45 replies to this topic

[kenj]

Hard to pick, and it would depend on HOW you'd want to interfere with aging ;-), but, FWIW: a trio with an OTOH stronger glucose/insulin/'inflammation modulating' effect:
Metformin, resveratrol and benaGene.

[zawy]

Well, you've encouraged me to looked into the anti-antioxidant info and I'm starting to agree that it does not look good. In particular, the WACS study (your second link that I initially rejected) seems hard to fake. It was conducted by 9 people from Harvard which usually causes me to immediately reject it based on their historical and extreme bias against all things supplemental. It doesn't help that the AMA published it. But still, it seems to be hard to fake.

http://archinte.ama-...ac249f11c1708b0

Edited by zawy, 14 May 2009 - 10:01 AM.

[nameless]

Well, you've encouraged me to looked into the anti-antioxidant info and I'm starting to agree that it does not look good. In particular, the WACS study (your second link that I initially rejected) seems hard to fake. It was conducted by 9 people from Harvard which usually causes me to immediately reject it based on their historical and extreme bias against all things supplemental. It doesn't help that the AMA published it. But still, it seems to be hard to fake.

http://archinte.ama-...ac249f11c1708b0

I've remember reading this study in several news articles, stating that the vitamins showed no benefit. But when taking into account noncompliance, didn't the vitamin E group in fact show a benefit?

22% reduction in MI, 27% reduction in stroke,9% reduction in CVD mortality.

And I think the vitamin C group trended towards a minor benefit for ischemic stroke.

Unless I completely misunderstood the study, it appears those who actually took vitamin E, benefited from it. Yet, the study authors claimed in their conclusion that no benefit was seen, basing it off of women who in fact didn't even take the vitamins they were studying. Sort of a weird conclusion.

[kismet]

I don't think that vitamin C trend is particularly meaningful with a P value of .47. The vitamin E findings - after they were adjusted for compliance - are indeed interesting. It's also quite interesting to note that when performing the same analysis on beta carotene it worsened the results (vitamin A derivatives at such doses are a scary thing). But excluding patients generally weakens the data and includes sources of bias, which is the reason why intention to treat analysis is preferred (to the best of my knowledge).

Edited by kismet, 14 May 2009 - 06:26 PM.

[nameless]

Yeah, the vitamin C benefit is iffy. At least it didn't sort of kill people, like beta carotene may have. I wonder what the mechanism there was? High dose A depleting D?

But for vitamin E, I understand the reasoning behind the 'intention to treat' analysis, but (in my opinion) including participants who weren't even taking the vitamin is even more flawed.

A proper E study, using all forms (including tocotrienols) would be interesting, if they ever eventually do one. Repeatedly using alpha E only, vitamin C and beta carotene for seemingly every study is getting a little tiresome.

And as to the original poster's question... umm... for life extension, I'd say probably nothing yet, as nothing has proven to extend lifespan. Maybe caloric restriction, but that's obviously not a supplement.

But for general health/preventing disease, which I suppose indirectly would extend lifespan:

Vitamin D
K2 (Mk-4 or 7)
Omega 3s
Polyphenols (grapeseed, green tea, cocoa, blueberries, pomegranate)

Edited by nameless, 14 May 2009 - 07:21 PM.

[zawy]

As a rough check on the study's statistics, using a simple SQRT(N) rule I get +/- 5 deaths of the 125 deaths in each group could be due to random error. So like the study, I estimate that only the 133 deaths in the C+E+beta-carotene group is in the realm of statistical significance. However, they are looking at 8 categories and so there are 8 chances for statistical error to occur. I could not do the theoretical statistics on this, so I ran a program 1,000,000 times to simulate 1,000,000 studies identical to this. 33% of the time at least 1 of the 8 categories showed statistical significance at the 95% level due to random chance alone. 10% of the time 2 categories showed statistical significance. So I don't consider it important that they found 1 category that was 3% out of the range I expected. But imagine the damage it does to the supplement industry that they were able to say that one category found harm.

Another problem with the study is that the average length of time that these over-middle-age people took the supplement was about 5 years before they died. So it's 500 mg/d vitamin C and 300 IU/d vitamin E for only 5 years, looking for the most part only at heart disease....I'm not really surprised that would not show anything. I plan on taking 10 times as much vitamin C over 6 times as long, for 2 times as many possibilities of illness (10x6x2=120 times difference). So maybe this study was checking only 1% of vitamin C usage.

