twice a month. A description is provided of the means and methods employed in this study, the originality and magnitude of which entail unique aspects which serve to remedy some problems of nutritional epidemiology, as well as the strategies employed for maintaining the active collaboration of the cohort and the exhaustive monitoring thereof. Two years into this study, the consolidation of the monitoring organization and the low drop-out rate afford the possibility of anticipating that the SU.VI.MAX study is going to provide some answers of interest with regard to the relationship between antioxidants and good health.
Abstract: Iron bioavailability from an infant cereal made of wheat flour with a low extraction rate (70%) and cow milk was measured in infants by using a stable-isotope technique. A dephytinized infant cereal was prepared by adding commercial phytase during manufacture, resulting in degradation of 88% of the native phytic acid. Paired comparisons were made to evaluate the effect of phytic acid on iron bioavailability. Both infant cereals contained identical amounts of ascorbic acid and had a molar ratio of ascorbic acid to iron of 2:1. Iron was added as ferrous sulfate. No difference in iron bioavailability was observed in this study; the geometric mean was 8.7% (range: 3.8-16.9%) and 8.5% (range: 3.4-21.4%) from the cereal with native phytic acid (0.08% phytic acid) and the dephytinized cereal (0.01% phytic acid), respectively. Dephytinization of infant cereals containing a relatively low native phytic acid content and high amounts of ascorbic acid is thus unnecessary to ensure adequate bioavailability of iron.
Abstract: Relatively high intakes of vegetables and fruit and relatively low intakes of fat are associated with lower rates of heart disease and many types of cancer. Biomarkers for vegetable and fruit consumption are most useful when applicable across different ages, body weights, diets, and varying patterns of fat intake. This study examined two biomarkers, serum concentrations of beta-carotene and vitamin C, as a function of anthropometric, dietary, and lifestyle factors in a community-based sample of French adults. The interview-based dietary-history method was used to assess dietary intakes of 361 males and 476 females aged 18-94 y resident in the Val-de-Marne district southeast of Paris. Serum beta-carotene was quantified by HPLC and vitamin C was measured by using an automated method. Serum beta-carotene and vitamin C concentrations were positively associated with vegetable and fruit intakes and were negatively linked to the consumption of energy, alcohol, and fat. Multiple-regression analyses showed that serum beta-carotene concentration was predicted by fruit and vegetable intakes but was inversely associated with body mass, energy and alcohol intakes, and tobacco use. Serum vitamin C concentration was positively associated with fruit consumption but was negatively associated with age, body mass, and tobacco use. Serum beta-carotene and vitamin C concentrations are useful biomarkers of vegetable and fruit consumption in the French diet. However, other dietary and lifestyle factors also have a significant effect on circulating concentrations of these antioxidant micronutrients.
Abstract: Guidelines for a healthy diet often recommend limiting dietary sugars and fats. Some researchers have called these aims mutually incompatible, suggesting that fat and sugar intakes, when expressed as percent dietary energy, are inversely linked. Others have argued that sugar, more specifically sucrose, acts as a vehicle for dietary fat and serves to suppress the overall quality of the diet. This study examined the relationship between age, sucrose and fat intakes, body mass index (BMI), and measures of dietary diversity and variety in a community-based sample of 837 French adults. Consistent with other studies, high consumption of added sucrose (in g/day or g/1000 kcal per day) was associated with higher consumption of energy and fat and lower consumption of vegetables and fruit. However, eating patterns were strongly influenced by age. High-sucrose consumers were significantly younger and had lower BMI values than did low-sucrose consumers, who were both older and had higher BMIs. High-sucrose diets had minimal effect on the diet diversity score and were associated with more varied diets, as evidenced by a higher dietary variety score.
Abstract: Many epidemiologic studies based on an observational approach indicate that a high dietary intake or high blood concentrations of some antioxidant micronutrients are associated with a reduced risk of cardiovascular diseases and cancer at several common sites. Inconsistent results of intervention trials suggest that low risk of pathologies may be related to multiple nutrients consumed, at nutritional doses, and in combination. This hypothesis was the rationale of the SU.VI.MAX. study, a randomized double-blind, placebo-controlled, primary-prevention trial designed to test the efficacy of a daily supplementation with antioxidant vitamins and minerals at nutritional doses in reducing the major health problems in industrialized countries, and especially the main causes of premature death (cancers and cardiovascular diseases).
Abstract: A randomized double-blind trial was performed in order to assess the efficacity of differing combinations of antioxidant nutrients on biochemical parameters of vitamin and trace element status, immunological parameters and free radical metabolism in elderly long term hospitalized subjects. A total of 756 institutionalized elderly subjects were recruited in 26 nursing homes in different areas of France. Four groups were constituted, receiving daily, for 1 year, either vitamins (beta-carotene, 6 mg; vitamin C, 120 mg; and vitamin E, 15 mg), trace elements (zinc, 20 mg and selenium, 100 micrograms), trace elements associated with vitamins, or a placebo. Biochemical indicators of trace elements and vitamin status and free radical parameters were measured before and after 6 months and 1 year of supplementation. Some immunological markers were investigated initially and after 6 months of supplementation on a subsample of 134 subjects. Mean plasma levels of alpha-tocopherol, gamma-tocopherol, vitamin C, alpha-carotene, beta-carotene and copper increased significantly after 6 months of supplementation in groups receiving vitamins alone or associated with trace elements. Serum selenium concentrations were significantly increased at 6 months of supplementation, and serum zinc only after one year in the trace element groups. Serum lycopene levels were significantly decreased by trace element supplementation. A significant increase in Se-glutathione peroxidase (GPx) levels was observed in groups receiving trace elements alone or associated with vitamins. No effect was noted on superoxide dismutase (SOD) activity or TBARs production. No effect of supplementation was found for in vitro lymphocyte proliferative responses or most lymphocyte subsets, except for a significantly lower percentage of CD2 subsets observed in groups receiving mineral supplementation either alone or associated with vitamins. A significant difference in CD19 subsets was found in groups receiving trace elements. Mean IL-1 production was significantly higher after 6 months of supplementation in the vitamin groups.
Abstract: To determine the impact of a trace element and vitamin supplementation on infectious morbidity, a double-blind controlled trial was performed on 81 elderly subjects in a geriatric center during a 2-year period. Subjects were randomly assigned to one of four treatment groups, and received daily: placebo; trace elements/zinc 20 mg; selenium 100 micrograms); vitamins (vitamin C 120 mg; beta-carotene 6 mg; alpha-tocopherol 15 mg); or a combination of trace elements and vitamins at equal doses. (1) Before supplementation, low serum values in vitamin C, folate, zinc and selenium were observed in more than two thirds of the patients. (2) After 6 months of supplementation, a significant increase in vitamin and trace element serum levels was obtained in the corresponding treatment groups: a plateau was then observed for the whole study. (3) Subjects who received trace elements (zinc and selenium) alone or associated with vitamins had significantly less infectious events during the 2 years of supplementation. These results indicate that supplementation with low doses of vitamins and trace elements is able to rapidly correct corresponding deficiencies in the institutionalized elderly. Moreover, zinc and selenium reduced infectious events.
Abstract: The vitamin D status of a general adult urban population was estimated between November and April in 1569 subjects selected from 20 French cities grouped in nine geographical regions (between latitude 43 degrees and 51 degrees N). Major differences in 25-hydroxyvitamin D (25(OH)D) concentration were found between regions, the lowest values being seen in the North and the greatest in the South, with a significant 'sun' effect (r = 0.72; p = 0.03) and latitude effect (r = -0.79; p = 0.01). In this healthy adult population, 14% of subjects exhibited 25(OH)D values < or = 30 nmol/l (12 ng/ml), which represents the lower limit (< 2 SD) for a normal adult population measured in winter with the same method (RIA Incstar). A significant negative correlation was found between serum intact parathyroid hormone (iPTH) and serum 25(OH)D values (p < 0.01). Serum iPTH held a stable plateau level at 36 pg/ml as long as serum 25(OH)D values were higher than 78 nmol/l (31 ng/ml), but increased when the serum 25(OH)D value fell below this. When the 25(OH)D concentration became equal to or lower than 11.3 nmol/l (4.6 ng/ml), the PTH values reached the upper limit of normal values (55 pg/ml) found in vitamin D replete subjects. These results showed that in French normal adults living in an urban environment with a lack of direct exposure to sunshine, diet failed to provide an adequate amount of vitamin D. It is important to pay attention to this rather high prevalence of vitamin D insufficiency in the general adult population and to discuss the clinical utility of winter supplementation with low doses of vitamin D.
