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      SELENIUM and CANCER

Abstract:  The long term use of a daily 100 mg supplement of selenium for a duration of 20 or more years can reduce risk of most types of cancer by nearly 40%.  This is an average benefit. confirmed from 62 of of 67  primary and secondary research study comparisons found.  An exception may be for women during their pre-menopausal years, and when most of selenium's potential benefit may be provided by other antioxidants.  Because selenium also can reduce risk of cardiovascular diseases, health-interested persons should consider taking a daily 100 mg supplement of selenium as a potentially important part of their program of health care.

See other papers of antioxidants and CV disease for Vitamin E;  Vitamin A;  Vitamin C; and selenium , papers of antioxidants and cancer for Vitamin E;  Vitamin A;  Vitamin C; and Antioxidants, Death from All Causes and Antioxidants, a Global Analysis.

Selenium Can Reduce the Risk of Cancer:  The Health Establishment has invested billions of dollars into the so-called war on Cancer.  Yet except for the benefits from a decline in cigarette smoking, very little other real reduction in this hated disease has been accomplished.  Yet there is a simple pill that taken everyday by every adult might eventually drop cancer rates of all kinds of cancer by 40%  This is not some wild speculation in a health advertisement for some dubious potion.  It is a summarized result from 67 research comparisons in 45 different research studies - all of those found published to 2008 that were useful for analysis.

This best kept of health 'Secrets' is that risk of cancer can often be reduced 40% by taking of a simple 100 mg  pill of selenium each day.  There are two important caveats, however.  First, the reduction in cancer probably will not take place immediately.  It will take 10 years of selenium supplement taking for a benefit to become clearly visible, and 20 years for full benefit to be achieved.  Second, if you are taking plenty of other antioxidants, the addition of selenium may not improve your benefit further.

Levels of cancer incidence in various geographical areas are related to selenium levels in local crops.  Thus selenium long has been considered as a possible anti-cancer agent. The extensive Medline data base of medical research articles includes more than 2,000 different mostly biochemical type studies relating selenium to cancer.  Table S appended provides the actual results of all useful studies found that related risk to populations intake or level of selenium. .  This research differs from that conducted for most other vitamins and minerals because most measured risks of cancer were related selenium in blood or in toenails.  But inportant clinical studies confirmed benefits for taking either selenium or other antioxidant supplements.

Results of Research on Selenium and Cancer:  Table A summarizes the results of 67 comparisons of selenium and cancer risk in the 45 studies listed in Table S.  This provides perhaps a most impressive verification of the health benefit of any of the antioxidants.  62 of 67 measured risk ratios or 92% showed selenium to have a benefit.  A majority of these research comparisons were individually significant to 95% or higher.  Results for each type of cancer showed benefits, with only breast cancer having  a possibly lower potential benefit than the 0.60 or 40% average reduction in risk.  Most of the values were obtained from blood measurements that should be more accurate basis for risk measurement than dietary intakes that are subject to problems of measurement and compliance. The average risk value of 0.60 should have 5% to 95% limits of about 0.51 to 0.69, an average of extremely high significance

                                  Table A     

                  Selenium and Risk of Cancer

Of particular interest are the results of clinical studies that unlike those of other antioxidant risks mostly show a benefit.  This  important study of diet by Clark represented by comparisons P2, CA1 and CL2  in Table S was a randomized clinical study of the use of 200 mg selenium supplements administered for 4.5 years and followed up for 1.9 more years. The study included about 1300 patients all of whom had suffered skin cancer but no other cancer. Thus the studied groups presumably had the start an above average risk of cancer per se.  Selenium had no effect on recurrence rate of skin cancers.  But use of the 200 mg supplements substantially slowed the development of other and much more serious types of cancer.  The risk ratio for selenium users vs. non-users for all types of internal cancer was 0.50 (range=0.31-0.90) for all kinds cancer mortality.  For specific types of cancer for which an adequate numbers of events were available the risks were 0.54 (0.30-0.98) for lung cancer, and 0.37 (0.18-0.71) for prostate cancer.  The number of cancer deaths in the selenium supplemented group were only half of those in the placebo group.  These are very large, consistent, and highly significant reductions in risk. 

