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Unsaturated Fatty Acid Intakes During Midlife Are Positively Associated with Later Cognitive Function in Older Adults with Modulating Effects of Antioxidant Supplementation.
Assmann, KE, Adjibade, M, Hercberg, S, Galan, P, Kesse-Guyot, E
The Journal of nutrition. 2018;(12):1938-1945
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Abstract
BACKGROUND Given the drastic demographic changes characterized as "population aging," the disease burden related to dementia is a major public health problem. The scientific literature documenting the link between mono- and polyunsaturated fatty acids (MUFAs, PUFAs) and cognitive function during aging is plentiful, but findings are inconsistent. OBJECTIVES We aimed to evaluate the association between intakes of unsaturated fatty acids at midlife and cognitive performance 13 y later in French adults, and to test for a modulating effect of antioxidant supplementation. METHODS Fatty acid intakes were estimated with the use of repeated 24-h records (1994-1996) among 3362 subjects (mean ± SD age: 65.5 ± 4.6 y) of the SU.VI.MAX (Supplementation with Antioxidant Vitamins and Minerals) study, including an intervention phase (1994-2002) during which participants were randomly assigned to an "antioxidant supplementation" or placebo group. Cognitive performance was assessed at follow-up only (in 2007-2009) via a battery of 6 standardized neuropsychological tests. A global cognitive score was calculated as the sum of T-scores of the 6 tests. Multivariable-adjusted regression analyses were performed to provide regression coefficients and 95% CIs. RESULTS In multivariable models, total MUFAs, total PUFAs, and n-6 PUFAs (ω-6 PUFAs) were positively associated with overall cognitive functioning. n-3 PUFA (ω-3 PUFA) intakes showed positive associations among supplemented participants only (mean difference Tertile3 versus Tertile1: 1.40; 95% CI: 0.30, 2.51; P-trend = 0.01, P-interaction = 0.01). A detrimental role of arachidonic acid for cognitive functioning was only detected in the placebo group (mean difference Tertile3 versus Tertile1: -1.38; 95% CI: -2.57, -0.18; P-trend = 0.02, P-interaction = 0.07). CONCLUSION Whereas higher total MUFA and n-6 PUFA intakes may be generally beneficial for maintaining cognitive health during aging, a higher consumption of n-3 fatty acids may only be beneficial among individuals with an adequate antioxidant status. These findings underline the importance of not only focusing on specific nutrients for dementia prevention, but also considering the complex interaction between consumed nutrients. This trial was registered at clinicaltrials.gov as NCT00272428.
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Antioxidant intake from diet and supplements and risk of digestive cancers in middle-aged adults: results from the prospective NutriNet-Santé cohort.
Egnell, M, Fassier, P, Lécuyer, L, Gonzalez, R, Zelek, L, Vasson, MP, Hercberg, S, Latino-Martel, P, Galan, P, Druesne-Pecollo, N, et al
The British journal of nutrition. 2017;(7):541-549
Abstract
Experimental studies suggest beneficial effects of antioxidants in digestive cancer prevention. However, epidemiological results are contrasting and few studies quantitatively assessed supplemental intake. This study aimed at investigating the associations between antioxidant intakes (dietary, supplemental and total) and digestive cancer risk. This prospective study included 38 812 middle-aged subjects (≥45 years) from the NutriNet-Santé cohort (2009-2016). Dietary data were collected using repeated 24 h records. A specific questionnaire assessed dietary supplement use over a 12-month period. A composition database of about 8000 dietary supplements was developed. Associations between continuous and sex-specific quartiles of vitamins C and E, β-carotene and Se intakes and digestive cancer risk were characterised using multivariable Cox proportional hazard models. A total of 167 incident digestive cancers (120 colorectal, twenty-six pancreatic, nine oesophagus, seven stomach and five liver) were diagnosed during follow-up investigation. Dietary (hazard ratios (HR)Q4 v. Q1=0·56; 95 % CI 0·34, 0·91, P trend=0·01) and total (HRQ4 v. Q1=0·51; 95 % CI 0·30, 0·84, P trend=0·008) vitamin C intakes, dietary (HRQ4 v. Q1=0·56; 95 % CI 0·34, 0·92, P trend=0·005) and total (HRQ4 v. Q1=0·58; 95 % CI 0·36, 0·94, P trend=0·003) vitamin E intakes, and dietary (HRfor an increment of 10 µg/d=0·92; 95 % CI 0·85, 1·00, P=0·04) and total (HRfor an increment of 10 µg/d=0·92; 95 % CI 0·86, 0·99, P=0·03) Se intakes were associated with a decreased digestive cancer risk. Statistically significant interactions were observed between dietary and total Se intakes and alcohol consumption as well as between total vitamin E intake and smoking status. This prospective cohort study with quantitative assessment of supplemental intakes suggests a potential protective effect of several antioxidants (vitamins C and E and Se) on digestive cancer risk, and a modulation of some of these relationships by alcohol consumption and smoking status.