Abstract: Magnesium intake was assessed using six 24-h dietary records during a 1-year period in 5,448 subjects (3,111 women 35-60 yrs old and 2,337 men 45-60 yrs old) in the SU.VI.MAX cohort, selected at a national level in France. The overall mean dietary intake was estimated at 369 +/- 106 mg/day in men and 280 +/- 84 mg/day in women. 77 per cent of women and 72 per cent of men had dietary magnesium intakes lower than recommended dietary allowances; 23 per cent of women and 18 per cent of men consumed less than 2/3 of these RDA. A strong positive correlation existed between energy and magnesium intake (r = 0.79; p < 10(-4)). Slight variations were observed according to socio-professional and educational levels and place of residence. Cereal products represented the main contribution in both men (21 per cent) and women (19.8 per cent). In men, the second source was represented by alcoholic beverages (11.7 per cent), which were a lower source of magnesium in women (5.5 per cent). Dairy products, vegetables, meat and poultry were the other main sources of dietary magnesium intake.
Abstract: We studied the effect of iron supplementation on the iron status of mothers and on biochemical iron status and clinical and anthropometric measures in their infants. The subjects were 197 pregnant women selected at 28 wk +/- 21 d of gestation at a mother-and-child health center in Niamey, Niger. Ninety-nine women received 100 mg elemental Fe/d throughout the remainder of their pregnancies and 98 received placebo. The prevalence of anemia and iron deficiency decreased markedly during the last trimester of pregnancy in the iron-supplemented group but remained constant in the placebo group. Three months after delivery, the prevalence of anemia was significantly higher in the placebo group. At delivery, there were no differences between the two groups in cord blood iron variables. Three months after delivery, serum ferritin concentrations were significantly higher in infants of women in the iron-supplemented group. Mean length and Apgar scores were significantly higher in infants with mothers in the iron group than in those with mothers in the placebo group.
Abstract: OBJECTIVES: To study the effect of supplementation with an association of small physiological amounts of antioxidant nutrients upon biochemical parameters and indicators of oxidative stress and antioxidant enzymes. DESIGN: The study included a double-blind placebo-controlled design. SETTING: Nursing homes in different areas in France. SUBJECTS: 575 elderly long term hospitalized subjects aged 65-103 years. INTERVENTION: Four groups were compared. They received daily: (V) vitamins (vitamin E, 15 mg and vitamin C, 120 mg) and beta-carotene, 6 mg; (T) trace elements (zinc, 20 mg, selenium, 100 micrograms); (VT) vitamins associated with trace elements; or (P) a placebo. Biological markers of vitamin and trace element status, and free radical parameters were measured initially and after 6 months of supplementation. RESULTS: An analysis of variance indicated a significant effect of vitamin supplementation on serum alpha-tocopherol, beta-carotene and vitamin C, a significant effect of trace element supplementation on serum zinc and both a significant trace element and a vitamin-trace element interaction on serum selenium. We observed significant effects of both trace element and vitamin supplementation on GPx activity (P < 0.01), an effect of vitamin supplementation on SOD activity (P < 0.05). CONCLUSION: Our results indicate that short-term supplementation with moderate doses of antioxidant vitamins and trace elements in elderly subjects clearly improves both non-enzymatic (alpha-tocopherol, beta-carotene, vitamin C) levels and enzymatic antioxidant (GPx and SOD) activity.
Abstract: OBJECTIVES. Assessing the quality of the total diet is a relatively new focus of studies in nutritional epidemiology. New indexes of healthful eating patterns have been largely limited to US populations. This study used evaluative criteria developed in the United States to assess diet quality and dietary diversity of French adults. METHODS. Habitual dietary intakes of a representative sample of 837 adults (361 men and 476 women) in the Val-de-Marne Dèpartement were evaluated. Evaluative measures of diet quality included a modified diet quality index (DQI), a dietary diversity (DD) score, and a dietary variety score (DVS). The 5-point DQI assessed compliance with the key guidelines of the US Department of Agriculture (USDA) for healthy people. The DD score counted the number of major food groups consumed whereas the DVS counted the total number of foods consumed on a regular basis. RESULTS. Few French adults consumed diets consistent with the USDA dietary recommendations. Only 14% of respondents derived less than 30% of energy from fat and only 4% derived less than 10% of energy from saturated fat. As a result, 63% of the sample had DQI scores of either 0 or I. In contrast, close to 90% of respondents scored a maximum of 5 in DD. Persons whose diets met US dietary recommendations also had the lowest DVSs. CONCLUSIONS. Methodologic factors and cultural biases may account for some of the observed differences between French and US data. Nevertheless, studies of diet quality and diversity are a promising new approach to the study of the total diet and associated health outcomes and may provide new insight into the French paradox.
Abstract: The iron status of 22 children and adolescents with Crohn's disease (mean age: 13 years) was evaluated. Eleven patients were suffering from active disease with inflammation, identified by at least one abnormal value for serum orosomucoid, C-reactive protein or sedimentation rate (group I). Eleven patients were in clinical remission and showed no biological evidence of inflammation (group II). Hemoglobin and red cell indices, erythrocyte protoporphyrin, serum iron, transferrin, serum ferritin and basic red cell ferritin were determined in all patients. The usual indicators of iron status, particularly serum ferritin, were affected by the inflammatory processes, but basic red cell ferritin appeared to be independent of inflammation. Basic red cell ferritin can therefore be considered to be a reliable indicator of iron status in children and adolescents with Crohn's disease.
Abstract: A biochemical assessment of the vitamin and trace element status of 756 institutionalized elderly men and women, 66-103 years old (average 83.5 +/- 7.6 y), was conducted in 26 nursing homes in different areas of France. Serum concentrations of beta- and alpha-carotene, beta-cryptoxanthin, lycopene, retinol, alpha- and gamma-tocopherol, vitamin C, zinc and selenium were measured. A difference in biochemical markers according to sex was observed for vitamins E and C: elderly women had higher levels of alpha-tocopherol and vitamin C than elderly men. When expressed as a ratio of cholesterol, the difference between sexes for alpha-tocopherol disappeared. Simple regression analysis showed that most vitamins and trace elements were significantly negatively correlated with age. A high prevalence of low concentrations of vitamin C, zinc and selenium was revealed.
Abstract: We compared post-abortion metrorrhagia in 185 women who used the mifepristone (600 mg) plus sulprostone (250 micrograms) drug combination and in 196 women who underwent vacuum aspiration. The patients were monitored for a 2 week period, with haemoglobin being measured on the day of the abortion and 2 weeks later. The women who had used the drug combination experienced a mean fall of 0.7 g/dl in haemoglobin (36% lost > 1 g/dl and 8% > 2 g/dl); haemoglobin concentrations remained stable in women who had had vacuum aspiration.
Abstract: In this paper, we try to understand the motivations and characteristics of people susceptible to be volunteers for the SU.VI.MAX study. The objective of this study will be to recruit and to follow during 8 years, a cohort of 15,000 subjects at a national level, for an intervention trial in the field of nutritional prevention. A short media campaign has been organised to recruit "1,000 volunteers to help to test and to validate tools specifically developed for the SU.VI.MAX study". In total, 15,789 subjects matching selection criteria answered to our invitation. All received a short questionnaire; 10,984 sent back correctly filled up questionnaires (70%) and 1005 were selected at random for a complete analysis. A lexical analysis of motivations disclosed 6 different groups organised in two poles. The pole of true altruists with a speech relative to notions such as "volunteers-benevolent" (7% of subjects), wishes to participate to a "humane task" (9% of subjects) or to progress of medical research (27% of subjects). The other pole corresponds to people interested personally by the theme of the project with 3 kinds of speech: personal past history (13% of subjects), interest for foods fortified with vitamins and/or minerals (19% of subjects) or for relationships between food consumption and health (22% of subjects).
