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Total and added sugar intakes, sugar types, and cancer risk: results from the prospective NutriNet-Santé cohort.
Debras, C, Chazelas, E, Srour, B, Kesse-Guyot, E, Julia, C, Zelek, L, Agaësse, C, Druesne-Pecollo, N, Galan, P, Hercberg, S, et al
The American journal of clinical nutrition. 2020;(5):1267-1279
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Abstract
BACKGROUND Excessive sugar intake is now recognized as a key risk factor for obesity, type 2 diabetes, and cardiovascular diseases. In contrast, evidence on the sugar-cancer link is less consistent. Experimental data suggest that sugars could play a role in cancer etiology through obesity but also through inflammatory and oxidative mechanisms and insulin resistance, even in the absence of weight gain. OBJECTIVE The objective was to study the associations between total and added sugar intake and cancer risk (overall, breast, and prostate), taking into account sugar types and sources. METHODS In total, 101,279 participants aged >18 y (median age, 40.8 y) from the French NutriNet-Santé prospective cohort study (2009-2019) were included (median follow-up time, 5.9 y). Sugar intake was assessed using repeated and validated 24-h dietary records, designed to register participants' usual consumption for >3500 food and beverage items. Associations between sugar intake and cancer risk were assessed by Cox proportional hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). RESULTS Total sugar intake was associated with higher overall cancer risk (n = 2503 cases; HR for quartile 4 compared with quartile 1: 1.17; 95% CI: 1.00, 1.37; Ptrend = 0.02). Breast cancer risks were increased (n = 783 cases; HRQ4vs.Q1 = 1.51; 95% CI: 1.14, 2.00; Ptrend = 0.0007). Results remained significant when weight gain during follow-up was adjusted for. In addition, significant associations with cancer risk were also observed for added sugars, free sugars, sucrose, sugars from milk-based desserts, dairy products, and sugary drinks (Ptrend ≤ 0.01). CONCLUSIONS These results suggest that sugars may represent a modifiable risk factor for cancer prevention (breast in particular), contributing to the current debate on the implementation of sugar taxation, marketing regulation, and other sugar-related policies. This trial was registered at clinicaltrials.gov as NCT03335644.
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Sugary drink consumption and risk of cancer: results from NutriNet-Santé prospective cohort.
Chazelas, E, Srour, B, Desmetz, E, Kesse-Guyot, E, Julia, C, Deschamps, V, Druesne-Pecollo, N, Galan, P, Hercberg, S, Latino-Martel, P, et al
BMJ (Clinical research ed.). 2019;:l2408
Abstract
OBJECTIVE To assess the associations between the consumption of sugary drinks (such as sugar sweetened beverages and 100% fruit juices), artificially sweetened beverages, and the risk of cancer. DESIGN Population based prospective cohort study. SETTING AND PARTICIPANTS Overall, 101 257 participants aged 18 and over (mean age 42.2, SD 14.4; median follow-up time 5.1 years) from the French NutriNet-Santé cohort (2009-2017) were included. Consumptions of sugary drinks and artificially sweetened beverages were assessed by using repeated 24 hour dietary records, which were designed to register participants' usual consumption for 3300 different food and beverage items. MAIN OUTCOME MEASURES Prospective associations between beverage consumption and the risk of overall, breast, prostate, and colorectal cancer were assessed by multi-adjusted Fine and Gray hazard models, accounting for competing risks. Subdistribution hazard ratios were computed. RESULTS The consumption of sugary drinks was significantly associated with the risk of overall cancer (n=2193 cases, subdistribution hazard ratio for a 100mL/d increase 1.18, 95% confidence interval 1.10 to 1.27, P<0.0001) and breast cancer (693, 1.22, 1.07 to 1.39, P=0.004). The consumption of artificially sweetened beverages was not associated with the risk of cancer. In specific subanalyses, the consumption of 100% fruit juice was significantly associated with the risk of overall cancer (2193, 1.12, 1.03 to 1.23, P=0.007). CONCLUSIONS In this large prospective study, the consumption of sugary drinks was positively associated with the risk of overall cancer and breast cancer. 100% fruit juices were also positively associated with the risk of overall cancer. These results need replication in other large scale prospective studies. They suggest that sugary drinks, which are widely consumed in Western countries, might represent a modifiable risk factor for cancer prevention. STUDY REGISTRATION ClinicalTrials.gov NCT03335644.
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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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Aspects of antioxidant foods and supplements in health and disease.
Herrera, E, Jiménez, R, Aruoma, OI, Hercberg, S, Sánchez-García, I, Fraga, C
Nutrition reviews. 2009;:S140-4
Abstract
Free radicals generated as byproducts of normal metabolism can damage biologically relevant molecules. When their generation is increased, damage can also be increased, resulting in the development of many pathological conditions. Antioxidant defenses protect the body from the detrimental effects of free radicals. Dietary fruits and vegetables provide a reasonable amount of compounds that act as physiological antioxidants. Although existing knowledge does not allow a final and conclusive assessment of the relevance of antioxidants for health, it does provide the basis for its rational consideration. This paper addresses the specific aspects of antioxidant supplementation in health and disease.
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Antioxidant vitamins and minerals in prevention of cancers: lessons from the SU.VI.MAX study.
Hercberg, S, Czernichow, S, Galan, P
The British journal of nutrition. 2006;:S28-30
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.
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Iron status and risk of cancers in the SU.VI.MAX cohort.
Hercberg, S, Estaquio, C, Czernichow, S, Mennen, L, Noisette, N, Bertrais, S, Renversez, JC, Briançon, S, Favier, A, Galan, P
The Journal of nutrition. 2005;(11):2664-8
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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.
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Antioxidant status and risk of cancer in the SU.VI.MAX study: is the effect of supplementation dependent on baseline levels?
Galan, P, Briançon, S, Favier, A, Bertrais, S, Preziosi, P, Faure, H, Arnaud, J, Arnault, N, Czernichow, S, Mennen, L, et al
The British journal of nutrition. 2005;(1):125-32
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.
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The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals.
Hercberg, S, Galan, P, Preziosi, P, Bertrais, S, Mennen, L, Malvy, D, Roussel, AM, Favier, A, Briançon, S
Archives of internal medicine. 2004;(21):2335-42
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.