Life Extension Magazine March 2012
Synthetic Alpha Tocopherol Shown to Increase Prostate Cancer Risk
By William Faloon
Longtime members of the Life Extension Foundation® have heard our warnings against synthetic alpha tocopherol many times.
In 1997, we reported that taking only the alpha tocopherol form of vitamin E displaces critically important gamma tocopherol in the body. By displacing gamma tocopherol, we feared that high doses of alpha tocopherol could increase cancer risks.
In fact, three years after Life Extension’s first warning, the Johns Hopkins School of Public Health released the results of a huge study (10,456 men). The findings showed that men with the highest gamma tocopherol blood levels had a fivefold reduction in prostate cancer risk. This same study showed that selenium and alpha tocopherol also reduced prostate cancer risk, but only when gamma tocopherol levels were high.1 Confirmatory studies document higher levels of gamma tocopherol to be strongly associated with reduced cancer risks.2-5
While both alpha and gamma tocopherol are potent antioxidants, gamma tocopherol has a unique function. Because of its different chemical structure, gamma tocopherol scavenges reactive nitrogen species, which can damage proteins, lipids, and DNA.6-8
Cancer is the end result of damage inflicted upon critical DNA genes that help regulate cellular growth and maturation. The fact that supplementation with isolated, synthetic alpha tocopherol depletes plasma gamma tocopherol levels means that the researchers who designed a study using only high-dose alpha tocopherol (the SELECT trial) created a biological catastrophe. The result of their ignorance is that men randomized to receive only synthetic alpha tocopherol suffered significant gamma tocopherol depletion and consequently, DNA damage from reactive nitrogen species. The fact that higher prostate cancer rates were observed in the group overloaded with synthetic alpha-tocopherol in the SELECT trial was predictable and expected based upon fundamental facts Life Extension understood as far back as 1997.
This costly government-funded study was initiated in the year 2001.
Life Extension was highly critical of this study design because it exposed healthy men to relatively high doses of synthetic alpha tocopherol without any supplemental gamma tocopherol to compensate. The results confirmed Life Extension’s worst fears. Compared to placebo, men taking synthetic alpha tocopherol had a 17% greater incidence of prostate cancer.9 This is a tragedy from the standpoint of the study participants who should not have been given alpha tocopherol by itself. It was also a waste of tax dollars used to fund a study that was designed to fail from the outset.
In another arm of the study where selenium was given in addition to alpha tocopherol, there was not a statistically significant increase in prostate cancer.9 The study’s authors commented on the protective effect of selenium, but never mentioned the damage they inflicted by failing to include gamma tocopherol in their study. Selenium boosts antioxidant defenses in the body (such as glutathione peroxidase) that would help compensate for the displacement of gamma tocopherol by alpha tocopherol.10
The doctors involved in the design of the study comprise a “who’s who” of the conventional cancer establishment. Virtually every major cancer center was involved in the study conception, and it seemed that virtually every pharmaceutical company had made generous payments to the study’s overseers. If there was ever a greater financial conflict of interest, we have yet to see it. It was in the economic interests of the drug companies, the cancer centers, and the mainstream doctors to see this study fail, and the harsh comments against dietary supplements by the mainstream doctors reveal a strong bias against over-the-counter dietary supplements.
While the study’s authors claim that there is not a “biological explanation” from their data to explain the increase in prostate cancer in the alpha tocopherol-only group, Life Extension® long ago predicted in writing this study would fail. As we expected, the men in this study that received alpha tocopherol experienced a 45% depletion of vital gamma tocopherol during the initial 5.5-year median study period.11
Myriad reports now point to the urgent need for Americans to obtain sufficient gamma tocopherol.8,12-22 Yet the vast majority of human clinical research focuses only on alpha tocopherol—as if it were the only form of vitamin E people require. This article explains the mechanisms involved in development of prostate cancer and why no single supplement can be counted on alone to prevent it.
Based on reports showing antioxidants reduce incidence of prostate cancer, the federal government spent over $114 million to see if synthetic alpha tocopherol and/or a single-sourced selenium supplement would prevent prostate cancer in a large placebo-controlled trial conducted at major cancer centers throughout the United States.11
The long-term follow-up of the SELECT study was published in the Journal of the American Medical Association on October 12, 2011.11 Long before this study’s findings were released, Life Extension® predicted that it would fail and warned that men taking high doses of alpha tocopherol without also taking gamma tocopherol faced increased disease risk.