Abstract: The iron status of a representative population sample in a district of Paris area (France) was assessed using a biochemical and dietary approach. Complete data were obtained for 1,108 subjects 6 months to 97 years old. Total iron intake increased up to adolescence and then remained stable in adult life. Iron intake was higher in men than in women. Most children and menstruating women presented a dietary iron intake below the recommended allowances. While anemia was not very common, iron deficiency (defined as the existence of at least two abnormal values in the four independent indicators of iron status: serum ferritin, erythrocyte protoporphyrin, transferrin saturation and MCV) was particularly common in infants, young children, menstruating women and elderly men. Serum ferritin, erythrocyte protoporphyrin and transferrin saturation were significantly correlated with inflammatory markers. Significant correlations were found between dietary total iron and serum ferritin (r = 0.29, p < 0.001) and hemoglobin (r = 0.44, p < 0.001). After adjustment for age, sex and inflammation, using multiple linear regression models, the relationship between both heme and nonheme iron intake and serum ferritin remained significant. Serum ferritin and hemoglobin levels were negatively correlated with calcium and phosphorus intake.
Abstract: The vitamin status of a representative population sample in a French district in the Paris area was assessed using a biochemical and dietary approach. Complete data were obtained for 1039 subjects 6 to 97 years old. Dietary intakes of most vitamins increased up to adolescence and then remained stable or decreased slightly in adult life. Total vitamin intakes were higher in men than in women (except for ascorbic acid), but the vitamin density of the diet was higher in females. Most subjects presented dietary intakes below the French recommended allowances for vitamin B1, B6, C, A and E. A variation in biochemical parameters according to age and sex was observed only for serum concentration of retinol, beta-carotene, vitamin E and C. Multiple regression analysis showed that dietary vitamin intakes were related to the biological status for vitamin B2, B6, C, folates, beta-carotene and vitamin E. Tobacco smoking, alcohol consumption and oral contraceptive were significantly correlated with biological status for several vitamins. While biochemical evidence of severe vitamin deficiency was not observed, a sizeable minority of the French population is not lavishly supplied with some vitamins, and this situation deserves investigation to see if any deleterious effects are associated with it.
Abstract: OBJECTIVES: Pregnant women in developing countries might be at risk of trace element deficiencies. These deficiencies could have deleterious effects on fetus. Therefore, serum trace elements were determined at delivery in Zairian mothers and their newborns. DESIGN: Prospective study. SETTING: Maternity ward of Kinshasa University Hospital (Zaire). SUBJECTS: 166 pregnant women admitted for delivery and their newborns. MAIN OUTCOME MEASURES: Zinc, copper and selenium were determined by atomic absorption spectrometry. Haematocrit, lymphocyte count, transferrin, ferritin and anthropometric indices (birth weight, length, head and arm circumferences; mother weight) were also evaluated. RESULTS: Serum selenium concentrations were high [mothers: 0.76-1.56 mumol/l (60-124 micrograms/l), newborns: 0.45-1.21 mumol/l (36-96 micrograms/l)]; zinc concentrations were low [mothers: 3.9-11.9 mumol/l (253-773 micrograms/l), newborns: 5.8-17.4 mumol/l (378-1130 micrograms/l)] and copper concentrations were in the range of previous works [mothers: 16.2-49.0 mumol/l (1020-3088 micrograms/l), newborns: 0.7-14.3 mumol/l (44-900 micrograms/l)]. Mother serum indices, age, weight and parity had little influence on newborn serum trace elements. In umbilical serum, copper was correlated to selenium (r = 0.340, P < 0.01); selenium (r = 0.310, P < 0.001) and copper (r = 0.404, P < 0.001) were correlated to transferrin. Newborn selenium (r = 0.310, P < 0.001) and copper (r = 0.257, P < 0.01) concentrations were related to head circumference. Newborn selenium concentration varied according to birth weight [< 2500 g: 0.58-0.86 mumol/l (45-67 micrograms/l); > 2500 g: 0.48-1.20 mumol/l (37-94 micrograms/l). Umbilical serum copper concentration was related to birth length (r = 0.197, P < 0.05). CONCLUSIONS: These results suggest that: (1) copper and selenium status at delivery in Zairian mothers are similar to those in developed countries, whereas zinc status is poor; (2) trace element and nutritional status in the mother and fetus are independent.
Abstract: A stable isotope technique has been developed which uses 57Fe and 58Fe as labels and which enables the simultaneous measurement of Fe absorption from two test meals in infants. The method was evaluated by measuring Fe absorption from a commercial whey-adjusted infant formula in nine healthy infants aged 13-25 weeks. Each infant was fed 210 ml formula, labelled with either 57Fe or 58Fe, on four consecutive mornings, in random order. The total Fe content in each feed was 2.5 mg Fe; either as 2.5 mg 57Fe, or 0.6 mg 58Fe plus 1.9 mg Fe with normal isotopic composition. Isotopic enrichment of Fe in erythrocytes was measured by thermal ionization mass spectrometry 14 d after the last administration, and Fe absorption was calculated based on isotope ratio shifts, total circulating Fe and intake of each isotope. Geometric mean absorption for the 57Fe and 58Fe labels was 6.72 and 6.58% respectively, and the absorption of the two isotopes was not significantly different (Student's paired t test). By this technique, paired comparisons of Fe absorption can be obtained and systematic studies of the influence of dietary factors on Fe absorption during infancy can be conducted.
Abstract: Urinary iodine excretion was assessed in 1222 healthy children aged 10 months (n = 456), 2 years (n = 368) and 4 years (n = 398) living in the Paris area and originating from continental France (55.2%), North Africa (15.7%), the West Indies (9.7%), West Africa (8.2%), Southeast Asia (5.5%), and southern Europe (5.7%). Iodine excretions (median values) were, respectively, 18.1, 13.4 and 11.6 micrograms/100 ml at 10 months, 2 years and 4 years, and risk of mild to moderate iodine deficiency (< 10 micrograms/100 ml) was 18.0%, 32.3% and 37.2% for the same age groups. Urinary iodine excretion was highest among Southeast Asian children, and lowest among West Africans. Hearing acuity was measured either by conventional mono-aural pure-tone audiometry or by binaural free field testing depending on the child's age. Hearing loss at 4000 Hz and average hearing impairment at speech frequencies (500, 1000 and 2000 Hz) were more severe among children at risk of mild to moderate iodine deficiency (less than 10 micrograms/100 ml) compared with those with urinary excretion above 10 micrograms/100 ml.
Abstract: The effect of iron and folate supplementation on the hemoglobin response and iron status was studied in male and female equatorian medical students: 66 in Quito (2,800 m altitude) and 40 in Guayaquil (sea level). At the end of the supplementation, there was a nearly complete disappearance of biochemical evidence of iron deficiency in the two groups of students. In Quito, 30% of the men and 26% of the women increased their hemoglobin concentration by more than 1 g/dl after one month of supplementation and could be considered as true anemics, compared to 31% of the men and 29% of the women in Guayaquil. This study shows that at sea level, cut-off points defined by WHO for hemoglobin, taking as reference the impact of a supplementation trial, have a specificity of 100% but poor sensitivity (58%). For people living at high altitudes, cut-off limits adjusted for altitude seem unsuitable: the specificity is 98% but the sensitivity is 0%. Studies taking into account all the factors impacting on the hemoglobin level could be useful for defining cut-off points for high-altitude anemia better than those currently recommended.
Abstract: The influence of phytic acid and ascorbic acid content of soy formula on iron (Fe) bioavailability was investigated in infants by analysis of the incorporation of stable isotopes of Fe into red blood cells 14 d after administration using a double stable isotope technique. Paired comparisons were made with each infant acting as his or her own control. The geometric mean fractional Fe incorporation into red blood cells increased from 5.5 to 6.8% (p < 0.05) when soy formula with the native content of phytic acid was compared with a 83% dephytinized formula. A more pronounced effect was shown with soy formula containing no phytic acid; the mean fractional Fe incorporation increased from 3.9 (native phytic acid) to 8.7% (zero phytic acid; p < 0.001). A significant (p < 0.01) effect was also demonstrated when the Fe:ascorbic acid molar ratio in the native phytate-containing formula was increased from 1:2.1 to 1:4.2; mean fractional Fe incorporation increased from 5.9 to 9.6%. These results demonstrate that the Fe bioavailability from soy-based infant formulas can be similarly increased by either removing phytic acid or increasing the ascorbic acid content.