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Prospective Association Between the Dietary Inflammatory Index and Cardiovascular Diseases in the SUpplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) Cohort.
Neufcourt, L, Assmann, KE, Fezeu, LK, Touvier, M, Graffouillère, L, Shivappa, N, Hébert, JR, Wirth, MD, Hercberg, S, Galan, P, et al
Journal of the American Heart Association. 2016;(3):e002735
Abstract
BACKGROUND Cardiovascular diseases (CVD) are the leading cause of death in the world, and diet plays a major role in CVD incidence, especially through lipid oxidation mechanisms. This, in turn, leads to tissue inflammation and formation of atheromatous plaques. METHODS AND RESULTS Our objective was to evaluate the association between the inflammatory potential of the diet and the incidence of overall CVD or its subclasses. We included 7743 participants from the Supplémentation en Vitamines et Minéraux AntioXydants (SU.VI.MAX) cohort. All cardiovascular events were recorded using self-reported information or clinical visits, and were validated. The dietary inflammatory index (DII) was computed using repeated 24-hour dietary records (mean=9.5±3.4 records/subject). Hazard ratio and 95% CI for outcomes (CVD and subclasses) were estimated across sex-specific quartiles of the DII using Cox proportional hazard models. A total of 292 cardiovascular events were recorded and validated during an average of 11.4 years of follow-up: 93 myocardial infarctions, 58 strokes, 128 angina pectoris and revascularization interventions, and 13 sudden deaths. When considering CVD subclasses, a diet with pro-inflammatory properties, as expressed by higher DII scores, was significantly associated with a higher risk of myocardial infarction (hazard ratioQuartile 4 versus Quartile 1=2.24, 95% CI: 1.08-4.67). No significant association was observed between the DII score and stroke or both angina pectoris and revascularization intervention. CONCLUSIONS A pro-inflammatory diet, as measured by a higher DII score, was prospectively associated with a higher risk of myocardial infarction. Promotion of a diet exhibiting anti-inflammatory properties may help prevent myocardial infarctions.
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Prospective association between the Dietary Inflammatory Index and mortality: modulation by antioxidant supplementation in the SU.VI.MAX randomized controlled trial.
Graffouillère, L, Deschasaux, M, Mariotti, F, Neufcourt, L, Shivappa, N, Hébert, JR, Wirth, MD, Latino-Martel, P, Hercberg, S, Galan, P, et al
The American journal of clinical nutrition. 2016;(3):878-85
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Abstract
BACKGROUND Chronic inflammation is a central mechanism involved in cardiovascular diseases, cancer, diabetes, and chronic respiratory diseases, 4 leading causes of mortality. Diet is a major source of pro- and anti-inflammatory bioactive compounds. The Dietary Inflammatory Index (DII) was designed to estimate the overall inflammatory potential of the diet. OBJECTIVE Our aim was to study the prospective association between the DII and mortality, as well as assess whether antioxidant supplementation could modulate this association. DESIGN The Supplémentation en Vitamines et Minéraux Antioxydants study was a randomized, double-blind, placebo-controlled trial in which participants received low-dose antioxidants or a placebo from 1994 to 2002. In this observational prospective analysis, 8089 participants (mean ± SD age at baseline: 49.0 ± 6.3 y) were followed between 1994 and 2007 (median: 12.4 y). The DII was calculated from repeated 24-h dietary records; higher scores correspond to more proinflammatory diets. A total of 207 deaths occurred during follow-up, including 123 due to cancer and 41 due to cardiovascular events. Multivariate Cox proportional hazards models were computed. RESULTS Sex-specific tertiles of the DII were positively associated with cardiovascular + cancer mortality (HR for tertile 3 compared with tertile 1 = 1.53; 95% CI: 1.01, 2.32; P-trend = 0.05) and specific cancer mortality (HR for tertile 3 compared with tertile 1 = 1.83; 95% CI: 1.12, 2.99; P-trend = 0.02). The corresponding P value was 0.07 for all-cause mortality. The DII was statistically significantly associated with increased all-cause mortality in the placebo group (HR for tertile 3 compared with tertile 1 = 2.10; 95% CI: 1.15, 3.84; P-trend = 0.02) but not in the antioxidant-supplemented group (P-trend = 0.8; P-interaction = 0.098). CONCLUSION These results suggest that a proinflammatory diet is associated with increased all-cause and cancer mortality and antioxidants may counteract some of the proinflammatory effects of the diet. This trial was registered at clinicaltrials.gov as NCT00272428.
