You say best, I say worst.
" They used the kind of Vitamin E (dl-alpha-tocopherol) and the dose (400 IU) that most men were taking. It is the kind of Vitamin E most available"
Most available in this case means cheapest and worthless. The most widely used magnesium is also cheap and worthless.
The SELECT trial used non-natural and chemically-derived vitamin E (dl-alpha tocopherol acetate) at a dose of 400 IU per day. Any time you see an “l” after the “d” in a vitamin E product throw it in the trash where it belongs. It has little or no antioxidant activity and is useless for human health – which was obvious long before the SELECT trial was started.
WHY SELECT FAILED: POTENTIAL REASONS
SELECT was initiated on the basis of reasonably strong evidence suggesting the potential efficacy of selenium and vitamin E in reducing the risk of PCa. Therefore, it is difficult to accept that vitamin E and/or selenium, when used smartly and appropriately, will be harmful rather than beneficial. We believe it is worth considering to try to explain the possible reasons why SELECT failed. A careful analysis of possible reasons may be useful for future studies in this direction. Below, we provide important reasons that could be useful in designing future studies.
First, the use of L-selenomethionine rather than high-selenium brewer’s yeast in SELECT was influenced by logistic factors, although the SELECT formulation was reasonably thought to be an adequate yeast surrogate. L-selenomethionine is only one of >20 selenium-containing species in brewer’s yeast (105). The oral doses or formulations required to deliver selenium metabolites to prostate cells in vivo have yet to be firmly established, and this may explain why SELECT did not duplicate the NPC results.
Second, the NPC study participants who clearly benefited from selenium administration had lower baseline selenium levels, but the relevance of this finding to SELECT is unclear. Of 51,529 men in the Health Professionals Follow-Up Study, an odds ratio of 0.35 for individuals in the highest versus the lowest toenail selenium concentration quintiles was found for risk of advanced PCa (106). It has been suggested that it might have been more beneficial to conduct a trial such as SELECT in a seleno-deficient region, to better replicate the conditions under which brewer’s yeast provided a benefit in NPC. However, a case-control study of 656 British men found no association between nail selenium concentration and PCa risk (107,108). These issues should be thoroughly considered for future studies.
Third, the higher dose of vitamin E used in SELECT did not match the dose of vitamin E used in the ATBC study. Referring to the NPC study on selenium, analysis of a higher-dose arm of the trial (400 μg rather than 200 μg) showed no increased PCa preventive effect (109). Therefore, in at least one case, increasing the dose of the study agent did not have an increased effect. As previously outlined, not all of the stereoisomers of vitamin E have the same biologic activity, and it is not known how administration of all-rac α-tocopherol may affect overall vitamin E bioactivity. Further, as discussed above, in recent preclinical studies, another formulation of vitamin E, γ-tocopherol, has been found to be effective. It is possible that high levels of supplemental vitamin E may reduce serum levels of γ-tocopherol, an effective agent.
It will be worthwhile to conduct well-designed preclinical studies to evaluate the different formulations of vitamin E, especially γ-tocopherol, for their possible PCa preventive effects. Then, on the basis of the outcome of these preclinical studies, a smaller clinical study should be undertaken.
Fourth, smoking status may also be important in considering the ATBC results, since in vitro studies have shown that cigarette smoke depletes α-tocopherol in human plasma (110). Analysis of the screening arm of the ongoing Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial showed a reduction in relative risk for both advanced and non-advanced PCa among current and former (within 10 years) smokers who supplemented their diets with vitamin E (111). The data indicate a statistically significant benefit associated with two factors: dose of at least 400 IU/d and adherence to supplementation for at least 10 years. These findings support the use of the approximately eight-fold higher dose in SELECT; however, as previously discussed, the biology of the tocopherols is incompletely understood, and the use of the higher dose in SELECT may have been a confounding factor, if the ATBC study was to be used as a preliminary study. Further, as discussed by Moyad (104), men with the highest serum levels of vitamin E had significantly lower testosterone, androstenedione, sex hormone–binding globulin and estrone levels. It is possible that vitamin E prevents PCa in smokers by lowering androgen levels. In this scenario, the smoker population will benefit most. This can be confirmed by a well-designed clinical trial in smokers.
Fifth, the ATBC study suggested obesity as a confounding factor, since the data from this trial demonstrated that the negative impact of extreme obesity was greater than the positive impact (32% decrease in risk) of taking the vitamin E supplement (104). Thus, obesity should also be taken into consideration when conducting future PCa trials.
That's worth a REPEAT...
SELECT was initiated on the basis of reasonably strong evidence suggesting the potential efficacy of selenium and vitamin E in reducing the risk of PCa. Therefore, it is difficult to accept that vitamin E and/or selenium, when used smartly and appropriately, will be harmful rather than beneficial.
Post Edited (bubbatc) : 7/25/2018 4:02:18 PM (GMT-6)