Use Of Some Antioxidant Supplements May Increase Mortality Risk

[johnyq]

Contradicting claims of disease prevention, an analysis of previous studies indicates that the antioxidant supplements beta carotene, vitamin A, and vitamin E may increase the risk of death, according to a meta-analysis and review article in JAMA.

Many people take antioxidant supplements, believing they improve their health and prevent diseases. Whether these supplements are beneficial or harmful is uncertain, according to background information in the article.

Goran Bjelakovic, M.D., Dr.Med.Sci., of the Center for Clinical Intervention Research, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues conducted an analysis of previous studies to examine the effects of antioxidant supplements (beta carotene, vitamins A and E, vitamin C [ascorbic acid], and selenium) on all-cause death of adults included in primary and secondary prevention trials. Using electronic databases and bibliographies, the researchers identified and included 68 randomized trials with 232,606 participants in the review and meta-analysis. The authors also classified the trials according to the risk of bias based on the quality of the methods used in the study, and stratified trials as "low-bias risk" (high quality) or "high-bias risk" (low quality).

In an analysis that pooled all low-bias risk and high bias risk trials, there was no significant association between antioxidant use and mortality. In 47 low-bias trials involving 180,938 participants, the antioxidant supplements were associated with a 5 percent increased risk of mortality. Among low-bias trials, use of beta carotene, vitamin A, and vitamin E was associated with 7 percent, 16 percent and 4 percent, respectively, increased risk of mortality, whereas there was no increased mortality risk associated with vitamin C or selenium use.

"Our systematic review contains a number of findings. Beta carotene, vitamin A, and vitamin E given singly or combined with other antioxidant supplements significantly increase mortality. There is no evidence that vitamin C may increase longevity. We lack evidence to refute a potential negative effect of vitamin C on survival. Selenium tended to reduce mortality, but we need more research on this question," the authors write.

"Our findings contradict the findings of observational studies, claiming that antioxidants improve health. Considering that 10 percent to 20 percent of the adult population (80-160 million people) in North America and Europe may consume the assessed supplements, the public health consequences may be substantial. We are exposed to intense marketing with a contrary statement, which is also reflected by the high number of publications per included randomized trial found in the present review."

"There are several possible explanations for the negative effect of antioxidant supplements on mortality. Although oxidative stress has a hypothesized role in the pathogenesis of many chronic diseases, it may be the consequence of pathological conditions. By eliminating free radicals from our organism, we interfere with some essential defensive mechanisms . Antioxidant supplements are synthetic and not subjected to the same rigorous toxicity studies as other pharmaceutical agents. Better understanding of mechanisms and actions of antioxidants in relation to a potential disease is needed," the researchers conclude.

found here:
medicalnewstoday.com/medicalnews.php?newsid=64117&nfid=41378

 

[BradCowin]

Those are all fat soluble right?

 

[Skye]

Those are all fat soluble right?

yes, and they have known for years that too much of them was bad. its kind of like people taking vit e, not likely that its bad for you but it is completely unecessary. using peanut oil once in a while will give you all you would ever need.

 

[Iron Warrior]

Were these observations seen with a particular dose, or is the dose not an issue ?

 

[bioman]

Were people who were using these various vitamins doing so because they already KNEW they had health problems?

Things to make ya go hmmmm.

 

[johnyq]

Were these observations seen with a particular dose, or is the dose not an issue ?

I was wondering the same thing, the overview article doesn't mention dosing at all.

 

[NO HYPE]

Whether these supplements are beneficial or harmful is uncertain,

I think the above excerpt says it all.... what a worthless article.

 

[bioman]

Meta analyses are pretty vague ways of looking for trends. One should not try to interpret too much from this report...and I would like to see who funded it.

 

[Mass_69]

Does anyone have any insight as to what may be meant by "all-cause death?" Sounds to me like they are factoring in people that were murdered, accidental deaths, etc., which doesn't make the overall assessment very accurate to me. We know vitamin E won't prevent death from an 18-wheeler plowing over your car...

 

[Iron Warrior]

Does anyone have any insight as to what may be meant by "all-cause death?" Sounds to me like they are factoring in people that were murdered, accidental deaths, etc., which doesn't make the overall assessment very accurate to me. We know vitamin E won't prevent death from an 18-wheeler plowing over your car...

Very good point, they didn't really determine what was a cause of death related to fat soluble vitamins.

Also, did they see some particular diseases with the same group who used the vitamins ? We all have to expire some day and they'll put something for the cause of death but if there's no correlation between specific causes of death then how accurate is this article ?

