Selenium & Prostate Cancer: Time to Un-SELECT

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OK, now is the time to Un-SELECT

Selenium2

The latest news hitting the news wires these days is that Selenium significantly increases the risk of prostate cancer – by a lot.
 
Review of the SELECT study and it’s recent findings:
 
    •    This study began in 2001 and ended early in 2008 when no benefit of vitamin E and selenium was found in prostate cancer prevention
 
    •    Researchers wanted to see if vitamin E (in the form alpha-tocopherol) and selenium (in the form of L-selenomethionine) could prevent prostate cancer. The trial was simply called the SELECT trial (SELenium and vitamin E Cancer prevention Trial).

    •    About 35,000 study subjects were randomly assigned to receive one of four interventions between August 2001 and June 2004 for a planned minimum follow-up of 7 years:

                                  L-selenomethionine (200 micrograms per day) and a vitamin E placebo;
                                  alpha–tocopherol (400 IU/day) and a selenium placebo;
                                   L-selenomethionine plus alpha-tocopherol; or  placebo.
    •    Initially the findings showed more prostate cancer in men taking vitamin E alone, and slightly more diabetes in men taking only selenium. But neither finding was statistically significant, meaning these findings were likely due to chance (Lippman et al. 2009).

    •    In 2011 the collected data was further analyzed showing that those who consumed vitamin E (400 IU/d) alone had a significant 17% increase risk of prostate cancer. There were no changes in the selenium group (Klein et al. 2011)

    •    Now, in 2014 after further analysis of the SELECT data, new findings suggest that taking selenium (selenomethionine) supplements increased the risk of high-grade cancer by 91% among men with high selenium status at baseline.

    •    When selenium supplements were taken by men who had high selenium status to begin with, the levels of selenium became toxic.

    •    Among men with low selenium status at baseline, vitamin E supplementation increased their total risk of prostate cancer by 63 %and increased the risk of high-grade cancer by 111%
 
HERE’S LINK TO DETAILS OF THE STUDY
The lead researcher, Dr. Kristal says;  “Men using these supplements should stop, period. Neither selenium nor vitamin E supplementation confers any known benefits – only risks,” he continued. “While there appear to be no risks from taking a standard multivitamin, the effects of high-dose single supplements are unpredictable, complex and often harmful. Taking a broad view of the recent scientific studies there is an emerging consistency about how we think about optimal intake of micronutrients.  There are optimal levels, and these are often the levels obtained from a healthful diet, but either below or above the levels there are risks.
 
The problem is that not all Selenium is the same
 

What is Selenium?

Selenium is a trace mineral we ingest from a variety of plants, most notably Brazil nuts and animal sources in several different forms. There are three forms of selenium most important in cancer prevention studies: selenomethionine, selenocysteine and methyl-selenocysteine. In general, the three selenium compounds complement one another in the ways they affect your body’s expression of important proteins involved in cancer prevention and suppression.In addition, all three selenium compounds induce cell death in various cancer types, but each compound is better at destroying some cancers than others.
 
What does Selenium do?

Selenium has numerous functions. Three of  which this trace element is most known for are:
1.     It serves as a co-factor to glutathione production. Glutathione a powerhouse anti-oxidant your body makes to keep you well and cancer free
2.    Helps with the proper balance of thyroid hormones.
3.     Serves as an antioxidant on it’s own.
 
Major problems continue with findings from SELECT

There’s a fundamental problem that continues to surface with the research of nutrition and cancer.  There are too many factors involved in the development and progression of prostate cancer— including low levels of testosterone, increased levels of estrogen, co-existing diabetes or metabolic syndrome, and over-consumption of saturated fats (Malley et al. 2006).
This multitude of confounding factors makes it difficult to study just one or two compounds and expect to arrive at a validated finding. Reductionist thinking, that is, one chemical to treat one disease, is faulty and over simplistic and leads to the disease epidemic of cancer, heart disease and rapid aging we are all witnessing. (OK, I’ll get off from my soapbox now)
Studying just the alpha-tocopherol form of vitamin E is faulty in design and methodology, especially when there is some evidence indicating that other members of the vitamin E family are even more important.
 
A Brief Review of Vitamin E studies and Prostate Cancer

Studies in the year 2000 emerged demonstrating that the alpha-tocopherol component of vitamin E DOES NOT protect men from prostate cancer without the other major component of vitamin E, gamma-tocopherol. In fact, the alpha tocopherol form of vitamin E depletes the cells of the more protective form of vitamin E, gamma tocopherol (Handelman et al. 1994).

When high doses of alpha-tocopherol vitamin E are consumed simply not protective without the synergistic benefit of gamma-tocopherol. 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. (Christen et al. 1997) Further more, researchers reported that it could be dangerous to take high levels of alpha-tocopherol vitamin E without also consuming gamma-tocopherol.

