106 replies to this topic

[sUper GeNius]

http://news.bbc.co.u...lth/8043456.stm

[Dmitri]

http://news.bbc.co.u...lth/8043456.stm

What a coincidence I was discussing the same issue with another member on a separate thread; thanks for posting these new results.

[nowayout]

The full text is available here: http://www.pnas.org/...6.full.pdf html

The doses were 1g vitamin C and 400 IU vitamin E a day. Some interesting quotes:

Based on the evidence derived from the current study, we here
propose an essential role for exercise-induced ROS formation in
promoting insulin sensitivity in humans. This induction appears
to involve the ROS-dependent transcriptional coactivators
PGC1 and PGC1
, and the transcription factor PPAR and
their targets SOD1, SOD2, GPx1, and, to a reduced extent, CAT.
Most importantly, these changes in gene expression and the
increase in insulin sensitivity following physical exercise are
almost completely abrogated by daily ingestion of the commonly
used antioxidants vitamin C and vitamin E. Thus, antioxidant
supplementation blocks many of the beneficial effects of exercise
on metabolism.

...most negative
effects of antioxidant supplements observed in the current study
occur irrespective of previous training status. While most effects
appear quantitatively more pronounced within the previously
untrained study group (i.e., Left arms of Figs. 1, 2, and S1), the
data do not support the assumption that antioxidant supplement
intake is less detrimental in previously trained subjects.

...the negative effects of antioxidants
on exercise training with regard to insulin sensitivity are similar
in untrained and pretrained individuals.

This direct molecular link between exercise-dependent formation
of ROS, activation of PGC1, PGC1
and PPAR on the
one hand and increased insulin sensitivity on the other hand,
strongly suggest that oxidative stress can be instrumental in
preventing type 2-diabetes.

Moreover, antioxidant use in type 2 diabetics
has been linked to increased prevalence of hypertension (31) and
use of antioxidant supplements has recently been proposed to
increase overall mortality in the general population (32). Taken
together, these previously published findings tentatively suggest
that fruits and vegetables may exert health-promoting effects
despite their antioxidant content and possibly due to other
bio-active compounds. However, it should be noted that the
current study applied comparably high doses of oral antioxidants,
which have been tested in healthy young men only

Taken together, we find that antioxidant supplements prevent
the induction of molecular regulators of insulin sensitivity and
endogenous antioxidant defense by physical exercise. Consistent
with the concept of mitohormesis, we propose that transiently
increased levels of oxidative stress reflect a potentially health promoting
process at least in regards to prevention of insulin
resistance and type 2 diabetes mellitus.

The abstract:

Antioxidants prevent health-promoting effects
of physical exercise in humans

Michael Ristowa,b,1,2, Kim Zarsea,2, Andreas Oberbachc,2, Nora Klo¨ tingc, Marc Birringera, Michael Kiehntopfd,
Michael Stumvollc, C. Ronald Kahne, and Matthias Blu¨ herc,2

aDepartment of Human Nutrition, Institute of Nutrition, University of Jena, Jena D-07743, Germany; bGerman Institute of Human Nutrition,
Potsdam-Rehbru¨ cke D-14558, Germany; cDepartment of Medicine, University of Leipzig, Leipzig D-04103, Germany; dInstitute of Clinical Chemistry and
Laboratory Medicine, University of Jena, Jena D-07743, Germany; and eResearch Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215
Contributed by C. Ronald Kahn, March 31, 2009 (sent for review March 14, 2009)

Exercise promotes longevity and ameliorates type 2 diabetes
mellitus and insulin resistance. However, exercise also increases
mitochondrial formation of presumably harmful reactive oxygen
species (ROS). Antioxidants are widely used as supplements but
whether they affect the health-promoting effects of exercise is
unknown. We evaluated the effects of a combination of vitamin C
(1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as
measured by glucose infusion rates (GIR) during a hyperinsulinemic,
euglycemic clamp in previously untrained (n
19) and pretrained
(n
20) healthy young men. Before and after a 4 week
intervention of physical exercise, GIR was determined, and muscle
biopsies for gene expression analyses as well as plasma samples
were obtained to compare changes over baseline and potential
influences of vitamins on exercise effects. Exercise increased parameters
of insulin sensitivity (GIR and plasma adiponectin) only in
the absence of antioxidants in both previously untrained (P <
0.001) and pretrained (P < 0.001) individuals. This was paralleled
by increased expression of ROS-sensitive transcriptional regulators
of insulin sensitivity and ROS defense capacity, peroxisomeproliferator-
activated receptor gamma (PPAR), and PPAR coactivators
PGC1 and PGC1 only in the absence of antioxidants (P <
0.001 for all). Molecular mediators of endogenous ROS defense
(superoxide dismutases 1 and 2; glutathione peroxidase) were also
induced by exercise, and this effect too was blocked by antioxidant
supplementation. Consistent with the concept of mitohormesis,
exercise-induced oxidative stress ameliorates insulin resistance
and causes an adaptive response promoting endogenous antioxidant
defense capacity. Supplementation with antioxidants may
preclude these health-promoting effects of exercise in humans.

