Are antioxidants worthless against heart disease?

Are antioxidants worthless against heart disease? By Neil E. Levin, CCN, DANLA 8/15/07 In a published report, A Randomized Factorial Trial of Vitamins C and E and Beta Carotene in the Secondary Prevention of Cardiovascular Events in Women (Results From the Women’s Antioxidant Cardiovascular Study), researchers concluded that, “There were no overall effects of ascorbic acid (vitamin C), vitamin E, or beta carotene on cardiovascular events among women at high risk for CVD.” (1) This is simply untrue. In order to reach that conclusion, the researchers had to count non-compliant subjects as taking vitamin E, even when it was obvious that they weren’t following the study protocol. Is that intellectually honest? I would have given the opposite conclusion. When subjects assigned to take vitamin E actually took their vitamin E, the results were significant and proved that the vitamin had benefits: “Censoring participants on noncompliance led to a significant 13% reduction in the primary end point…Reductions in secondary study end points were also stronger, with a 22% reduction in MI … a 27% reduction in stroke … and a 9% reduction in CVD mortality … There was a 23% reduction in the combination of MI, stroke, or CVD death…Among those with prior CVD, the active vitamin E group experienced fewer major CVD events …” [-11%] "A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior cardiovascular disease (RR, 0.89; 95% CI, 0.79 - 1.00 [P = .04]; P value for interaction = .07). There were no significant interactions between agents for the primary end point, but those randomized to both active vitamins C and E experienced fewer strokes (P value for interaction = .03)." Why did the researchers gloss over these admitted benefits (that those assigned to take vitamin E who actually did take it had "significant" benefitsand those with prior CVD who took the relatively low levels of C plus E experience fewer strokes)? This was wholly ignored in the study's conclusion, as well as the subsequent press release and extensive news coverage. I have found and published (2) criticisms of this particular failing (reaching improper conclusions not truly supported by the data) before: (3-10) REFERENCES: 1. Cook N, et al. A Randomized Factorial Trial of Vitamins C and E and Beta Carotene in the Secondary Prevention of Cardiovascular Events in Women. ARCH INTERN MED. VOL 167 (NO. 15), AUG 13/27, 2007 2. Levin N. Land of Confusion: How Poor Science and Misleading Media Coverage Create Public Confusion About How Dietary Supplements Affect Health. J App Nutr, Vol 55, No. 1, 2005 8-15 3. Edgar R. Miller, III, MD, PhD; et al. High-dose vitamin E supplementation may increase all-cause mortality, a dose response meta-analysis of randomized trials. Annals of Internal Medicine: Online: Nov. 10, 2004: Print: 4 January 2005 | Volume 142 Issue 1 4. A study conducted by USA Today found that more than half of the experts hired to advise the government on the safety and effectiveness of medicine had a direct financial interest in the drug or topic they were asked to evaluate. An analysis of financial conflicts of interest at 159 FDA advisory committee meetings from January 1, 1998, through June 30, 2000, found that at 92% of the meetings, at least one member had a financial conflict of interest, while at 55% of meetings, half or more of the FDA advisers had conflicts of interest. These conflicts included helping a pharmaceutical company develop a medicine, then serving on an FDA advisory committee that judges the drug. 5. Lonn E, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005 Mar 16;293(11):1338–47. PMID: 15769967 6. Blumenthal M, Farnsworth NR. Echinacea angustifolia rhinovirus infections [letter]. N Engl J Med. Nov.3, 2005;353(18):1971–1972. 7. 21 C.F.R. Pt. 119, Final Rule Declaring Dietary Supplements Containing Ephedrine Alkaloids Adulterated Because They Present an Unreasonable Risk (Published February 11, 2004) (Effective April 12, 2004) available at http://www.fda.gov/ohrms/dockets/98fr/1995n-0304-nfr0001.pdf 8. Taylor JA, Weber W, Standish L, Quinn H, Goesling J, McGann M, Calabrese C. Efficacy and safety of Echinacea in treating upper respiratory tract infections in children: A randomized controlled trial. J Amer Med Assn Dec 3, 2003;290(21):2824–30. 9. Fugh-Berman A, Myers A. Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research. Exp Biol Med (Maywood). 2004 Sep;229(8):698–704. Review. PMID: 15337824 10. Effects of Long-term Vitamin E Supplementation on Cardiovascular Events and Cancer. JAMA. Vol. 293 No. 11, Vol. 293 No. 11, March 16, 2005

