Vitamins C and E and Beta Carotene Supplementation and Cancer Risk: A Randomized Controlled Trial

Abstract

Background: Observational studies suggested that a diet high in fruits and vegetables, both of which are rich with antioxidants, may prevent cancer development. However, findings from randomized trials of the association between antioxidant use and cancer risk have been mostly negative. Methods: From 8171 women who were randomly assigned in the Women's Antioxidant Cardiovascular Study, a double-blind, placebo-controlled 2×2×2 factorial trial of vitamin C (500 mg of ascorbic acid daily), natural-source vitamin E (600 IU of α-tocopherol every other day), and beta-carotene (50 mg every other day), 7627 women who were free of cancer before random assignment were selected for this study. Diagnoses and deaths from cancer at a specific site were confirmed by use of hospital reports and the National Death Index. Cox proportional hazards regression models were used to assess hazard ratios (represented as relative risks [RRs]) of common cancers associated with use of antioxidants, either individually or in combination. Subgroup analyses were conducted to determine if duration of use modified the association of supplement use with cancer risk. All statistical tests were two-sided. Results: During an average 9.4 years of treatment, 624 women developed incident invasive cancer and 176 women died from cancer. There were no statistically significant effects of use of any antioxidant on total cancer incidence. Compared with the placebo group, the RRs were 1.11 (95% confidence interval [CI] = 0.95 to 1.30) in the vitamin C group, 0.93 (95% CI = 0.79 to 1.09) in the vitamin E group, and 1.00 (95% CI = 0.85 to 1.17) in the beta-carotene group. Similarly, no effects of these antioxidants were observed on cancer mortality. Compared with the placebo group, the RRs were 1.28 (95% CI = 0.95 to 1.73) in the vitamin C group, 0.87 (95% CI =0.65 to 1.17) in the vitamin E group, and 0.84 (95% CI =0.62 to 1.13) in the beta-carotene group. Duration and combined use of the three antioxidants also had no effect on cancer incidence and cancer death. Conclusions: Supplementation with vitamins C, vitamin E, or beta-carotene offers no overall benefits in the primary prevention of total cancer incidence or cancer mortality.

Oxidative Shielding or Oxidative Stress?

“…Vitamin E supplementation, alone or in combination with ␤-carotene, was shown to increase the risk of lung cancer in smokers (The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group, 1994). Vitamin C supplementation was found to double the risk of cancer death in nonobese women [relative risk (RR) ϭ 2.0; 95% CI ϭ 1.12-3.58], while having no effect in obese women (Lin et al, 2009). The SELECT clinical trial of vitamin E and selenium was terminated early because of an apparent increase in the risk of new onset diabetes in the selenium group and a 1.6-fold increased risk in prostate cancer in the vitamin E group (Lippman et al, 2009;Klein et al, 2011).…”

Chemoprevention of colorectal cancer: systematic review and economic evaluation

“…109,113,114,116,118,122,125,127,130,133,134,137,140,142 Six studies were based in the USA 113,118,122,127,137,142 and two were international studies.…”

Reconvene and Reconnect the Antioxidant Hypothesis in Human Health and Disease

“…In summary, by the turn of the century, the undue fear for OS injury in human health started waning and the appreciation for their contribution in cellular physiology began growing [10, 37-41, 44, 45, 140]. Obviously, an opposite view became progressively louder for AO [52,53,56,133,[141][142][143][144].…”