Edited by andre, 12 May 2009 - 12:13 PM.

[Bluenoise]

http://news.bbc.co.u...lth/8043456.stm

So to start, that BBC article is horrible. Here is the abstract and a link to the study which is freely accessible.

Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance. However, exercise also increases

mitochondrial formation of presumably harmful reactive oxygen species (ROS). Antioxidants are widely used as supplements but

whether they affect the health-promoting effects of exercise is unknown. We evaluated the effects of a combination of vitamin C

(1000 mg/day) and vitamin E (400 IU/day) on insulin sensitivity as measured by glucose infusion rates (GIR) during a hyperinsulinemic,

euglycemic clamp in previously untrained (n
19) and pretrained (n
20) healthy young men. Before and after a 4 week

intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples

were obtained to compare changes over baseline and potential influences of vitamins on exercise effects. Exercise increased parameters

of insulin sensitivity (GIR and plasma adiponectin) only in the absence of antioxidants in both previously untrained (P <

0.001) and pretrained (P < 0.001) individuals. This was paralleled by increased expression of ROS-sensitive transcriptional regulators

of insulin sensitivity and ROS defense capacity, peroxisomeproliferator- activated receptor gamma (PPAR), and PPAR coactivators

PGC1 and PGC1 only in the absence of antioxidants (P < 0.001 for all). Molecular mediators of endogenous ROS defense

(superoxide dismutases 1 and 2; glutathione peroxidase) were also induced by exercise, and this effect too was blocked by antioxidant

supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance

and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may

preclude these health-promoting effects of exercise in humans.

http://www.pnas.org/content/early/2009/05/11/0903485106.abstract?sid=d632306a-0411-433b-b5b3-93023b463395


An interesting point to note is this large discrpency is mainly seen in individuals with no previous training. The test subjects that had trained regularly prior to this study already had high insulin levels, and thus saw little change with exercise anyways. Hinting that this change is likely most significant in physically unfit individuals. Also except for insulin all the genes they looked at were involved in ROS defense. Which is pretty obvious to happen if you have more ROS. Personally I find their logic flawed. They state that the individuals who supplement have less ROS, but then conclude that due to lower induction of ROS-defense they would be more prone to disease (assuming from more ROS).

From this it seems that it would likley not be much of an issue in people who exercise regularily.

Another issue with this study is that they look at both Vitamin C and E simulataniously and then conclude that all the effects they see are likley entirely due to mopping up of free radicals. Especially since vitamin E has already been previously linked to increased mortality (if I remember correctly). They should have examined these compounds seperatley. Also they used really high amounts of both vitamins, the level of vitamin E they use is about 15 times the RDI.
I should note that I don't supplement either of these vitamins, and the few antioxidants I do take (Cacoa and resveratrol), are linked with positive effects on diabetes and insulin levels. So obviously this isn't a clear cut case of a strictly anti-oxidant effect...

Edited by Bluenoise, 12 May 2009 - 12:16 PM.

[nowayout]

An interesting point to note is this large discrpency is mainly seen in individuals with no previous training. The test subjects that had trained regularly prior to this study already had high insulin levels, and thus saw little change with exercise anyways.

No, it appears from the graphs that even for trained individuals the vitamins significantly prevented further improvement during the four weeks and even caused a slight deterioration in some cases. IME few people who exercise want to just stay at the same level or keep doing exactly the same program forever. It is also possible that over a longer time the slight deterioration could become a significant deterioration.

Hinting that this change is likely most significant in physically unfit individuals. Also except for insulin all the genes they looked at were involved in ROS defense. Which is pretty obvious to happen if you have more ROS. Personally I find their logic flawed. They state that the individuals who supplement have less ROS, but then conclude that due to lower induction of ROS-defense they would be more prone to disease (assuming from more ROS).

No, their logic (see the discussion at the end) is that the increase of ROS with exercise is transient. Presumably the rate of damage at rest could be lower due to upregulation of endogenous defenses.

Another issue with this study is that they look at both Vitamin C and E simulataniously and then conclude that all the effects they see are likley entirely due to mopping up of free radicals. Especially since vitamin E has already been previously linked to increased mortality (if I remember correctly). They should have examined these compounds seperately.

There are some other studies showing similar or related effects from these vitamins in isolation (at least for C, if I remember correctly).

Edited by andre, 12 May 2009 - 03:57 PM.

[Imagination]

I'm getting pretty sure there just making stuff up now to fill the news.

[Mind]

The two recent discussions related to this topic - free radical theory questioned: discussion #1, and discussion #2.

[nameless]

Very interesting study, thanks for posting it.

Dmitri and myself were having a similar discussion in another thread. This certainly does seem to back up the idea that antioxidants + exercise don't mix so well.

Although some unanswered questions:
Does time of dosing matter? I didn't see exactly when the supplements were taken in this study, but vitamin C was twice daily, so I expect dosing was somewhat close to when exercise occurred. Due to vitamin C's short half-life, would dosing 4-8 hrs after exercise make a difference?

