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Providing perspectives on recent research into vitamins and nutritionals


Cancer, PHS II, EPIC and Measuring Vitamin Status

By Michael McBurney

The Physicians’ Health Study II (PHS II) tested the effects of low-dose multivitamin-mineral supplementation in 18,350 men who had volunteered for a randomized controlled trial (RCT) involving aspirin and/or beta-carotene beginning in 1982.  Multivitamin-mineral use was associated with a 39% reduction in fatal heart attacks (myocardial infarction, MI).

Rautianinen and colleagues wanted to know if healthy physicians who were using multivitamins at baseline had a lower risk of cardiovascular disease (CVD). Men who said they were using multivitamins at baseline (1982) were more likely to smoke, to be physically active, and less likely to consume alcohol.  Men who reported ≥20 y of multivitamin use at baseline had a lower risk of CVD events. This study does not demonstrate that multivitamin use is beneficial.

Although PHS II establishes that multivitamin use is associated with other healthy behaviors, the investigators did not assess nutritional status. Compare PHS II (+/- supplement) with the European Investigation into Cancer (EPIC) approach.

Agnoli and colleagues measured plasma concentrations rather than relying upon self-reported intakes. In a nested case-control study among women (35-65y) at recruitment and followed for a median of 14.9y, higher plasma vitamin B6 concentrations were associated with a 22% reduced risk of breast cancer. Among alcohol consumers, high plasma vitamin B6 concentrations were associated with a 29% reduced risk. High plasma riboflavin was associated with a 55% reduced risk in premenopausal women.

If asked whether self-reported behaviors, such as multivitamin use, or blood concentrations are better estimations of vitamin status, there is no doubt in my mind. Always choose the clinical marker. Physicians don’t rely upon cholesterol and saturated fat intake as an indicator of CVD risk. Blood cholesterol and LDL-cholesterol concentrations are measured to assess risk. Diabetologists don’t ask about sugar intake to screen for diabetes, they measure fasting blood glucose and/or glycosylated blood hemoglobin (HbA1c) concentrations. Vitamins are essential for normal cellular function. When blood concentrations are low, it follows that cellular access may be limiting.

Choose nutrient dense foods. Use a multivitamin-mineral supplement. They can help increase vitamin concentrations. Sustain your body.

Main Citations

Rautiainen S, Rist PM, Glynn RJ, Buring JE, Gaziano JM, Sesso HD. Multivitamin use and the risk of cardiovascular disease in men. 2016 J Nutr doi: 10.3945/jn.115.227884

Agnoli C, Grioni S, Krogh V, Pala V, Allione A, Matullo G, Di Gaetano C, Tagliabue G, Pedraglio S, Garrone G, Cancarini I, Cavalleri A, Sieri S. Plasma riboflavin and vitamin B6, but not homocystein, folate, or vitamin B12, are inversely associated with breast cancer risk in the European Prospective Investigation into Cancer and Nutrition-Varese Cohort. 2016 J Nutr doi: 10.3945/jn.115.225433

Other Citations

Christen WG, Gaziano JM, Hennekens CH. Design of Physicians’ Health Study II – a randomized controlled trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. 2000 Am Epidemiol doi: 10.1016/S1047-2797(99)00042-3

Sesso HD, Christen WB, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JE, Glynn RJ, Buring JE, Gaziano JM. Multivitamins in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. 2012 JAMA doi: 10.1001/jama.2012.14805

Rautiainen S, Wang L, Gaziano JM, Sesso HD. Who uses multivitamins? A cross-sectional study in the Physicians‘ Health Study. 2014 Eur J Nutr doi: 10.1007/s00394-013-0608-5