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Latest Negative Vitamin E/Selenium Study

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 Posted 2/24/2014 8:16:28 PM
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Has LEF formed a response to this latest study showing possible dangers of vitamin E/selenium supplementation?  

My guess is that LEF will emphasize that the study used only the alpha tocopherol form of E, but what about what the study suggests regarding selenium?  Is it dangerous for a subset of men (who for dietary or other reasons have high levels of selenium) to be supplementing with 100-200mcg of selenium?  (Also, for many years, the Super Booster contained 200mcg of selenium so LEF members taking it conjunction with a LEF multi were getting 400mcg.  Was that a dangerous level?)

Here is news article referring to the study in the Journal of the National Cancer Institute.  

Post #12026
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 Posted 2/25/2014 6:41:17 AM
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hi Rob,

The response is as follows:

Baseline Selenium Status and Effects of Selenium and Vitamin E Supplementation on Prostate Cancer Risk1

A re-analysis of old study data has created inaccurate and misleading media headlines claiming selenium and/or vitamin E supplementation increase prostate cancer risk.

Thisis not a "new study" as proclaimed by some media outlets. This is a subgroup analysis of pre-existing data from an old study (SELECT) that has generated at least three publications on the same topic.

Subgroup analysis as conducted in this latest study may be unreliable statistically, and fraught with potential for confounding errors.2-4

Moreover, the principal study upon which this analysis is based – the SELECT trial – was fundamentally flawed. In fact, in January 2008, in an article available here, Life Extension® 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.

Our prediction has been vindicated time and again with each re-analysis of the flawed SELECT trial data; this case is no exception.

Study Does Not Provide Evidence That Selenium or Vitamin E Cause Prostate Cancer

By design, in retrospective case-control studies, it is difficult to match “cases”with “controls” in terms of baseline risk factors, thus weakening the study data. This type of study involves selecting subjects who the researchers know developed a specific outcome, in this case prostate cancer, and comparing themto subjects who are known not to have reached the outcome during the same period. A family history of prostate cancer was present in about twice as many cases compared to controls in this study, and about 3 times as many men in thecase group had baseline prostate-specific antigen (PSA) values above 2 µg/mL. These correlations were highly statistically significant, whereas the association of selenium and/or vitamin Esupplementation with prostate cancer risk failed to consistently achieve astrong statistical link.

This type of study cannot establish a causal relationship, in this instance betweenselenium and/or vitamin E supplementation and prostate cancer risk. Thesevariables (seleniumand vitamin E supplementation) were intermingled with major baselinedisparities between groups (eg, baseline PSA levels and family history ofprostate cancer) severely weakening the data. This leads to a great potential for errors and incorrect assumptions in this study.

Case-controlstudies are designed to identify possible links that are later studied in aprospective, randomized, controlled trial in order to establish a causalrelationship. Unfortunately, the mass media fails to understand this and is misleading the public by suggesting this analysis provides evidence thatvitamin E and/or selenium supplementation directly increased prostate cancer risk; this is simply not an accurate depiction of the data.

Results Conflictwith Previous Research

For example, other clinical studies with selenium supplements show strong benefit in prostate cancer as well as a variety of other deadly cancers5-8:

  • A study of 1,312 individuals who received 200 mcg of selenium daily or a placebo showed almost 50% lower risk of prostate cancer in the supplemented group than in the control group in men who had relatively low PSA levels and low initial selenium levels.5
  • A study of 5,141 men taking a selenium-containing supplement or a placebo for eight years, with biochemical markers of prostate disease measured at the beginning and end of the study, showed that among men who had normal PSA levels at the study’s outset, a significant risk reduction of nearly 50% was achieved.6
  • In a 2005 study focusing on selenium’s effects in preventing prostate cancer, patients with early prostate cancer took selenium, vitamin E, both L-selenomethionine and vitamin E, or a placebo for three to six weeks before undergoing prostatectomy (removal of the prostate). Levels of cancer markers were measured and compared with healthy control subjects. The result was a change in classification from cancerous to healthy in the serum markers of disease in the men who took supplements compared to those who did not.7
  • A study in men at high risk of lung cancer with low dietary selenium intake were randomly assigned to receive either 300 mcg of selenium or a placebo daily for one year. As expected, selenium blood levels rose dramatically in the supplemented group, while serum levels of the antioxidant enzyme glutathione peroxidase increased by 156%. At the same time, levels of lipid peroxide (a measure of cell membrane damage that leads to cancer) were reduced by 75% in the supplemented group, and there was laboratory evidence of protection from DNA damage, another prerequisite for cancer formation.8

