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Huge New Trial: Selenium Vs Prostate Cancer


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#1 Michael

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Posted 30 October 2008 - 10:12 PM


All:

It's supplement company dogma that selenium supplements higher than the 55 mcg RDA prevent cancer and reduce mortality; this is based on (to quote myself):

the Nutritional Prevention of Cancer Study, the big RCT of selenium vs skin cancer whose initial results were very promising for Se: there was no reduction in skin cancer risk (the primary endpoint), but "Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR; 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality ..., total cancer incidence ..., and incidences of lung, colorectal, and prostate cancers." (1) Subsequent reports detailed those results, parsing them out for individual cancer sites.

This result led to every damned Se supplement out there containing the 200 mcg dose used in the trial, and is cited everywhere as definitive proof of Se supplementation's ability to reduce cancer incidence & mortality. This was initially a reasonable enough conclusion (tho' it was not properly emphasized that the population was intentionally chosen from an area with unusually low-selenium soils (the Eastern USA), thus making the cohort result dubiously-extrapolable to the population at large (there would be many more frankly deficient people in this group than most places in the industrialized world) -- and even here, according to this new report on diabetes risk (7), "the average dietary selenium intake is 90 mcg/d; this value is low for the United States but is much greater than that required to optimize selenoenzyme activities" -- which is the cutoff on whose basis they set the RDA (of "only" 55 mcg). ...

Since then, however, additional analysis has shown this to be a dangerous oversimplification. Subsequent reports from the NPC (1-5) as well as animal studies (eg, (6)) have shown that this dose of Se gives no add'l benefit to some cancers, and may INCREASE the risk of others. These studies find that basically all of the benefits come from correcting frank (sub-RDA) selenium deficiency, with people who already have normal Se intake in their diet getting no benefit for some cancers, and increases in risk for others. The ongoing, unqualified, dogmatic repetition of the cancer claim now constitutes borderline-criminally-negligent oversimplification -- especially when, as when a Certain Supplement Company with which I used to be in a competitive relationship was wont to do, companies cite multiple reports from this SAME STUDY as if they were SEPARATE trials, each independently confirming Se's ability to protect from cancer...


... and, as detailed in that post (which I encourage you to read either before or after this one, for much more detail & proper citations), they then went on to find an increase in diabetes in the supplemented group.

With that as background: it was on the basis of the original result of the Nutritional Prevention of Cancer Study that the National Cancer Institute launched SELECT:

the Selenium and Vitamin E Cancer Prevention Trial, a clinical trial to see if one or both of these substances can help prevent prostate cancer when taken as dietary supplements. ... Enrollment for the trial began in 2001 and ended in 2004. More than 400 sites in the United States, Puerto Rico, and Canada are taking part in the study. Over 35,000 men are participating in SELECT ... The amount of selenium (provided as l-selenomethionine) was 200 micrograms (µg) daily. ... The amount of vitamin E (provided as dl-alpha-tocopherol acetate) was 400 milligrams (mg), which is equivalent to 400 International Units (IU) per day.


Well, now they've pulled the plug on it early, because the results are coming in similarly to the ultimate conclusions of the smaller NPCS:

Prostate Cancer Prevention Study Halted - Vitamin E, Selenium No Help in Preventing Prostate Cancer
By Daniel J. DeNoon
WebMD Health News
Reviewed by Louise Chang, MD

Oct. 28, 2008 -- The National Cancer Institute has halted its $114 million study of whether vitamin E and selenium can prevent prostate cancer.

They can't [prevent prostate cancer] -- at least not in the formulations and dosages used in the study, called SELECT (SELenium and vitamin ECancer prevention Trial). The safety panel for the 35,000-man study called for a halt when an early look at the data showed no benefit for the treatment.

There were slightly more prostate cancers in men taking vitamin E alone, and slightly more diabetes in men taking only selenium. But neither finding was statistically significant, meaning they were likely due to chance. [Actually, since these same results were also found in the NPCS (for diabetes) and in other RCTs using alpha-tocopherol (for prostate cancer), I'm inclined to suspect a real, but small, effect -MR].

"The data to date suggest, but do not prove, that vitamin E may slightly increase the chance of getting prostate cancer, and that selenium may increase the chance of getting diabetes mellitus," warns a letter sent to study participants by the Southwest Oncology Group, which ran the NCI-funded study. [That's a better summary IMO - MR].

