22 replies to this topic

[lucid]

Here is a BBC article that came out today saying that a study done by Copenhagen University suggested that some vitamins shorten people's lifespan.
http://news.bbc.co.u...lth/6399773.stm

Here is a summary:
--Beta-carotene produced an approximate 7% increased risk.
--Vitamin E a 4% increased risk.
--Vitamin A a 16% increased risk.
**Risk is risk of death
This was a survey of lots of 815 studies (68 were selected to be included in the results)
They were unclear what the criteria was for selecting studies.

Not knowing a tremendous amount about vitamins or studies pertaining to them, I don't know what to think about this. I imagine people on this forum feel pretty strongly about this issue.
How much evidence is out there for the benefit of these vitamins in humans?

Edited by lucid, 01 March 2007 - 02:54 AM.

[shifter]

I believe they would have used synthetic isolated forms of the vitamins. Not recommended. I get my vitamins and minerals from powdered 'food' like algae, grasses, maca & sea vegetable so no worries from me.

[bgwowk]

How much evidence is out there for the benefit of vitamins in humans?

How much evidence is out there for the benefit of any substance in humans? If a meta-analysis showed that certain drugs increased the death rate of people with certain conditions by 10%, would headlines report, "Drugs don't work?" Would such a generalization be justified?

Scientifically, there shouldn't even be a distinction between drugs and supplements. Conclusions about the efficacy of substances should be based on the chemical identity of substances, not their political classification (drug or supplement).

[lucid]

Right my bad. By vitamins, I specifically meant Vit A, Vit E, and Beta-carotene. I of course didn't mean to group all vitamins together. So to rephrase:

How much evidence is out there for the benefit of vitamins A, vitamins B, Beta-carotene in humans?

Someone just posted this topic again.. (for the record mine was first) heh

[maxwatt]

FWIW, most vitamins have an inverted "U" shaped dose/benefit curve. The standard vitamin E pill is 400 units, but some think 200 units provides the maximum benefit. Too much may act as a pro-oxidant.

As for getting your vitamins from food, I don't think your body cares if a molecule came from a lab or from a plant or animal, but food sources are more likely to contain cofactors and as-yet unknown essential nutrients.

Edited by maxwatt, 01 March 2007 - 09:54 PM.

[ajnast4r]

i hate this thread

[ironchet]

I believe they would have used synthetic isolated forms of the vitamins. Not recommended. I get my vitamins and minerals from powdered 'food' like algae, grasses, maca & sea vegetable so no worries from me.

I believe most of us here take the higher quality food derived vitamins but the majority of supplement buyers do not know the difference, as this article (link below) points out the importance of getting natural form of vitamins and supplements..

Dietary Supplments: What the Industry does NOT want you to know

A number of forms of synthetic vitamins A and D are used in supplements. All should be strictly avoided--even small amounts of the synthetic forms of fat-soluble vitamins may be toxic. In fact, the toxicity of these synthetic forms has contributed to the media frenzy about the alleged dangers of vitamins A and D. The media and the medical establishment do not distinguish between the synthetic forms and natural vitamins A and D as found in or derived from animal fats.

Vitamin E is another nutrient for which it is very important to select the proper form. Synthetic vitamin E is labeled, "d, l- alpha." This mixture of "d" and "l" forms is biochemically different from natural vitamin E which is labeled "d-alpha." Like synthetic vitamins A and D, synthetic vitamin E has detrimental effects. It is incompletely metabolized and may even disrupt the metabolism of natural vitamin E in the liver. The most beneficial natural vitamin E products come as mixtures of the alpha, beta, gamma, and delta tocopherol fractions.