The study design, the way of looking at the statistics, and what is chosen to be said in the abstract are the methods I usually see to draw negative conclusions from an "anti-supplement" group like this one (Harvard). I was violating my rule about ignoring "everything-supplement-and-pharmaceutical" from Harvard because it's hard to get data from a study this large. I don't know if the source of funding (National Heart, Lung, and Blood Institute) is infested with pharmaceutical influence like the National Cancer Institute. But I have to wonder why they chose Harvard and not someone less rabidly anti-supplement.

* The SQRT(N) rule works like this: 830-70 dropouts in each category gives N=760 so SQRT(760)/760 = 3.6% range of random error for 95% confidence. 3.6% of 125 samples is +/- 4.5

Edited by zawy, 15 May 2009 - 01:48 PM.

[Dmitri]

As a rough check on the study's statistics, using a simple SQRT(N) rule I get +/- 5 deaths of the 125 deaths in each group could be due to random error. So like the study, I estimate that only the 133 deaths in the C+E+beta-carotene group is in the realm of statistical significance. However, they are looking at 8 categories and so there are 8 chances for statistical error to occur. I could not do the theoretical statistics on this, so I ran a program 1,000,000 times to simulate 1,000,000 studies identical to this. 33% of the time at least 1 of the 8 categories showed statistical significance at the 95% level due to random chance alone. 10% of the time 2 categories showed statistical significance. So I don't consider it important that they found 1 category that was 3% out of the range I expected. But imagine the damage it does to the supplement industry that they were able to say that one category found harm.

Another problem with the study is that the average length of time that these over-middle-age people took the supplement was about 5 years before they died. So it's 500 mg/d vitamin C and 300 IU/d vitamin E for only 5 years, looking for the most part only at heart disease....I'm not really surprised that would not show anything. I plan on taking 10 times as much vitamin C over 6 times as long, for 2 times as many possibilities of illness (10x6x2=120 times difference). So maybe this study was checking only 1% of vitamin C usage.

The study design, the way of looking at the statistics, and what is chosen to be said in the abstract are the methods I usually see to draw negative conclusions from an "anti-supplement" group like this one (Harvard). I was violating my rule about ignoring "everything-supplement-and-pharmaceutical" from Harvard because it's hard to get data from a study this large. I don't know if the source of funding (National Heart, Lung, and Blood Institute) is infested with pharmaceutical influence like the National Cancer Institute. But I have to wonder why they chose Harvard and not someone less rabidly anti-supplement.

* The SQRT(N) rule works like this: 830-70 dropouts in each category gives N=760 so SQRT(760)/760 = 3.6% range of random error for 95% confidence. 3.6% of 125 samples is +/- 4.5

Are you going to blame every failed study on Big Pharma? I don't see what they would gain considering many produce health products (non-drugs) themselves.

Anyway, here's a study that mentions how alpha tocopherol lowers other types of Vitamin E in the body, which the researchers speculate is the reason why Alpha tocopherol alone has failed to yield results.

Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans.

Huang HY, Appel LJ.
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. hyhuang@jhsph.edu

Despite promising evidence from in vitro experiments and observational studies, supplementation of diets with alpha-tocopherol has not reduced the risk of cardiovascular disease and cancer in most large-scale clinical trials. One plausible explanation is that the potential health benefits of alpha-tocopherol supplements are offset by deleterious changes in the bioavailability and/or bioactivity of other nutrients. We studied the effects of supplementing diets with RRR-alpha-tocopheryl acetate (400 IU/d) on serum concentrations of gamma- and delta-tocopherol in a randomized, placebo-controlled trial in 184 adult nonsmokers. Outcomes were changes in serum concentrations of gamma- and delta-tocopherol from baseline to the end of the 2-mo experimental period. Compared with placebo, supplementation with alpha-tocopherol reduced serum gamma-tocopherol concentrations by a median change of 58% [95% CI = (51%, 66%), P < 0.0001], and reduced the number of individuals with detectable delta-tocopherol concentrations (P < 0.0001). Consistent with trial results were the results from baseline cross-sectional analyses, in which prior vitamin E supplement users had significantly lower serum gamma-tocopherol than nonusers. In view of the potential benefits of gamma- and delta-tocopherol, the efficacy of alpha-tocopherol supplementation may be reduced due to decreases in serum gamma- and delta-tocopherol levels. Additional research is clearly warranted.

Edited by Dmitri, 15 May 2009 - 05:06 PM.

[zawy]

Are you going to blame every failed study on Big Pharma?