Abstract: Cancer is a disease of the genome and free-radicals can damage genomic DNA, hence the interest in the potential protective antioxidant effect of vitamin and minerals. Indeed, the findings of most retrospective studies suggest that diets rich in fruits and vegetables have a protective effect against cancer. Prospective randomized trials have however given controversial results. Beta-carotene, the precursor of vitamin A has been shown to induce regression of precancerous lesions and 13-cis retinoic acid has a preventive effect on the development of a second cancer in patients with epidermoid cancer of the buccal cavity, the pharynx or the larynx although no effect has been observed on the primary cancer. Current research also suggests vitamin C has a potential anticancer effect, particularly for cancer of the stomach, the rectum and the cervix. For vitamin E, epidemiological data give less conclusive results. Several prospective studies suggest the absence of any correlation between vitamin E intake and general risk of cancer. A Chinese trial has shown a decreased incidence of oesophageal and gastric carcinoma while a Finnish trial revealed increased incidence of cancer among smokers treated by beta-carotene and vitamin E. Selenium and zinc intake, based on geographical correlations, has also been suggested to affect cancer incidence, but the results of prospective studies are conflicting. For example in 10 such trials analyzing blood selenium levels and risk of cancer, 4 have demonstrated a significant correlation. Further research is needed but is hindered by the absence of an adequate animal model and the difficulty in conducting large clinical trials. Nevertheless, positive data collected to date must be validated to determine the real effect of dietary preventive measures in the fight against cancer.
Abstract: The calcium, magnesium and iron intakes provided by food must be sufficient to fulfil the physiological demands of each individual, to avoid the clinical manifestations of mineral deficiencies and to ensure an optimal state of health. For these reasons, it is desirable to ensure a sufficient calcium intake (notably by milk products) at all ages and particularly in children, adolescents and young adults up to the age of 25 (and also in elderly people to prevent osteoporosis); to recommend the consumption of magnesium-rich foods, such a little sifted cereals and dry vegetables to ensure sufficient intakes; to prescribe pharmaceutical preparations on iron systematically in pregnant women and by repeated courses in infants aged 10 to 36 months (to avoid complications due to iron deficiency and notably its harmful influence on haematopoiesis). The consumption of "second age" milks for older children must also be encouraged. Finally, the consumption of foodstuffs with a high vitamin C content should be recommended as it increases the bioavailability of nutritional iron, and the consumption of substances, such as tea and coffee, which inhibit iron absorption must be reduced.
Abstract: The effects of iron deficiency on immunity remain controversial. This study was designed to assess the impact of iron supplementation on the immune status, in 81 children aged 6 months-3 years, at high risk for iron deficiency, using a longitudinal double blind randomised and placebo-controlled study. Lymphocytes of iron-deficient children produced less interleukin-2 in vitro. Iron supplementation for 2 months increased mean corpuscular volume, serum ferritin and serum transferrin, but had no effect on the parameters of T-cell mediated immunity. The lower interleukin-2 levels in iron-deficient suggest that cell-mediated immunity may be impaired in iron deficiency.
Abstract: Selenium (Se) was determined in human milk from women residing in Niamey (Niger) at different periods of lactation. To this purpose, a rapid electrothermal atomic absorption spectrometric (EAAS) method using Zeeman background correction and palladium matrix modifier was developed. Linear range (10 nmol/L-6.25 mumol/L, 0.8-494 micrograms/L), within-run (7.6%), between-run (10.4%), precision and recovery of standard addition (101 +/- 7%) were sufficient to allow routine determination of Se in breast milk. Values of breast milk Se decreased from 5 days to 6 months postpartum. No significant correlation was found between the milk Se and any of the following parameters: mother serum Se, parity, age of the mother, age of the previous child. In mother serum, Se concentration increased from delivery to 3 months postpartum and remained stable afterwards. The Se concentrations found in breast milk and in mother serum suggest that Se status is adequate in Niger.
Abstract: Trace element concentrations in serum and breast milk were studied longitudinally in 197 Nigerian women from 6 months of gestation to 6 months postpartum; 99 of them received a daily iron supplement of 100 mg from 6 months of gestation to delivery. During the last 3 months of pregnancy, serum selenium declined, whereas serum zinc remained unchanged and serum copper increased. After delivery, copper concentration in maternal serum decreased, whereas serum zinc increased from delivery to 3 months postpartum and then reached a plateau. Serum selenium increased from delivery to 6 months postpartum. In breast milk, selenium and zinc decreased from 5 days to 6 months postpartum. Copper in breast milk also declined during the course of lactation but reached a plateau by 3 months postpartum. Iron concentration in breast milk remained unchanged during the study. Iron supplementation had no significant effect upon the concentrations of copper, selenium and zinc in mother serum and breast milk. In umbilical serum, iron status, copper and zinc levels were similar in the two groups, whereas, unexpectedly, selenium concentration was significantly decreased (p < 0.03) in the iron-supplemented group. Taken together, our results suggest that the beneficial effect of iron supplementation on iron deficiency was not associated with an adverse effect on copper and zinc status. On the other hand, our results suggest that Nigerian women had a marginal zinc status but an adequate selenium status.
Abstract: The relationship between iron status and degree of infection by Schistosoma haematobium was studied in 174 schoolchildren from Niger in an area endemic for urinary schistosomiasis. Iron deficiency was defined by a combination of three reliable indicators: a low serum ferritin level combined with a low transferrin saturation, a high erythrocyte protoporphyrin level, or both. Hematuria and proteinuria were found in 76.4% and 79.9% of the children, respectively, while 95.4% excreted eggs (geometric mean egg count of 31.5 eggs per 10 ml of urine). Anemia was observed in 59.7% of the subjects. The prevalence of iron deficiency was 47.1%. Anemia was associated with iron deficiency in 57.7% of the cases. The hemoglobin level and transferrin saturation decreased significantly when the degree of hematuria increased, while prevalence of anemia and prevalence of iron deficiency increased significantly. The hemoglobin level and the hematocrit were negatively correlated with egg count, while prevalence of anemia increased with increasing egg count. This inverse relationship between degree of infection by S. haematobium and iron status shows a deleterious consequence of urinary schistosomiasis on nutrition and hematopoietic status, which should be considered in the design of nutrition intervention programs.
Abstract: Nutritional anaemia is recognized as a major public health problem throughout the world, especially in developing countries. Infants, young children, menstruating women and, in particular, pregnant women are most frequently affected. Sufficient evidence suggests that iron deficiency is the most common cause of nutritional anaemia in the world. Folate deficiency is considered as the second most common cause. In this chapter we discuss the factors determining nutritional inadequacy in iron and folate requirements versus iron and folate intake, particularly in different age/sex categories; the amounts of iron and folate involved in daily exchange and the role of the diet and physiological and pathological variations in losses and requirements are reviewed. The consequences in terms of health of iron and folate deficiencies and methods for assessing iron and folate status of populations are also presented.
Abstract: The relationship between iron status and capacity for IL-2 production by lymphocytes was assessed in 81 children from 6 mo to 3 yr of age selected at random from a population with low socioeconomic status, undergoing free systematic examination in four children's health centers in the Paris area. Iron deficiency was defined by the existence of at least two abnormal values among the three indicators of iron status: serum ferritin level less than or equal to 12 micrograms/L, transferrin saturation less than 12%, and erythrocyte protoporphyrin concentration greater than 3 micrograms/g hemoglobin. According to this definition, 53 children were classified as iron deficient and 28 as iron sufficient. No differences were observed between the iron-deficient and iron-sufficient groups in terms of the IL-2 concentration without stimulation by PHA. IL-2 production by lymphocytes stimulated with PHA, as well as the stimulation index (ratio of IL-2 concentration following stimulation by PHA to that of IL-2 concentration without stimulation by PHA) were significantly lower in iron-deficient children. The reduction in IL-2 production by activated lymphocytes observed in our study of iron-deficient children may be responsible for impairments in immunity found by other authors, particularly in cell-mediated immunity.
Abstract: An evaluation of iron and folate status was carried out on 166 Zairian pregnant women from Kinshasa at delivery and in cord blood from their newborns. Anemia, defined as a low hematocrit value (less than 33%), was observed in 38% of pregnant women. Iron deficiency, recognized by a combination of abnormal values for serum ferritin level (less than or equal to 12 micrograms/l) and transferrin saturation (less than 16%) was present in 54% of pregnant women. Folate deficiency, defined by a red blood cell folate of less than 100 micrograms/l, was observed in 6% of cases. In anemic mothers, anemia was associated with iron deficiency in 57% of cases and with folate deficiency in 5%. Correlations between maternal and newborn iron and folate indicators were found. This study points out the necessity for developing strategies in African countries to combat nutritional anemias during pregnancy by specific measures combined with general strategies.
