“Natural” Cancer Prevention

Science  28 Jun 1996:
Vol. 272, Issue 5270, pp. 1857f-1861f
DOI: 10.1126/science.272.5270.1857f

I would like to comment on the News & Comment article “‘Natural’ cancer prevention trial halted” by Kim Peterson (26 Jan., p. 441), in which it is implied that there is “less anomalous” toxicity for beta carotene because of the findings of the Beta Carotene and Retinol Efficacy Trial (CARET) study (1) and the earlier Alpha-Tocopherol, Beta Carotene (ATBC) study (2) of smokers.

Albanes (the principal investigator in the ATBC study) made presentations at antioxidant meetings in Berlin (fall 1994) to that effect that the increased incidence of lung cancer in the beta carotene cohort occurred only in smokers who were also heavy alcohol abusers. In other words, the smokers on beta carotene who were not heavy drinkers did not have increased lung cancer. No harm occurred, but no benefit could be expected, because beta carotene is not a suitable therapy for thwarting the consequences of heavy smoking. A similar co-morbidity occurred in the CARET study, where vitamin A (conservatively estimated at 50,000 international units per day for 4 years, because the conversion of beta carotene to vitamin A is likely enhanced in the presence of vitamin A) was found to be toxic and to induce liver pathology not unlike that of alcohol damage.

The scientific literature (3) and the 1980 and 1989 U.S. Recommended Dietary Allowances make it clear that 50,000 international units of retinol per day for months is unwise and leads to vitamin A toxicity. Beta carotene has a record of safety in humans who have ingested large doses (150 to 300 milligrams per day) over 15 years to control the symptoms of the genetic disease erythropoietic protoporphyria. Ironically, in developing nations, vitamin A deficiency is a major problem in spite of carotenes in food (4).

There is a likelihood that autopsy materials are available for some of the subjects in the ATBC and CARET trials, and the funding agency would be remiss if at least the liver tissues were not examined. Fur- ther, no clinical trials of these costly dimensions should be designed without peer review by experts in the biochemistry and toxicity of the agents under test.


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