[ryan1113]

Here is a BBC article that came out today saying that a study done by Copenhagen University suggested that some vitamins shorten people's lifespan.
http://news.bbc.co.u...lth/6399773.stm

Here is a summary:
--Beta-carotene produced an approximate 7% increased risk.
--Vitamin E a 4% increased risk.
--Vitamin A a 16% increased risk.
**Risk is risk of death

None of these are high priorities as far as slowing aging. We already know this from animal studies. Vitamin E is actually comprised of a whole family of tocopherols and tocotrienols, eight altogether (seven according to a few). Studies using synthetic racemate of vitamin E, d/l tocopherol, are misleading, as the l stereoisomer has been shown to be mildly toxic, and some are more sensitive to it than others. Aside from this, even high amounts of natural d-alpha tocopherol in isolation has been shown to reduce plasma levels of gamma tocopherol, which in and of itself may not be healthy. A recent study showed gamma tocopherol in humans might play some role in inducing certain heat shock proteins, which might have a positive effect on aging rate. Some researchers argue that gamma tocopherol must not be very important because it's actively metabolized and excreted, but what evidence there is suggests that it is important if you look at the animal studies. Vitamin E should only be taken in its natural form and full spectrum, meaning the whole family of vitamers. D and d/l-alpha tocopherol has been shown separately to raise oxidative stress a little when taken in isolation. It should also be noted that the 4% increase is itself very marginal, and given the methods used it might not even be statistically relevant.

We've had discussion on here recently about the fixation with Vitamin E, Vitamin C, and beta-carotene. Decades ago, these three substances become synonomous with what everyone thought of when they heard the word "antioxidant" when the understanding of antioxidants were still very primitive. Unfortunately, this trend has held, and instead of exploring the vast array of other more promising substances for human studies as is being done with animals, the old farts conducting the human trials seem to think that this trio thoroughly represents antioxidants as a whole, and this is very false. Alpha tocopherol "in vitro" is a decent antioxidant, but it doesn't hold true in high dosages in isolation in animals except in artificially induced excessive states of oxidative stress. Carnosine is perhaps a little weaker in vitro as an antioxidant than alpha tocopherol, but in vivo in high dosages it maintains its significant antioxidant punch where high dosage alpha-tocopherol might actually have a net pro-oxidant effect in healthy animals. There isn't always a direct correlation between what happens in very simple test tube experiments and what happens inside the body.

It's time to move away from the fixation on d/l alpha-tocopherol, vitamin c, and beta-carotene and stop repeating all the same work that's been done on these for the last three decades and start trying something else. We should start writing letters to people who are fixated on these exclusively as the antioxidants for human use and tell them to take their heads out of their as*es.

R-ALA (when including DHLA as part of its antioxidant action) has an antioxidant ability of over 1000 times alpha tocopherol and vitamin C combined, has far superior bioavailability to various cell components including the mitochondria which is key, and seems to do a long list of other things to help correct certain abnormalities in cellular function that might not even be directly related to its antioxidant function. It also is less likely to become pro-oxidant and recycles itself. We have extended release forms of this now as well, yet do we see any human trials with it as we do with the others..... no, of course not. A couple that are finally getting more attention in human trials are lycopene and green tea. Green tea is showing more benefit in vivo in humans than the other three put together.....

Edited by ryan1113, 01 March 2007 - 01:04 AM.

[zoolander]

yes yes this meta-analysis is causing quite a stir

here is the original article

Vol. 297 No. 8, February 28, 2007 

Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention

Systematic Review and Meta-analysis

Goran Bjelakovic, MD, DrMedSci; Dimitrinka Nikolova, MA; Lise Lotte Gluud, MD, DrMedSci; Rosa G. Simonetti, MD; Christian Gluud, MD, DrMedSci

JAMA. 2007;297:842-857.

Context  Antioxidant supplements are used for prevention of several diseases.

Objective  To assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention trials.

Data Sources and Trial Selection  We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials.

Data Extraction  We included 68 randomized trials with 232 606 participants (385 publications).

Data Synthesis  When all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.05-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality.

Conclusions  Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.


Author Affiliations: The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Bjelakovic, L. L. Gluud, Simonetti, and C. Gluud and Ms Nikolova); Department of Internal Medicine, Gastroenterology and Hepatology, University of Nis, Nis, Serbia (Dr Bjelakovic); and Divisione di Medicina, Ospedale V. Cervello, Palermo, Italy (Dr Simonetti).

