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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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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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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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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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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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Incidence of skin cancers during 5-year follow-up after stopping antioxidant vitamins and mineral supplementation.
Ezzedine, K, Latreille, J, Kesse-Guyot, E, Galan, P, Hercberg, S, Guinot, C, Malvy, D
European journal of cancer (Oxford, England : 1990). 2010;(18):3316-22
Abstract
CONTEXT In the SU.VI.MAX study, antioxidant supplementation for 7.5 years was found to increase skin cancer risk in women but not in men. OBJECTIVE To investigate the potential residual or delayed effect of antioxidant supplementation on skin cancer incidence after a 5-year post-intervention follow-up. DESIGN, SETTING AND PARTICIPANTS Assessment of skin cancer including melanoma and non-melanoma during the post-intervention follow-up (September 2002-August 2007). The SU.VI.MAX study was a double-blind, placebo-controlled, randomised trial, in which 12,741 French adults (7713 women aged 35-60 years and 5028 men aged 45-60 years) received daily a placebo or a combination of ascorbic acid (120 mg), vitamin E (30 mg), β-carotene (6 mg), selenium (100 μg) and zinc (20mg), from inclusion in 1994 to September 2002. MAIN OUTCOME MEASURES Total skin cancer incidence, including melanoma, squamous cell carcinoma and basal cell carcinoma. RESULTS During the post-intervention period, 10 melanomas appeared in women and 9 in men (26 and 18, respectively, for the total period of supplementation+post-supplementation). Six squamous cell carcinomas were found in women and 15 in men (10 and 25, respectively, for the total period). Finally, 40 basal cell carcinomas appeared in women and 36 in men (98 and 94, respectively, for the total period). Regarding potential residual or delayed effects of supplementation in women, no increased risk of melanoma was observed during the post-intervention follow-up period. No delayed effects, either on melanoma or non-melanoma skin cancers, were observed for either gender. CONCLUSIONS The risk of skin cancers associated with antioxidant intake declines following interruption of supplementation. This supports a causative role for antioxidants in the evolution of skin cancers.
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Incidence of cancers, ischemic cardiovascular diseases and mortality during 5-year follow-up after stopping antioxidant vitamins and minerals supplements: a postintervention follow-up in the SU.VI.MAX Study.
Hercberg, S, Kesse-Guyot, E, Druesne-Pecollo, N, Touvier, M, Favier, A, Latino-Martel, P, Briançon, S, Galan, P
International journal of cancer. 2010;(8):1875-81
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The Supplementation in Vitamins and Mineral Antioxidants Study was a double-blind, placebo-controlled, randomized trial, in which 12,741 French adults (7,713 women aged 35-60 years and 5,028 men aged 45-60 years) received a combination of ascorbic acid (120 mg), vitamin E (30 mg), beta-carotene (6 mg), selenium (100 microg) and zinc (20 mg), or placebo daily for a median follow-up time of 7.5 years [October 1994 to September 2002]. Antioxidant supplementation decreased total cancer incidence and total mortality in men. Postintervention follow-up assessment of total cancer incidence, ischemic cardiovascular disease incidence and total mortality was carried out for 5 years [September 1, 2002, to September 1, 2007]. No late effect of antioxidant supplementation was revealed 5 years after ending the intervention neither on ischemic cardiovascular disease incidence and mortality in both genders nor on cancer incidence in women. Regarding duration of intervention effects in men, the reduced risk of total cancer incidence and total mortality was no longer evident after the 5-year postintervention follow-up. During the postsupplementation period, the relative risk (RR) for total cancer incidence (n = 126) was 0.98 (95% confidence interval [CI], 0.75-1.27) among antioxidant recipients compared to nonrecipients. For total mortality (n = 90), the RR was 0.98 (95% CI, 0.75-1.26) for men receiving antioxidants compared to nonrecipients. In conclusion, beneficial effects of antioxidant supplementation in men disappeared during postintervention follow-up.
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Dietary patterns and blood pressure change over 5-y follow-up in the SU.VI.MAX cohort.
Dauchet, L, Kesse-Guyot, E, Czernichow, S, Bertrais, S, Estaquio, C, Péneau, S, Vergnaud, AC, Chat-Yung, S, Castetbon, K, Deschamps, V, et al
The American journal of clinical nutrition. 2007;(6):1650-6
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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.