The Clark study results are of particular interest because they were obtained mostly over the short mean or average time to event of only about 4.5 years. Other clinical studies of antioxidants and cancer for this time period usually could not find any effect because the biochemical processes involved operate over very long time periods.  It seems likely that the selected populations that had skin cancer were able to develop other cancers without the usual long time lag usually needed for measurement of a cancer risk.  If an average population had been used, it seems unlikely that the selenium would benefit risk of cancer within this short time period.  However, it remains possible that selenium might protect via some other mechanism that can provide a direct anti-cancer effect in short time. Another clinical study called SU.VI.MAX also found a useful benefit for prostate cancers for men having normal levels of PSA, but this was for an excessive  and probably overkill combination of antioxidants.

The principal 'non-confirming' research on selenium is that from the large Women's Health study on  about 63,000 nurses. Selenium was measured by amounts in toenails that have been fairly well correlated with amounts of selenium in blood. Results of this study are noted for Hunter for breast cancer and Garland for other types of cancer.  No benefit for selenium for either breast or other cancers was found, and these results are clearly statistically inconsistent with the well confirmed and highly significant results of other research.  The question here is "Why are these results on the Nurses so different?   Four possibilities emerge. First, are the results based on toenail measurements useful?  Second, did the nurses as a selected population use much more other antioxidants in diet and supplements than usual?  Third, is there a difference for the effect of selenium on women vs. men?  and fourth, this population involved mostly pre-menopausal women whereas other studies involved older women.  Did the estrogen rich environment of the mostly pre-menopausal women in this study remove the potential benefit of antioxidants?  A possible involvement of more than one or even all of these theories could contribute to the difference in results which appears well established.

Other study results found no difference between the effect of selenium on men vs. women.  Other studies did find the usually measured effect when using the toenails basis.  But the risk reduction from adding selenium to an average diet obtained by the Nurses probably was reduced by their use of their more healthful diet than average diet.  An average amount of Vitamins C, E, and Beta Carotene in the Nurse's diet was significantly higher than that in the US average diet. A Life Ahead computation of the expected advantage for adding a daily 100 mg of selenium to a diet that matched the Vitamin C, E, and Beta carotene cited in the Nurses diet produced an expected risk ratio for all cancer of only 0.87.  Thus this becomes a likely part reason for the different result in the Nurses study.

The fourth above theory - that pre-menopausal women may not obtain much if any reduction of cancer from antioxidants also appears as a very likely possibility.  Estrogen provides an added antioxidant environment.  Study #11 that found a 0.50 risk ratio for women was done entirely on post-menopausal women, and most women in the Clark study of average age 63 were post-menopausal. Study CA2 found a large benefit for men that for women.  Other research appears to have been done on all or mostly post-menopausal women.  This mechanism also is further confirmed by negative results from the Women's Health study for vitamins and cancer, and is discussed further there and for the Life Ahead antioxidant model.  The Nurses study on cancer and Vitamin E did find a 10% lesser reduction in cancer risk for pre-menopausal than for  post-menopausal women.  A combination of the higher antioxidants in their diets and fraction of pre-menopausal women involved thus could explain easily much of the difference in result for the Nurses vs. that from all other populations researched.  This problem should be studied further because the long range potential for reducing cancer on our population with selenium based on other research to date is enormous. 

