The Su.Vi.Max. study — SUpplementation en VItamines et Minéraux AntioXydants — was a big randomized, double-blind, placebo-controlled study carried out with typical French efficiency. Even though I have written the name of the study in French, there are so many English cognates that I am sure you can read the full name of the study.
The study was designed to test the health benefits of daily supplementation with a number of vitamins and minerals at nutritional dosages (roughly, one to three times the daily recommended dietary intakes) [Hercberg 1998]:
- selenium, 100 micrograms
- vitamin C, 120 mg
- vitamin E, 30 mg
- beta-carotene, 6 mg
- zinc, 20 mg
In particular, the French researchers wanted to see the effect of the daily supplementation over a long period, approximately 7.5 years, from 1994 to 2002, on the prevention of cancer and cardiovascular disease, both of which have been linked to oxidative stress and oxidative damage and might, therefore, be affected by supplementation with antioxidants.
Selenium as an antioxidant component
In the body, selenium is incorporated into selenoproteins. Among the selenium containing proteins are the glutathione peroxidases (GPx), which are a family of antioxidants that neutralize hydrogen peroxide and various hydroperoxide radicals. The GPx selenoproteins are among the most important antioxidants protecting the human body against free radical damage. Another selenium containing protein with some antioxidant function is the Selenoprotein P (SEPP1) [Rayman 2012].
In addition to reducing oxidative stress, some selenoproteins are known to reduce inflammation levels [Rayman 2012]. All in all, there was and is good reason to think that selenium supplementation of low-selenium-status individuals can reduce the frequency of degenerative diseases and premature deaths.
Su.Vi.Max. = a big study of selenium and other antioxidants
The researchers enrolled 12,741 adult study participants, both women aged 35 to 60 years and men aged 45 to 60 years. There were 7713 women and 5028 men enrolled [Ezzedine 2010]. This large study sample was drawn to represent the general adult population of France, to be representative of all adults of all health conditions and not just representative of high-risk individuals [Hercberg 1998]. As such, the results of the Su.Vi. Max. study should be applicable to adults in all western industrialized countries.
The random assignment of individuals to an active treatment group (receiving daily nutritional supplements) or to a control group (receiving daily placebos) was intended to ensure, as far as possible, that the only real difference between the two test groups was the exposure or non-exposure to the selenium and other antioxidants. The researchers wanted to ensure that differences in outcomes between the two groups would be the result of the supplementation itself and not the result of confounding variables such as age or sex or diet or exercise or disease condition.
The study was double-blind so that there would be no effect on the outcome of the researchers’ or the participants’ expectations. The use of a control group was intended, of course, to provide a basis for comparison of the outcomes of taking daily selenium and antioxidant supplements for a long period.
Interesting outcomes from the Su.Vi.Max. study of selenium and antioxidants
After following the data from the Su.Vi.Max. participants for nearly 8 years, the researchers published their findings:
Serum selenium levels
The study participants’ serum antioxidant concentrations were influenced by such variables as age, alcohol consumption, body weight, diet, sex, and tobacco smoking [Galan 2005].
Selenium and cancer
The daily supplementation with selenium and other antioxidants for 7.5 years lowered total cancer incidence and all-cause mortality in men but not in women [Hercberg 2004].
Selenium and ageing
The results from a follow-up Su.Vi.Max 2 study that assessed the extent of healthy ageing of a sub-group of the original cohort in the years 2007 – 2009 revealed that the Su.Vi.Max. supplementation was associated with a greater healthy aging among the men but not among the women and, consequently, not in the sub-group as a whole [Assmann 2015].
Sex-related differences in response to selenium
These sex-differentiated results from the Su.Vi.Max. study were among the first indications of a possible sex-related difference in the response to selenium supplementation.
Interestingly, the nine-year longitudinal EVA (Epidemiology of Vascular Ageing) study in France showed higher plasma selenium concentrations associated with a marginally significant decreased risk of dysglycemia (impaired fasting glucose or diabetes) in men but not in women [Akbaraly 2010]. We would like to see more studies of sex differences in the response to selenium.
Selenium and contraceptive treatment and age
Among women, the findings of the Su.Vi.Max. study showed significant differences in serum selenium concentrations according to the contraceptive treatment and age [Arnaud 2007]. Increased selenium concentrations were associated with increased serum lipid levels and/or decreased bleeding.
Selenium and cognitive function
Further follow-up showed that study participants who had received the active selenium and antioxidant supplementation had better episodic memory scores, better verbal memory, and better executive functioning. However, the improvement in verbal memory was seen only in nonsmokers [Kesse-Guyot 2011].
Selenium and metabolic syndrome and glucose levels
7.5 years of daily supplementation with selenium and other antioxidant micronutrients in physiological dosages did not affect the risk of metabolic syndrome. The supplementation had no beneficial or harmful effect on metabolic syndrome [Czernichow 2009].
Metabolic syndrome is the umbrella term for a group of factors that increase the risk of heart disease, stroke, and diabetes, so the finding that there was no harmful effect of the supplementation is a good result.