Abstract: 1. Three groups of weanling C57BL/6 female mice were fed one of two folate-deficient diets (0 and 0.1 mg folic acid/kg diet) or a normal folate-containing diet (2 mg folic acid/kg diet) for 8 weeks. A control pair-fed group was introduced with the most severe folate-deficient diet. Seven mice were fed the 0 mg folic acid/kg diet for 8 weeks, then rehabilitated (R) on the 2 mg folic acid/kg diet for 10 days. 2. Mice fed 0 mg folic acid/kg diet were severely folate-deficient (SFD), whereas mice fed 0.1 mg folic acid/kg diet were moderately folate-deficient (MFD), as shown by their folate status parameters. 3. Thymus weight, thymocyte content and positive immature CD4+8+ cells were decreased in SFD mice compared to controls. These values were normalized after 10 days of rehabilitation. 4. Mesenteric lymph node cells were apparently not affected by folate deficiency. 5. The proportion of Thy-1+ splenocytes was mildly lower in SFD mice than in controls. In R mice, mean spleen weight and spleen cellularity were increased compared to the other groups, but the proportions of Thy-1+, CD4+8- and CD4-8+ cells were markedly lower than control values.
Abstract: Three groups of weanling female mice were fed one of two iron-deficient diets (5 and 12 mg Fe/kg diet) or a normal diet (30 mg Fe/kg diet) for 6 wk. A control pair-fed group was included. Seven mice received the 5 mg Fe/kg diet for 6 wk, then were rehabilitated using the 30 mg Fe/kg diet for 10 d. Mice fed the 5 mg Fe/kg diet were moderately iron-deficient, as shown by indices of iron status. No significant differences were observed in thymus weight or in the proportion and number of thymocyte subsets in thymuses of anemic, moderately iron-deficient and control mice. Thymus weight was decreased in pair-fed mice. No significant difference was found in lymph node subsets. In the spleen of anemic mice, the proportions and total number of Thy-1+ splenocytes, CD4-8+ and CD4+8- cells were very low compared with control (P less than 0.01) and iron-deficient (P less than 0.02) mice. The decrease was not only observed for the percentage of subsets but also for the absolute number of cell subtypes per spleen. Thy-1+ splenocyte subpopulations were normalized after rehabilitation. These quantitative modifications could explain alterations in the blastogenic response of splenic lymphocytes described by other authors.
Abstract: An evaluation of iron status was carried out on 364 Nigerian pregnant women from Niamey at delivery and in cord blood from their newborns. Anemia, defined as a low hematocrit value, was observed in 46% of pregnant women. Iron deficiency, recognized by a combination of, at least, 2 abnormal values in the 3 independent indicators measured (serum ferritin level, erythrocyte protoporphyrin concentration and transferrin saturation) was present in 47.8% of pregnant women. Anemia was associated with iron deficiency in 60.1% of cases in anemic mothers. A correlation between maternal and newborn iron indicators was found. This study points out the necessity for developing strategies in Sahelian countries to combat iron deficiency during pregnancy by specific measures in combination with more general interventions.
Abstract: The effect of the increasing consumption of dairy products upon the iron absorption was tested in vivo on volunteers using the extrinsic tag method (with 55 Fe and 59 Fe). The total iron absorption coefficient of a typical French meal and of the same meal after addition of a glass of low-fat skimmed milk or plain yoghurt was measured. Non-heme iron absorption was 2.2% for the standard meal alone, 2.0% with the yogurt and 2.1% with the glass of milk. Total iron absorption (i.e. measured non-heme iron absorption plus estimated heme iron absorption) for the three meals was, respectively, 9.7%, 9.5% and 9.4%. These results suggest that, under real-life conditions, increasing the amount of dairy products probably has no effect upon iron absorption in meals containing appreciable amounts of dairy products.
Abstract: Mineral and vitamin intakes were assessed among 1108 subjects, aged 6 months to 97 years in 12 of 47 towns and cities in the district of Val-de-Marne (Paris area), using the telephone directory as random sampling base. Micronutrients intake was evaluated by individual interviews at home by specialized dietitians (dietary history method). Mineral and vitamin intake was found to vary widely with age. In absolute value, overall mineral and vitamin dietary intakes was higher in men than in women (except for vitamin C). Conversely, the dietary density for mineral and vitamins was higher in females. For a large part of the studied population, it would appear difficult to satisfy recommended dietary allowances for many micronutrients (iron, zinc, vit. B1, B6, C, A et E). These results bring to light possible difficulties in covering certain mineral and vitamin requirements in the French population.
Abstract: Blood donors are considered as a group with increased risk of iron deficiency. Therefore it seems particularly useful to have a simple screening test at one's disposal in blood centers to detect easily early iron deficiency. Erythrocyte protoporphyrin assay on an hematofluorometer is very easy and of a low cost. So we studied its diagnostic value on a sample of 285 blood donors (131 men and 154 women). Prevalence of iron deficiency, defined by the coexistence of, at least, two abnormal indicators (serum ferritin, transferrin saturation, erythrocyte protoporphyrin, mean corpuscular volume), was 5.6% in this sample; sensitivity of erythrocyte protoporphyrin used alone was 75% and its specificity was 91.5%. We used a decision analysis to evaluate the opportunity of screening with this test, accompanied where indicated by iron supplements. The results, though preliminary, suggest that erythrocyte protoporphyrin measurement could be of interest in screening blood donors for iron deficiency.
Abstract: Dietary intakes and its nutritional value were assessed during a nutritional survey performed in a population living in a district in the Paris area (Val-de-Marne). Data were obtained from 1108 subjects, aged 6 months to 97 years, randomly selected from the telephone directories of 12 of 47 towns and cities in the district. Dietary intake was evaluated in individual home interviews conducted by specialized dietitians, using the dietary history method. Age appears to be an important determining factor in variations in nutritional intake. Large differences exist between men and women for most types of food consumption. But the relative contribution of the main groups of food groups to the structure of energy intake is very similar in both sexes and virtually constant in the different age groups after the age of 6.
Abstract: Folic acid plays a crucial role in DNA and protein synthesis, suggesting that every mechanism in which cell proliferation intervenes may be altered. Cell-mediated immunity is especially affected by folate deficiency: the blastogenic response of T lymphocytes to certain mitogens is decreased in folate-deficient humans and animals, and the thymus is preferentially altered. The effects of folic acid deficiency upon humoral immunity have been more thoroughly investigated in animals than in humans, and the antibody responses to several antigens have been shown to decrease. Conversely, the phagocytic and bactericidal capacities of polymorphonuclear cells have been studied mainly in folate-deficient humans. However results in this field are controversial. Alterations in immune system functions could lead to decreased resistance to infections, as commonly observed in folate-deficient humans and animals.
Abstract: This paper describes an assessment of the nutritional value (carbohydrates, proteins, fats) of food intake studied in a population residing in the Val-de-Marne district of the Paris region. Data were collected from 1,108 subjects, aged 6 months to 97 years, randomly selected from the public telephone directories of 12 of the 47 towns and cities in the district. Dietary intake was evaluated from individual home interviews by specialized dietitians, using the dietary history method. Age was shown to be a major determinant of macro nutrient intake (expressed in absolute value) in both sexes. The amount of food consumed differed between men and women. Expressed as a relative value of energy intake (after exclusion of alcohol-related calories), the proportion of different macronutrients was similar in all age groups, for both sexes, and was not in agreement with recommended dietary allowances: too high levels of fats and insufficient levels of carbohydrates, especially starch.
Abstract: From the evaluation of losses and savings, the authors specify, according to the reserves before pregnancy and the true diet intake, the indications for therapeutic supplement during pregnancy.
Abstract: 1. Food selenium content, selenium supply and selenium needs are presented, along with methods of evaluation of selenium status. Glutathione peroxidase, a selenium-containing enzyme, is ubiquitous in the organism. 2. Some experimental studies on animal models reported a positive relationship between selenium status and resistance against infections. 3. Only one study in humans concerned the mechanisms of immune functions in selenium deficiency. Several experimental works suggest that severe selenium deficiency compromises T-cell dependent immune functions such as the blastogenic response to mitogens, but selenium deficiency was concomitant with vitamin E deficiency in most of them. Delayed hypersensitivity response is controversial in selenium-supplemented rats and guinea-pigs. 4. Selenium deficiency in animals decreases the antibody response, especially if associated with vitamin E deficiency. Low dietary selenium supplementation of healthy animals has a positive effect upon humoral responses. 5. Despite some controversies, most experimental studies on selenium-deficient animals report normal phagocytosis and an altered bactericidal capacity of neutrophils. The decrease in glutathione peroxidase activity of polymorphonuclear cells following selenium deficiency could explain some of these alterations. 6. Splenic Natural Killer cells activity is enhanced in selenium-supplemented, healthy animals.