Study participants were told to stop taking the two pills they'd been taking every day since the trial opened in 2001. The men received either vitamin E (400 milligrams) and selenium (200 micrograms), vitamin E and placebo, selenium and placebo, or placebos alone.

Now, people (especially, but not only, supplement companies) are going to say that the results were not statistically significant -- which is true, but again, they are consistent with previous such reports, which makes me suspect a small, but real, effect; certainly, having one trial after another come in with no benefit or a small risk makes it pretty darned clear that they aren't doing anything good.

People will also say that they used the wrong forms. I'm inclined to suspect this may very well be true. It's pretty darned clear that people need to stop taking straight alpha-tocopherol; I suspect that the 'right' supplement, if such exists, is high-gamma mixed tocopherols and tocotrienols with <30% total alpha-tocopherol (and, I'm inclined to say, <30 IU of total alpha-tocopherol IAC), and for Se, Se-methylselenocysteine -- please see my discl0sure, which is extremely relevant to both of these recommendations. But take a step back. There is not anywhere near the level of evidence in support of a benefit of these supplements (largely very artificial animal studies; far fewer total scientific reports vs the standard forms; and no human clinical trials with clinical outcomes).

And, of course, supplement companies and others will pretend that a zillion other studies contradict these. But they'll use much weaker kinds of evidence -- epidemiology instead of clinical trials, or clinical trials with surrogate outcomes, or they'll play 'echo chamber' by citing multiple reports of the same benefit from the same study as if they were separate clinical trials, as was routinely done with the NPCS.

I put it to you all that this engine of marketing and speculation is not a good basis on which to gamble your long-term health.

I strongly urge everyone to go over your collection of pill bottles, and ask yourself, seriously, why you're taking it. What is the evidence, in normal, healthy humans, of a benefit? Is this a supplement proven beneficial for a specific disease that you already have by large, long-term, randomized clinical trials? Have you carefully analyzed your quotidian diet using excellent nutritional software like CRON-O-Meter, and decided to take a specific supplement to correct your own diet's specific nutritional shortcomings, using doses similar to what is available from a healthy diet and/or the RDA?

If not, what are you putting into your body, and why?

The day of megadosing as a reasonable gamble for life-extensionists -- of 'it can't hurt, and it might help', of a speculative 'bridge to a bridge' -- is over. The evidence actually available is that high-dose vitamins and minerals don't help, and may harm; the "evidence" to the contrary is speculation and bluster.

You can't reach 'escape velocity' if you kill yourself first.

-Michael

Edited by Michael, 30 October 2008 - 10:20 PM.

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#2 Mind

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Posted 30 October 2008 - 11:03 PM

Another recent topic that dove tails nicely with this discussion.

Thanks for the informative post Michael!

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#3 kismet

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Posted 30 October 2008 - 11:31 PM

That's pretty bad news if turns out to be true. Once again tinkering with human metabolism, "the gerontological approach" to health, produces no results. Even with orthomolecular medicine it's difficult to do any good when messing with the body, very disillusioning.
Your proposed "engineering" approach looks more appealing by the minute, even though altering the metabolism should be superior ultimately (if and when we figure out every detail of metabolism).

#4 rwac

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Posted 31 October 2008 - 07:04 AM

It's possible selenium causes Diabetes by affecting the thyroid.

Here's a link between hypothyroidism and selenium.

Perhaps some Iodine supplementation is needed to go with the selenium ?

Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium.
  • Good Point x 1

#5 tham

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Posted 31 October 2008 - 05:19 PM

These kind of results are not surprising.

The SELECT trial was flawed right from the beginning. I had thought about posting on this here shortly after it was started, but forgot about it (instead posted it in an astrology forum some time ago which happens to be one of my interests, for the benefit of one lady who was concerned that a lump in her breast might be cancer !).

http://forum.astro.c...192234863/37#37

They used :

1. Selenomethionine (basically useless if you are going to take it in an attempt to fight cancer), when most of the studies showing DIRECT cytotoxic action on cancer pointed to inorganic sodium selenite or sodium selenate as a second choice.

2. Oily Tocopherol acetate, when most studies of vitamin E showing cancer therapeutic or preventative properties used dry vitamin E, tocopherol succinate. Twelve years ago, when I faxed Abram Hoffer asking his advice for a regimen of supplements for a lung cancer lady in one of our offices, he specifically mentioned vitamin E as tocopherol succinate.