Similarly, 7.5. years of daily supplementation with 100 micrograms of selenium had no effect on fasting plasma glucose levels in men or women [Czernichow 2006].
Selenium and thyroid function
The Su.Vi.Max. findings suggest that findings suggest that selenium may protect against goiter and that selenium may also protect against autoimmune thyroid disease [Derumeaux 2003].
Conclusions from the Su.Vi.Max. study
Professor Serge Hercberg concluded that the health benefits of daily nutritional supplementation with selenium and antioxidants depend on the following factors [Hercberg 2006]:
- the dosages (nutritional versus pharmacological)
- the study participants’ baseline antioxidant status
- the study participants’ sex
- the study participants’ diets
- the study participants’ health status of subjects
Long-term daily supplementation with selenium and other antioxidant supplements had beneficial effects on cancer prevention and healthy ageing in men (but not in women) and beneficial effects on thyroid function and cognitive function in both men and women. There were not effects, neither beneficial nor harmful, on any aspects of metabolic syndrome, to include fasting plasma glucose levels.
Sources
Akbaraly,T.N., Arnaud,J., Rayman,M.P., Hininger-Favier, J., Roussel, A.M., Berr, C., & Fontbonne, A.
Plasma selenium and risk of dysglycemia in an elderly French population: Results from the prospective Epidemiology of Vascular Ageing Study. Nutr Metab. 2010;7(21).
Arnaud, J., Arnault, N., Roussel, A., Bertrais, S., Ruffieux, D., Galan, P., & Hercberg, S. (2007). Relationships between selenium, lipids, iron status and hormonal therapy in women of the SU.VI.M.AX cohort. Journal of Trace Elements in Medicine and Biology, 21 Suppl 166-69.
Assmann, K. E., Andreeva, V. A., Jeandel, C., Hercberg, S., Galan, P., & Kesse-Guyot, E. (2015). 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. American Journal of Epidemiology, 182(8), 694-704.
Czernichow, S., Vergnaud, A., Galan, P., Arnaud, J., Favier, A., Faure, H., & Ahluwalia, N. (2009). Effects of long-term antioxidant supplementation and association of serum antioxidant concentrations with risk of metabolic syndrome in adults. The American Journal of Clinical Nutrition, 90(2), 329-335.
Czernichow, S., Couthouis, A., Bertrais, S., Vergnaud, A., Dauchet, L., Galan, P., & Hercberg, S. (2006). Antioxidant supplementation does not affect fasting plasma glucose in the Supplementation with Antioxidant Vitamins and Minerals (SU.VI.MAX) study in France: association with dietary intake and plasma concentrations. The American Journal of Clinical Nutrition, 84(2), 395-399.
Derumeaux, H., Valeix, P., Castetbon, K., Bensimon, M., Boutron-Ruault, M., Arnaud, J., & Hercberg, S. (2003). Association of selenium with thyroid volume and echostructure in 35- to 60-year-old French adults. European Journal of Endocrinology, 148(3), 309-315.
Ezzedine, K., Latreille, J., Kesse-Guyot, E., Galan, P., Hercberg, S., Guinot, C., & Malvy, D. (2010). Incidence of skin cancers during 5-year follow-up after stopping antioxidant vitamins and mineral supplementation. European Journal of Cancer (Oxford, England: 1990), 46(18), 3316-3322.
Galan, P., Viteri, F. E., Bertrais, S., Czernichow, S., Faure, H., Arnaud, J., & … Hercberg, S. (2005). Serum concentrations of beta-carotene, vitamins C and E, zinc and selenium are influenced by sex, age, diet, smoking status, alcohol consumption and corpulence in a general French adult population. European Journal of Clinical Nutrition, 59(10), 1181-1190.
Hercberg, S. (2006). [The SU.VI.MAX study, a randomized, placebo-controlled trial on the effects of antioxidant vitamins and minerals on health]. Annales Pharmaceutiques Francaises, 64(6), 397-401.
Hercberg, S., Galan, P., Preziosi, P., Bertrais, S., Mennen, L., Malvy, D., & … Briançon, S. (2004). The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Archives Of Internal Medicine, 164(21), 2335-2342.
Hercberg, S., Galan, P., Preziosi, P., Roussel, A. M., Arnaud, J., Richard, M. J., & … Favier, A. (1998). Background and rationale behind the SU.VI.MAX Study, a prevention trial using nutritional doses of a combination of antioxidant vitamins and minerals to reduce cardiovascular diseases and cancers. SUpplementation en VItamines et Minéraux AntioXydants Study. International Journal for Vitamin and Nutrition Research, 68(1), 3-20.
Kesse-Guyot, E., Fezeu, L., Jeandel, C., Ferry, M., Andreeva, V., Amieva, H., & … Galan, P. (2011). French adults’ cognitive performance after daily supplementation with antioxidant vitamins and minerals at nutritional doses: a post hoc analysis of the Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) trial. The American Journal of Clinical Nutrition, 94(3), 892-899.
Rayman, M. P. (2012). Selenium and human health. Lancet (London, England), 379(9822), 1256-1268.
Disclaimer: The information presented in this review article is not intended as medical advice and should not be used as such.
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