Did the form of vitamin E used in this particular study matter? I'd guess probably not, seeing as they were just looking for antioxidant activity, although I really wish scientists realized there are other forms of vitamin E instead of 400IU alpha tocopherol. It seems every study on vitamin E uses this form, and this dose, even though it repeatedly has shown negative consequences.

Do antioxidants from food have the same effect? According to study, perhaps not, as the incidence of diabetes + antioxidants from food sources (as reviewed from other studies) didn't increase. Although this doesn't necessarily mean high ORAC foods are in the clear.

Do antioxidants besides C + E have this same effect? What about supplements that aren't entirely considered just antioxidants, but have some antioxidant effects? Green tea, CoQ10, grapeseed, curcumin come to mind.

And although I'm not sure if there is a relation, this study reminded me of that niacin-statin study done several years ago. An antioxidant cocktail (C, E, Beta Carotene, Selenium) blunted the benefits seen, especially regarding HDL. Now, could this be due to similar mechanism as the above study, or because the antioxidants reduced the benefits of exercise in the participants? Exercise is known to raise HDL, but if the benefits are reduced by antioxidants, perhaps not in this case.

Edited by nameless, 12 May 2009 - 06:44 PM.

[happy]

Edit: This was posted in a separate thread; I merged it here. It's the NYT version of the report. -moderator

May 12, 2009
Vitamins Found to Curb Exercise Benefits
By NICHOLAS WADE

If you exercise to improve your metabolism and prevent diabetes, you may want to avoid antioxidants like vitamins C and E.

That is the message of a surprising new look at the body’s reaction to exercise, reported on Monday by researchers in Germany and Boston.

Exercise is known to have many beneficial effects on health, including on the body’s sensitivity to insulin. “Get more exercise” is often among the first recommendations given by doctors to people at risk of diabetes.

But exercise makes the muscle cells metabolize glucose, by combining its carbon atoms with oxygen and extracting the energy that is released. In the process, some highly reactive oxygen molecules escape and make chemical attacks on anything in sight.

These reactive oxygen compounds are known to damage the body’s tissues. The amount of oxidative damage increases with age, and according to one theory of aging it is a major cause of the body’s decline.

The body has its own defense system for combating oxidative damage, but it does not always do enough. So antioxidants, which mop up the reactive oxygen compounds, may seem like a logical solution.

The researchers, led by Dr. Michael Ristow, a nutritionist at the University of Jena in Germany, tested this proposition by having young men exercise, giving half of them moderate doses of vitamins C and E and measuring sensitivity to insulin as well as indicators of the body’s natural defenses to oxidative damage.

The Jena team found that in the group taking the vitamins there was no improvement in insulin sensitivity and almost no activation of the body’s natural defense mechanism against oxidative damage.

The reason, they suggest, is that the reactive oxygen compounds, inevitable byproducts of exercise, are a natural trigger for both of these responses. The vitamins, by efficiently destroying the reactive oxygen, short-circuit the body’s natural response to exercise.

“If you exercise to promote health, you shouldn’t take large amounts of antioxidants,” Dr. Ristow said. A second message of the study, he said, “is that antioxidants in general cause certain effects that inhibit otherwise positive effects of exercise, dieting and other interventions.” The findings appear in this week’s issue of The Proceedings of the National Academy of Sciences.

The effect of vitamins on exercise and glucose metabolism “is really quite significant,” said Dr. C. Ronald Kahn of the Joslin Diabetes Center in Boston, a co-author of the report. “If people are trying to exercise, this is blocking the effects of insulin on the metabolic response.”

The advice does not apply to fruits and vegetables, Dr. Ristow said; even though they are high in antioxidants, the many other substances they contain presumably outweigh any negative effect.

Dr. Kahn said it might be that reactive oxygen is beneficial in small doses, because it touches off the body’s natural defense system, but harmful in higher doses.

Andrew Shao of the Council for Responsible Nutrition, a trade association of dietary supplement makers, said the new study was well designed but was just one bit of evidence in a complex issue. Most available evidence points to the opposite conclusion, that antioxidants benefit health by reducing oxidative stress, he said.

“I wouldn’t change recommendations for anyone based on one study,” he said. “This is one small piece of the puzzle.”

Edited by niner, 13 May 2009 - 02:14 AM.

[Bluenoise]

No, it appears from the graphs that even for trained individuals the vitamins significantly prevented further improvement during the four weeks and even caused a slight deterioration in some cases. IME few people who exercise want to just stay at the same level or keep doing exactly the same program forever. It is also possible that over a longer time the slight deterioration could become a significant deterioration.

I guess we disagree what significant means. Most of the values have overlapping error bars. If I saw that with my research I wouldn't trust the data for a second...

[bgwithadd]

No, it appears from the graphs that even for trained individuals the vitamins significantly prevented further improvement during the four weeks and even caused a slight deterioration in some cases. IME few people who exercise want to just stay at the same level or keep doing exactly the same program forever. It is also possible that over a longer time the slight deterioration could become a significant deterioration.