I'm not blaming big pharma. I'm blaming Harvard, AMA, and American media for promoting this "non-issue" paper as a reason to not take vitamin C and vitamin E for heart health and then it being recycled as evidence for overall mortality. It's basically a 5 year study (for the average death) taking low levels of vitamin C and mild levels of vitamin E, in a group of women that were dying at a fast pace from pre-existing heart disease. At best it shows vitamin E is not a miracle cure for that group. I fully support big pharma's right to manipulate the media and government like all other industries. I do not support organizations like Harvard, NCI, AMA, sloan-kettering, etc in claiming that they are acting in the best interests of american's health.

[nameless]

At what dosage of alpha tocopherol does it begin to deplete gamma, etc? Any studies on this?

The above study Dmitri mentioned used 400IU, which is quite a bit.

One interesting and somewhat contradictory bit of info I recall reading (assuming it's correct) is that the diet of Europeans is typically alpha tocopherol dominant, while for Americians it is Gamma. But perhaps the amount of alpha they consume isn't enough to deplete gamma, delta, etc.

[Dmitri]

Are you going to blame every failed study on Big Pharma?

I'm not blaming big pharma. I'm blaming Harvard, AMA, and American media for promoting this "non-issue" paper as a reason to not take vitamin C and vitamin E for heart health and then it being recycled as evidence for overall mortality. It's basically a 5 year study (for the average death) taking low levels of vitamin C and mild levels of vitamin E, in a group of women that were dying at a fast pace from pre-existing heart disease. At best it shows vitamin E is not a miracle cure for that group. I fully support big pharma's right to manipulate the media and government like all other industries. I do not support organizations like Harvard, NCI, AMA, sloan-kettering, etc in claiming that they are acting in the best interests of american's health.

In your previous post you made it sound like Big Pharma was at fault: This is what you said:

I don't know if the source of funding (National Heart, Lung, and Blood Institute) is infested with pharmaceutical influence like the National Cancer Institute.

Therefore, your new claims make no sense to me, first you blame pharma influence on NCI (and other institutes) then you say you support Big Pharma manipulation but not when it comes to NCI? Why even complain about Pharma influence if you support it?

[zawy]

I support big pharma engaging in normal American business practices. I do not support government-funded institutions falling for it, especially when they also seek donations from the public for heart and cancer research that only goes to support the big pharma position. There's no contradiction in this position.

[niner]

I support big pharma engaging in normal American business practices. I do not support government-funded institutions falling for it, especially when they also seek donations from the public for heart and cancer research that only goes to support the big pharma position. There's no contradiction in this position.

You support big pharma's "right" to manipulate the media, yet you don't want publicly funded institutions to claim they are acting in the public's best interest, but really be falling for pharma's line. I would argue that no one has a right to manipulate the media, since that would seem to imply getting media to publicize something that is a lie. I agree with you that publicly funded institutions should hold the public's interest uppermost. However, media manipulation is contrary to public interest and is ethically wrong. Looking at this from a public interest viewpoint makes these positions contradictory, though you may be using a different viewpoint such as free market primacy.

[zawy]

I think my position is because I don't see big pharma doing anything worse than any other industry like Microsoft, big oil, or the weapons industry. And I wonder sometimes if any of them are as bad as local AC "repair" companies. An old widow needing to change a clogged filter could end up buying a new system. I don't support outright fraud in any of the above, which is partly what I am accusing the "health institutions" of. Sure big pharma does some nasty stuff in some studies, but for the most part I blame the government for letting itself be influenced. But then you could say that's only because people won't vote right. The blame game can shift all over the place. As a simple summary you can say "big pharma", but as long as they aren't breaking any laws how can we point the finger at them? Maybe the invasion of iraq and watching "sicko" (he only good movie and a must see that is on youtube in its entirety) and "who killed the electric car"...these kind of things is where i finally got a deep sense of how bad our government has failed us. The credit crisis was (is) just another example, but no longer a surprise. What's next, a nuclear bomb going off in DC or NY? China controlling entire crucial industries because we don't value rare metals?

[Dmitri]

Are you going to blame every failed study on Big Pharma?

I'm not blaming big pharma. I'm blaming Harvard, AMA, and American media for promoting this "non-issue" paper as a reason to not take vitamin C and vitamin E for heart health and then it being recycled as evidence for overall mortality. It's basically a 5 year study (for the average death) taking low levels of vitamin C and mild levels of vitamin E, in a group of women that were dying at a fast pace from pre-existing heart disease. At best it shows vitamin E is not a miracle cure for that group. I fully support big pharma's right to manipulate the media and government like all other industries. I do not support organizations like Harvard, NCI, AMA, sloan-kettering, etc in claiming that they are acting in the best interests of american's health.