I had emailed the SELECT website then, pointing out the flaws, but, as expected, receive no reply. I remember they used a different website.

http://www.crab.org/select/

Here they say that the yeast-based form should have been used for prevention, but inorganic selenite, or at least sodium selenate, is the way to go if you already have cancer. Even for prevention alone, I would still hedge my chances on selenite.

http://www.bio-medic...mentati-3365-1/


http://www.ncbi.nlm....l=pubmed_docsum


Even Se-methylselenocysteine is not the form of choice. Dr Drake's reply to my mail about his above study, asking if the highly-touted Se-Msc might be superior to selenite.


*From:* "Ed Drake" <endrake@airbits.com>
*To:* <tham@linuxmail.org>
*Cc: *
*Subject: * Selenium and Cancer
*Date: * Fri, 16 Feb 2007 12:01:43 -0700

------------------------------------------------------------------------
Dear Mr. Wai Keong,

Thank you for your supportive email regarding the NCI clinical trial. We certainly need more individuals who have the interest to read critically the literature on nutrients and cancer. With respect to your interest in Se-methylselenocysteine, you would be encouraged by selenium researchers to think positively about the anticarcinogenic effectiveness of this compound. I am familiar with Dr. An-Sik Chung's work, and we have had some selenium discussions at the most recent meeting of the International Symposium on Selenium in Biology and Medicine in Madison, Wisconsin.

If you read the entire manuscript, you might notice that the concentrations of Se-methylselenocysteine used are substantially greater than those of selenite. The effects of all drugs, nutrients, etc. are dose dependent.Indeed, the FDA in the U.S. has not approved the use of any selenium compound in doses sufficient to produce these cellular concentrations. The interest in Se-methylselenocysteine seems to stem from the fact that it can be converted directly to the putative cancer chemopreventive compound, methylselenol, by action of the enzyme beta-lyase.

Unfortunately, the only incidence in which Se-methylselenocysteine has been shown to be effective as an antitumor agent at doses comparable to selenite or methylseleninic acid is an experiment in mice, where the amount of beta-lyase is thought to be 800 times larger than humans. Thanks again for you interest.

Kind regards,

Ed Drake


[Edited by Michael to restore full margins; not one word was changed]
.

Edited by Michael, 31 October 2008 - 07:18 PM.

  • Good Point x 1

#6 Forever21

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Posted 31 October 2008 - 05:42 PM

Thanks for that Michael.

I've given up my supplement regimen recently.

#7 Dmitri

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Posted 31 October 2008 - 06:07 PM

Thanks for that Michael.

I've given up my supplement regimen recently.


I'm going to do the same thing; I will hold of on using quercetin, r-lipoid acid and Vit. C and simply stick with Vit. D3, green tea and a multi (3-4 days a week). I used the cron-o-meter Michael posted and it appears I already get more than what the RDA recommends in my diet so I don't need supplementation excluding omega 3,6 and Vit D which was 0% only because their database does not contain rice milk. My diet also consists of antioxidant rich foods so I'm covered there as well.

#8 sUper GeNius

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Posted 31 October 2008 - 08:13 PM

Yep, I've stopped many of the supplements I used to take. Less is more for me now. I'm taking raw cocoa powder, a multivitamin a few days a week, omega 3, (about a gram or so) curcumin, because I have excellent results with it, green tea extract, about 200mg, vitamin D, about 2000IU, and about 300-500mg resveratrol daily.

That and a broad plant based diet, some meat and chicken. Hate fish.

Also some intermittent fasting, which lately has become difficult. My body has begun to resist; my hunger had gotten stronger.

#9 davidd

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Posted 01 November 2008 - 01:42 AM

Michael,

I'd like your input on something. Where do you stand on RDA being a bare minimum and that the optimum amount for health may be above RDA, but not in true mega-doses? It seems your post is indicating not to mega-dose on vitamins, etc., but does that mean stick with the RDA, or try to find a happy ground inbetween RDA and mega-dosing (leaning toward the RDA end of the scale) on a case by case basis?

Thanks for any feedback you can provide.

David

#10 nameless

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Posted 01 November 2008 - 03:32 AM

If not, what are you putting into your body, and why?

The day of megadosing as a reasonable gamble for life-extensionists -- of 'it can't hurt, and it might help', of a speculative 'bridge to a bridge' -- is over. The evidence actually available is that high-dose vitamins and minerals don't help, and may harm; the "evidence" to the contrary is speculation and bluster.