Vitamins don't affect athletic performance, and since when do most people exercise to increase insulin levels?

I'm not sure vitamin e is actually useful for much of anything and it's obvious that antioxidants are not going to increase lifespan, but I don't think there's any question as to whether it's better to have vitamin c in pill form compared to not at all.

[niner]

Vitamins don't affect athletic performance, and since when do most people exercise to increase insulin levels?

I'm not sure vitamin e is actually useful for much of anything and it's obvious that antioxidants are not going to increase lifespan, but I don't think there's any question as to whether it's better to have vitamin c in pill form compared to not at all.

When I stopped using antioxidants on days that I work out, I broke through a very long standing plateau. Sure, vitamin C is fine, just don't take it around your workout if you want maximum benefit from the workout. Lots of things affect athletic performance, both positively and negatively. In this case, I think C and E fall into the negative category if they are on board during or shortly after exercise.

[nowayout]

Vitamins don't affect athletic performance,

Source?

... and since when do most people exercise to increase insulin levels?

No, it is insulin sensitivity.

... I don't think there's any question as to whether it's better to have vitamin c in pill form compared to not at all.

I can cite many sources arguing the opposite.

[zawy]

A fatal flaw in this study is the "hyperinsulinemic euglycemic clamp" test they used to determine "insulin sensitivity". Nothing is wrong with the test, it's just that you can't use it the same way on someone who has ingested vitamin C. This test involves giving someone insulin and then seeing how much glucose is needed to maintain blood sugar. More glucose required is a good sign that you are "insulin sensitive". The problem is that vitamin C makes you more sensitive to insulin, elevates glucose, reducing the need for sugar, which would make it appear as a negative outcome:

http://www.ajcn.org/...stract/60/5/735

"These data indicate that elevated plasma AA delays the insulin response to a glucose challenge in normoglycemic adults, thereby prolonging the postprandial hyperglycemia."

Vitamin C is converted directly from glucose in 99.9% of animals and the two are transported similarly due to very similar structures. Someone on Vit C needs less insulin to maintain blood sugar. It can be used by diabetics to make them more sensitive to insulin so that they can reduce insulin needs by 2 units for each 1,000 mg Vit C taken (Dice and Daniel 1973). This indicates maybe 50% of diabetics could go without insulin if they took 10,000 mg Vit C/day. This is 1973 information. I doubt there is much "new information" out there to contradict or expand upon this. This is another example of how "new studies" should not be taken too seriously if they contradict the past 30 years of research. These 9 researchers from Harvard and Germany did not pay attention to what was published in 1973. Harvard BTW had the most ridiculous publications against nutritional supplements for decades. I would not be surprised if they are still saying you should never take supplements and only get nutrients from food. The last I read is that they agreed that 200 mcg/day selenium as a supplement reduced 50% of all cases of cancers in two huge studies but they still said not take it, but that you should wait until you get cancer to begin chemotherapy. My mouth just dropped open and its the last thing I read from their medical school newsletter.

The masses will never be aware of this argument agaist this study. Only the negative outcomes against vitamins, that contradict the past 50 years of research, will make the biggest news. The reason things like this make big news is the same reason it's usually wrong.

There are other arguments and things to consider that could negate the other findings of the paper. For example why not increase exercise rather than decreasing antioxidents. But I like the idea of a 1 hour oxidative stress every other day, so i may delay vit C after a workout. But I still do not know if that is a good idea or not. As a side note, I have seen 4,000 mg doses right after a "heat stress test" do amazingly good things in my elderly mother who likes to over-work in the yard. She can kill herself and be wiped out for 48 hours....if she doesn't follow it with 4,000 mg.

Edited by zawy, 13 May 2009 - 03:22 PM.

[JLL]

Do antioxidants besides C + E have this same effect? What about supplements that aren't entirely considered just antioxidants, but have some antioxidant effects? Green tea, CoQ10, grapeseed, curcumin come to mind.

Here's a review of studies on coenzyme Q10's effect on exercise.

At least for weight loss purposes, green tea seems to be a good addition to exercise: green tea enhances abdominal fat loss from exercise and increases insulin sensitivity & fat burning during exercise. Maybe there's a difference between anaerobic and aerobic exercise when taking antioxidants? In any case, if you wanted to avoid combining the two, you should avoid drinking green tea for at least 2 hours before exercise; the antioxidant peak in plasma occurs 20-40 minutes after drinking it but continues for at least 2 hours.

Edited by JLL, 13 May 2009 - 03:09 PM.

[kismet]

Vitamins don't affect athletic performance, and since when do most people exercise to increase insulin levels?

Actually, in some cases they negatively affect performance, sometimes they don't.

Am J Clin Nutr. 2008 Jan;87(1):142-9.
Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance.
Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, Sastre J, Viña J.