In over ten thousand men studied at the prestigious Johns Hopkins School of Public Health, men who had the highest blood levels of gamma-tocopherol were five times less likely to get prostate cancer (Helzlsouer et al. 2000). In addition to the finding that higher levels of gamma-tocopherol significantly reduced prostate cancer risk, the study also showed that selenium and alpha-tocopherol also reduced prostate cancer incidence, but only when gamma-tocopherol levels are high.
Other researchers have also found that gamma-tocopherol offers a protective effect against prostate cancer (Huang et al. 2003).

In a 2012 research paper by Dr. Chung S. Yang from Rutgers Ernest Mario School of Pharmacy wrote extensively on this topic:
 “Our message is that the vitamin E form of gamma-tocopherols, the most abundant form of vitamin E in the American diet, and delta-tocopherols, also found in vegetable oils, are beneficial in preventing cancers while the form of vitamin E, alpha- tocopherol, the most commonly used in vitamin E supplements, has no such benefit.”
 
And
 
“When animals are exposed to cancer-causing substances, the group that was fed these tocopherols in their diet had fewer and smaller tumors,” Yang says. “When cancer cells were injected into mice these tocopherols also slowed down the development of tumors.”
 
And lastly
 
“For people who think that they need to take vitamin E supplements,” Yang says, “taking a mixture of vitamin E that resembles what is in our diet would be the most prudent supplement to take.”
                                                                                                  – (Yang el al. 2012)
 

 

Previous research shows protective benefits of selenium against prostate cancer

The connection between selenium and cancer was originally demonstrated in epidemiological studies linking increased cancer risk with low blood selenium levels. (Nomura et al. 2000)

A prospective study of over 50,000 male health professionals in the U.S. found a significant inverse relationship between toenail selenium content and the risk prostate cancer. In this study, individuals whose toenail selenium content was consistent with an average dietary intake of 159 mcg/day of selenium daily had a 65% lower risk of advanced prostate cancer compared to those with toenail selenium content consistent with an average intake of 86 mcg/day.( Yoshizawa et al. 1998)

A case-control study found that men with pre-diagnostic low blood selenium levels were four to five times more likely to develop prostate cancer than those in the highest quartile (Brooks et al 2001)
 

The type of selenium in SELECT simply does NOT work

Dr. David McCormick at the Experimental Toxicology and Carcinogenesis Division, IIT Research Institute in Chicago found no effects with selenomethionine supplementation on the prevention of prostate cancer in rats (McCormick & Rao. 1999).
High-Selenium Yeast, on the other hand, has been found to be more effective than selenomethionine in the reducing DNA damage and an increase in epithelial cell apoptosis (natural cell death) within  aging canine prostate cells. (Waters et al. 2003)
Lastly, a 2011 meta-analysis of nine randomized controlled clinical trials including 152,538 participants established that selenium supplementation cut risk for all cancers by 24%. The cancer-preventive effect rose to 36% in people with low baseline selenium levels. (Lee et al. 2011)

Current interest in the relationship between selenium and prostate cancer is based largely on a landmark, 1996 clinical intervention study that demonstrated supplementation with 200 micrograms /day in the form of selenized yeast resulted in a 60% decrease in prostate cancer over a period of about 4.5 years. (Clark et al. 1998)

The Nutritional Prevention of Cancer Trial, a randomized clinical study, showed the efficacy of selenium as selenized yeast at 200 micrograms/day in over 1300 skin cancer patients by reducing the incidence prostate cancer. The selenium effect was associated mostly to males and was most pronounced in former smokers. (Duffield-Lillico et al. 2002)

 

My Take On This
 

Well, here we go again, eh? This is the latest edition of a GIGO (garbage in, garbage out) study. To consume any form of selenium without gamma-tocopherol vitamin E is inadequate and a waste of money. There seems to be synergistic value between selenium and gamma-tocopherol vitamin E as highlighted by Helzlsouer et al. who looked at over 10,000 men and found (worth reiterating) that selenium and alpha-tocopherol also reduced prostate cancer incidence, BUT ONLY when gamma-tocopherol levels are high. Futhermore, benefits of selenium are pronounced ONLY in its yeast form and NOT so much in the form of selenomethionine alone.
 

My interview with an expert

Last night I felt compelled to do a little investigative journalism and call Dr. Mark Whitacre, Ph.D, a selenium biochemist graduate from Cornell University to ask him, “ what’s the deal with selenium in SELECT.”