In the initial results of the SELECT study over a median 5.5-year period, men supplemented with synthetic alpha tocopherol experienced significant gamma tocopherol depletion of 45%. Men supplemented with alpha tocopherol plus selenium experienced a 48% depletion of gamma tocopherol. These gamma tocopherol depletions occurred by 6 months and were sustained during the course of a median trial period of 5.5 years.11
It should be noted that serious supplement users choose natural alpha tocopherol because it has been shown to exert superior biological effects in the body.23,24 The synthetic form of alpha tocopherol is most often used in brand-name multivitamins made by pharmaceutical companies that are widely advertised on national television. Organizations like Life Extension have resisted the cheap price of synthetic vitamin E and use the more expensive natural form of alpha tocopherol in nutrient formulations.
It should also be noted that the only form of selenium used in this study was L-selenomethionine (200 mcg). Yet scientific studies dating back to the 1970s show that other forms of selenium might provide greater protection against cancer. That’s why most Life Extension members obtain their selenium from more than one source that includes Se-methyl L-selenocysteine and/or, other anti-cancer forms of selenium.25-30
Life Extension has conducted a thorough review of the SELECT study that is now being used as a basis to attack dietary supplements. The more of this article you read, the more you will understand why the SELECT study was designed to fail from the outset.
Initial SELECT Report Showed No Risk or Benefit
When data was first reported from the SELECT trial on December 9, 2008, it found no reduction in prostate cancer incidence in men taking alpha tocopherol or selenium over a median period of 5.5 years.11
This was not surprising since we have known for the past 14 years that when alpha tocopherol is taken by itself, it displaces critically important gamma tocopherol in our cells.31-34 An abundance of evidence points to the gamma tocopherol form of vitamin E as the most protective against prostate cancer.2,35-37
By supplementing aging men with only alpha tocopherol, doctors increased these men’s prostate cancer risk by depriving prostate cells of critical gamma tocopherol. This is only a tiny part of the real story behind this flawed study.
The American Medical Association used the initial finding of no benefit to discredit vitamin E and selenium supplements. An editorial by the American Medical Association concluded by advising:“… physicians should not recommend selenium or vitamin E—or any other antioxidant supplements—to their patients for preventing prostate cancer.”38
In January 2008, as part of our article titled “Merv Griffin’s Tragic Death from Prostate Cancer,”39 we predicted that the SELECT trial would fail. We also stated that this faulty SELECT study would be misused by the medical establishment to discredit by extrapolation, other low-cost efficacious nutrients like vitamin D and fish oil.
How Gamma Tocopherol Protects Against Cancer
Gamma tocopherol exerts anticancer effects through a variety of important mechanisms, giving it an especially broad spectrum of action against a host of tumor types. At the very beginning of the cancer development process, gamma tocopherol traps reactive nitrogen species and other free radicals that cause mutations in DNA strands and render cells vulnerable to malignant transformation.6-8 This is a crucial step in the prevention of cancer.
Gamma tocopherol inhibits cancer cell growth in culture through a number of different mechanisms.37 It downregulates control molecules known as cyclins, which traps cancer cells in the midst of their reproduction cycle and prevent them from reproducing and spreading.36 This anticancer effect appears to be based on a mechanism separate from the vitamin’s well-known antioxidant powers.