·        The U.S. Nutritional Prevention of Cancer Trial demonstrated a statistically significant reduction in lung cancer incidence with selenium supplementation, with 200 mcg per day cutting the incidence of cancer by nearly50%.9 A later re-analysis with additional data showed the effect tobe most significant in people with low baseline selenium levels, again suggesting that supplementation is preventive when initiated early.10

High quality reviews indicate that low selenium status may increase risk for prostate cancer.

·        A review and meta-analysis of twelve studies with a total of 13,254 participants found the risk for prostate cancer decreased with increasing selenium levels.11

·        One review and meta-analysis found a26-28% reduced risk for prostate cancer for any intake of selenium. The authors also noted “A dose-response trend was observed when we stratified the studies by disease severity.”12

·        Another meta-analysis found aninverse relationship between selenium levels and risk of prostate cancer.13

·        A Cochrane review and meta-analysis of 14 studies with a total of more than 416,000 participants found “that peoplewith higher selenium levels or intake had a lower frequency of certain cancers(such as bladder or prostate cancer)…”14

·        A review by the American Institutefor Cancer Research that provides a comprehensive series of recommendations to reduce the risk of cancer states “Foods containing selenium (also found in animal foods) probably protect against prostate cancer; and there is limited evidence suggesting that they protect against stomach and colorectal cancers.”15 



Men Were Supplementedwith Isolated, Synthetic Alpha Tocopherol and Only One Form of Selenium

The authors of this subgroup analysis admit it is possible “…that the results would differ if alternative supplement formulations were used.” For example, the men in SELECT were not supplemented with the critically important gamma-tocopherolor additional forms of selenium.



When high doses of alpha-tocopherol vitamin E are consumed, it displaces critically important gamma-tocopherol in the cells.

While alpha-tocopherol inhibits the production of free radicals, it is the gamma-tocopherol form of vitamin E that is required to trap and neutralize free radicals. In a study published in the Proceedings of the National Academy of Sciences,16 researchers reported that it could be dangerous to take high levels of alpha-tocopherol vitamin E without also consuming gamma-tocopherol. The reason for this is that too muchalpha-tocopherol could deprive the cells of the gamma form of vitamin E that is needed to neutralize existing oxidizing agents such as the peroxynitriteradical, which can be especially damaging.

In the initial results of the SELECT study over a median 5.5-year period, men supplemented with synthetic alpha tocopherol experienced a significant gamma tocopherol depletion of 45%. Men supplemented with alpha tocopherol plusselenium experienced a 48% depletion of gamma tocopherol. These gammatocopherol depletions occurred by 6 months that were sustained during the course of a median trial period of 5.5 years.17

In addition, itshould also be noted that the only form of selenium used in this study wasL-selenomethionine (200 mcg). However, 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 morethan one source that includes se-methylselenocysteine and/or sodium seleniteplus L-selenomethionine.18-24