Selenium and Antioxidant Safety

My letter criticizing their editorial in Annals of Internal Medicine was accepted and published online by that journal: http://www.annals.org/cgi/eletters/0000605-200708210-00177v1#21702 It is unfortunate that synergistic nutrients are tested individually, like drugs. This is a pharmaceutical practice, not human nutrition, and shouldn’t imply that comprehensive mixtures of nutrients (like a multivitamin) would have the same effects. I dispute that “randomized, controlled clinical trials have shown that ß-carotene and vitamin E supplements, which were widely believed to be safe, increase mortality and morbidity”. The choices, increasing variables, and manipulation by statistical models in meta-analyses are often questionable. In this report, prediabetic symptoms were not even considered as a variable. Buijsse noted that high carotenoid intake, confirmed by measures of blood levels, was associated with lower mortality rates among the elderly over a ten-year period, countering the claim that ß-carotene dangers are proven. The Miller meta-analysis, cited as proof of vitamin E’s dangers, was heavily criticized in published responses, and its conclusions were NOT replicated when the same data was re-analyzed (Hathcock). It should therefore not be cited as proof of the vitamin’s danger. Another meta-analysis cited (Bjelakovic) reported that antioxidant vitamins may increase death rates. But the authors did not determine a dose-dependent or cause-and-effect relationship between antioxidants and deaths (from all causes) of study participants. The researchers pooled 68 published trials, excluding 405 published studies with no deaths reported. Too wide a range of potencies (Vitamin A 1333 IU - 200,000 IU, vitamin E 10 IU to 1000 IU), and durations (28 days to 12 years) were lumped together. The statement, “No dietary supplement, including selenium, has proven useful so far for the prevention of cardiovascular disease or cancer in the general U.S. population,” is questionable. The Alpha-Tocopherol, Beta- Carotene Cancer Prevention (ATBC) Study published by the National Cancer Institute demonstrated a 32% reduction in prostate cancer incidence in response to daily alpha-tocopherol supplementation. The Women’s Health Study (JAMA) reported a significant 24% reduction in cardiovascular death with supplemental vitamin E. The NIH reports, “Taking a daily supplement containing 200 μg of selenium … significantly reduced the occurrence and death from total cancers. The incidence of prostate cancer, colorectal cancer, and lung cancer was notably lower in the group given selenium supplements.” Yet you suggest lowering consumption below the Daily Value (70 μg) used in multivitamins and far below the current upper limit. On the contrary, the Lewin Group reports that the use of antioxidants could save the vision and independence of many senior citizens, saving billions of dollars in healthcare costs. REFERENCES: Bjelakovic G, et.al. Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis. JAMA 2007. 297(8):842-857 Buijsse B, et al. Plasma carotene and alpha-tocopherol in relation to 10-y all-cause and cause-specific mortality in European elderly: The Survey in Europe on Nutrition and the Elderly, a Concerted Action (SENECA). Am J Clin Nutr 2005;82:879–886. DaVanzo JE, et al. An Evidence-Based Study of the Role of Dietary Supplements in Helping Seniors Maintain their Independence. The Lewin Group Inc. January 20, 2006 Hathcock JN, et al. Vitamins E and C are safe across a broad range of intakes. Am J Clin Nutr. 2005 Apr;81(4):736-45. Review. PMID: 15817846 Weinstein SJ, et al. Serum α -Tocopherol and γ-Tocopherol in Relation to Prostate Cancer Risk in a Prospective Study. J. Natl. Cancer Inst. 2005 97: 396-399; doi:10.1093/jnci/dji045

LAND OF CONFUSION: How Poor Science and Misleading Media Coverage Create Public Confusion About How Dietary Supplements Affect Health

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