Here is one review of the article (Source Pharmaconutrition Reviewed)

The Meta-Analysis published by Bjelakovic et al. addresses an issue that is getting more and more controversial, recently, i.e. whether antioxidant supplements are actually health-beneficial, show no effect or are even detrimental. Based on the analysis of 69 randomized trials with more than 200.000 participants, the authors conclude that
a) vitamin C and selenium have no effect on mortality
b) beta-carotene, vitamin A and vitamin E (singly or combined) significantly increase mortality

What do these results tell us?
First of all, I am curious to read the comments this article will certainly provoke. The widely cited Miller et al. study on vitamin E and mortality, for example, caused a quite heated debate, especially regarding the statistics used.
Secondly, we (at least most of us) are not only consuming nutrients – but food; although I haven’t fully digested this meta-analysis, yet, the results are – if valid – not that surprising, because when antioxidants are taken in as part of real food they actually exert quite different effects I contrast to supplements. Also, the argument that the antioxidant supplements might reduce “beneficial ROS” is a bit sketchy.
I just wonder, how the food supplement industry is going to react to this study – I think it cannot get a lot more worse for them.

Those of you that have a subscription to the GRG list would have noticed that they are also giving the paper a critique.

[doug123]

Here is a BBC article that came out today saying that a study done by Copenhagen University suggested that some vitamins shorten people's lifespan.
http://news.bbc.co.u...lth/6399773.stm

Here is a summary:
--Beta-carotene produced an approximate 7% increased risk.
--Vitamin E a 4% increased risk.
--Vitamin A a 16% increased risk.
**Risk is risk of death
This was a survey of lots of 815 studies (68 were selected to be included in the results)
They were unclear what the criteria was for selecting studies.

Not knowing a tremendous amount about vitamins or studies pertaining to them, I don't know what to think about this. I imagine people on this forum feel pretty strongly about this issue.
How much evidence is out there for the benefit of vitamins in humans?

Source: http://www.spiritind...icles-7064.html

Antioxidant :: Antioxidants provide benefits for maintaining good health

A new meta-analysis examining the effect of antioxidant supplements on all-cause mortality published in the Feb. 28, 2007 issue of the Journal of the American Medical Association (JAMA) misuses meta-analysis methods to create generalized conclusions that may inappropriately confuse and alarm consumers who can benefit from supplementing with antioxidants, said the Council for Responsible Nutrition (CRN), the leading trade association for the dietary supplement industry.

“Healthy consumers can feel confident in continuing to take antioxidants for the benefits they provide. This meta-analysis does nothing to change those facts,” said CRN’s Andrew Shao, Ph.D., vice president, scientific and regulatory affairs. “While meta-analyses can be useful when the included studies are very similar in design and study population, this meta-analysis combined studies that differ vastly from each other in a number of important ways that compromise the results.”

For example, the meta-analysis included clinical trials that varied widely in terms of dosage, duration, study population and nutrients tested—such as data from a one-day study with a vitamin A dose of 200,000 IU mixed with data from other studies lasting years. In addition, many of the clinical trials included in the meta-analysis tested nutrients beyond those that were the focus of the article (vitamins A, C, and E; beta-carotene; selenium), including lutein and zinc, making it difficult to appropriately evaluate the contribution of those trials to the overall meta-analysis.

“It’s like comparing apples and oranges,” said Dr. Shao.

Moreover, the overwhelming majority of the clinical trials included in the meta-analysis tested for secondary prevention, looking at how a nutrient works in those who already are diseased, instead of primary prevention studies in healthy populations.

“Combining secondary prevention and primary prevention trials and then making conclusions for the entire population is an unsound scientific approach,” said Dr. Shao. “Additionally, many of the treatment trials had limitations, including the expectation that a simple antioxidant vitamin could be expected to overturn serious illness, such as cancer or heart disease. These trials likely statistically skewed the results.”