J Int Soc Sports Nutr. 2006 Dec 13;3:37-44.
Vitamin C and e supplementation effects in professional soccer players under regular training.
Zoppi CC, Hohl R, Silva FC, Lazarim FL, Neto JM, Stancanneli M, Macedo DV.
http://www.pubmedcen...bmedid=18500971

I guess we disagree what significant means. Most of the values have overlapping error bars. If I saw that with my research I wouldn't trust the data for a second...

Doesn't matter, because the most important variables, i.e. markers of insulin sensitivity, were visibly & significantly inhibited.

Edited by kismet, 13 May 2009 - 03:18 PM.

[kismet]

Only the negative outcomes against vitamins, that contradict the past 50 years of research, will make the biggest news. The reason things like this make big news is the same reason it's usually wrong.

Come on! Don't be ridiculous, up to this point this was a great post, but all-cause mortality and morbidity measured in interventional trials trumps mechanistical evidence. The failure of Vitamin A and E (and most multivitamins) in the general population at intakes, regimens and formulations studied is fact, get over it.
Let's focus on vitamin C, which has not been demonstrated to be dangerous and may (or may not) have some benefits.

"These data indicate that elevated plasma AA delays the insulin response to a glucose challenge in normoglycemic adults, thereby prolonging the postprandial hyperglycemia."

So focusing on the insulin issue - I'm wondering how this a good thing? Overall insulin output may be similar, but hyperglycemia per se is thought to be detrimental. You're right that the authors of the study in PNAS might have measured this phenomenon and not a true influence on long term insulin sensitivity, but prolonging hyperglycemia is not a good thing in my book.
How does vitamin C affect glucsoe area under the curve (or some such long term measure)? Although, I'm not sure if AUC is a good measure of glycemic damage (as it may rise exponentially?)

Edited by kismet, 13 May 2009 - 03:37 PM.

[zawy]

Come on! Don't be ridiculous, up to this point this was a great post, but all-cause mortality and morbidity measured in interventional trials trumps mechanistical evidence.

I agree but you're probably referring to a meta-analysis of selected studies. A quick search on the internet gave me this:

" 'Four hundred five studies which showed no deaths were excluded from the meta-analysis, which if included, clearly would have altered the outcome of the meta-analysis,' said Andrew Shao, Ph.D., vice president of scientific and regulatory affairs for the Council for Responsible Nutrition, a supplement industry trade association in Washington, D.C."

They kept 67 studies covering 9 supplements. It seems like a highly-selected group. Do you have a link to the full article of the meta-analysis that you're trusting so much? I just figured it didn't amount to much, but I guess i need to review it. In particular I would like to see what papers they rejected and why.

It was published in JAMA that has a well-known bias. How many pro-supplement meta-analysis papers has JAMA rejected? The question is important because if pro-supplement papers are rejected, then there is a statistical bias against them. For example, at 95% confidence interval and 20 pro-supplement rejections for each anti-supplement accepted, then there is a 50% chance at the 95% confidence that you're just looking at statistical error. It applies doubly if we get our information from popular media outlets that profit from sensational "news". This doesn't apply to us if we get our info by doing pubmed searches AND if pro-supplement research financing is equal to anti-supplement research financing. I immediately reject any papers by supplement companies like LEF, harvard medical school, NCI, and sloan-kettering because of their biases. In those cases there is a bias well before it gets to a journal.

The paper also said all-cause mortality from vitamin C intake showed no significance. I know at least that parts wrong. Two of the largest studies on that came out positive showing huge benefits for men in 1 of them. A search gave me the NHAMES 1, showing 35% decreased mortality in men for highest vitamin C intakes, probably for around only 1 g/d at the high end.

http://www.ncbi.nlm..../pubmed/1591317

Or maybe you would be interested that 34,000 women showed almost 1/3 the risk of heart disease from having the highest vitamin E intake:
http://books.google....-...t&resnum=10

I could probably find 10 huge studies concerning vit E, vit C, vit A, vit D, and selenium that I trust much more individually than a meta-analysis. And 75% of them would be very positive about these supplements. There's 20 or 30 years worth of large studies.

Edited by zawy, 13 May 2009 - 06:04 PM.

[bgwithadd]

Vitamins don't affect athletic performance,

Source?

... and since when do most people exercise to increase insulin levels?

No, it is insulin sensitivity.

... I don't think there's any question as to whether it's better to have vitamin c in pill form compared to not at all.

I can cite many sources arguing the opposite.

I don't need a source. You need a source proving otherwise. The whole 'science' thing again. For a 'scientist' you are pretty sketchy on logic.

"sensitivity" - it is both. Maybe you should actually read the thing you're citing. That's not the point, though. the point is that's not why anyone exercises, except a few diabetics.

"I can cite many sources arguing the opposite." - no you can't. Because having zero vitamin C will kill you, and the two choices provided were supplements or none (which for many people is probably reality). Except for a small percentage of the population that produces their own.

I try to ignore you, but it's astounding how many ridiculous things you spew out with such an authoritative air.

[kismet]

Come on! Don't be ridiculous, up to this point this was a great post, but all-cause mortality and morbidity measured in interventional trials trumps mechanistical evidence.

