COMMENTS ON THE 1994 FINNISH ANTIOXIDANT AND LUNG CANCER STUDY (Heinonen OP et al. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. New England J of Med 330:1029-1035, 1994.) The report of the study in Finland of Vitamin E and beta carotene on the incidence of cancer in male smokers is important, not because of its scientific value, but for the way it was treated in the national press. The news media headlines carried the grim message - vitamins may increase cancer (1). This is the message that many of my patients received, and for the next few days I received anxious calls even though my patients are much more sophisticated about vitamins than are the average individuals. They wanted reassurance that it was safe to continue with their Vitamin C, or Vitamin E and beta carotene. The media did not distinguish between the vitamins. There is a tendency in the public (including physicians) to have a global view of vitamins. If there is bad news about one, it means it is bad for them all. The vitamin critics were given one more opportunity to blast the use of vitamins, and to return to their ancient position that only food was safe and no one needed added vitamins. But this is not what the dozens of authors of this study concluded. They found that these two antioxidants did not decrease the incidence of lung cancer, and because there was an increase in risk in the treated group suggested the possibility that it might increase it. It is therefore very important to know exactly what this study did. They used a large population of male smokers ages 50 to 69. One group was given the synthetic dl-alpha tocopherol (vitamin E) equivalent to 50 mg of d-alpha tocopherol. (There is 12.5 percent d alpha tocopherol in the synthetic mixture of 8 tocopherols.) This means that the total amount of tocopherols includes the levo- form which the body cannot use, and other isomers not nearly as active as d alpha. What is the effect of giving this mixture? For many years, orthomolecular physicians have recognized that "trans" (synthetic) fatty acids are harmful. These are present in hydrogenated fats like margarine. The question is whether levo-tocopherols, present in four times greater amounts, are also harmful. Another group was given 20 mg of beta carotene, a third group was on placebo, and the fourth group received both antioxidants. All the subjects smoked 5 or more cigarettes daily, mean 20 for over 35 years. They were followed for 5 to 8 years. But the beta-carotene group smoked one year more than the no-beta-carotene group, a difference of 3 percent. How significant is one year more of heavy smoking in increasing the number of advanced lung cancers? The authors do not discuss this. Smokers have lower vitamin C blood levels. Their vitamin E blood levels are within the normal range but washings from their lungs show they also are 30% lower in vitamin E. What is the effect on beta carotene? At the end of the study, the men in the placebo group with the highest blood levels of these two antioxidants had the lowest incidence of lung cancer. In the dl-alpha tocopherol group there was a insignificant 2% reduction in incidence of lung cancer (P = 0.8). We do not know what the effect would have been if all the tocopherol had been d alpha tocopherol, the natural form. In the beta carotene group there was an "18% increase" in incidence. Out of 14,560 men on beta carotene, 474 developed cancer, while out of 14,573 men not on beta carotene 402 did. The incidence increased from 2.76% for the control group to 3.26% for the treated group. I suggest that this minor difference is surely not of clinical significance, even though it is statistically significant. In this statistically sophisticated study, comparing 3.26 to 2.76 yields the much larger number of 18 percent, which appears enormous and will be the only figure the unwary reader will remember and probably the only figure which will be used by the popular press. With large sample sizes such as these, a minor variation becomes fully blown up to a major finding. An inspection of Figures 2 and 3 will immediately show that none of the findings with every one of the cancers they examined showed any significant difference. But large scale studies have a tendency to show statistical significance which too many people equate with clinical or practical significance. There must have been something very odd about that Finnish group of men. For one thing, the authors reported that 34% of the men (on a mere 20 mg of beta carotene daily) developed yellow skin. This is totally foreign to my experience. I have started at least 500 subjects on this amount of beta carotene and more, and have never seen any yellowing of the skin with this dose but have seen some with higher doses. Does this mean that these heavy smokers had so compromised their livers that they could not deal even with normal doses of beta carotene? I will not say much about the minor doses of the synthetic alpha tocopherol. I consider the 50 mg dose equivalent of d-alpha tocopherol to be virtually a homeopathic one when it come to preventing and treating cancer. The authors do point out the many possible factors which might have given them these results, and in an editorial in the same issue, the commentators also refer to them. These authors write, "Finally, study findings regarded as showing supplementation to be beneficial or harmful may occur by chance" when referring to the literature. But both in the original paper and in the commentary they still draw the hasty conclusion that these antioxidants might increase the incidence of cancer. There is one comment they did not make, which is simply that if you run statistical trials you can expect that every now and then they will yield spurious results, as did the original double blind controlled studies which showed that l-dopa did not help patients with Parkinsonism, and more recently a large scale study which showed that folic acid did not prevent spina bifida. These last two studies were properly dismissed as anomalous. Finally I wish to make clear the significance of the words "may" or "might." For example, one person claims that vitamin C "may" cause kidney stones. He never has written that it will nor has he given any probability statistics. Since there are no reported cases proving an association between consumption of vitamin C and kidney stones from the millions of people routinely taking large doses of this vitamin for decades, the probability is infinitesimally small. One can say that vitamin C "may" cause kidney stones but that the probability that it will do so is zero or close to it. However the claimants, that vitamin C may cause stones, always leave out the second part of the statement and by so doing perpetrate lies and misinform the public. I consider that this study simply proved nothing, except that if you give tiny doses of Vitamin E nothing will happen, and if you give heavy chronic smokers 20 mg of beta carotene their incidence of lung cancer will not change. I suspect that the authors of this study were disappointed with the negative results they eventually saw and tried to salvage something so that the paper could be published. Or else it might have made it easier to have it published by the New England Journal of Medicine, which traditionally finds it easier to publish negative reports when large doses of vitamins are used. Cancer is probably present and undetectable in patients for a long time, perhaps several years, before it is finally discovered. The truly preventive study should therefor start long before any tumors have started, which could mean many years. With this group of heavy smokers it is certain that a large fraction already had the cancer. This was therefor a mixed study: (1) treatment for those already with cancer, (2) prevention for those who did not have any. Unfortunately, it will never be possible to say how much each group contributed. I would suggest that future studies start with a much younger population in whom there is much less chance of already having cancer. (1) "Vitamin Supplements are Seen as No Guard Against Diseases" and "Study Sees No Benefit in Vitamins on Cancer or Heart Disease". New York Times, April 14, 1994. By Abram Hoffer, MD Orthomolecular Medicine, 6/03 Thanks to doctoryourself.com Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.