Dr. Shao further pointed out, “The study authors concluded that overall there was no effect of antioxidant supplements on all-cause mortality. It was only after the researchers divided the chosen clinical trials into ‘high risk bias’ and ‘low risk bias’ groups, using their own criteria, that they observed a statistically significant effect on mortality. This meta-analysis appears to be a predetermined conclusion in search of a method to support it.”

(Last updated on Wednesday, February 28, 2007, and first posted on Wednesday, February 28, 2007)

[eternaltraveler]

Those of you that have a subscription to the GRG list would have noticed that they are also giving the paper a critique.

eh, not much of one yet.

[zoolander]

You're right actually elrond. I woke this morning and read a few people commenting on the report from a few different areas.

from the grg lis

To Members and Friends of the Los Angeles Gerontology Research Group:

        Studies that vitamin supplements help increase longevity come largely from
the unregulated health-food industry with billions of dollars behind them.  But the
statistical methods used in the meta analysis below are also questionable. So
who are we to believe? -- Steve Coles 

and

Continuing the thought from previous discussions, we find the advocate for vitamins (below) has a usual monetary conflict-of-interest:

The complaints were echoed by Andrew Shao, a scientist at the Council for Responsible Nutrition, a supplement trade association.

        "Only when they included and excluded certain trials were they able to find this
alleged increase in mortality, which they themselves can't explain," Shao said. "There is plenty of data out there that show regular use of antioxidant supplements help to maintain health."
A very twisted spin of the below data. I think a sample size of 180,000 is enough to draw conclusions.

Still to determine is whether 'vitamins' have health benefits when obtained through food. It's easy to say but do we have studies for this?

Sincerely
Robert Young

there's a reasonable interview with Dr. Shao (quoted above) here that discusses the use of antioxidants by consumers

[tom a]

Reading all of these rebuttals to the meta-analysis, I guess I find myself wondering, are there ANY good, large scale studies on HEALTHY people that show the positive effects of any of these antioxidants taken as supplements?

[lucid]

Well its never simple. Its its important to distinguish between all the antioxidants.

http://www.pubmedcen...rez&artid=15777
Vitamin E reduces chromosomal damage and inhibits hepatic tumor formation in a transgenic mouse
Title of article says it all.

I'm no expert in the field, but it seems to me that there are good studies 'in vitro' and in mice that pretty conclusively show the benefits of various antioxidants. The problem is that we need to see long term effects on large groups of people. There have been some studies done (I know of some in China and the Netherlands). But there doesn't seem to be a clear consensus, hence the 'need' for the meta-analysis. Hopefully someone has a better answer.

[biknut]

I think it's a problem of balance. To much of one thing without enough of another thing. Easy to do with supplements, not as easy with real foods if you eat a good diet.

[tom a]

I guess I don't fully understand the rebuttals to the meta-analysis.

The basic objection seems to be that the meta-analysis focused on studies involving people with medical conditions, instead of focusing on those with healthy people.

But what does that mean? Were there, in fact, ANY large studies conducted on healthy people using ANY of these supplements, or not? If there were, did they show positive effects, or no effect, or, indeed, a negative effect?

[xanadu]

I suspect this was financed by the pharm industry just as so many of those phony studies that "debunked" global warming were financed by big oil companies. I have seen a steady series of articles attacking vitamins, herbs and other alternative medical treatments. When you look closer, you find that the studies were almost invariably flawed, like starting with diseased subjects and expecting the substance to cure them when it was never claimed that it was a cure, merely a preventive. It didn't cure the disease so it must be no good at all. Same with this meta analysis. It was a conclusion in search of a methodology to support it.

[tom a]

xanadu,

I can imagine that industry forces may skew some or many results, but is it really the case that NO large scale study involving antioxidant supplements has been released that focuses on healthy subjects?

This isn't a rhetorical question -- I just don't know the answer.

[lucid]

Well, you really can't talk about 'antioxidant' studies because there are lots of different types. They all work on different things and in different ways. Some recycle so that they end up doing oxidative damage anyways. Some don't recycle. China did some big studies on EGCG, the stuff in green tea. They conducted it on healthy people and found egcg helps. A group in the netherlands did a study on EGCG as well; they found that it did not have benifits. I haven't read the details of these studies, I just read about them on the national cancer institute site.