I agree but you're probably referring to a meta-analysis of selected studies. A quick search on the internet gave me this:

JAMA and more recently Cochrane (1) and the women's health initiative (160k participiants combined observational/interventional arms, failure of multivitamins) (2), but interpretation of the Cochrane analysis is difficult. I think they included some of the smoker trials & they may show some sort of selection bias as you mention (or not). Then there's the issue of mixed vs isolated tocopherols, balancing K, D, E and A, dose, etc. One thing we can tell for sure, we know which formulations don't work, while there's a lack of solid data on those antioxidants that might work and there are millions of possible combinations. However, speculation is inherently dangerous, as shown by the antioxidant craze which was spawned by a "might work" and some preliminary trials (and mostly epidemiologic data!)

Vitamin E shows no effect or is slightly detrimental depending on the statistical model used. (3) So the tested regimens are expensive, cost money and might harm you. That's a huge failure. 
Beta-carotene mortality as shown in (1) may be confined to smokers (4).
Similarly vitamin A mortality (1) may be confined to smokers and/or people with low vitamin D status. I think that's the status quo of our speculation thread on vitamin D & A. 

But it shows clearly that the population at large was harmed by their one-sided intake of badly formulated antioxidants (and at best, if we're pretty damn lucky and Cochrane et al. screwed up big time with their interpretation, it was simply a multi-billion dollar waste of our valuable time). I'm not sure if anyone will have the balls to try orthocore-like multivitamins or mixed tocopherols/carotenoids, combinations of D, K & A in a bigger cohort any time soon (imagine the response of the ethics committee "You want to do WHAT?"). 

I believe MR has extensively reviewed the issue and he also repeatedly pointed out the failures shown in many well-designed bigger interventional trials on our forums. He brought the issue to my attention and I trust (and was able to corroborate) his verdict so far.

A search gave me the NHAMES 1, showing 35% decreased mortality in men for highest vitamin C intakes, probably for around only 1 g/d at the high end.

Well, it's epidemiology so that's a huge issue. Even if they adjusted for vegetable/fruit intake, confounding might remain. If they didn't, we can only conclude that a diet rich in natural sources of vitamin C apparently seems to prevent disease pretty well. I've seen some interesting papers on vitamin C supplementation (which is one of the better antioxidant supplements it seems), but nothing truely impressive and well-designed and credible at the same time. Vitamin C & bone health; stress & immune function; etc.
I suppose it's not just a myth: foods rich in vitamin E are rich in mixed tocopherols & trienols and not just alpha-tocopherol and they also contain a lot of polyphenols. Then there's always the issue of reverse causation (healthy foods <-> healthy lifestyles).

The epidemiologic data shows a defnitive benefit from foods rich in vitamins and thus hints at a possible benefit of food extracts and well-formulated multivitamins e.g. orthocore (formulated by MR).

Some recent trials that may be of interest (I haven't really delved into those in particular; I'm not really into vitamin research and such):
(1) Cochrane Database Syst Rev. 2008 Apr 16;(2):CD007176.
Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C.
http://mrw.interscie...7176/frame.html
(2) Multivitamin use and risk of cancer and cardiovascular disease in the Women's Health Initiative cohorts.
Neuhouser ML, Wassertheil-Smoller S, Thomson C, Aragaki A, Anderson GL, Manson JE, Patterson RE, Rohan TE, van Horn L, Shikany JM, Thomas A, LaCroix A, Prentice RL.
(3) Bayesian model averaging in meta-analysis: vitamin E supplementation and mortality.
Berry D, Wathen JK, Newell M.
Clin Trials. 2009 Feb;6(1):28-41.
(4) Cancer. 2008 Jul 1;113(1):150-7.
Beta-carotene in multivitamins and the possible risk of lung cancer among smokers versus former smokers: a meta-analysis and evaluation of national brands.
Tanvetyanon T, Bepler G.

Edited by kismet, 13 May 2009 - 06:23 PM.

[nameless]

Here's a review of studies on coenzyme Q10's effect on exercise.

At least for weight loss purposes, green tea seems to be a good addition to exercise: green tea enhances abdominal fat loss from exercise and increases insulin sensitivity & fat burning during exercise. Maybe there's a difference between anaerobic and aerobic exercise when taking antioxidants? In any case, if you wanted to avoid combining the two, you should avoid drinking green tea for at least 2 hours before exercise; the antioxidant peak in plasma occurs 20-40 minutes after drinking it but continues for at least 2 hours.

Thanks for the reply. For green tea, I go the supplement route because of stomach upset, so I take it with food. I also take CoQ10 with food, as fats increase it's absorption. I guess I could skip dosing CoQ10 before exercise, although not sure if that matters, as by dinnertime I would need to dose.

What about dosing vitamin C in the evening, 4-8 hours after exercise? I suppose there are no studies that have looked at that yet.

The failure of Vitamin A and E (and most multivitamins) in the general population at intakes, regimens and formulations studied is fact, get over it.

