Henri Faure

Serum concentrations of β -carotene, vitamins C and E, zinc and selenium are influenced by sex, age, diet, smoking status, alcohol consumption and corpulence in a general French adult population

Objective:To assess relationships between energy, nutrient and food intakes, alcohol consumption, smoking status and body mass index (BMI), and serum concentrations of β-carotene, α-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 β-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 β-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 β-carotene, vitamin C and selenium, and, only in women, of vitamin E, than nonsmokers. Alcohol consumers had lower concentrations of serum β-carotene and higher selenium concentrations. Serum β-carotene and vitamin C concentrations were lower in obese subjects. There were positive associations of dietary β-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 β-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.

Effects of long-term antioxidant supplementation and association of serum antioxidant concentrations with risk of metabolic syndrome in adults.

BACKGROUND Limited observational evidence suggests lower antioxidant concentrations in individuals with the metabolic syndrome (MetS); few randomized controlled trials have addressed the effect of multiple antioxidants on the risk of MetS. OBJECTIVE The objective was to examine the effect of antioxidant supplementation for 7.5 y on the incidence of MetS and the epidemiologic association between baseline serum antioxidant concentrations and the prospective risk of MetS. DESIGN Adults (n = 5220) participating in the SUpplementation en VItamines et Minéraux AntioXydants (SU.VI.MAX) primary prevention trial were randomly assigned to receive a supplement containing a combination of antioxidants (vitamins C and E, beta-carotene, zinc, and selenium) at nutritional doses or a placebo. Subjects were free of MetS at baseline and were followed for 7.5 y. RESULTS Antioxidant supplementation for 7.5 y did not affect the risk of MetS. Baseline serum antioxidant concentrations of beta-carotene and vitamin C, however, were negatively associated with the risk of MetS; the adjusted odds ratios (and 95% CIs) for the highest compared with the lowest tertile were 0.34 (0.21, 0.53; P for trend = 0.0002) and 0.53 (0.35, 0.80; P for trend = 0.01), respectively. Baseline serum zinc concentrations were positively associated with the risk of developing MetS; the adjusted odds ratio (and 95% CI) for the highest compared with the lowest tertile was 1.81 (1.20, 2.72; P for trend = 0.01). CONCLUSIONS The experimental finding of no beneficial effects of antioxidant supplementation in a generally well-nourished population is consistent with recent reports of a lack of efficacy of antioxidant supplements. However, the relations observed between the risk of MetS and baseline serum antioxidant concentrations, which probably reflect associations with overall dietary patterns, do support the current recommendations to consume antioxidant-rich foods. This trial was registered at clinicaltrials.gov as NCT00272428.

FACTORS INFLUENCING BLOOD CONCENTRATION OF RETINOL, ALPHA-TOCOPHEROL, VITAMIN C, AND BETA-CAROTENE IN THE FRENCH PARTICIPANTS OF THE SU.VI.MAX TRIAL

Objectives:The data was collected during the inclusion step of the SUpplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) study. This article deals with the studys first stage before any supplementation. The collected data shows factors influencing blood vitamin concentrations and may reflect the vitamin status of volunteers.Material and methods:A total of 12 741 volunteers were enrolled in the SU.VI.MAX study 7713 women 35–60 years of age and 5028 men 50–60 years of age.The serum concentrations of retinol, α-tocopherol, and β-carotene were measured by HPLC, and vitamin C concentration was measured by spectrofluorimetry using a Technicon continuous flow analysis apparatus.The volunteers recorded their 24 h diet by means of a specific terminal that was connected to the main central computer of the SU.VI.MAX study. Volunteers recorded the food they consumed daily and estimated its quantity by comparing pictures of dishes.Results:Retinol concentration was significantly higher in older volunteers, and was higher in male than in female volunteers. Smoking had no effect on serum retinol, but the latter was higher in the autumn than in the winter. Serum retinol concentrations were higher in the Southwest region and lower in the Ile-de-France and East-Centre regions. Serum α-tocopherol was slightly higher in older volunteers and also higher in male volunteers. Serum α-tocopherol was significantly lower in smokers, and former smokers showed intermediate levels. Like retinol, serum α-tocopherol was higher in the autumn, and higher in the Southwest as compared to the East-Centre Serum β-carotene was slightly higher in younger volunteers, and concentrations were higher in female than in male volunteers. Tobacco smoking decreased serum β-carotene, which was higher in the autumn, and higher in the East, West, and North regions. Serum vitamin C was higher in female volunteers, and was not age related. Serum vitamin C was lower in smokers, was season-dependant, but contrary to fat-soluble vitamins, concentrations were higher in the winter and spring. Serum vitamin C was higher in the Southeast and East-Centre, but lower in the North region.Conclusion:These results suggest that serum retinol concentrations depend on gender, age, seasons, and location of residence. Similarly, serum α-tocopherol concentrations were slightly influenced by age, but more by tobacco smoking, seasons, dietary intake, and location of residence. Serum concentrations of β-carotene depend on gender, age, smoking status, dietary intake, and location of residence. Serum vitamin C concentrations depend on gender, age, smoking status, seasons, dietary intake, and location of residence. Contrary to β-carotene, retinol concentrations were higher in male than in female volunteers. Such a reversed relation suggests a higher β-carotene-retinol conversion in male volunteers.