 

[jvangard]

Generally studies looking at antioxidant vitamins examine chronic conditions such as heart disease or smoking related pathologies, so when they refer to mortality it generally means by the specific pathology they were trying to treat. I have in the past read a few of the studies on vit e and a, and yes indeed supplementation with these vits do sometines seem correlated with increased mortality. What's interesting though is that the treatments are usually given in very large doses over a long period of time and as a single agent.

One hypothesis as to why the fat soluble anti-oxidant/free radical scavengers are toxic is they they themselves become radicals--which is actually part of their mechanism, but not normally a problem. Our bodies have a variety of scavenging mechanisms and when you take say tons of vit e, you overwhelm the mechanism by which the vit e radical is eliminated (ie. involving vit C), and this stable radical itself becomes toxic.

This idea of testing one or a couple vitamins only at a time, comes from a "magic bullet" paradigm perpetrated through classical pharmacology, where it is thought ONE component must be key to a pathology. This works to a certain extent for therapeutics, like penicillin, but not it seems for nutrition. Really the point should be to look to food from a complex intractive standpoint, and why say vit A from a carrot is more effective than beta carotene from a pill. The more "the carrot" is researched, the more and more interacting nutritional components are found. The whole picture becomes increasingly complex, and I suspect the end result will be pharma trying to recreate the carrot. So, why not just eat the carrot and save a lot of time and expense?

 

[Mass_69]

Generally studies looking at antioxidant vitamins examine chronic conditions such as heart disease or smoking related pathologies, so when they refer to mortality it generally means by the specific pathology they were trying to treat. I have in the past read a few of the studies on vit e and a, and yes indeed supplementation with these vits do sometines seem correlated with increased mortality. What's interesting though is that the treatments are usually given in very large doses over a long period of time and as a single agent.

---->

Does anyone have any insight as to what may be meant by "all-cause death?"

That's the thing, they did not specify or imply a specific pathology... they stated "all-cause death." Sound to me that it included all causes.

 

[jvangard]

Okay, ("sigh") I walked across the street to get the complete article. Yes, indeed they do not distinguish between causes of mortality. They even concede this in the discussion p854:

"We only assessed all-cause mortality. We are not able to determine the cause of increased mortality. It is likely that increased cancer and cardiovascular mortality are the main reasons for the increased all-cause mortality (103-104)...we fear that its assessment may be difficult due to varying definitions in the included trials."

Keep in mind that they analysed 68 clinical trials with around 232,000 participants, with large healthy control groups included as well. So this wasn't just a small study of people from a single socioeconomic group (who are prone to vehicle accidents let's say), this was a very large varied population epidemiological meta analysis. Their point is that they found a "trend" for (slightly) increased mortality in all treatment groups associated with antioxidant supplementation.

Two things to keep in mind, good or bad, are that A) this is only a correlation and does not infer cause and effect and B) as far as epidemiology is concerned dead is dead no matter the cause. So what if more people died from accidents, isn't that important as well? Does vitamin A impair neurological function causing people to get into accidents? Now, before you get mad and start typing, read on as I will trash the paper in a bit. All I am saying is that just because they didn't distinguish between causes of death, doesn't mean their results might not be important. There are lots of other reasons to discount the paper, however.

Now comes the trashing part. Besides the fact that the mean age of the study participants was 62 years, it's also important to note that this trend is extremely small. It's not like half the participants died prematurely in the supplementation group. Actually, while they did find significant differences the relative risk (RR) is very small.
Generally people believe RR if it above like 2, discount RR if it is near 1. A RR of 1 means there is no effect, and less than 1 means a positive effect. In this analysis they found a relative risk of mortality with vitamin A supplementation of 1.00006! I dunno about you, but that looks alot like 1 to me. There's a lesson in there: just because there is a statistical significance doesn't mean there is biological relevance.

In all honesty, what they really found with their analysis was antioxidant supplementation really didn't do anything to affect mortality, good or bad.

 

[bioman]

:goodpost:

"There's a lesson in there: just because there is a statistical significance doesn't mean there is biological relevance."

I chant this in my sleep sometimes. lol

I agree, there is "Some" trend going on here, but it will take a lot more investigation to find out what, if anything is causing it. As I alluded to earlier, the supplemented population may actually be supplementing for a specific reason..ie , they already know they are in failing health and are trying to take proactive measure for it based on what Reader's Digest tells them lol.

That's my hypothesis, and I'm sticking with it.