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

https://doi.org/10.1016/S0197-2456(98)00015-4Get rights and content

Abstract

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 daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 μg; and zinc, 20 mg) at nutrition-level doses (one to three times the daily recommended dietary allowances) in reducing several major health problems in industrialized countries, especially the main causes of premature death, cancers and cardiovascular diseases. The present report describes the design, implementation, and baseline characteristics of participants in this 8-year cohort study, which started in 1994 in France; 12,735 eligible subjects (women aged 35–60, and men aged 45–60) were included in 1994 and will be followed for 8 years. Participants undergo a yearly visit consisting, every other year, of either biological sampling or clinical examination. They also regularly provide information on health events and dietary intake by filling out computerized questionnaires using the Minitel Telematic Network. Data on baseline characteristics of the participants suggest that the present sample is close to the national population in terms of geographic density, socioeconomic status, and the distribution of various major risk factors for the diseases under study. The choice of the study population should allow the results of this trial to apply to adult populations of both sexes in France and other industrialized countries.

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.

References (34)

  • M.J. Stampfer et al.

    A review of the epidemiology of dietary antioxidants and risk of coronary heart disease

    Can J Cardiol

    (1993)
  • T. Byers et al.

    Dietary carotenes, vitamin C, and vitamin E as protective antioxidants in human cancers

    Annu Rev Nutr

    (1992)
  • G. Block et al.

    Fruit, vegetables, and cancer preventiona review of the epidemiological evidence

    Nutr Cancer

    (1992)
  • W.J. Blot et al.

    Nutrition intervention trials in Linxian, Chinasupplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population

    J Natl Cancer Inst

    (1993)
  • The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group. The effect of vitamin E and beta-carotene on the...
  • G.S. Omenn et al.

    Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease

    N Eng J Med

    (1996)
  • C.H. Hennekens et al.

    Lack of effect of long-term supplementation with beta-carotene on the incidence of malignant neoplasms and cardiovascular disease

    N Eng J Med

    (1996)
  • Cited by (0)

    View full text