Mostly true, although if I remember correctly, the meta analysis studies on vitamin E and mortality showed a slight decrease in mortality as one approached 50IU, then leveled off and didn't increase mortality until after the 150IU mark.

And there are multivitamin-type studies that have shown benefits. It's the high dose studies that tend to have bad outcomes.

[zawy]

Kismet, 1) is the meta-analysis I was complaining and wondering about. I haven't seen it so I can't really evaluate why it disagrees with large studies. 3) appears to be based on 1). 2) is just for multivitamins and I believe it. I no longer take beta-carotene because of 4) eventhough I haven't looked at it critically and I'm not a smoker.

[nowayout]

I don't need a source. You need a source proving otherwise. The whole 'science' thing again. For a 'scientist' you are pretty sketchy on logic.

Excuse me? You made a categorical claim that vitamins do not affect athletic performance. And I need a source proving otherwise? What planet are you from?

"sensitivity" - it is both. Maybe you should actually read the thing you're citing. That's not the point, though. the point is that's not why anyone exercises, except a few diabetics.

Improving insulin sensitivity is big in the weightlifting/bodybuilding world. And the point for the rest is to prevent diabetes, you dunce.

Edited by andre, 13 May 2009 - 08:30 PM.

[BioFactor]

I don't need a source. You need a source proving otherwise. The whole 'science' thing again. For a 'scientist' you are pretty sketchy on logic.

Excuse me? You made a categorical claim that vitamins do not affect athletic performance. And I need a source proving otherwise? What planet are you from?

"sensitivity" - it is both. Maybe you should actually read the thing you're citing. That's not the point, though. the point is that's not why anyone exercises, except a few diabetics.

Improving insulin sensitivity is big in the weightlifting/bodybuilding world. And the point for the rest is to prevent diabetes, you dunce.

This reeks of Codex Alimentarius. Let's classify all supplements as harmful and useless. Something stinks here. Also, CNN admitted this was a very very small study.

[zawy]

I found the full text to that anti-antioxident research:

http://www.cochrane....ants_review.pdf

I hate google because it's search results on research topics are secretly paid links and they hide the relevant search results. The results usually do not even have the keywords you're looking for unless you pay for the content. This is something they swore they would never do. So now when doing research on anything, I have to use yahoo or something else.

I'll take some time to look it over. The Cochrane group that it comes from seems strict about not letting funding come from biased sources.

[Mixter]

Alpha-Lipoic Acid does the opposite, it improves insulin resistance: http://www.ncbi.nlm....pubmed/15326564 Up to a point where it can help reverse Type II Diabetes.
Not to speak of Resveratrol research regarding insulin sensitization, exercise mimicing and the huge ongoing Diabetes trials.

Dear Researchers, what about designing a proper study and including secondary antioxidants???

But yes, if someone supplements with only Vitamin C and alpha-Tocopherol, with 0 secondary antioxidants and prior to ROS inducing exercise, that does reduce its effects and can indeed be quite harmful. This is useless at best and junk science at worst, maybe it should be published in one of those fake journals.

PS: But yes, if you want full mito-hormesis benefits then take resveratrol and up your ALCAR : Antioxidants ratio before exercise. Or just don't take antioxidants before exercising and reserve them for meals, due to which the majority of the metabolic damage happens.

Edited by mixter, 13 May 2009 - 09:26 PM.

[kismet]

This reeks of Codex Alimentarius. Let's classify all supplements as harmful and useless.

They are, they are. In comparison to what is necessary and what is possible they are useless; and they have side-effects similarly to most other drugs (i.e. some have less, others more). The truth may hurt you now, but as soon as you get over it: support biomedical research, SENS, mfoundation and others.

Edited by kismet, 13 May 2009 - 10:43 PM.

[zawy]

OK, here is my little investigation into that meta-analysis that concluded anti-oxidents did not increase lifespan.

Vitamin C

70% of the mortality results come from 3 studies. 40% from the "Heart Protection Study" which used 250 mg vit C. It's been criticized in wiki as being biased in favor of the pharmaceuticals and not making the data available: http://en.wikipedia....rotection_Study

The other 2 were from the Nutrition Intervention Trial in china that used 120 mg and 180 mg vit C.

So according to this meta-analysis, they have concluded that vitamin C in doses of 1 orange per day has no effect on mortality. This is not very interesting.

I could not find a reference to any NHAMES studies for vitamin C. I consider my reference to the NHAMES much better than this meta-analysis.

Vitamin E

50% of the vitamin E results came from Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC). They used 50 IU. This is the same study that concluded 20 mg of beta-carotene in smokers was harmful. Seems like that study is being recycled a bit more than its fair share using really small doses.