In Dr. Whitacre’s words: “Selenium Yeast not only consist of selenomethionine but also contains a wide variety of organically bound selenium compounds like selenocysteine and methylselenocysteine, which very likely could have greater anti-carcinogenic activity than selenomethionine alone.” He continues, “there seems to be synergistic value in these main forms of selenium compared to just one form and maybe that’s why the data suggest’ that selenium yeast is more protective against multiple cancers.” Lastly, with a sound of what seemed to be a smirk on his face, he mentions: “and by the way, the SELECT trial was not $114 million but more like $300 million. I know researchers involved in that study.”
 

OUCH! $ 300 million of tax payer money spent on a garbage designed study
 
If anything, the SELECT study demonstrates the following:
1.     You cannot always depend on the latest research for accurate information. The last study is not always the best.
2.     When consuming nutrients outside of their natural state, not only will they not work, but they can be toxic
3.     Gamma-tocopherol vitamin E combined with yeast selenium might work well in combination with proper eating habits and exercise in the prevention of prostate cancer
 
The Doggy Bag Message

  • Nutrients in its natural form work best, i.e. Mixed tocopherol vitamin E not only alpha tocopherol vitamin E, Yeast selenium with all 3 main forms , selenomethionine, selenocysteine and methyl-selenocysteine NOT only               selenomethionine.                                                                                                                                                                                                       And mixed carotenoids, for that matter, instead of only beta-carotene, which has shown, when taken alone, to increase mortality and other problems. (Bjelakovic et al. 2014)
  • Supplements do not replace good eating habits, healthy lifestyle and exercise
  •  Nutritionally oriented physicians like licensed naturopathic doctors can be invaluable in helping patients navigate through “GIGO” research and provide effective protocols for maximal health outcomes.
  • And no, you cannot get all the nutrients you need from food. Although the idea is nice,  very few people eat 100% from local farms, organic, grass-fed meats, clean fish and whole grains.

 
I’m so SELECTed- OUT by now ;-((
 
References:

Phone interview with Dr. Whitacre, 9:15 pm EST, February 24, 2014, from NYU Urology office. Special thanks to Dr. Whitacre for sharing his thoughts with me on this topic so late at night.

Lippman 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. 2009;301(1):39 -51.

Huang, H.Y., Alberg, A.J., Norkus, E.P., Hoffman, S.C., Comstock, G.W., Helzlsouer, K.J., et al. (2003). Prospective study of antioxidant micronutrients in the blood and the risk of developing prostate cancer. American Journal of Epidemiology, 157(4), 335-344.

Handelman, G.J., Epstein, W.L., Peerson, J., Spiegelman, D., Machlin, L.J., & Dratz, E.A. (1994). Human adipose alpha-tocopherol and gamma-tocopherol kinetics during and after 1 y of alpha-tocopherol supplementation. American Journal of Clinical Nutrition, 59(5), 1025-1032.

Klein et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011 Oct 12;306(14):1549-56.

Christen S, et al. gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements alpha–tocopherol: physiological implications. Proc Natl Acad Sci U S A 1997 Apr 1;94(7):3217-22

Helzlsouer KJ, et al. Association Between alpha–Tocopherol, gamma-Tocopherol, Selenium, and Subsequent Prostate Cancer. J Natl Cancer Inst 2000 Dec 20;92(24):2018-2023.

Helzlsouer, K.J., Huang, H.Y., Alberg, A.J., Hoffman, S., Burke, A., & Norkus, E.P., et al. (2000). Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. Journal of National Cancer Institute, 92(24), 2018-2023.

Huang, H.Y., Alberg, A.J., Norkus, E.P., Hoffman, S.C., Comstock, G.W., Helzlsouer, K.J., et al. (2003). Prospective study of antioxidant micronutrients in the blood and the risk of developing prostate cancer. American Journal of Epidemiology, 157(4), 335-344.

Yang CS, Suh N, Kong AN.Does Vitamin E Prevent or Promote Cancer? Cancer Prev Res (Phila). 2012 Apr 16

Duffield-Lillico AJ, Reid ME, Turnbull BW, et al. Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial. Cancer Epidemiol Biomarkers Prev 2002;11:630-639.

Brooks JD, Metter EJ, Chan DW, et al. Plasma selenium level before diagnosis and the risk of prostate cancer development. J Urol. 2001;166(6):2034-2038.

Clark LC, Dalkin B, Krongrad A, et al. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol 1998;81:730-734.

Yoshizawa K, Willett WC, Morris SJ, et al. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. J Natl Cancer Inst. 1998;90(16):1219-1224.

McCormick DL, Rao KV. Chemoprevention of hormone-dependent prostate cancer in the Wistar-Unilever rat. Eur Urol. 1999;35(5-6):464-7.