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Dietary iron intake and breast cancer risk: modulation by an antioxidant supplementation.
Diallo, A, Deschasaux, M, Partula, V, Latino-Martel, P, Srour, B, Hercberg, S, Galan, P, Fassier, P, Guéraud, F, Pierre, FH, et al
Oncotarget. 2016;(48):79008-79016
Abstract
Experimental results suggested that iron-induced lipid peroxidation may explain the direct associations observed between red/processed meat intakes and colorectal and breast cancer risk. However, epidemiological evidence is lacking. Thus, we investigated the association between dietary iron intake and breast cancer risk, and its potential modulation by an antioxidant supplementation and lipid intake. This prospective study included 4646 women from the SU.VI.MAX trial (daily low-dose antioxidants vs. placebo). 188 incident breast cancers were diagnosed (median follow-up=12.6y). Dietary iron intake was assessed using repeated 24h dietary records. Multivariable Cox proportional hazards models were computed. Dietary iron intake was associated with an increased breast cancer risk (HRT3vs.T1=1.67 (1.02-2.71), P-trend=0.04). This association was observed in the placebo group (HRT3vs.T1=2.80 (1.42-5.54), P-trend=0.003), but not in the antioxidant-supplemented group (P-trend=0.7, P-interaction=0.1). Besides, in the placebo group, the increased breast cancer risk associated with dietary iron intake was more specifically observed in women with higher lipid intake (P-trend=0.046). These findings suggest that dietary iron intake may be associated with an increased breast cancer risk, especially in women who did not received antioxidants during the trial and who consumed more lipids. This supports the experimental results suggesting that breast cancer risk may be increased by iron-induced lipid peroxidation.
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Healthy Aging 5 Years After a Period of Daily Supplementation With Antioxidant Nutrients: A Post Hoc Analysis of the French Randomized Trial SU.VI.MAX.
Assmann, KE, Andreeva, VA, Jeandel, C, Hercberg, S, Galan, P, Kesse-Guyot, E
American journal of epidemiology. 2015;(8):694-704
Abstract
This study's objective was to investigate healthy aging in older French adults 5 years after a period of daily nutritional-dose supplementation with antioxidant nutrients. The study was based on the double-blind, randomized trial, Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) Study (1994-2002) and the SU.VI.MAX 2 Follow-up Study (2007-2009). During 1994-2002, participants received a daily combination of vitamin C (120 mg), β-carotene (6 mg), vitamin E (30 mg), selenium (100 µg), and zinc (20 mg) or placebo. Healthy aging was assessed in 2007-2009 by using multiple criteria, including the absence of major chronic disease and good physical and cognitive functioning. Data from a subsample of the SU.VI.MAX 2 cohort, initially free of major chronic disease, with a mean age of 65.3 years in 2007-2009 (n = 3,966), were used to calculate relative risks. Supplementation was associated with a greater healthy aging probability among men (relative risk = 1.16, 95% confidence interval: 1.04, 1.29) but not among women (relative risk = 0.98, 95% confidence interval: 0.86, 1.11) or all participants (relative risk = 1.07, 95% confidence interval: 0.99, 1.16). Moreover, exploratory subgroup analyses indicated effect modification by initial serum concentrations of zinc and vitamin C. In conclusion, an adequate supply of antioxidant nutrients (equivalent to quantities provided by a balanced diet rich in fruits and vegetables) may have a beneficial role for healthy aging.
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Antioxidant status and the risk of elevated C-reactive protein 12 years later.
Julia, C, Galan, P, Touvier, M, Meunier, N, Papet, I, Sapin, V, Cano, N, Faure, P, Hercberg, S, Kesse-Guyot, E
Annals of nutrition & metabolism. 2014;(4):289-98
Abstract
BACKGROUND/AIMS: Low-grade inflammation is an independent risk factor for cardiovascular disease. Relationships between the antioxidant status and inflammatory biomarkers could give new insights into cardiovascular disease prevention. We investigated long-term associations between the antioxidant nutrient (vitamin C, α-tocopherol, β-carotene) status and C-reactive protein (CRP) in a population-based cohort. METHODS Subjects included in the French SU.VI.MAX trial study who had available data on baseline (1994-1995) blood nutrient concentrations and CRP measurements 12 years later (2007-2009) were included. Associations between baseline antioxidant circulating concentrations and elevated CRP (>3 mg/l) were investigated in multivariate logistic regression models. Subgroup analyses were performed according to gender, supplementation group of the initial trial, smoking status, and alcohol intake. RESULTS Serum α-tocopherol (n = 2,060) and vitamin C (n = 1,719) concentrations [odds ratio (OR) and 95% confidence interval (95% CI) quintile 5 vs. 1: OR 1.10 (95% CI 0.71-1.73), p for trend = 0.533, vs. OR 0.79 (95% CI 0.48-1.29), p for trend = 0.121, respectively] were not associated with elevated CRP concentrations. The β-carotene status (n = 2,048) was inversely associated with elevated CRP [adjusted OR quintile 5 vs. 1: OR 0.61 (95% CI 0.38-0.98), p for trend = 0.01]. Subgroup analyses showed that associations were stronger in women (p for trend = 0.004), never smokers (p for trend = 0.009) and subjects in the supplementation group (p for trend = 0.002). CONCLUSIONS Our results suggest that the β-carotene status may be inversely associated with low-grade inflammation in the long term.