Vitamin A

38% of the vit A conclusion comes from the very negative CARET study which used 25,000 IU retinyl palmitate. The very negative results amplified its 38% weighting factor. This was published in the J of NCI. I previously posted I would reject out of hand anything from the NCI pro-chemotherapy group. The researchers were from "Fred Hutchinson Cancer Research Center" which was the "best funded institute" of 2007 which doesn't bode well for wondering how much pharmaceutical money it gets. It also seems closely connected to NCI. "The Hutchinson Center also enjoys a number of academic and industry partnerships that enhance its mission." It seems well-connected to all those 50 year-old chemotherapy experiments that are just a way to funnel government, pharmaceutical, and private money to cancer medical community. Nothing looks good about the source of the CARET study. At first I thought I had found at least one good anti-vitamin study I could trust. The two chinese studies were 5% positive and used 5,000 and 10,000 IU.

Summary

The vitamin C and vitamin E conclusions were drawn from small amounts of the vitamins. The results are based mostly on 1 negative study each that I don't consider useful or trustworthy. The vitamin A negative findings are likewise a repeat of a previous single negative study from one of the least-trustworthy medical communities: american cancer research.

At first I completely trusted the authors of the meta-analysis, but i don't understand why they didn't use any good research. For example their paper references 3 different NHAMES studies (Balluz, Millen, and Radimer) 3 or 4 times in its discussion, but I could not find any reference to these large and important works in their meta-analysis. What's up with THAT ??

Is this meta-analysis not garbage?

Edited by zawy, 13 May 2009 - 11:00 PM.

[VespeneGas]

Vitamins don't affect athletic performance,

Source?

... and since when do most people exercise to increase insulin levels?

No, it is insulin sensitivity.

... I don't think there's any question as to whether it's better to have vitamin c in pill form compared to not at all.

I can cite many sources arguing the opposite.

I don't need a source. You need a source proving otherwise. The whole 'science' thing again. For a 'scientist' you are pretty sketchy on logic.

"sensitivity" - it is both. Maybe you should actually read the thing you're citing. That's not the point, though. the point is that's not why anyone exercises, except a few diabetics.

"I can cite many sources arguing the opposite." - no you can't. Because having zero vitamin C will kill you, and the two choices provided were supplements or none (which for many people is probably reality). Except for a small percentage of the population that produces their own.

I try to ignore you, but it's astounding how many ridiculous things you spew out with such an authoritative air.

Naw man, not belligerent at all.

[markymark]

snip

others find differend results in different study designs, these persons in the paper (see abstract below) were overweight etc....

However to call their paper :"Antioxidants prevent health-promoting effects of physical exercise in humans." i.e to use d-alpha-toc (without gamma-toc and tocotrienols) and ascorbate and then to take all "antioxidants" under custody is at best not intelligent, if not a bit stupid.

However the study was well quite designed and made me think too...
The model of hormesis, (the authors use this term in the keyword list) is soooo interesting/important for us life extensionists , e. g. see:

PMID: 19371409 [PubMed - in process]

and

Neuromolecular Med. 2008;10(4):236-46. Epub 2008 Jun 10.
Hormetic dietary phytochemicals.
Son TG, Camandola S, Mattson MP.

regs
mm


1: Metabolism. 2009 Feb;58(2):254-62.

Effects of antioxidant supplementation on insulin sensitivity, endothelial
adhesion molecules, and oxidative stress in normal-weight and overweight young
adults.

Vincent HK, Bourguignon CM, Weltman AL, Vincent KR, Barrett E, Innes KE, Taylor
AG.

Department of Orthopaedics and Rehabilitation, University of Florida,
Gainesville, PO Box 112727, FL 32608, USA. vincehk@ortho.ufl.edu

The objective of the study was to determine whether short-term antioxidant (AOX)
supplementation affects insulin sensitivity, endothelial adhesion molecule
levels, and oxidative stress in overweight young adults. A randomized,
double-blind, controlled study tested the effects of AOXs on measures of insulin
sensitivity (homeostasis model assessment [HOMA]) and quantitative insulin
sensitivity check index), endothelial adhesion molecules (soluble intercellular
adhesion molecule-1, vascular adhesion molecule, and endothelial-leukocyte
adhesion molecule-1), adiponectin, and oxidative stress (lipid hydroperoxides) in
overweight and normal-weight individuals (N = 48, 18-30 years). Participants
received either AOX (vitamin E, 800 IU; vitamin C, 500 mg; beta-carotene, 10 mg)
or placebo for 8 weeks. The HOMA values were initially higher in the overweight
subjects and were lowered with AOX by week 8 (15% reduction, P = .02).
Adiponectin increased in both AOX groups. Soluble intercellular adhesion
molecule-1 and endothelial-leukocyte adhesion molecule-1 decreased in overweight
AOX-treated groups by 6% and 13%, respectively (P < .05). Plasma lipid
hydroperoxides were reduced by 0.31 and 0.70 nmol/mL in the normal-weight and
overweight AOX-treated groups, respectively, by week 8 (P < .05). Antioxidant
supplementation moderately lowers HOMA and endothelial adhesion molecule levels
in overweight young adults. A potential mechanism to explain this finding is the
reduction in oxidative stress by AOX. Long-term studies are needed to determine
whether AOXs are effective in suppressing diabetes or vascular activation over
time.


PMID: 19154960 [PubMed - indexed for MEDLINE]