Part of the problem is there is very little comparative incentive to do research on supplements since nothing can be patented. It takes lots of money to push things through the fda, so they don't spend much time on supplements either. There are lots of studies done on mice, and those have some pretty conclusive results. But they are done on mice... And without a huge sample group, its difficult to test the effects of a supplement on overall lifespan etc in a without a lot of money (especially in a short period of time). Its alot easier to study effects on a specific disease as opposed to effects on overall health.

[rhodan]

Reading all of these rebuttals to the meta-analysis, I guess I find myself wondering, are there ANY good, large scale studies on HEALTHY people that show the positive effects of any of these antioxidants taken as supplements?

A 7.5 years supplementation study with synthetic antioxidants showed some protection against cancer in men, but not women :

SUVIMAX

Daily dose :
120 mg of ascorbic acid
30 mg of vitamin E
6 mg of beta carotene
100 µg of selenium
20 mg of zinc

[zoolander]

from science blog Nobel Intent.....

---------------------------------------------------

February 27, 2007 @ 4:15PM - posted by Jonathan M. Gitlin
Antioxidant vitamins are bad for your health

Yesterday, I wrote about research that debunked the notion that garlic supplements could lower LDL cholesterol. Today it's more bad news for the supplement industry with a report of a meta-analysis study that examines the effects of antioxidants on mortality.

A range of different vitamins and minerals have been identified as having antioxidant properties, including vitamins A and C, beta carotene and selenium. Although a well-balanced diet with plenty of fresh fruit and vegetables contains ample amounts of these antioxidants, an army of talking heads and 'experts' make their living by promoting the use of supplementary antioxidants at ever-increasing doses as cure-alls against cancer, aging, and any number of other ailments. Even Linus Pauling, noted Nobel Laureate, spent the latter years of his career claiming that vitamin C was a panacea for just about every complaint he could think of.

However, a new meta-analysis of existing studies published in JAMA regarding the use of antioxidant supplements shows that far from prolonging longevity, beta carotene, vitamin A, and vitamin E usage were associated with increased mortality. Dr Bjelakovic and his team at Copenhagen University Hospital identified 68 different trials, encompassing 232,606 patients in total. These were sorted into high-bias risk and low-bias risk, based on the quality of the methods employed.

When all of these trials were pooled there was no significant finding, but when the 47 low-bias trials were examined, there was a five percent increased risk of mortality. Individually, beta carotene increased risk of mortality by seven percent, vitamin A increased risk of mortality by 16 percent, and vitamin E increased risk of mortality by four percent.

Although this is contrary to common sense, the authors suggest a reason for this finding. Although antioxidant production is associated with a number of diseases, many physiologic processes also involve free radical generation. They propose that "eliminating free radicals from our organism, we interfere with some essential defensive mechanisms like apoptosis, phagocytosis, and detoxification." As ever, the best advice would seem to be to make sure you get those five portions of fresh fruit and vegetables a day, and lay off the pills.

---------------------------------------------------

[Athanasios]

LEF has its say on the study here:

http://www.lef.org/f...lert_020307.htm

Overview

Oxidative stress is a well-recognized factor directly implicated in a number of human diseases1-2, and a great deal of scientific information supports and validates the role of antioxidants to decrease oxidative damage.3-6.

The latest attack against antioxidants emblazoned across headlines is from a convoluted statistical review published in the February 28, 2007 edition of JAMA (Journal of the American Medical Association).

This statistical review was developed by the same group of researchers that denounced antioxidants as without significant benefit in an article published in 20047. It takes the bold step of not only discounting all of the well-established scientific support for antioxidants in preventing disease, but brazenly declares that antioxidant vitamins increase all-cause mortality (death from all causes).

[Shepard]

Michael Eades talked about this in his blog, too:

http://www.proteinpo...m/drmike/?p=543