5-Hydroxymethyluracil excretion, plasma tbars and plasma antioxidant vitamins in adriamycin-treated patients

The thymine oxidative lesion-5-hydroxymethyluracil (HMUra)-was measured in urine collected from cancer patients. These patients all received chemotherapy using Adriamycin. Adriamycin (ADR) intercalates DNA coils and interferes with normal cell metabolism through diverse biochemical mechanisms that may explain its different actions. The anticancer action of ADR could derive from its interaction with topoisomerase II, resulting in DNA nicking followed by DNA fragmentation and apoptosis. Side effects of ADR-mainly its cardiotoxicity-may derive from the fact that ADR generates superoxide and hydroxyl radicals in two ways: redox-cycling and a Haber-Weiss type reaction due to Fe-ADR complexes. The oxygen free radicals, particularly .OH, are thought to be produced by ADR directly in genomic material and attack all its components. 5-Hydroxymethyluracil is a thymine lesion provoked by these attacks, and it has been proposed as a marker of DNA alterations. In this article, we report the results of a study involving 14 cancer patients treated with ADR. We found that urine HMUra is significantly increased by the anticancer therapy (HMUra (nmol/24 h): 74.4 9.46 vs. 96.3 8.74; p < .01), this increase reveals a higher risk of mutagenesis. Our study is the first to show an in vivo alteration of DNA by ADR. Results also show that thiobarbituric acid reactants increase significantly, and that the vitamin levels for retinol and alpha-tocopherol, which are antioxidant vitamins, are lower at the end of chemotherapy. We suggest to supplement these patients with vitamins A and E, and selenium to reduce the side effects of ADR.

Effects of a combined micronutrient supplementation on maternal biological status and newborn anthropometrics measurements: a randomized double-blind, placebo-controlled trial in apparently healthy pregnant women

Objective: To investigate the possible beneficial effects of a micronutrient supplementation to apparently healthy pregnant women on maternal biological status and new born anthropometric characteristics.Setting: Departments of Obstetric of the University Hospital of Grenoble (France) and Lyon (France), Laboratoire of Biology of Oxidative Stress, UFR de Pharmacie. Grenoble (France).Study design: Double-blind, randomized placebo-controlled intervention trial.Subjects: A total of 100 apparently healthy pregnant women were recruited at 14±2 weeks of gestation to delivery. At the end, they were 65 women to follow out the study.Interventions: Daily consumption over gestation of a miconutrients supplement or placebo.Main outcome measures: Plasma micronutrient levels and oxidative stress parameters were measured in mothers at 14 and 38 weeks of gestation. New borns anthropometric characteristics were measured at delivery.Results: In the supplemented group, folic acid, vitamin C, E, B2, B6 and β-carotene levels were higher than in the placebo group. Oxidative stress parameters were not different between the groups. Birth weights were increased by 10% and the number of low newborn weights (<2700g) decreased significantly when the mother received the supplementation. Maternal plasma Zn levels were positively correlated to the newborn heights.Conclusion: A regular intake of a micronutrient supplement at nutritional dose may be sufficient to improve micronutrient status of apparently healthy pregnant women and could prevent low birth weight of newborn.Sponsorship: The supplement and placebo were supplied and the study was partially funded by BOIRON Pharmaceutical Company.