The general formula adopted to develop likely long term use of selenium in reducing cancer is:

Risk ratio RR of selenium for cancer where  amt  is amount in diet in mg/day and  yrs  is yrs of duration of use is

          RR pr year of duration = exp( -0.00215 * yrs * amt^0.5)

This formula that is similar to the one for selenium and cardiovascular disease produces an approximation of most results in Table S that follow.  Values for risk from this formula are:

                                           Table A

                                  Risk of Cancer vs

                  Amount and Duration of use of Selenium

Life Ahead provides a conservative valuation of the benefits of selenium in reducing risk of cancer.  A maximum of 100 mg/day is accepted for computed benefit from supplements, and no effect of selenium or other anti-oxidant supplements on cancer is computed for women during their pre-menopausal years. Thus computed benefits for women below about age 60 may be minimal. The antioxidant model also shows that if adequate amounts of Vitamin E, C, and A are present, no further advantage will be computed for use of selenium.  The program suggests an addition of 100 mg to a usual dietary amount of 90 mg/day, or a target value for best health of 190 mg/day.  The RDA for selenium is cited as 70 mg/day, but it is not clear just what this was based on.  This value is much too low for best protection against either heart disease or cancer. And it remains possible that larger amounts of selenium supplement - at least to 200 mg/day - might provide further benefit.

Highest sources of selenium in foods are in junk foods, meats, chicken, fish and nuts, especially peanuts.  A listing of selenium values for foods in order of amount can be viewed from the Life Ahead food library option in the sort menu display for any diet entry.  Some fast foods are high in selenium but poor in other nutrients.  But an ounce per day of selenium rich nuts can supply the needed amount, and nuts have been confirmed independently to reduce risk of cardiovascular diseases. But taking a selenium supplement of at least 100 mg/day would appear to be a useful action for any health-interested person.  Its advantage for coronary disease appears likely for both men and women, there is a large  indicated reduction in cancer risk for men, and there is a probable a benefit in reducing cancer risk for post-menopausal women.  Although Life Ahead now credits Well-Days only for up to 100 mg. of added selenium,  further benefits from up to 200 mg are quite possible, and no adverse problems have been found for use of 200 mg/day f selenium. 

The present Life Ahead basis assumes that selenium may act mostly as another antioxidant and in combination with the other vitamin antioxidants may be too conservative.  The very large reductions in risk noted for combinations of selenium and Vitamin E - even if far from adequately confirmed - suggest that selenium may operate to benefit risk of cancer in part by some alternate mechanism.  Thus at this time it seems prudent for a health-interested person to take a 100 mg supplement of selenium each day even if sufficient other antioxidants are available to produce minimum risk via the present Life ahead method.

A widespread dogma in health research is that a clinical study is best for verifying the effect of a population lifestyle. Although a clinical study is clearly best for test value of a new drug, it is not a useful method for identying the value of a population lifestyle such as use of an antioxidant that develops risk for multiple nutrients over long periods of time.  It seems unlikely that another clinical study will be useful for a best conclusion about selenium use. The resolution power of practical clinical studies is much to low to identify risks usefully for the type of value a clinical study can be expected to produce within 10 or fewer years.   See more on this.  A more accurate scientific analysis of relationships between blood values, diet, and a better understanding of today's extensive published results from multiple antioxidants should be far more meaningful.

Results from Table S include the actual results of all useful research studies found published on selenium and cardiovascular disease.  The key result of these studies is the risk ratio or RR produced from each study.  A best test of benefit is to view how the RR values vary.  Values below unity show a benefit.  Those of 1.0 or higher show no or a negative benefit.   If most studies show a beneficial value, the confirms strongly that the nutrient is producing a benefit   If RR values are mixed with a similar number positive and negative, this suggests no benefit is being found.  This table may provide a first convenient listing of results from this research because it eliminates the highly confusing and scientifically invalid practice in health research of comparing results in each study with a 95% statistical value of significance.  Many studies in Table S do not have the resolution power to develop this 95% level of significance, and a common practice of calling all such results as "no effect found" is not valid and produces continuing confusion.  Combined results from multiple studies can produce values of very high significance even though individual values have a lesser than 95% significance. If both values of the error range of a comparisons are below 1.0, it is likely that a tis individual result is significant to the 95% level.  Most values in Table S, however, are confirmed at higher than the 95% of significance target.

                                                                                        Table S

                                                        Selenium and Risk of Cancer