I came across this 3 days ago:
"Vitamin E causes prostate cancer."
Yes, it was in bold letters.
From Wikipedia, we quickly learn that there are 8 vitamin E variations - 4 tocopherols & 4 tocotrienols. Fat soluble, so more bioavailable in a meal containing fat. & deficiency is rare. [1]
Vitamin E was discovered less than 100 years ago. As a vitamin, it cannot be manufactured in the body & must be present in the diet. It is an antioxidant and an immunomodulator.
Data from the HPFS [Health Professionals Follow-up Study] shows that 52% used a supplement in 1998, but this had dropped to 24.5% by 2006 [2]. It was over-hyped in the past & the SELECT study (2011 paper [3]) would not have helped.
The SELECT intervention study.
The Selenium and Vitamin E Cancer Prevention Trial [SELECT] enrolled 35,000 men between 2001 & 2004. It cost $114 million. In terms of execution, it can hardly be faulted, but the hypothesis that 200 μg/day L-selenomethionine &/or 400 IU/d of all rac-α-tocopheryl acetate might prevent PCa in the North American population was deeply flawed.
In 2002, Mark Moyad sounded a warning [4] in Selenium and Vitamin E Supplements for Prostate Cancer: Evidence or Embellishment?:
"Selenium supplements {provide} a benefit only for those individuals who {have} lower levels of baseline plasma selenium. Other subjects, with normal or higher levels, {do} not benefit and may have an increased risk for prostate cancer."
The U.S./Canadian populations are well-nourished in terms of selenium, since domestic wheat is grown in selenium-rich soil. In contrast, European bread is a poor source of selenium, as is almost all European food. If the selenium arm of the study had occurred in Britain, say, the results would have been much different IMO. Why? Because deficiency & insufficiency is common - but also, high-dose supplementation is rare.
Moyad again:
"In 4 recent prospective studies, vitamin E was found to reduce the risk of prostate cancer in past/recent and current smokers and those with low levels of this vitamin. Vitamin E supplements in higher doses (> or =100 IU) were also associated with a higher risk of aggressive or fatal prostate cancer in nonsmokers from a past prospective study. The dose of vitamin E in the SELECT trial (400 IU/day) is 8 times higher than what has been suggested to be effective (50 IU/day) by the largest randomized prospective trial in which the incidence rate of prostate cancer was used as an endpoint. Recent research also suggests that dietary vitamin E may be associated with a lower risk of prostate cancer than the vitamin E supplement."
Moyad is essentially pointing out that, sure, selenium & vitamin E are important, but where do those doses come from?: And how does vitamin E in food differ from supplements?
"Some evidence for the use of these supplements exists, but serious embellishment of study findings may be leading to an inappropriate use of these supplements in a clinical setting."
He got that right!
I would go further & suggest that it was criminally irresponsible to give supplements to those at the high end of intake - particularly to those who were already taking high dose supplements. This may have resulted in avoidable deaths.
There is a muddying factor here. Men who were interested in enrolling in SELECT would include some who felt themselves at high risk for PCa & were already using those supplements. If a high-risk man develops PCa, the supplements cannot automatically be said to have caused the cancer.
From the 2011 SELECT paper [3]:
"Extended follow-up of SELECT participants shows that healthy men with average risk of prostate cancer subjected to contemporary community standards of screening and biopsy who took a common dose and formulation of vitamin E (400 IU per day) have a significantly increased risk of prostate cancer. The observed 17% increase in prostate cancer incidence demonstrates the potential for seemingly innocuous yet biologically active substances such as vitamins to cause harm. The lack of benefit from dietary supplementation with vitamin E or other agents with respect to preventing common health conditions and cancers or improving overall survival, and their potential harm, underscore the need for consumers to be skeptical of health claims for unregulated over-the-counter products in the absence of strong evidence of benefit from clinical trials."
Fair enough, but read on.
Why 400 IU/d of all rac-α-tocopheryl acetate?
I just searched for vitamin E on iHerb:
- Lake Avenue Nutrition, Vitamin E (as d-Alpha Tocopheryl Acetate), 400 IU, 120 Veggie Softgels
- California Gold Nutrition, Sunflower Vitamin E (as d-Alpha Tocopherol), with Mixed Tocopherols, 400 IU, 90 Veggie Softgels
- Dr. Mercola, Vitamin E (as d-Alpha Tocopherol)134 mg893%, 30 Capsules. That's about 200 IU, I believe.
- Mason Natural, Vitamin E (as dl-alpha tocopheryl acetate), 400 IU, 100 Softgels
OK, without going through all 3,870 hits, it looks as though 400 IU alpha tocopherol is not uncommon (d-Alpha Tocopheryl Acetate converts to alpha tocopherol).
Here's a question for those who subscribe to the "Vitamin E causes prostate cancer" hypothesis: Why doesn't the FDA require a warning on the labels?
In 2003, we had a paper from Johns Hopkins [5]:
Supplementation of Diets With Alpha-Tocopherol Reduces Serum Concentrations of Gamma- And Delta-Tocopherol in Humans
"Despite promising evidence from in vitro experiments and observational studies, supplementation of diets with alpha-tocopherol has not reduced the risk of cardiovascular disease and cancer in most large-scale clinical trials. One plausible explanation is that the potential health benefits of alpha-tocopherol supplements are offset by deleterious changes in the bioavailability and/or bioactivity of other nutrients."
Mark Moyad, Han-Yao Huang & Lawrence J Appel - why were you not consulted on the massively expensive SELECT trial?
"Compared with placebo, supplementation with alpha-tocopherol reduced serum gamma-tocopherol concentrations by a median change of 58%"
Ironically, the gamma form has anti-PCa properties; the alpha does not!
"In view of the potential benefits of gamma- and delta-tocopherol, the efficacy of alpha-tocopherol supplementation may be reduced due to decreases in serum gamma- and delta-tocopherol levels. Additional research is clearly warranted."
I wasn't diagnosed until 2004, but I already had access to disturbing data:
[6] Johns Hopkins [2000]"
"The association between selenium and prostate cancer risk was in the protective direction with individuals in the top four fifths of the distribution having a reduced risk of prostate cancer compared with individuals in the bottom fifth ..."
In other words, for Americans there was no dose benefit above the lowest quintile.
"Statistically significant protective associations for high levels of selenium and alpha-tocopherol were observed only when gamma-tocopherol concentrations were high."
"For gamma-tocopherol, men in the highest fifth of the distribution had a fivefold reduction in the risk of developing prostate cancer than men in the lowest fifth".
To understand the benefit of vitamin E isoforms in PCa, one must bring a nuanced appreciation of the literature & an open mind regarding supplementation.
-Patrick
[1] en.wikipedia.org/wiki/Vitam...
[2] ncbi.nlm.nih.gov/pmc/articl...
[3] ncbi.nlm.nih.gov/pmc/articl...
[4] pubmed.ncbi.nlm.nih.gov/119...
Radiation - View Ray- Kishan
