The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Looks at Prostate and Stomach Cancers

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The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Looks at Prostate and Stomach Cancers

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) is one of the randomized double-blinded reports of a few years ago finding synthetic beta-carotene in smokers led to an increased risk of lung cancer compared to placebo.(1) It's also the report that studied the effects of vitamin E at a remarkably low dose -- 50 IU per day.

The data from that trial have now been reanalyzed, focusing on 246 cases and 62 deaths from prostate cancer that developed during follow-up (median of 6.1 years) of the over 29,000 middle-aged male smokers in the study.(2) The results are both complex and startling.

Those randomized to low-dose vitamin E (d-alpha tocopherol) alone showed a 36% decreased incidence (95% CI = -56% to -6%) and 41% decreased mortality (95% CI = -65% to -1%) for prostate cancer. When only stages II-IV were looked at, the decrease in incidence was 40%. Recall that selenium which, through glutathione peroxidase, functions similarly to vitamin E, has also been found in a double-blinded trial to dramatically reduce incidence and mortality of prostate cancer, and that the numbers were also more impressive with higher stage (and therefore more life-threatening) disease.(3)

However, in sync with the increased lung cancer incidence in male smokers previously reported by this and other research groups, synthetic beta-carotene (33,333IU/d) taken alone correlated with an increased risk of prostate cancer incidence though this increase was not statistically significant (RR 1.20, 95% CI = -13% to +66%). When only stages II to IV were studied, the increased risk caused by synthetic beta-carotene did achieve statistical significance (RR = 1.35, 95% CI = 1% to 80%). Mortality from prostate cancer also increased in the carotene group, though this increase was not statistically significant (RR=1.15, 95% CI= -30% to +89%). Taking the low-dose vitamin E with synthetic beta-carotene wiped out the apparent harmful effect of the synthetic beta-carotene.

These data seem to provide yet another nail in the coffin of synthetic beta-carotene. Also, the dramatic protective effects reported here with vitamin E even at 50 IU per day, and elsewhere with selenium at only 200 mcg per day, strongly suggest that future research needs to focus on the effects of these two nutrients in protecting men from prostate cancer. In the meantime, supplementing both sounds like a reasonable response to the published data, at least to this writer. Finally, studies using beta-carotene need to examine the effects of the natural product because, as previously reviewed in this column, data exist from both China and Israel suggesting that natural beta-carotene (containing some of the 9-cis isomer not present in the synthetic) may help protect even when the synthetic all-trans molecule fares no better or even worse than placebo.

Yet, in the fine print of this trial, the plot thickens. When alcohol intake was considered, the damaging effects of synthetic beta-carotene were found only in drinkers. In fact, men supplementing synthetic beta-carotene and not drinking any alcohol actually had a 32% decreased risk of prostate cancer, while the upper three tertiles of alcohol intake were associated with increases of 25%, 42%, and 40% respectively despite the fact that this apparently damaging interaction did not reach statistical significance. An accompanying editorial reminds us that others have also found a link between synthetic beta-carotene supplementation, alcohol intake, and trouble.(4)

In another recent report from the same study, 2,132 middle-aged smoking men with low serum pepsinogen levels (indicative of atrophic gastritis, and therefore of potentially higher risk for stomach cancer) were identified.(5) With an average of 5.1 years of supplementation of the same doses of synthetic beta-carotene and alpha-tocopherol, those randomly assigned to vitamin E had the same risk of stomach cancer as those receiving placebo (RR = 0.98), and although it did not reach statistical significance, again the beta-carotene showed a small increase in risk (RR=1.13, 95% CI, 0.65-1.95). Thus the protective effect of vitamin E on prostate cancer risk did not appear to extend to stomach cancer risk.

(1) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group. N Engl J Med 1994; 330:1029-35.

(2) Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998; 90:440-6.

(3) Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. JAMA 1997; 276:1957-63.

(4) Olson KB, Pienta KJ. Vitamin A and E; Further clues for prostate cancer prevention. J Natl Cancer Inst 1998; 90:414-5 [editorial].

(5) Varis K, Taylor PR, Sipponen P, et al. Gastric cancer and premalignant lesions in atrophic gastritis: a controlled trial on the effect of supplementation with alpha-tocopherol and beta-carotene. Scand J Gastroenterol 1998; 33:294-300.

Natural Product Research Consultants, Inc.

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By Steve Austin

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