A good clear explanation of the problems with the SELECT study, and...

Why some of us feel a more open discussion would be helpful to those who come here seeking help.
---
http://www.lifeextension.com/magazine/2012/3/synthetic-alpha-tocopherol-shown-increase/page-01
-
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.
In 1997, Life Extension reported that taking only the alpha tocopherol form of vitamin E displaces gamma tocopherol in the body.
A 2000 study showed that men with the highest blood levels of gamma tocopherol had a 5-fold reduction in prostate cancer risk. Alpha tocopherol and selenium also reduced prostate risk, but only when gamma tocopherol was high.
In the SELECT study, synthetic vitamin E was linked with an increased risk of prostate cancer. Men receiving selenium plus vitamin E did not experience increased prostate cancer risk.
Abundant evidence points to gamma tocopherol as the form of vitamin E that is most protective against prostate and other cancers.
Many factors contribute to the initiation and development of prostate cancer, including dietary factors, estrogen levels, and low vitamin D levels.
The SELECT study attempted to reduce prostate cancer risk using one or two nutrients; however, dozens of factors are involved in the development of prostate cancer. It is no surprise that this flawed study failed to find a protective effect for vitamin E supplements.

In my opinion, Life Extension is one of the biggest purveyors of "fake news" on the internet. You would do better to rely on peer-reviewed professional publications and not companies trying to sell product. SELECT was an NIH study and was the best randomized clinical trial ever done on supplements. It showed clearly that Vitamin E increased the risk of prostate cancer. If you want to take it - that's up to you.

Tall Allen said...
In my opinion, Life Extension is one of the biggest purveyors of "fake news" on the internet. You would do better to rely on peer-reviewed professional publications and not companies trying to sell product. SELECT was an NIH study and was the best randomized clinical trial ever done on supplements. It showed clearly that Vitamin E increased the risk of prostate cancer. If you want to take it - that's up to you.

--
The best randomized clinical trial ever done on supplements?????????

Post Edited (tommyc) : 6/18/2017 2:58:03 PM (GMT-6)

Tommy, as previously noted we DO seek to let threads run and "encourage open discussion" as you said in your opening comments. However, your comment, ("original comment deleted by OP so by me as well") is flaming and as such a violation of Rule #3. This is what gets threads locked or comments edited and deleted.

If you have a more courteous response to Allen's comments feel free to share it. If not, this this thread is headed for a quick lock.

Jim

Thanks. I have edited my post to delete it as well.

Jim

A few more on the more technical side
--Gamma-tocotrienols (γ-T3) is one of the vitamin-E constituents, which have been shown to have anticancer effects against a wide range of human cancers
http://onlinelibrary.wiley.com/doi/10.1002/ijc.25546/full
--gamma tocopherol had a significant reduction in the risk of developing prostate cancer.
https://www.google.com/patents/WO2004056348A2?cl=en
--study involving more than 20,000 men, patients who developed prostate cancer had significantly lower blood levels of gamma(γ)-tocopherol than men who did not,
http://www.lmreview.com/articles/view/beyond-tocopherol-a-review-of-natural-vitamin-es-therapeutic-potential-in-human-health-and-disease-part-II/
--This study examines the potential of gamma tocopherol (GT) and gamma
tocotrienol (GT3) to reduce prostate cancer proliferation
http://dc.etsu.edu/cgi/viewcontent.cgi?article=1024&context=honors
--We have recently showed that gamma-tocopherol, but not alpha-tocopherol, inhibits growth and induces cell dealth in prostate and lung cancer cells
https://www.purdue.edu/hhs/nutr/directory/faculty/jiang_qing.html
--At the supranutritional levels, however, g-T and d-T are cancer preventive
http://cancerpreventionresearch.aacrjournals.org/content/canprevres/5/5/701.full.pdf
--Newly recognized properties of γ-tocopherol provide a basis for its superior cancer preventive activity.
http://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-3-25
--Men in the highest quintile of plasma gtocopherol concentrations had a striking 5-fold reduction in prostate cancer
http://www.croh-online.com/article/S1040-8428(03)00042-8/pdf
--The risk of developing prostate cancer was five times lower for the men who had the highest fifth of gamma-tocopherol levels
http://www.bhset.net/Cancer-Library/testing/screening-tools/prostate-cancer-screening.aspx
--there is promising evidence indicating the benefit of γ-Tocopherol in prevention and treatment of carcinoma of the prostate.
https://www.jscimedcentral.com/Urology/urology-1-1002.pdf

tommyc-

At the risk of dampening your enthusiasm, may I suggest you google "Levels of Evidence" - it may help you sift through data dumps like that and separate the gold from the dross. Unfortunately, with supplements, it's almost entirely dross. You may not know this, but the reason the SELECT trial was done in the first place was because Vitamin E seemed to be beneficial based on an earlier epidemiological study, which was at a much lower level of evidence. SELECT disproved it (RCTs usually do not confirm such studies).

SELECT used the form of Vitamin E that almost all men use. Any other form has to be independently proved and should be considered unsafe until proved safe.

If you look into levels of evidence, and I highly recommend you do, you will see that lab studies like most of those you cited are close to the bottom. Lab studies are almost never vindicated by RCTs. I was too flippant of me to label them "dross" - they have some value. Their value is in developing hypotheses for clinical testing. To the authors' credit, they were never meant to be abused by patients drawing unwarranted clinical conclusions. You will notice that the authors never draw conclusions like you do.

I didn't say you abuse or misinterpret her, I said you drew unwarranted conclusions from low level evidence, conclusions that the author would never draw. If you want to risk harming yourself, that's your right.

When I end up just repeating what I've already said, it's clear you are not listening and it's time to end this pointless conversation.

---Same exact cheap synthetic, just much less of it.
However in contrast to the SELECT trial is the Alphatocopherol
beta-carotene trial (ATBC). The ATBC trial was a
double-blind RCT trial that tested the consumption of 50IU/day
of α-T on male smokers. The study found a 35% reduction in PCa
risk in the men who did consume the 50IU/day of α-T with no
impact on total mortality. The SELECT trial α-T dose was
700% that of the ATBC trial. Therefore there is some disparity
between the two dosages and their impact on PCa that warrants
further research and analysis.

More gamma
In two case-control studies correlations were found between
serum γ-T levels and the risk of prostate cancer, finding men with
higher serum γ-T levels had a statistically significant decreased
risk of PCa, with no such impact from α-T. Helzlsouer et al. noticed
the correlation to be more significant in men with stage II disease
or higher. A prospective study analyzing the National
Institute of Health American Association of Retired Persons
Diet showed an increase in dietary γ-T was associated with a
decreased incidence of prostate cancer (RR, 0.68; 95% CI, 0.56-
0.84; Ptrend = 0.001). In the same study, there was no association
with supplemental α-T. This suggests there is a significant
difference in the biological impact between the different isomers
of supplemental and dietary forms of vitamin E.

Exactly BillyBob!!!
I eat them too, every day. Especially black walnuts, they are the highest source, nearly all the E they contain is gamma E. I'm sure you already have, but if you look up the benefits of walnuts they are many.
http://www.whfoods.com/genpage.php?tname=foodspice&dbid=99
But sadly no RCTs, so what are we to do

Post Edited (tommyc) : 6/20/2017 7:01:10 PM (GMT-6)