Abstract: Weanling Wistar rats were given a low-iron diet (4-5 mg Fe/kg), a medium-iron diet (20 mg Fe/kg) or a control diet (40 mg Fe/kg) for 7 weeks. Pair-fed rats received the control diet in amounts equivalent to that consumed by animals on a low-Fe diet. Blood samples from the tail vein were taken after 4 weeks of diet and weekly during the following 3 weeks for determination of iron status parameters. Animals were weighed weekly. After 4 weeks of diet, the rats fed the 5 mg iron/kg diet were severely anemic and rats fed 20 mg iron/kg diet were moderately iron-deficient. Ad libitum and pair-fed controls had normal iron status. Total liver iron stores were lowest in anemic rats (p less than 0.001) and were also low in moderately iron-deficient animals (p less than 0.05). Growth rates decreased early in anemic and pair-fed rats. Both groups were smaller than controls and moderately iron-deficient rats after 2 weeks (p less than 0.05) and this continued until the end of the experiment (p less than 0.001). Body weights of pair-fed rats were lower than those of anemic rats from the 1st to the 3rd week of diet; thereafter, differences between the two groups were no longer significant.
Abstract: Iron absorption from three typical West African meals was measured in fourteen subjects using the extrinsic-tag technique with 59Fe and 55Fe. All meals consisted of maize as the staple food. Meals were prepared in Benin under realistic conditions from locally grown foods. Of the non-haem-Fe in the meals 39-73% did not exchange with the added inorganic radio-Fe tracer, depending on the degree of Fe contamination of meals. Non-haem-Fe absorption was low in each maize meal, but was even lower for those eaten with a vegetable sauce than for those eaten with a fish sauce. When haem-Fe absorption was included, 70.0-160 micrograms Fe was absorbed. Expressed on an energy basis, the bioavailable nutrient density was 3.2-7.0 micrograms/100 kJ (13.4-29.5 micrograms/100 kcal). These findings suggest that total Fe available in the typical diets of West African countries does not meet the physiological requirements of large proportions of the population.
Abstract: Iron absorption from two typical French meals and three typical Spanish meals was measured, using the extrinsic tag technique (with 55Fe and 59Fe) on French and Spanish volunteers. The total iron absorption coefficient varied up to three-fold (between 3.4 and 11.4 per cent) according to the contents of haem and non-haem iron and the presence of non-haem iron absorption enhancers and inhibitors. Expressed for iron absorption of 40 per cent of the reference dose (corresponding to subjects with theoretical depleted iron stores), those coefficients varied up to four-fold (between 4.9 and 18.9 per cent). The bioavailable nutrient density ranged from 0.30 to 0.77 mg/1000 kcal in subjects with good iron stores and from 0.50 to 1.12 mg/1000 kcal for subjects with theoretical depleted iron stores. This low bioavailable iron density enabled understanding of why iron balance is especially critical in women of childbearing age in industrialized countries, where iron enrichment of food is not practised.
Abstract: The effects of severe and moderate iron deficiency upon the antibody response to influenza virus were investigated in rats. Three groups of weanling male Wistar rats were fed one of two iron-deficient diets (5 mg and 15 mg iron/kg diet) or a normal iron-containing diet (35 mg iron/kg diet). A group of individually pair-fed rats was introduced with the low iron-consuming rats. The effects of the diets upon various iron status parameters were followed during the 4th, 5th, 6th, and 7th week of diet. After 4 weeks of feeding different diets, an intraperitoneal injection of inactivated influenza virus A/New Jersey/76 was performed and a recall injection was done at 5 weeks. Primary and secondary antibody responses were assayed. Rats were sacrificed at 7 weeks of diet. After 4 weeks of feeding different diets, the rats fed the 5 mg iron/kg diet were severely anemic and rats fed 15 mg iron/kg diet were moderately iron-deficient, as shown by their iron status parameters. Growth was delayed in anemic and matched pair-fed rats. A primary antibody response was almost nonexistent in all groups. Secondary antibody titers were significantly weaker in anemic rats than in ad libitum controls, but were not different from those of pair-fed rats. This response was similar in moderately iron-deficient, ad libitum, and pair-fed rats. These results show that antibody synthesis in response to the influenza virus vaccine is preserved in moderate iron deficiency but is reduced in severe anemia. The reduction in energy consumption associated with severe iron deficiency in the rat could play a part in the altered humoral response.
Abstract: Iron status was evaluated in 103 elderly institutionalized individuals using haemoglobin concentration, red cell indices, serum iron, serum transferrin, serum ferritin and basic red cell ferritin. Inflammatory processes were identified by measuring concentrations of orosomucoid and C-reactive protein in serum and leukocyte counts. Anaemia was present in 16.5% of the individuals. No serum ferritin values were in the range of depleted iron stores; however 6% of the elderly individuals presented basic red cell ferritin less than 3 attog/cell (3 x 10(-18) g/cell). Serum ferritin was positively correlated with markers of inflammation. Basic red cell ferritin measurement was not influenced by inflammation and may provide a reliable indicator of iron status in the elderly.
Abstract: An iron supplementation trial versus placebo was performed in double blind on 191 attending at 3 month the antenatal clinic of Poissy maternity. Iron status of mothers and newborns was assessed at 3, 5, 7 month, during the delivery and 2 months after the delivery, using biochemical indicators (hemoglobin level, serum ferritin). The compliance was good in 165 pregnant women (86% of the initial sample): 81 in the iron group, 84 in the placebo group. Among the placebo group, anemia (Hb less than 11 g/dl) was observed at the end of the pregnancy in 30% of women. Depletion of iron stores started at 5 month. In the iron group, hemoglobin level increased significantly during the pregnancy and anemia was observed only in 3% of women at the delivery. Iron status of newborns and two months after delivery was related to mothers iron status at delivery and particularly at the 7th month of pregnancy.
Abstract: 1. The importance of iron on immune functions is reviewed. 2. The consequences of iron deficiency upon resistance to infection in men (adults and children) and animals are controversial. 3. Cellular immunity is often altered in iron-deficient humans and in murine species. 4. Humoral immune responses seem far less affected in iron-deficient humans than is cellular immunity, but is impaired in iron-deficient animals. Results on complement are scarce and controversial. 5. There is almost no perturbation of phagocytosis but bactericidal activity is decreased in most studies on iron-deficient subjects. 6. Natural Killer activity is decreased in iron-deficient mice. Iron deficiency also affects lymphokine production in mice and rats.
Abstract: The consequences of iron deprivation on iron-containing enzymes of different tissues in rat and/or human is reviewed. Iron participates in a wide variety of biochemical processes, including mitochondrial electron transport, catecholamine metabolism and DNA synthesis. Recently, a broad spectrum of biochemical abnormalities resulting from iron deficiency have been described. Effects on skeletal muscle, cardiac muscle, brain tissue, liver tissue gastrointestinal tractus, body temperature regulation, DNA synthesis are successively discussed. The key liabilities of tissue iron deficiency, even at a mild degree relate to decrease in intellectual performance, and in physical capacity during exercise, alteration of temperature regulation, immune function.
Abstract: Four groups of weanling male rats were fed one of three iron-deficient diets (6, 18 and 23 mg iron/kg diet) or a normal iron-containing diet (41 mg iron/kg diet) for 30 d. The effects of the diets on various iron status parameters were determined and four enzymes were assayed: cytochrome P450 (P450) and NADPH cytochrome P450 reductase (P450-RED) in liver and intestine microsomes, and glucose-6-phosphate dehydrogenase (G6P-DH) and 6-phosphogluconate dehydrogenase (6PG-DH) in liver, intestine and erythrocyte cytosol. Rats fed 6 mg iron/kg diet were severely anemic, whereas rats fed 18 or 23 mg iron/kg diet were moderately or mildly iron-deficient, as shown by their hemoglobin levels, hematocrit, red blood cell parameters, erythrocyte protoporphyrin and liver iron stores. P450 concentration and P450-RED activity in liver were unaffected by iron deficiency, but P450 concentration was markedly lower in the intestine of the three iron-deficient groups than in the controls. Activities of G6P-DH and 6PG-DH were not impaired in liver or intestine, except that liver 6PG-DH activity of severely anemic rats was less than that of control rats. However, severe and moderate iron deprivation resulted in a stimulation of G6P-DH and 6PG-DH activities per million erythrocytes. These results demonstrate that even moderate iron deficiency may alter fundamental enzymatic systems intervening in drug metabolism and in the pentose phosphate pathway.
