Clinical trial NCT00272428: Primary Prevention Trial of the Health Effects of Antioxidant Vitamins and Minerals.
Official title: The SU.VI.MAX Study. A Randomized, Placebo-controlled Prevention Trial of the Health Effects of Antioxidant Vitamins and Minerals.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Healthy
Keywords: Prevention trial
Antioxydant vitamins and minerals
Cancer
Ischemic disease
Mortality
Health related quality of life
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
Collaborators: name: French private agencies
First posted: 2006-01-06
Enrollment: 13000
Sex: ALL
Minimum age (years): 35
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: From experimental studies it is known that free radicals may induce numerous pathological processes, and it has been suggested that, because of their antioxidant capacity, nutrients such as beta-carotene, vitamin C, vitamin E, selenium and zinc may prevent such harmful effects. Epidemiological data from cross-sectional, case-control, and prospective studies have indeed shown a strong relationship between the intake of antioxidant vitamins and minerals, or foods rich in these nutrients, and the risk of cancer and ischaemic cardiovascular diseases (CVD). However, randomised placebo-controlled primary prevention trials, in which antioxidant micronutrients alone or in pairs were given at high doses over long periods, have not been able to prove this potential beneficial effect, and two of these even suggested harmful effects. The seemingly contradictory results between the observational studies and these randomised trials can be explained by the fact that the doses used in clinical trials were much higher than the highest levels reachable by usual dietary intake which have been found to be associated in observational studies with the lowest risk of cancer and CVD. In fact, the only trial which did observe a beneficial effect on total mortality and cancer incidence used nutritional doses of a combination of several vitamins and minerals and was performed on Chinese population with very low baseline micronutrient status, due to poor life conditions in this region (9).

The objective of the "SUpplementation en VItamines et Minéraux AntioXydants" (SU.VI.MAX) study, was to test in a randomised, placebo-controlled trial, if an adequate and well balanced intake of antioxidant nutrients reduces the incidence of cancers and ischaemic cardiovascular diseases in a middle-age general population.

Eligibility criteria: Inclusion Criteria:

* women aged 35-60 years, men aged 45-60 years
* acceptance of the possibility to be given a placebo and acceptance of the constraints of participation
* lack of previous regular supplementation with any of the vitamins or minerals in the supplement provided
* absence of extreme beliefs or behavior regarding diet

Exclusion Criteria:

* disease likely to hinder active participation or threatened 5-year survival

Primary outcomes:
measure: Major fatal and non fatal ischemic cardiovascular events
measure: Cancer any kind except for basal cell skin carcinoma
Secondary outcomes:
measure: All cause mortality
measure: Health-related quality of life
measure: Intermediate criteria of clinical status
measure: Intermediate criteria of biological status
measure: Intermediate criteria of anthropometric status
Other outcomes:
Locations:
city: Paris
country: France
facility: U557 Inserm
Study officials:
affiliation: U557 Inserm (UMR Inserm/Inra/CNAM), Institut Scientifique et Technique de la Nutrition et de l'Alimentation/CNAM
name: Serge Hercberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, Roussel AM, Favier A, Briancon S. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004 Nov 22;164(21):2335-42. doi: 10.1001/archinte.164.21.2335.
citation: Andreeva VA, Peneau S, Julia C, Shivappa N, Hebert JR, Wirth MD, Touvier M, Hercberg S, Galan P, Kesse-Guyot E. The inflammatory potential of the diet is prospectively associated with subjective hearing loss. Eur J Nutr. 2021 Oct;60(7):3669-3678. doi: 10.1007/s00394-021-02531-1. Epub 2021 Mar 18.
citation: Lecuyer L, Dalle C, Micheau P, Petera M, Centeno D, Lyan B, Lagree M, Galan P, Hercberg S, Rossary A, Demidem A, Vasson MP, Partula V, Deschasaux M, Srour B, Latino-Martel P, Druesne-Pecollo N, Kesse-Guyot E, Durand S, Pujos-Guillot E, Manach C, Touvier M. Untargeted plasma metabolomic profiles associated with overall diet in women from the SU.VI.MAX cohort. Eur J Nutr. 2020 Dec;59(8):3425-3439. doi: 10.1007/s00394-020-02177-5. Epub 2020 Jan 11.
citation: Lecuyer L, Dalle C, Lyan B, Demidem A, Rossary A, Vasson MP, Petera M, Lagree M, Ferreira T, Centeno D, Galan P, Hercberg S, Deschasaux M, Partula V, Srour B, Latino-Martel P, Kesse-Guyot E, Druesne-Pecollo N, Durand S, Pujos-Guillot E, Touvier M. Plasma Metabolomic Signatures Associated with Long-term Breast Cancer Risk in the SU.VI.MAX Prospective Cohort. Cancer Epidemiol Biomarkers Prev. 2019 Aug;28(8):1300-1307. doi: 10.1158/1055-9965.EPI-19-0154. Epub 2019 Jun 4.
citation: Assmann KE, Adjibade M, Hercberg S, Galan P, Kesse-Guyot E. Unsaturated Fatty Acid Intakes During Midlife Are Positively Associated with Later Cognitive Function in Older Adults with Modulating Effects of Antioxidant Supplementation. J Nutr. 2018 Dec 1;148(12):1938-1945. doi: 10.1093/jn/nxy206.
citation: Wiernik E, Lemogne C, Fezeu L, Arnault N, Hercberg S, Kesse-Guyot E, Galan P. Association Between Alexithymia and Risk of Incident Cardiovascular Diseases in the SUpplementation en VItamines et Mineraux AntioXydants (SU.VI.MAX) Cohort. Psychosom Med. 2018 Jun;80(5):460-467. doi: 10.1097/PSY.0000000000000592.
citation: Assmann KE, Adjibade M, Shivappa N, Hebert JR, Wirth MD, Touvier M, Akbaraly T, Hercberg S, Galan P, Julia C, Kesse-Guyot E. The Inflammatory Potential of the Diet at Midlife Is Associated with Later Healthy Aging in French Adults. J Nutr. 2018 Mar 1;148(3):437-444. doi: 10.1093/jn/nxx061.
citation: Ruhunuhewa I, Adjibade M, Andreeva VA, Galan P, Hercberg S, Assmann KE, Kesse-Guyot E. Prospective association between body mass index at midlife and healthy aging among French adults. Obesity (Silver Spring). 2017 Jul;25(7):1254-1262. doi: 10.1002/oby.21853. Epub 2017 May 11.
citation: Adjibade M, Andreeva VA, Lemogne C, Touvier M, Shivappa N, Hebert JR, Wirth MD, Hercberg S, Galan P, Julia C, Assmann KE, Kesse-Guyot E. The Inflammatory Potential of the Diet Is Associated with Depressive Symptoms in Different Subgroups of the General Population. J Nutr. 2017 May;147(5):879-887. doi: 10.3945/jn.116.245167. Epub 2017 Mar 29.
citation: Walker V, Perret-Guillaume C, Kesse-Guyot E, Agrinier N, Hercberg S, Galan P, Assmann KE, Briancon S, Rotonda C. Effect of Multimorbidity on Health-Related Quality of Life in Adults Aged 55 Years or Older: Results from the SU.VI.MAX 2 Cohort. PLoS One. 2016 Dec 29;11(12):e0169282. doi: 10.1371/journal.pone.0169282. eCollection 2016.
citation: Kesse-Guyot E, Assmann KE, Andreeva VA, Touvier M, Neufcourt L, Shivappa N, Hebert JR, Wirth MD, Hercberg S, Galan P, Julia C. Long-term association between the dietary inflammatory index and cognitive functioning: findings from the SU.VI.MAX study. Eur J Nutr. 2017 Jun;56(4):1647-1655. doi: 10.1007/s00394-016-1211-3. Epub 2016 Apr 7.
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citation: Graffouillere L, Deschasaux M, Mariotti F, Neufcourt L, Shivappa N, Hebert JR, Wirth MD, Latino-Martel P, Hercberg S, Galan P, Julia C, Kesse-Guyot E, Touvier M. Prospective association between the Dietary Inflammatory Index and mortality: modulation by antioxidant supplementation in the SU.VI.MAX randomized controlled trial. Am J Clin Nutr. 2016 Mar;103(3):878-85. doi: 10.3945/ajcn.115.126243. Epub 2016 Feb 10.
citation: Deschasaux M, Souberbielle JC, Latino-Martel P, Sutton A, Charnaux N, Druesne-Pecollo N, Galan P, Hercberg S, Le Clerc S, Kesse-Guyot E, Ezzedine K, Touvier M. Weight Status and Alcohol Intake Modify the Association between Vitamin D and Breast Cancer Risk. J Nutr. 2016 Mar;146(3):576-85. doi: 10.3945/jn.115.221481. Epub 2016 Jan 27.
citation: Kesse-Guyot E, Assmann KE, Andreeva VA, Ferry M, Hercberg S, Galan P; SU.VI.MAX 2 Research Group. Consumption of Dairy Products and Cognitive Functioning: Findings from the SU.VI.MAX 2 Study. J Nutr Health Aging. 2016 Feb;20(2):128-37. doi: 10.1007/s12603-015-0593-x.
citation: Deschasaux M, Souberbielle JC, Latino-Martel P, Sutton A, Charnaux N, Druesne-Pecollo N, Galan P, Hercberg S, Le Clerc S, Kesse-Guyot E, Ezzedine K, Touvier M. Prospective associations between vitamin D status, vitamin D-related gene polymorphisms, and risk of tobacco-related cancers. Am J Clin Nutr. 2015 Nov;102(5):1207-15. doi: 10.3945/ajcn.115.110510. Epub 2015 Oct 7.
citation: Kesse-Guyot E, Lassale C, Assmann KE, Andreeva VA, Julia C, Blacher J, Fezeu L, Hercberg S, Galan P. Are different vascular risk scores calculated at midlife uniformly associated with subsequent poor cognitive performance? Atherosclerosis. 2015 Nov;243(1):286-92. doi: 10.1016/j.atherosclerosis.2015.09.023. Epub 2015 Sep 21.
citation: Donnenfeld M, Deschasaux M, Latino-Martel P, Diallo A, Galan P, Hercberg S, Ezzedine K, Touvier M. Prospective association between dietary folate intake and skin cancer risk: results from the Supplementation en Vitamines et Mineraux Antioxydants cohort. Am J Clin Nutr. 2015 Aug;102(2):471-8. doi: 10.3945/ajcn.115.109041. Epub 2015 Jul 8.
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citation: Julia C, Touvier M, Meunier N, Papet I, Galan P, Hercberg S, Kesse-Guyot E. Intakes of PUFAs were inversely associated with plasma C-reactive protein 12 years later in a middle-aged population with vitamin E intake as an effect modifier. J Nutr. 2013 Nov;143(11):1760-6. doi: 10.3945/jn.113.180943. Epub 2013 Sep 11.
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citation: Kesse-Guyot E, Charreire H, Andreeva VA, Touvier M, Hercberg S, Galan P, Oppert JM. Cross-sectional and longitudinal associations of different sedentary behaviors with cognitive performance in older adults. PLoS One. 2012;7(10):e47831. doi: 10.1371/journal.pone.0047831. Epub 2012 Oct 17.
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