References

1.    Kristal AR, Darke AK, Morris JS, et. al. Baseline Selenium Status and Effects of Selenium and Vitamin E Supplementation on Prostate Cancer Risk. Journal of the National Cancer Institute. 2014:1-8.
2.    Hirji KF, Fagerland MW. Outcome based subgroup analysis: a neglected concern. Trials. 2009;10:33.
3.    Brookes ST, Whitley E, Peters TJ, Mulheran PA, Egger M, Davey Smith G. Subgroupanalyses in randomised controlled trials: quantifying the risks of false-positives and false-negatives. HealthTechnology Assessment (Winchester, England). 2001;5(33):1-56.
4.    Guillemin F. Primer: the fallacy of subgroup analysis. Nature Clinical Practice. Rheumatology. Jul 2007;3(7):407-413.
5.    Combs GF, Jr., Clark LC, Turnbull BW. Reduction of cancer risk with an oralsupplement of selenium. Biomedical andenvironmental sciences : BES. Sep 1997;10(2-3):227-234.
6.    Meyer F, Galan P, Douville P, et al. Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial. International Journal of cancer. Journal International du Cancer. Aug20 2005;116(2):182-186.
7.    Kim J, Sun P, Lam YW, et al. Changes in serum proteomic patterns by presurgical alpha-tocopherol and L-selenomethionine supplementation in prostate cancer. Cancer Epidemiology, Biomarkers &Prevention : a publication of the American Association for Cancer Research,cosponsored by the American Society of Preventive Oncology. Jul 2005;14(7):1697-1702.
8.    Yu SY, Mao BL, Xiao P, et al. Intervention trial with selenium for the preventionof lung cancer among tin miners in Yunnan, China. A pilot study. Biological Trace Element Research. Feb1990;24(2):105-108.
9.    Clark LC, Combs GF, Jr., Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA : The journal of the American Medical Association. Dec 25 1996;276(24):1957-1963.
10.  Reid ME, Duffield-Lillico AJ, Garland L, Turnbull BW, Clark LC, Marshall JR. Selenium supplementation and lung cancer incidence: an update of the nutritional prevention of cancer trial. Cancer Epidemiology, Biomarkers & Prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society ofPreventive Oncology. Nov 2002;11(11):1285-1291.
11.  Hurst R, Hooper L, Norat T, et al. Selenium and prostate cancer: systematic review and meta-analysis. The American Journalof clinical Nutrition. Jul 2012;96(1):111-122.
12.  Etminan M, FitzGerald JM, Gleave M, Chambers K. Intake of selenium in the prevention of prostate cancer: a systematic review and meta-analysis. Cancer Causes & Control : CCC. Nov 2005;16(9):1125-1131.
13.  Brinkman M, Reulen RC, Kellen E, Buntinx F, Zeegers MP. Are men with low selenium levels at increased risk of prostate cancer? European Journal of Cancer (Oxford, England : 1990). Oct 2006;42(15):2463-2471.
14.  Dennert G, Zwahlen M, Brinkman M, Vinceti M, Zeegers MP, Horneber M. Selenium forpreventing cancer. The Cochrane Databaseof Systematic Reviews. 2011(5):Cd005195.
15.  World Cancer Research Fund/AICR. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Available at:  http://www.aicr.org/assets/docs/pdf/reports/Second_Expert_Report.pdf . Washington, DC: AICR.
16.  Christen S, Woodall AA, Shigenaga MK, Southwell-Keely PT, Duncan MW, Ames BN. gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements alpha-tocopherol: physiological implications. Proceedings of the National Academy of Sciences of the United States ofAmerica. Apr 1 1997;94(7):3217-3222.
17.  Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA : the journal of theAmerican Medical Association. Jan 7 2009;301(1):39-51.
18.  Dong Y, Lisk D, Block E, Ip C. Characterization of the biological activity of gamma-glutamyl-Se-methylselenocysteine:a novel, naturally occurring anticancer agent from garlic. Cancer research. Apr 1 2001;61(7):2923-2928.
19.  Kim T, Jung U, Cho DY, Chung AS. Se-methylselenocysteine induces apoptosis through caspase activation in HL-60 cells. Carcinogenesis.Apr 2001;22(4):559-565.
20.  Medina D, Thompson H, Ganther H, Ip C. Se-methylselenocysteine: a new compound forchemoprevention of breast cancer. Nutrition and Cancer. 2001;40(1):12-17.
21.  Yeo JK, Cha SD, Cho CH, et al. Se-methylselenocysteine induces apoptosis through caspase activation and Bax cleavage mediated by calpain in SKOV-3 ovarian cancer cells. Cancer letters. Aug 82002;182(1):83-92.
22.  Yang Y, Huang F, Ren Y, et al. The anticancer effects of sodium selenite and selenomethionine on human colorectal carcinoma cell lines in nude mice. Oncology Research. 2009;18(1):1-8.
23.  Pei Z, Li H, Guo Y, Jin Y, Lin D. Sodium selenite inhibits the expression of VEGF,TGFbeta(1) and IL-6 induced by LPS in human PC3 cells via TLR4-NF-(K)B signaling blockage. International Immunopharmacology. Jan 2010;10(1):50-56.
24.  Corcoran NM, Hovens CM, Michael M, Rosenthal MA, Costello AJ. Open-label, phase I dose-escalation study of sodium selenate, a novel activator of PP2A, in patients with castration-resistant prostatecancer. British Journal of Cancer. Aug10 2010;103(4):462-468. 

  


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