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A healthy dietary pattern at midlife is associated with subsequent cognitive performance.
Kesse-Guyot, E, Andreeva, VA, Jeandel, C, Ferry, M, Hercberg, S, Galan, P
The Journal of nutrition. 2012;(5):909-15
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Abstract
Few studies have investigated the long-term impact of overall dietary patterns (DP) on cognition. We evaluated the association between empirically derived DP in midlife and cognitive performance 13 y later. Dietary data were based on 24-h dietary records obtained from a subsample of the Supplémentation en Vitamines et Minéraux Antioxydant Study. Cognitive performance was assessed via a battery of neuropsychological tests that included verbal fluency, the RI-48 cued recall test, the trail-making test, and forward and backward digit span. Three composite variables, for global cognitive function, verbal memory, and executive functioning, were built. The multivariate analyses were adjusted for baseline characteristics (age, gender, intervention group, education, alcohol and energy intake, number of dietary records, physical activity, BMI, tobacco use, self-reported memory troubles, diabetes, hypertension, and, for women, menopausal status and hormone therapy use), follow-up time, history of cardiovascular disease, and depressive symptoms. Adjusted means ± SEM of composite variables across quartiles (Q4 vs. Q1) of DP were estimated using ANCOVA. A healthy and a traditional DP were identified. In the multivariate model, the healthy pattern was associated with better global cognitive function (50.1 ± 0.7 vs. 48.9 ± 0.7; P-trend = 0.001) and verbal memory (49.7 ± 0.4 vs. 48.7 ± 0.4; P-trend = 0.01). These relationships were stronger in participants scoring below the gender-specific median values for energy intake (<2490 kcal for men and <1810 for women) than in those scoring at or above those values. Adherence to a healthy DP in middle life may help preserve global cognitive function, especially verbal memory, when total energy intake is regulated.
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Adherence to nutritional recommendations and subsequent cognitive performance: findings from the prospective Supplementation with Antioxidant Vitamins and Minerals 2 (SU.VI.MAX 2) study.
Kesse-Guyot, E, Amieva, H, Castetbon, K, Henegar, A, Ferry, M, Jeandel, C, Hercberg, S, Galan, P, ,
The American journal of clinical nutrition. 2011;(1):200-10
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BACKGROUND Few studies have investigated the long-term effect of overall nutritional recommendations on cognition. OBJECTIVE In a French cohort of middle-aged adults, we evaluated the association between the French National Nutrition and Health Program (Program National Nutrition Santé) Guideline Score (PNNS-GS) assessed at baseline and cognitive performance evaluated 13 y later. DESIGN The PNNS-GS was estimated at baseline (1994-1996) (maximum score: 15 points) in 2135 subjects in the SU.VI.MAX (Supplementation with Antioxidant Vitamins and Minerals) study. We assessed cognitive performance of subjects in 2007-2009 via a battery of 4 neuropsychologic tests that included phonemic and semantic fluency, the RI-48 (rappel indicé-48 item) cued-recall test, the trail-making test, and forward and backward digit spans. A principal components analysis was performed to account for correlations in test scores. Multivariate linear regression models or analyses of covariance were also performed. RESULTS In a multivariate model, we observed a positive association between the PNNS-GS and the cued-recall test and semantic and phonemic fluency tasks, whereas no association was observed with digit spans. The principal components analysis revealed 2 factors interpreted as reflecting verbal memory and executive functioning. Better adherence to nutritional recommendations was significantly associated with the verbal memory factor (β = 0.41; 95% CI: 0.17, 0.64), whereas no association was shown with the executive functioning factor. Removing specific components from the PNNS-GS did not modify the findings. CONCLUSION This study suggests that strong compliance with nutritional recommendations in midlife is associated in elderly individuals with better verbal memory, which is a cognitive domain that is particularly vulnerable to pathologic aging and Alzheimer disease. This trial was registered at clinicaltrials.gov as NCT00272428.
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Antioxidant supplements and their risk of skin cancers.
Ezzedine, K, Hercberg, S, Malvy, D
Clinics in dermatology. 2010;(6):695-6