A Primary Prevention Trial Using Nutritional Doses of Antioxidant Vitamins and Minerals in Cardiovascular Diseases and Cancers in a General Population: The SU.VI.MAX Study—Design, Methods, and Participant Characteristics
Introduction
In the past several years, many basic and clinical research investigations have pointed to the role of reactive metabolites of oxygen, or free radicals, in numerous pathologic processes and have suggested the protective effect of antioxidant nutrients such as beta-carotene, vitamin C, vitamin E, selenium, and zinc 1, 2, 3, 4, 5. Epidemiologic data obtained by cross-sectional, case-control, and prospective studies have also raised strong supportive arguments for an inverse relationship between the intake of antioxidant vitamins and trace elements and the risk of cancer, cardiovascular disease, cataracts, and infectious diseases 6, 7, 8, 9, 10, 11, 12, 13; however, the observational nature of these studies has not enabled the establishment of a causal relationship. Few randomized placebo-controlled trials testing different antioxidants on different target populations are available, and results appear to be conflicting 14, 15, 16, 17. Most of these interventional studies involved higher levels of antioxidants than the dietary intake found in observational studies to be associated with the lowest risk of cancer and cardiovascular disease.
The SUpplementation en VItamines et Minéraux AntioXydants (SU.VI.MAX) Study is a randomized, double-blind, placebo-controlled, primary-prevention trial designed to test the efficacy of a supplementation with antioxidant vitamins (vitamin C, vitamin E, and beta-carotene) and minerals (selenium and zinc) at nutrition-like doses (one to three times the daily recommended dietary allowances) in reducing several major health problems in industrialized countries, and especially in reducing the main causes of premature death.
A previous paper described the background and rationale behind the SU.VI.MAX study, particularly the advantage of using a combination of antioxidant vitamins and minerals at low, nutrition-level doses [18]. Many reasons support the hypothesis of the particular efficiency of a combination of antioxidants. Some metabolic interrelationships exist between antioxidant nutrients and beneficial mutual protection and regeneration. Moreover, antioxidant nutrients have a complementary scavenging capacity toward free radicals. An accumulation of mechanistic data suggests that antioxidants act not only individually but also cooperatively and, in some cases, synergistically. The intrinsic chemical reactivity of individual antioxidants, their different locations in the membrane and lipoproteins, their additive or synergistic effects, their multiple interactions, and their cooperative action led us to test, in the SU.VI.MAX study, not a single antioxidant nutrient but, rather, a balanced combination of antioxidants that might provide maximal efficacy along with maximal safety. The present report describes the design, implementation, and baseline characteristics of participants in this 8-year cohort study, which started in 1994 in France.
Section snippets
Objectives
The primary objective of this experimental epidemiologic study is to substantiate and quantify, in a general population of adults, the preventive effect of a combination of antioxidant vitamins and minerals, namely beta-carotene, vitamin C, vitamin E, selenium, and zinc at doses considered to be nutritional and nonpharmacologic, on the incidence of cancers (all sites) and ischemic heart diseases. Secondary objectives are to assess the effect of the supplementation on the incidence of the main
Study design
The SU.VI.MAX Study has been approved by the ethical committee for studies with human subjects, the Comité Consultatif pour la Protection des Personnes se prêtant à la Recherche Biomédicale (CCPPRB number 706) of Paris-Cochin, and by the Comité National Informatique et Liberté (CNIL number 334641), which ensures that all medical information is kept confidential and anonymous.
Participant characteristics at baseline
The SU.VI.MAX cohort included a total of 7679 women and 5056 men during the first recruitment period. Mean age is 46.4 ± 6.7 years for women and 51.1 ± 4.7 years for men. Table 3 shows principal characteristics of participants at the start of intervention for multivitamin and mineral supplement or placebo groups. Groups are comparable for all studied characteristics.
Comments
The SU.VI.MAX Study was designed and initiated to test the hypothesis that a combination of antioxidant and trace elements, given at nutrition-level doses in a general population of adults, may reduce the incidence of cancer and cardiovascular disease, thereby decreasing premature mortality. The objectives and the specific design of this intervention study are linked to its public health aim. The targeted population is the general population, not simply high-risk subjects; the antioxidant
Acknowledgements
The project SU.VI.MAX has support from public and private sectors. Special acknowledgments are addressed to Fruit d’Or Recherche, Candia, Lipton, Kellogg’s, Céréal, CERIN, Grands Moulins de Paris, Centre d’Information sur Canderel, Orangina, Estée Lauder, L’Oréal, Peugeot, Jet Service, RP Scherer, Sodexho, France Telecom, Santogen, Becton Dickinson, Fould Springer, Boehringer Diagnostic, Seppic Givaudan Lavirotte, and Le Grand Canal.
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