Antioxidant status and risk of cancer in the SU.VI.MAX study: is the effect of supplementation dependent on baseline levels?

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.

Determination of the major zinc fractions in human serum by ultrafiltration

In this paper we report a method for measuring ultrafiltrable zinc in human serum by electrothermal atomic absorption spectrophtometry. We show also that ultrafiltration permits to determine alpha-2 macroglobulin bound zinc and losely bound zinc if a strong zinc ligand (EDTA) is added to serum before ultrafiltration. This last fraction, after deduction of ultrafiltrable zinc, represents roughly all albumin bound zinc. In 20 controls we found that ultrafiltrable zinc amounted 0.311 μmol/L (S.D.=0.117 μmol/L), alpha-2 macroglobulin bound zinc 3.08 μmol/L (S.D.=0.221 μmol/L), and albumin bound zinc 12.11 μmol/L (S.D.=1.95 μmol/L). Our method needs only a small volume of serum, it is simple and rapid but also very accurate and reliable. The losely bound fraction is very dynamic and, representing the physiologically active part of serum zinc, it could be a good marker of zinc deficiency.

Gas chromatographic–mass spectrometric determination of total homocysteine in human plasma by stable isotope dilution: method and clinical applications

The detection and quantitation of slight increases of plasma homocysteine levels is of growing interest. This has prompted us to develop a highly sensitive and accurate capillary gas chromatography-mass spectrometry (GC-MS) method. The method proved to be highly sensitive (DL=0.17 micromol/l) with between- and within-run precision less than 6% and 7%, respectively. Reference values of plasma total homocysteine have been determined for men (n=39) and women (n=36), showing a significant difference (P=0.003) between gender. Preliminary results in cerebrovascular accidents and in venous thrombosis are presented.

No antioxidant effect of combined HRT on LDL oxidizability and oxidative stress biomarkers in treated post-menopausal women.

Objective: To compare oxidative stress and LDL oxidizability in postmenopausal women with and without HRT. Methods: In a cross sectional study, two groups of women, with or without combined per os HRT (1.5–2 mg estrogen associated with 10 mg dydrogesteron), were age and duration of menopause matched. Women were recruited after medical examination at LBSO (Oxidative Stress Laboratory), Joseph Fourier University, Grenoble, and Department of Gynecology, Grenoble University Hospital, France. Main outcome measures included determination of lipid profile and oxidative stress biomarkers (TBARS, LDL oxidizability, auto-antibodies against oxidized-LDL). Measurement of circulating levels of vitamin C, E, β-carotene, lycopene and total antioxidant plasma capacity. Results: HRT led to decreased plasma total and LDL cholesterol (p < 0.05), but did not affect oxidizability and oxidation of LDL. Circulating levels of antioxidant vitamins (β-carotene, vitamin C, vitamin E/triglycerides) and total antioxidant capacity of plasma and lipid peroxidation, assessed by plasma TBARs, were not different from controls in postmenopausal women receiving HRT. Conclusion: This study suggests that even if combined HRT modifies the blood lipid profile, it does not appear to influence oxidative status.

Gas chromatographic-mass spectrometric determination of 5-hydroxymethyluracil in human urine by stable isotope dilution

A method for the determination of 5-hydroxymethyluracil in urine is described. 5-Hydroxymethyluracil was extracted by reversed-phase chromatography and quantified by gas chromatography-mass spectrometry as tert.-butyldimethylsilyl derivative. Since natural 5-hydroxymethyluracil contained ca. 22% of M + 2 species, an internal standard consisting of [1,3-15N2,5-2H2]hydroxymethyluracil was used to correct losses during extraction, evaporation and derivatization. Between-run precision of this method was 7.79%, and concentrations as low as 1.87 nM could be measured. This sensitivity and precision could not be obtained with trimethylsilyl derivatives.