A cell membrane receptor called PPAR-gamma (peroxisome proliferator-activated receptor-gamma) is a promising target for anticancer therapies because it affects genes that control cancer cell growth and death.40 This is why PPAR-activating drugs are being researched and developed by pharmaceutical companies as anticancer drugs. Gamma tocopherol is more powerful than alpha tocopherol at stimulating PPAR-gamma activity, especially in colon cancer cells.12,41 In prostate cancer cells, PPAR-gamma stimulation by gamma tocopherol resulted in a complete cessation of cancer cell growth.12
Once cancerous transformation has taken place, there are still biological opportunities to prevent full-blown tumor development. One of these ways is the induction of deliberate cell death through built-in genetic programs, a process called apoptosis. In a variety of cancer tissues, gamma tocopherol has been found to be superior to alpha tocopherol at inducing apoptosis, triggering a number of desirable cell disposal-pathways.2,42 In prostate cancer cells, gamma tocopherol induced cell death by blocking synthesis of important cell membrane components.43 Gamma tocopherol also reduces the development of new blood vessel formation in tumors, depriving them of the nutrients they need to thrive.44
To date, all of these mechanisms have been shown to inhibit cancers of the colon, prostate, breast, and lung in animal models, with many more under active investigation.45
A study found that women who consumed most vitamin E from food sources had a 60% reduction in the risk of breast cancer, compared to women with the lowest consumption. The form of vitamin E that strongly predominates in food sources is gamma tocopherol.46
In the December 2000 issue of the Journal of the National Cancer Institute, researchers at the Johns Hopkins School of Public Health published results of a huge study of 10,456 men showing that those with the highest gamma tocopherol blood levels had a fivefold reduction in prostate cancer risk. This same study showed that selenium and alpha tocopherol also reduced prostate cancer risk, but only when gamma tocopherol levels were high.1
These findings should have been glaringly apparent to those involved in the SELECT human clinical trial that began one year later (in 2001), yet the SELECT study design called for men to be given a high dose of synthetic alpha tocopherol that resulted in depletion of vital gamma tocopherol by 45% during the initial 5.5-year median trial period! This is one reason why we believe the SELECT study was “designed to fail.”
We know that free radical-induced damage to DNA genes can cause cancer, but there are other risk factors beyond oxidative stress to blame for most prostate tumors.
Prostate Cancer Is Initiated Early in Life
While prostate cancer is not usually diagnosed until men reach older ages, it can be initiated 15-25 years prior to clinical manifestation. In fact, there is convincing evidence that the initiating DNA damage inflicted by estrogen to prostate cells can occur before a man is even born.47
Studies show that as early as the second and third trimester of life, exposure to elevated estrogens in the womb can initiate prostate cancer that may not manifest for 80 years.48-53 A man’s lifetime exposure to higher-than-normal estrogen may be a contributing factor to prostate cancer development. There is no evidence that antioxidants like alpha tocopherol and selenium would protect against this kind of prostate cancer induced by prolonged excess estrogen exposure.
Please don’t feel helpless about this, as it requires more than mere initiation for cancer to fully develop. Dietary and other lifestyle factors have an enormous impact on whether men will develop prostate cancer, even if they are genetically predisposed.
The Cause of All Cancers
Cancer can be defined in one sentence as follows:
“Cancer is the accumulation of mutations in genes that regulate cellular proliferation.”54
All cancers are caused by gene mutations. Every time a cell divides, there are slight mutations to one’s genes. Oxidative stress accelerates gene mutation, but is by no means the primary factor. While selenium and vitamin E reduce some types of oxidative stress, the aged men in the SELECT study had already sustained considerable genetic mutations that are not reversible by taking antioxidants.
Fortunately, there are nutrients that have been shown to favorably reverse the gene alterations involved in cancer initiation and progression. One promising nutrient is vitamin D, which has been shown to slash prostate cancer risk in some studies.55 Serum levels of vitamin D were not assessed in the SELECT study, so it was not possible to know which men had protective levels of vitamin D and those who had insufficient or even deficient levels. If men in the placebo group had even slightly higher vitamin D status, they should have been less likely to contract prostate cancer.
What researchers fail to comprehend is that giving aged men a single antioxidant like alpha tocopherol is not going to reverse seven decades of genetic damage to prostate DNA. Fortunately, we know of other mechanisms that fuel prostate cancer progression that can be mitigated.
Eating Your Way to Prostate Cancer
Cancer cells lurk in the prostate glands of most aging men, yet only one in six men are ever diagnosed with prostate cancer. If one looks at what is required for a single cancer cell to develop into a detectable tumor, it becomes obvious that natural barriers exist to protect people against full-blown cancer.2,43-46
Unfortunately, the dietary choices of most men living in the modern Western world circumvent the body’s natural protective barriers. The end result is that most men unwittingly provide biological fuel for existing prostate cancer cells to propagate and metastasize.
Fortunately, an understanding of the biological roles of diet and specific nutrients can enable aging men to achieve a considerable amount of control over whether isolated cancer cells in their prostate gland will ever show up as a clinically diagnosed disease.
The impact of the food we ingest on cell growth and death is so pronounced that in some ways it can be identical to the effects displayed by some anticancer drugs. As it relates to the SELECT study on alpha tocopherol and/or selenium, the study participants’ diet was not taken into consideration. This fact alone could have rendered the findings highly suspect. Read on to see what we mean.