You can't reach 'escape velocity' if you kill yourself first.

-Michael


I have wondered about the large amount of supplements people take here, and if they have scientific reasons for doing so. It seems lots are taking mega doses of Resveratrol, for instance, and I am not aware of a single human study stating it has any real benefit in regard to life extension. Even the rodent studies didn't look so good, really.

Michael: What supplements, if any, do you recommend for general health?

My current supplementation consists of a multi, half-dose daily, fish oil/omega 3s (for heart health/triglyceride control), Coenzyme Q10 (for cardiomyopathy), vitamin D (due to deficiency), D/K2 dots, 1-2 weeky (heart/vascular), grape seed (for vascular and perhaps benefits for allergies/asthma) and some extra magnesium (good for hearts).

And how do you feel about using blood testing, instead of the Cron-o-meter, to determine optimal supplement intake? Most vitamins + minerals can be tested via serum, so would that be a better way to determine if a person is getting a proper amount via diet alone?

#11 E.T.

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Posted 22 November 2008 - 10:36 AM

I've given up my supplement regimen recently.


So it appears to me that it's "back to the drawing board" for you and others regarding life extension. It may be decades before a new method is invented for life-extension.

#12 kismet

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Posted 23 November 2008 - 07:23 PM

I've given up my supplement regimen recently.


So it appears to me that it's "back to the drawing board" for you and others regarding life extension. It may be decades before a new method is invented for life-extension.


Back to what? What has this to do with the topic? Selenium is not and was not claimed to be life extending per se.
Just wondering if Forever21 knows that MR also uses supplements (or at least used to, but I don't think he stopped, did you?) quite a lot...

#13 albedo

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Posted 28 December 2011 - 03:23 PM

I could not score higher Michael's post, would have given 5 if I could .... thank you for taking time to post here. It is a "hard-to-swallow" but "healthy" message to review all I am doing with supplements. I went trough all MR's 2004 lecture. Just great, lot of information, no marketing.

Take back message: " I strongly urge everyone to go over your collection of pill bottles, and ask yourself, seriously, why you're taking it. What is the evidence, in normal, healthy humans, of a benefit? Is this a supplement proven beneficial for a specific disease that you already have by large, long-term, randomized clinical trials? Have you carefully analyzed your quotidian diet using excellent nutritional software like CRON-O-Meter, and decided to take a specific supplement to correct your own diet's specific nutritional shortcomings, using doses similar to what is available from a healthy diet and/or the RDA?"

Edited by albedo, 28 December 2011 - 03:23 PM.


#14 Clarity

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Posted 28 December 2011 - 05:52 PM

It's possible selenium causes Diabetes by affecting the thyroid.

Here's a link between hypothyroidism and selenium.

Perhaps some Iodine supplementation is needed to go with the selenium ?

Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium.


I wish I had more time to read these forums. Tossing that bottle of selenium I started giving husband & I over a month ago. Geezus. Maybe that's why my BS has been going up, and my temperatures going way down.

#15 albedo

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Posted 29 December 2011 - 06:19 PM

For those supplementing with high doses of selenium I suggest checking historic of HbA1c marker as high selenium dosage might negatively affect glucose metabolism; e.g. see:

http://www.mendeley....ype-2-diabetes/

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#16 Clarity

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Posted 29 December 2011 - 06:48 PM

For those supplementing with high doses of selenium I suggest checking historic of HbA1c marker as high selenium dosage might negatively affect glucose metabolism; e.g. see:

http://www.mendeley....ype-2-diabetes/


Interesting, very interesting. I have supplemented sellenium intermittently, and have had intermittent high'ish (as well as low) blood sugar. I stopped yesterday and didn't take my multi either. My fasting glucose was almost normal (101). The muscle aches I had been getting since this last period of supplementing also abated. Maybe coincidence - I'll have to see what happens over next few days. But I was just reading a study of a case of a mfg. whose selenium supplement was much higher than the dose claimed and there were cases of selenium toxicity in 2008. They did not name the mfg. I'm being careful for now about what I take.

I have not had my HBA1C checked in awhile, but will soon. I always thought it would be relatively inaccurate for me because I have swung between high and low and thought it would avg out to normal (which it usually does).

Edited by Clarity, 29 December 2011 - 06:51 PM.





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