Synthetic Vitamin E May Increase Prostate Cancer Risk
Most of us assume that vitamin E is healthy. Few of us thought supplemented synthetic vitamin E could raise the risk of prostate cancer.
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Vitamin E and prostate cancer
Medical researchers are surprised with study results that indicate taking a synthesized form of vitamin E in high doses significantly increased the risk of prostate cancer.
The study, published in the Journal of the American Medical Association, gave rac-α-tocopheryl acetate, a synthesized molecule referred to (incorrectly) as vitamin E, or selenium, or both (or placebo) to 34,887 men in the U.S., Canada and Puerto Rico. The study found that by 2011, those who had taken the synthesized vitamin E form during the trial period had a 17% higher incidence of prostrate cancer than the group that took a placebo during the trial period.
The trial dosing was discontinued in 2008, when the researchers found a 13% increased incidence of prostate cancer among the synthesized vitamin E (rac-α-tocopheryl acetate) group. The result surprised researchers because other vitamin E studies, including those on rats, have found that vitamin E prevents cancers of various types.
Vitamin E dosing
The dose of the synthetic rac-α-tocopheryl acetate vitamin E form was 400 IU (international units) – equal to 363 milligrams, which is 27 times higher than the 15 IU per day U.S. DV (daily value) for men over 50 years old for vitamin E.
Types of natural vitamin E
Natural vitamin E actually has eight different forms:
These different vitamin E forms work in a synergistic way within the body. The tocopherols are known antioxidants. But the tocotrienols have also been shown to have significant, if not sometimes greater antioxidant potency.
Research has found that the tocotrienols have greater cancer prevention potential compared to the tocopherols.
Compare this to synthetic vitamin E
Synthetic vitamin E (αlpha-tocopherol in the form of rac-α-tocopheryl acetate) as offered by most commercial supplement producers, is a different molecule altogether than these forms of natural vitamin E.
Illustrating this, research has shown that this synthesized version of isolated vitamin E, rac-α-tocopheryl acetate, has been shown to produce a foreign metabolite called alpha-CEHC (2,5,7,8-tetramethyl-2(2′-carboxyethyl)-6-hydroxychroman). This metabolite is believed to be produced in the liver. α-CEHC analysis shows the molecule contains a truncated phytyl tail.
In 1998, researchers from Germany’s Institute for Human Nutrition gave six humans 150 milligrams each of either the natural form of alpha-tocopherol vitamin E, d3RRR-α-tocopherol, or the synthesized version, rac-α-tocopheryl acetate. The researchers tested plasma immediately, at six hours, twelve hours and 24 hours after the dosages. Urine was tested every day for the first five days, and then on day 8.
The researchers found that while most of the natural form of alpha-tocopherol remained in the bloodstream, much of the synthesized vitamin E isolate “preferentially metabolized” to α-CEHC, which was excreted through the urine. In general, the excretion of the synthetic vitamin E was two-to-three times the excretion of the natural form as measured over several days.
After a thorough review of the results, the researchers concluded that the difference in the metabolite secretion wasn’t simply the speed of metabolite production in the liver: “The lower biological activity of synthetic vitamin E cannot be quantitatively attributed to its higher rate of metabolism. Although nearly 3 times as much metabolite was made from synthetic compared with natural vitamin E, the amounts of the metabolite produced and excreted in the urine account for only a few percent of the deuterated vitamin E consumed.” In other words, something else is going on with synthetic vitamin E metabolism.
Other research confirms problematic synthetic vitamin E
Last year, medical researchers from Rutgers School of Pharmacy published results of various vitamin E trials, including a careful review of the research on vitamin E to date. They studied the various effects of vitamin E and the contrary results of several cancer studies. Their research determined that the multiple forms of natural vitamin E acted synergistically within the body. For example, larger doses of alpha-tocopherol actually decrease levels of delta-tocopherol in the bloodstream and tissues. They also found that gamma-tocopherol significantly decreased prostate tumor growth, as well as colon, breast and lung cancer.
This research and others found that the different vitamin E forms had cross-signalling capability, and were not redundant in their effects. In other words, the different forms are interactive rather than duplicating. This issue also appears in some multivitamin use as well.
Unfortunately, medical researchers have not thoroughly investigated this. Another study, done by researchers from Ohio State University’s Medical School, determined that less than 1% of the research on vitamin E even considered or tested the tocotrienol forms of vitamin E. They commented that:
“Tocotrienols possess powerful neuroprotective, anti-cancer and cholesterol lowering properties that are often not exhibited by tocopherols.”
This study, published in late 2010, also warned of hasty conclusions about vitamin E using only one form – not to speak of that form being synthetic rather than the natural form: “For example, evidence for toxicity of a specific form of tocopherol in excess may not be used to conclude that high-dosage “vitamin E” supplementation may increase all-cause mortality. Such conclusion incorrectly implies that tocotrienols are toxic as well under conditions where tocotrienols were not even considered.”
The bottom line is that nature provides nutrients that are cancer-preventative, and nature’s forms of vitamin E have been shown to be significantly antioxidant and anticarcinogenic. However, problems arise when we make hasty assumptions and ignore nature’s interactive and synergistic effects, and we try to reproduce these effects by synthesizing nutrients. Assuming that nature is not intelligent (or we are more intelligent) has dire consequences, as researchers learned in this synthetic vitamin E study that increased prostate cancer incidence among its subjects.
Pomegranate inhibits prostate cancer according to other research. Button mushrooms also reduce PSA in prostate cancer.
EA Klein, IM Thompson Jr, CM Tangen, JJ Crowley, MS Lucia, PJ Goodman, et al. Vitamin E and the Risk of Prostate Cancer The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549-1556.
Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, Parnes HL, Minasian LM, Gaziano JM, Hartline JA, Parsons JK, Bearden JD 3rd, Crawford ED, Goodman GE, Claudio J, Winquist E, Cook ED, Karp DD, Walther P, Lieber MM, Kristal AR, Darke AK, Arnold KB, Ganz PA, Santella RM, Albanes D, Taylor PR, Probstfield JL, Jagpal TJ, Crowley JJ, Meyskens FL Jr, Baker LH, Coltman CA Jr. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009 Jan 7;301(1):39-51.
Traber MG, Elsner A, Brigelius-Flohé R. Synthetic as compared with natural vitamin E is preferentially excreted as alpha-CEHC in human urine: studies using deuterated alpha-tocopheryl acetates. FEBS Lett. 1998 Oct 16;437(1-2):145-8.
Wada S. Cancer Preventive Effects of Vitamin E. Curr Pharm Biotechnol. 2011 Apr 5.
Ju J, Picinich SC, Yang Z, Zhao Y, Suh N, Kong AN, Yang CS. Cancer-preventive activities of tocopherols and tocotrienols. Carcinogenesis. 2010 Apr;31(4):533-42.