Abstract: Prevalence of anemia was estimated by two methods in 1235 healthy children 10 months old undergoing a free-of-charge medical checkup in a Parisian Child Health Examination Center. According to the classical method, the frequency of anemia, defined as the percentage of children with hemoglobin concentration below the WHO cut-off point (11 g/dl), amounts to 16.8% of 797 French children, 24.0% of 289 North African children and 43.6% of 149 sub-saharan children. The second method defines the frequency of anemia as the percentage of children whose hemoglobin values are shifted downwards relative to a gaussian hemoglobin distribution in non-anemic children. According to this method, anemia was present in 0.8%, 5.4% and 12.6% of children, respectively. The conventional cut-off point probably tends to overestimate the true frequency of anemia in this age group.
Abstract: Iron status was assessed using a combination of several biochemical indicators (serum ferritin, erythrocyte protoporphyrin, serum iron, MCV, hemoglobin) in 3,676 apparently healthy children. Children who were 10 months, 2 years and 4 years of age were selected from the population undergoing a free medical check up in a Paris Child Health Center. The prevalence of iron deficiency in children of parents from continental France was 29% in the 10 month olds, 13% in the 2 year olds and 7% in those who were 4 years of age. Corresponding figures in children born of immigrant parents were 50%, 44% and 15% respectively. Iron deficiency anemia was found in 8% of 10 month olds from continental France versus 23% in the other group. Children born of parents from the South Sahara were found to be at high risk for iron deficiency.
Abstract: Serum ferritin, serum iron, total iron-binding capacity (TIBC) and erythrocyte protoporphyrin were measured in a group of 69 children (6.4 +/- 3.6 years) living in a rural area of Mauritania. The predictive value of low serum ferritin was calculated for each iron parameter. A serum ferritin value above 12 micrograms/l was present in 50.2% of children with abnormal serum iron, in 59.0% of those with abnormal TIBC, in 60.3% of those with abnormal transferrin saturation and in 60.0% of those with abnormal erythrocyte protoporphyrin. The percentages varied from 88.0 to 94.8% for a predictive value of serum ferritin of less than 50 micrograms/l. Nearly 35% of children had biochemical evidence of iron deficiency, i.e. 2 abnormal independent iron parameters or more, including serum ferritin of less than 12 micrograms/l. Nearly 32% had probable iron deficiency, i.e. 2 abnormal independent iron parameters, with a serum ferritin value between 13 and 50 micrograms/l.
Abstract: Indicators of iron status, markers of inflammatory processes, serum immunoglobulins and C3 and C4 components of complement were assessed in 142 children 10-months old. All the iron parameters and most of the indicators of humoral immunity were correlated with markers of inflammation. Sixty-two children presented biochemical indications of inflammation (high CRP or orosomucoid level, or hyperleukocytosis), while 80 children were free of it. In the latter group, the use of a combination of iron indicators enabled separation of iron-sufficient children from those with different degrees of iron deficiency, ranging from iron depletion to iron-deficiency anemia. Serum IgG and IgA were significantly lower only in the group of iron-depleted children. Serum ferritin was significantly positively correlated with IgA, IgM and C4. Iron depletion may be responsible for a decrease humoral immunity. This effect was not visible at more advanced stages of iron deficiency.
Abstract: Frequency of anaemia was estimated by two methods for 254 menstruating women living in South-eastern Algeria. One method defines the frequency of anaemia as the percentage of women with haemoglobin concentrations below the cut-off point defined by WHO (12 g/dl). The second method defines the frequency of anaemia as the percentage of women whose haemoglobin values are shifted downwards relative to a Gaussian distribution of haemoglobin of nonanaemic women. The conventional cut-off point probably tends to overestimate the true frequency of anaemia: 7% of women with haemoglobin concentration less than 12 g/dl were not found as anaemic using the cumulative frequency method. The contribution of iron deficiency folate deficiency and inflammatory process was estimated using the cumulative frequency distribution after excluding respectively women with biological evidence of iron deficiency (serum ferritin of 12 micrograms/l or less, transferrin saturation less than 15% and/or MCV less than 80 fl), of folate deficiency (red blood cell folates less than 100 micrograms/l) and of inflammatory process (C. Reactive Protein more than 12 mg/l, orosomucoid more than 1.4 g/l or white cell counts of more than 10,000/mm3). According to this method iron deficiency represented the most important cause of anaemia in the context of our sample: iron deficiency contributed to 77% of anaemia. Folate deficiency and inflammatory processes do not in themselves appear to contribute to anaemia.
Abstract: An assessment of iron status was performed on 112 pregnant women at delivery (and on their newborns in 70 cases) and on 114 menstruating women in N'Djamena, Chad. Anaemia (according to the haematocrit value) was observed in 25.0% of pregnant women and in 23.7% of menstruating women. Iron deficiency was defined as the combination of a low serum ferritin level (less than or equal to 12 micrograms/l), a low transferrin saturation (less than 16%) and/or a high erythrocyte protoporphyrin (greater than 3 micrograms/g Hb). A moderate increase in the serum ferritin level (between 13 and 50 micrograms/l) associated with a low transferrin saturation and/or a high erythrocyte protoporphyrin concentration indicated iron-deficiency in an inflammatory context. Iron deficiency was present in 66.9% of pregnant women and in 30.7% of menstruating women. Anaemia was associated with iron deficiency in 78.6% of cases in anaemic pregnant women and in 44.4% of cases in anaemic menstruating women. A correlation between maternal and newborn haematopoiesis was found, and some iron parameters in newborns were related to the iron status of mothers.
Abstract: We assessed the nutritional status of 302 menstruating women living in three urban, semi-rural and rural areas of eastern Algeria. The anthropometric data and the biochemical measurements (serum levels of total proteins, albumin, transferrin and prealbumin) have shown the absence of protein malnutrition and the evidence of problems of overweight, whatever the criterion used (body mass index or relative weight). There were no differences according to the residence. Anemia (defined by WHO references) was observed in 28% of urban women, 19% of semi-rural women and in 32% of rural women. Iron deficiency (defined by the association of serum ferritin level of 12 micrograms/l or less and transferrin saturation less than 15%) was observed in 29, 27 and 22% of the cases, respectively. Folate deficiency (defined by concentration of red blood cell folates of less than 100 micrograms/l) was observed in 48, 45 and 22% of cases, respectively. Finally, 81% of anemia were associated with biochemical evidence of iron and/or folate deficiency.
Abstract: An evaluation of iron status was performed in 84 pregnant women at delivery (and in cord blood from their newborn) and in a control group of 32 menstruating women living in Quito (2800 m altitude). Anemia as defined according to the WHO references adjusted to altitude was observed in 46% of pregnant women. Iron deficiency was defined as the combination of a low serum ferritin level (12 micrograms/l or less) and a low transferrin saturation percentage (less than 16%). A moderate elevation in the serum ferritin concentration (between 13 and 50 micrograms/l) associated with low transferrin saturation indicated iron deficiency in an inflammatory context. Iron deficiency was present in 46% of pregnant women. Anemia was associated with iron deficiency in 59% of cases. A correlation between maternal and cord blood hemoglobin was found and some iron parameters in cord blood were related to maternal iron status, and especially to maternal iron stores assessed by serum ferritin concentration.
Abstract: Hemoglobin, hematocrit, serum iron and total iron-binding capacity were measured in 38 apparently healthy children living in Quito (2:800 meters in altitude). One child was considered anemic according to the WHO reference adjusted to altitude (hemoglobin less than 12.3 g/dl) and 10 had transferrin saturation of less than 15%. Thirty children received orally 2 mg/kg per day of elemental iron for 3 mth. A significant increase in hemoglobin level, serum iron-concentration, and transferrin saturation, and a significant decrease in total iron-binding capacity were observed. Nine children increased their hemoglobin concentration by greater than 1 g/100 ml and could be considered as true anemics. At the end of the supplementation, only one child had a transferrin saturation coefficient of less than 15%. WHO references for hemoglobin adjusted to altitude seem to underestimate the prevalence of anemia for populations living at high altitudes.
