by Craig Weatherby
Often, when researchers test supplements containing isolated food-borne nutrients they fail to perform as hoped.
Two clinical trials published in the Journal of the American Medical Association (JAMA) focused on the preventive power of vitamins C and E versus heart disease, and the effects of selenium and vitamin E versus prostate cancer.
After eight years, researchers detected no reductions in heart risk among male physicians who agreed to take vitamin C and E supplements (Sesso HD et al. 2008).
And no prostate-prevention benefits were seen in men over 50 who took selenium and/or vitamin E for even fewer years (Lippman SM et al.).
Scientists have been interested in testing vitamin E and C and selenium for three good reasons:
- They exhibit promising effects in test tube or animal studies.
- They possess properties that should, logically, help prevent cancer and heart disease.
- They abound in foods linked to reduced risk of cancer and heart disease, such as fruits, vegetables, and whole grains.
Editorial in JAMA decries reductionist approach to nutrients
Given the study designs, we were not very surprised by these negative findings, and neither was JAMA editorialist Peter Gann, MD, ScD, from the University of Illinois at Chicago.
Dr. Gann penned an accompanying editorial in JAMA in which he critiqued the reliability of randomized clinical trials for determining the value of food-borne nutrients taken as isolated supplements.
Gann made three important points:
- “…single-agent interventions, even in combinations, may be an ineffective approach to primary prevention in average-risk populations.
- “It may be time to give up the idea that the protective influence of diet on prostate cancer risk...can be emulated by isolated dietary molecules given alone or in combination to middle-aged and older men.
- “If it requires whole foods, extracts, or dietary patterns [to reduce disease risk], it may be necessary to give up the reductionist need to know which molecule is most responsible and perhaps give up the notion of placebo controls as well.”
Dr. Shao said that one reason for the “apparent conflict” between the new studies and previous studies that found positive effects could be due to effects of nutrients in the human body being complex and influenced by many variables:
- “Understanding the causality of chronic disease is equally complex. Randomized clinical trials (RCTs) may be inherently limited in their capacity to address the unique challenges presented by nutrients and dietary interventions. Nutrients appear to work best in combination with other nutrients, yet RCTs tend to examine effects of unique chemical molecules in isolation—which is how pharmaceuticals work.
- “Further, in using RCTs to study nutrition questions, there is the challenge of being able to create a true control or placebo group. For example, in contrast to pharmaceuticals, it is both impossible and unethical to ensure participants in the control group are not exposed at any level to vitamins and minerals.
- “Perhaps we need to revise our expectations that one single healthy habit will serve as a ‘magic bullet.’”
So is a study with one dose of one nutrient in a well-nourished population enough to conclude that selenium, vitamin E, and/or vitamin C are ineffective in reducing prostate cancer risk?
In other words, they’re comparing someone eating a good diet with someone with a good diet plus a little extra vitamin C.
And placebo group participants may also be taking supplements on the side.
This is exactly what happened a few years back in the Women’s Health Initiative study, which showed no differences between people in the calcium-plus-vitamin D group and the placebo group.
It turned out many of the participants in the placebo group were also taking calcium pills, many of which included vitamin D, which would explain why no difference was seen.
Finally, it can take 10 to 15 years or more for cancer or heart diseases to develop, and if study participants are free of the disease at its outset, we cannot conclude that a given nutrient is useless if we see no benefits after a few years of supplementation.
Vitamin C and E not linked to reduced heart or cancer risk
Harvard-affiliated scientists found that supplementation with vitamins C and E did not affect the risk of developing cancer or heart disease (Sesso HD et al. 2008).
This large-scale study involved 14,461 male doctors over 50 years of age who participated in the Physicians' Health Study II.
Participants received 400 international units (IU) of vitamin E or placebo every other day and 500 milligrams of vitamin C or placebo daily. The participants were followed for an average of eight years.
Vitamin C and vitamin E supplementation did not reduce the risk of cancer compared to placebo.
According to the authors, vitamin E did not have a significant effect on prostate cancer, and neither vitamin C nor E reduced the risk of cancer overall.
The authors also found that the incidence of heart attack, stroke, congestive heart failure and angina was similar among groups.
In addition, vitamin supplementation did not decrease the need for cardiac revascularization surgery to help restore blood flow to the heart.
Selenium supplements fail to prevent cancer of the prostate
This study comes soon after the failure of a major study testing the effects of vitamin E and selenium, taken alone or together, on preventing prostate cancer (Lippman SM et al.).
And results from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed that—no surprise—the supplements were ineffective at preventing prostate cancer in the short term.
The trial included 35,533 men, aged 55 years or older (50 years or older for African-American men) from the U.S., Canada, and Puerto Rico.
The participants were randomly assigned to receive one of four interventions between August 2001 and June 2004 for a planned minimum follow-up of seven years:
- Selenium (200 mcg/day; about four times the US RDA)
- Vitamin E (400 IU/day; the US RDA)
- Selenium + vitamin E
- Placebo pills
In addition, slightly more men who took vitamin E alone developed prostate cancer, and slightly more men who took selenium alone developed type 2 diabetes.
However, these negative results were not statistically significant, meaning they could be due to chance.
- Gann PH. Randomized Trials of Antioxidant Supplementation for Cancer Prevention: First Bias, Now Chance: Next, Cause. JAMA 2009, Volume 301, Issue 1, doi:10.1001/jama.2008.863
- Heaney ML, et al. Vitamin C Antagonizes the Cytotoxic Effects of Antineoplastic Drugs. Cancer Research 68, 8031-8038, October 1, 2008. Seventh Annual American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research.
- Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005 Jul 6;294(1):56-65.
- Pak RW, Lanteri VJ, Scheuch JR, et al. Review of vitamin E and selenium in the prevention of prostate cancer: implications of the selenium and vitamin E chemoprevention trial. Integr Cancer Ther. 2002 Dec;1(4):338-44.
- Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Glynn RJ, Gaziano JM. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2008 Nov 12;300(18):2123-33. Epub 2008 Nov 9.
- Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Glynn RJ, Gaziano JM. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2008 Nov 12;300(18):2123-33.
- Lippman SM, et al. Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2008 Dec 9. [Epub ahead of print