Waters DJ, Shen S, Cooley DM, Bostwick DG, Qian J, Combs GF Jr, Glickman LT, Oteham C, Schlittler D, Morris JS. Effects of dietary selenium supplementation on DNA damage and apoptosis in canine prostate. J Natl Cancer Inst. 2003 Feb 5;95(3):237-41.

Lee EH, Myung SK, Jeon YJ, et al. Effects of selenium supplements on cancer prevention: Meta-analysis of randomized controlled trials. Nutr Cancer. 2011 Oct 17.

Bjelakovic G, Nikolova D, Gluud C. Antioxidant supplements and mortality. Curr Opin Clin Nutr Metab Care. 2014 Jan;17(1):40-4.
 




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by Dr. Geo

2 comments… add one
  • Ann Fonfa 02/25/2014, 9:47 AM

    Many years ago I attended the very first meeting of Frontiers in Cancer Prevention Research, as a Patient Advocate. I heard about the soon-to-start SELECT trial and jumped up to PROTEST.

    The group planned to give the men dl alpha-tocopherol, a SYNTHETIC form of one aspect of vit E. We already KNEW that artificial and synthetic vitamins don’t penetrate the nucleus of the cell – 8th grade biology – and that matters. Additionally it was known that vit E was not JUST alph-tocopherol but a variety of tocopherols (beta, gamma, delta) and tocotrientols (similarly). So I objected to the choice of this dietary supplement. I was told it has already been used in the past, so was chosen to use again. I also had qualms about the choice of selenium.

    AND I worried that neither would be activated without vit C. I was told the men would be allowed to take a multi-vitamin of the RESEARCHERs CHOICE. I called that company, got a faxed list of ingredients. First of ALL were synthetic and artificial and ALL were (of course) at the RDA levels.
    These levels are too low to really help the body, just set to prevent scurvy or Beri Beri. Not really adequate in this day and age.

    So I ‘predicted’ from the start that this trial would NOT be successful for the reasons above. There is never a good effort to offer lifestyle information, JUST to test either thing separately. Those men should have been given (trained in) exercise and physical activity, stress reduction and a healthy nutritional plan with lots of fresh (organic when possible) fruits and vegetables.

    Sadly it is all too easy to create a study of dietary supplements that will fail as this one did.

    I am the founder of Annie Appleseed Project, a 20+ yr cancer survivor and an Advocate for all with cancer, from the Patient perspective.

    Reply
  • Rita Shimniok 03/30/2015, 5:50 PM

    Thank you for an excellent article/rebuttal on the SELECT study. Our oncologist just brought this up to us three days ago – and I began to dig in and investigate.
    Besides the poor choice of supplements, and lack of establishing patient baseline/deficiencies – I uncovered this…
    Irony?

    A report on SELECT, as written in National Institute of Health News/Southwest Oncology Group released October 27, 2008 has a very interesting notation, as follows…
    >>It should be noted that in 2003, while SELECT was recruiting men, a different SWOG sponsored study reported that the drug finasteride reduced the incidence of prostate cancer by 25 percent. When this was discovered, men on SELECT were informed and allowed to take finasteride. Finasteride has not yet been approved by the U.S. Food and Drug Administration for prostate cancer prevention.<<

    DOES THIS MEAN SELECT PARTICIPANTS were also taking an unapproved drug? I am not an MD/ND but as a health advocate, this is what I am gathering from the above paragraph excerpt.

    Rxlist.com provides a list of side effects for prescription drugs. The following is from the site:
    Proscar (finasteride) is used to treat symptoms of benign prostatic hyperplasia (BPH) in men with an enlarged prostate. It works by decreasing the amount of a natural body hormone dihydrotestosterone (DHT) that causes growth of the prostate.
    Long-Term Data
    High-Grade Prostate Cancer
    The PCPT trial was a 7-year randomized, double-blind, placebo-controlled trial that enrolled 18,882 men ≥ 55 years of age with a normal digital rectal examination and a PSA ≤ 3.0 ng/mL. Men received either PROSCAR (finasteride 5 mg) or placebo daily. Patients were evaluated annually with PSA and digital rectal exams. Biopsies were performed for elevated PSA, an abnormal digital rectal exam, or the end of study. The incidence of Gleason score 8-10 prostate cancer was higher in men treated with finasteride (1.8%) than in those treated with placebo (1.1%) [see INDICATIONS AND USAGE]. In a 4-year placebo-controlled clinical trial with another 5α-reductase inhibitor (dutasteride, AVODART), similar results for Gleason score 8-10 prostate cancer were observed (1% dutasteride vs 0.5% placebo).
    No clinical benefit has been demonstrated in patients with prostate cancer treated with PROSCAR.

    Perhaps, Dr.Geo, I am misunderstanding what the NIH report was alluding to – but I cannot imagine any credible scientific study being done allowing such a breach of control to take place…

    Reply

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