Abstract: An assessment of iron and folic acid status, blood thick film and haemoglobin (Hb) electrophoresis was performed on 126 pregnant women (and their newborn infants) and in ninety-five menstruating women in Cotonou (Benin). Anaemia (according to the World Health Organization (1972] was observed in 55% of pregnant women and in 39% of menstruating women. Fe-deficiency was defined as a low serum ferritin concentration (12 micrograms/l or less), combined with a low transferrin saturation (less than 16%) or a high erythrocyte protoporphyrin level (more than 3 micrograms/g Hb), or both. A moderate elevation in the serum ferritin concentration (between 13 and 50 micrograms/l), associated with a low transferrin saturation or a high erythrocyte protoporphyrin level, or both, indicated Fe-deficiency in an inflammatory context. Fe-deficiency was present in 73% of pregnant women and in 41% of menstruating women. Folate deficiency (defined as erythrocyte folate below 160 micrograms/l) was observed in 45% of pregnant women. In pregnant women, anaemia was associated with Fe-deficiency in 83% of cases and with folate deficiency in 48% of cases. Haemoglobinopathies were mainly heterozygous and did not seem to contribute significantly to anaemia. Intensity of malaria was not related to Hb level, but Plasmodium falciparum was found in 99% of subjects. Hb concentration and mean corpuscular volume were significantly lower in babies born of Fe-deficient mothers than in babies born of Fe-sufficient mothers. Hb concentration in newborn infants was positively correlated with maternal serum ferritin.
Abstract: Iron status, folacin status, haemoglobinopathies, malarial infection and intestinal parasitosis frequencies were assessed in a representative sample of 586 subjects living in a rural district of South Benin. Anaemia according to WHO reference values for haemoglobin was observed in 42 per cent of subjects. The prevalence was higher in children and menstruating women. Iron deficiency, defined by two or more abnormal values in the four independent indicators of iron status used (transferrin saturation, erythrocyte protoporphyrin, serum ferritin, and mean corpuscular volume) was present in 30 per cent of subjects. Half of the anaemias were associated with iron deficiency. Folate deficiency was associated with anaemia in 20 per cent of subjects. Anaemia, iron and folacin status were not significantly related to the degree of malarial infection nor to the type of haemoglobin. Although hookworm infection was very common, there was no significant relationship between egg count and haemoglobin level or haematological parameters of iron and folacin status. The lack of correlation can be explained by the low wormload observed.
Abstract: Serum ferritin, haemoglobin, serum iron and total iron binding capacity were determined in 203 healthy menstruating women (32.9 +/- 0.6 years). Demographic and medical data were collected in the whole sample. Dietary intakes were evaluated by the dietary history method in a randomized subsample of 127 women. One fifth of the women had exhausted iron stores, as defined by a serum ferritin of 12 micrograms/l or less. The duration of menses influenced the serum ferritin concentration but contraception did not. Most of women had daily iron intake below the recommended dietary allowances for menstruating women. Serum ferritin was not correlated with daily total iron intake. But a relationship was found between serum ferritin and dietary intakes; intakes of meat, dairy products and coffee had a significant effect of serum ferritin concentration.
Abstract: Serum ferritin, hemoglobin, serum iron and transferrin iron-binding capacity were evaluated in 107 healthy female students. 21 women had a serum ferritin of 12 micrograms/l or less, corresponding to an exhaustion of body iron stores. After 1 month of iron supplementation, significant increase of hemoglobin concentration and decrease of total iron-binding capacity were observed. Mean serum ferritin had increased from 24 to 41 micrograms/l, and all women had a serum ferritin above 12 micrograms/l. 1 month after the end of the trial, serum ferritin fell significantly. This study points out the problem of serum ferritin reference values and the definition of normal iron stores in menstruating women.
Abstract: Serum ferritin and haematological variables were determined in 476 healthy French students (21.3 +/- 0.2 years). Information was collected on the duration of menses and contraceptive uses. Dietary intakes were assessed by the dietary history method in a randomized subsample of 157 women. The proportion of anaemic subjects was low, but 16 per cent of women had exhausted iron stores (serum ferritin less than or equal to 12 micrograms/l). Duration of menses was negatively correlated with serum ferritin concentration. The mean iron intake was 10.92 +/- 0.02 mg/d. Only fewer than 5 per cent of the students had daily iron intakes corresponding to the recommended dietary allowances for menstruating women (greater than or equal to 16 mg/d). There was a positive correlation between energy consumption and iron intake (r = 0.79, P less than 10(-9) ). Tea and dairy products intakes appeared to have a significant negative correlation with serum ferritin. The positive correlation between serum ferritin and haemoglobin suggests that decreased or depleted iron stores are associated with suboptimal haemoglobin values. This raises the problem of the definition of normal serum ferritin and haemoglobin values in menstruating women.
Abstract: Iron deficiency constitutes a major problem of Public Health affecting 10 to 20% of the world population. Although developing countries are specially susceptible, developed countries are also at risk. The use of reliable indicators of iron status is essential for assessing the magnitude and the distribution of iron deficiency in populations, and for developing effective public health measures. In this paper, the different indicators of iron status are briefly reviewed. The signification of these indicators, as reflect of a change in different body iron compartmentalization is also presented. In addition, their limitations in epidemiological surveys have been evaluated. It appears that no single iron parameter monitors the entire spectrum of iron deficiency. A combination of indicators, depending on the objectives of the study, the characteristics of the study population and the working conditions is required to measure the body iron content of individuals and to evaluate the iron status of the population.
Abstract: Serum ferritin, haemoglobin, erythrocyte constants, serum iron and the fixation capacity of transferrin were determined in 233 pregnant women consulting a maternity clinic in the Paris area. 1 metropolitan frenchwoman out of 9 and almost half of the immigrants were found to suffer from anaemia at term. A virtual absence of iron reserves (serum ferritin less than microgram/l) was found in 20% of the metropolitan women during the 3rd month of pregnancy, in 60% during the 6th month and in 75% during the 9th month. The figures were 60%, 100% and 90% respectively in the immigrant group. Considering the anaemia-related risks and the eventual repercussions of iron deficiency on a pregnancy, the health of the mother and the foetus, a systematic increase in iron as of the 2nd trimester of pregnancy is recommended.
Abstract: The effects of iron deficiency in rat and/or man on iron-containing enzymes of different tissues is reviewed. Iron deficiency results in a decrease of skeletal muscle iron containing proteins e.g. myoglobin, cytochromes c, a + a3, and alpha-glycerophosphate oxidase. Iron deficiency produces a reduction in the activity of several respiratory enzymes in the mitochondrial fraction of cardiac muscle, particularly: NADH cytochrome c reductase, succinic cytochrome c reductase, succinic dehydrogenase and NADH ferricyanide oxidoreductase. The effects of iron deficiency on brain tissue is emphasized with respect to cytochromes, monoaminoxidase and amino acids metabolism. Host defence to infection (controversial data), decrease in body temperature, alteration of DNA synthesis, collagen and lipid metabolism, liver and gastrointestinal mucous cytochromes activity perturbations are discussed.
Abstract: Dietary iron intake has been estimated in 337 healthy, menstruating women, of high social conditions by dietary histories. The mean daily iron intake was 11 +/- 0.13 mg, of which 33% was supplied by meat and fish, whereas fruits and vegetables supplied 29%. The mean daily energy intake was 2,088 +/- 27 kcal (8,723 +/- 113 kJ). In 96.5% of the women, iron intake was lower than the Recommended Dietary Allowances (16-18 mg daily). There was a significantly positive correlation between energy intake and iron intake (r = 0.77; p less than 10(-9]. Therefore, the low iron intake may be considered as a consequence of a decrease in the energy intake observed during the last decades in industrialized countries. Iron fortification of one or several foods seems to be advisable to compensate, at least, partly iron intake deficiency.
Abstract: The iron levels were evaluated in 124 pregnant women towards the end of their pregnancies and in their newborn babies in 4 maternity units in Paris and in the surroundings. Two-third of the women studied had total absence of iron reserves (shown by a serum ferritin level less than or equal to 12 micrograms/l). Those who were at the greatest risk of having iron deficiency or anaemia were immigrant, non continental french and multiparous women. The tissue reserves of iron in the newborn are not directly linked to the levels of iron in the mother but are probably linked to the foetal and maternal haemoglobin-synthesis.