I see that you ignored the study about alpha tocopherol decreasing other forms of Vitamin E in the body, what are your thoughts on that issue? The Life Extension foundation brought up this issue in it's criticism of JAMA's new selenium and Vitamin E study that showed no prostate cancer prevention results.

http://www.lef.org/f...Trial-study.htm

Life Extension has conducted a thorough review of this latest study used to attack dietary supplements. In fact, Life Extension’s members were made aware of a fundamental fact 8 years ago that all but guaranteed trial failure of this latest attack against dietary supplements.

In the current JAMA trial, men supplemented with all-racemic alpha-tocopherol experienced significant gamma-tocopherol depletion. A careful review of the actual full-text JAMA publication reveals gamma-tocopherol depletion among those men supplemented with all-racemic alpha-tocopherol. Men supplemented with all-racemic alpha-tocopherol and alpha-tocopherol plus selenium experienced a 45% and 48%, respectively, depletion in gamma-tocopherol levels by 6 months that was sustained during the course of this 5-year trial.

As far back as March, 2001 in the article “Avoiding Prostate Cancer,”8 Life Extension identified the importance of gamma-tocopherol supplementation in dramatically lowering the risk of developing prostate cancer — in fact, a study of 10,456 men showed that men who had the highest blood levels of gamma-tocopherol were five times less likely to get prostate cancer.

I too have issues with some studies using supplements and this one appears to show that perhaps all 8 forms of Vitamin E would be better then simply mega-dosing with alpha tocopherol alone as you once recommended.

[outsider]

Your first reference was from a school that is named after receiving funding from the founder of a pharmaceutical company, so i don't know how deep the influence of the pharmaceutical money runs in that organization. Part of their abstract is telling:

Our goal was to bring this controversy to an end

They only used studies that were accepted in the meta-analyses eventhough the primary objection was the selection of studies. And yet the abstract claims they were seeking to lay the objections to rest. It makes sense only if you view them as biased.

In your second study, the "significant" result was on a small number of people (I would guess about 100 people based on the large 1.03 to 2.20 CI range) out of 8,400 with a particular condition. Let's say the other "nonsignificant" result of 20% increased risk from vit E on 220 people was accurate. What about the other 8,200 people? Did those taking vitamin E show an increase or decrease in all-cause mortality?

You reject the research because it's funded by pharmaceutical companies (a lot of pharm companies make supplements), yet you trust research from decades ago? 30-50 years ago we didn't know much about our body's biochemistry and how vitamins interacted with our systems, which is part of the reason why the medical community rejected using vitamins for treatment (could be a flaw of past research?). You mention the Shute brothers in a previous post, their blind devotion for E was so strong that they continued their research despite being shunned by the medical community, are you willing to say these men had no biases? Also, were past studies long term or short term? Recent studies that point to no effect or harmful effects of alpha tocopherol alone were conducted over a period of years.

Here's a 7 year study:

http://news.bio-medi...-failure-209-1/

The proponents of Vitamin E argue that the study is flawed because only one form of E was used.

Here's another 8 year study(conducted by Doctors) that showed no benefit when combined with Vitamin C:

http://www.usatoday....nts-study_N.htm

Anyway, would you like to discuss Big Pharma here: http://www.imminst.o...showtopic=29911

It is really simple why the big pharma reject the vitamins and herbs in general. It's all about the money. It is much more profitable to patent a molecule and sell it at a high price.

For exemple they never use the natural body hormones in hormone replacement therapy, they use patented almost the same molecules with more side effects I believe. They use cortisone instead of the natural body hormone cortisol. Doctor rarely use the original molecules. Why? Because patented molecules means cash for the industry.

[AgeVivo]

to not take vitamin C and vitamin E for heart health and then it being recycled as evidence for overall mortality. It's basically a 5 year study (for the average death) taking low levels of vitamin C and mild levels of vitamin E, in a group of women that were dying at a fast pace from pre-existing heart disease. At best it shows vitamin E is not a miracle cure for that group. (...) big pharma's right to manipulate the media and government like all other industries.

want to know if some particular vitamins, herbs, supplements or drugs where tested on lifespan in normal animals? that would be a minimal thing to know, right? well, just ask the question in this thread, we'll look for the answer

Edited by AgeVivo, 19 May 2009 - 08:16 AM.