31 replies to this topic

[geo12the]

What do people make of this?:

http://www.nutraingr...est-researchers

[Spinlock]

But now, new research at The University of Copenhagen surprisingly suggests that eating a diet rich in antioxidants may actually counteract many of the health benefits of exercise, including reduced blood pressure and cholesterol.

The study is not wuantative and only mentions older men. Doesn't sound like it's going to make current restorative users reconsider.

[niner]

Spinlock, I think you're looking at a different study. The one that geo12the linked is a double blind placebo controlled trial of 250mg/d resveratrol in older men. It showed that the resveratrol reduced some of the beneficial response to exercise. That seems like a problem.

[balance]

I wonder if it's in the same category as the vitamin C and NAC studies that showed a negative effect on exercise recovery/performance. It may have to do with timing of supplementation during the day. Ideally you'd want to take it as far away as possible from exercise. Let's say first thing in the morning when cortisol is highest anyways (being less ideal for exercising) and then do some exercise between 5-8pm. And then keep this in mind:

http://www.youtube.com/watch?v=Y6U728AZnV0


And if all else fails, we still got some hope here:

http://www.ncbi.nlm....pubmed/23417481

http://www.ncbi.nlm....pubmed/23146777

http://www.ncbi.nlm....pubmed/10444409

http://www.ncbi.nlm....pubmed/21497497

http://ajpregu.physi.../R2168.abstract

http://www.jissn.com.../1/14/abstract/

http://jn.nutrition....100966.abstract

http://www.ncbi.nlm....pubmed/19028079

Edited by piet3r, 23 July 2013 - 03:39 AM.

[maxwatt]

The abstract of the journal article is here http://jp.physoc.org...258061.abstract, and access to the article if you have institutional privileges.

Abstract

Aging is thought to be associated with decreased vascular function partly due to oxidative stress. Resveratrol is a polyphenol, which, in animal studies has been shown to decrease atherosclerosis, improve cardiovascular health and physical capacity, in part through its effects on Sirtuin 1 signaling and through an improved antioxidant capacity. We tested the hypothesis that resveratrol supplementation enhances training-induced improvements in cardiovascular health parameters in aged men. Twenty-seven healthy physically inactive aged men (age: 65 ± 1 years; BMI: 25.4 ± 0.7 kg/m2; MAP: 95.8 ± 2.2 mmHg; maximal oxygen uptake: 2488 ± 72 ml O2 min-1) were randomized into 8 weeks of either daily intake of either 250 mg trans resveratrol (n = 14) or of placebo (n = 13) concomitant with high-intensity exercise training. Exercise training lead to a 45% greater (P < 0.05) increase in maximal oxygen uptake in the placebo group than in the resveratrol group and to a decrease in MAP in the placebo group only (-4.8 ± 1.7 mmHg; P < 0.05). The interstitial level of vasodilator prostacyclin was lower in the resveratrol than in the placebo group after training (980 ± 90 versus 1174 ± 121 pg ml-1; P < 0.02) and muscle TBX synthase was higher in the resveratrol group after training (P < 0.05). Resveratrol administration also abolished the positive effects of exercise on LDL, TC/HDL ratio and triglycerides concentrations in blood (P < 0.05). Resveratrol did not potentiate the effect of exercise training on atherosclerosis marker VCAM-1. Sirtuin 1 protein levels were not affected by resveratrol supplementation. These findings indicate that, whereas exercise training effectively improves several cardiovascular health parameters in aged men, concomitant resveratrol supplementation blunts most of these effects.

The article is behind a pay wall, but from the abstract the dose was 250 mg daily for 8 weeks.
That the results contradict some reports we have seen here from users may be due to the use of a higher dosage ( >= 400 mg) or to a placebo effect (?).
Note also they found no increase in Sirtuin expression, which is supposed to be the hallmark of resveratrol's effect.

Edited by maxwatt, 23 July 2013 - 11:38 AM.

[maxwatt]

...further reflections on the article: the men tested were untrained, whereas those who have reported on exercise effects here started from a trained state. Their noticed their exercise tolerance improved (as did mine), but I have no knowledge of their blood lipids, which may have gotten worse, or not. I know from my own experience that there was no effect on my blood glucose levels nor LDL-HDL-triglycerides; they remained remained high-normal. The reason I have continued taking resveratrol is that it has a positive effect on my osteo-arthritis. When I discontinue use, it gets worse.

(I am editing the preceding post to include the abstract.)

[blood]

Note also they found no increase in Sirtuin expression, which is supposed to be the hallmark of resveratrol's effect.

Interestingly there is a human study showing quercetin producing a small increase (which didn't reach significance) in skeletal messenger RNA for sirtuin 1.

Perhaps Bill Sardi was right about lower doses of resveratrol being healthier?

Edited by blood, 23 July 2013 - 11:52 AM.

[maxwatt]

Not really. First, a result that does not reach statistical significance is a negative result. (You can perhaps design a more sensitive study to perhaps find a significant result, but it will be perhaps too slight to matter.) Secondly, a quercetin metabolite blocks the expression of Sirt 1, so ????

One third of the studies we like to cite are eventually contradicted by another study, and one third are never repeated.* If you saw how grad students, and professors, strive to get significant effects, then you wouldn't trust any individual paper, just a steady preponderant and consistent result. Not saying there is deliberate fraud, but a desired result is more likely than an undesired one. Consider Das, whose papers are all suspect now that some were withdrawn for suspected fraud. And perhaps this was over-eager grad students trying to please the professor?

When a new miracle supplement comes along, better hurry and take it while it still works.

* According to a paper than analyzed papers in scientific journals. Of course this paper is subject to the same doubts that it incites.

[sthira]

One third of the studies we like to cite are eventually contradicted by another study, and one third are never repeated.* If you saw how grad students, and professors, strive to get significant effects, then you wouldn't trust any individual paper, just a steady preponderant and consistent result. Not saying there is deliberate fraud, but a desired result is more likely than an undesired one. Consider Das, whose papers are all suspect now that some were withdrawn for suspected fraud. And perhaps this was over-eager grad students trying to please the professor?

When a new miracle supplement comes along, better hurry and take it while it still works.

These words should be posted ubiquitously at this site.

[geo12the]

If you saw how grad students, and professors, strive to get significant effects, then you wouldn't trust any individual paper, just a steady preponderant and consistent result.

Quite true. Kind off topic but the same can be said about drug companies and their clinical trials.

[VP.]

That's it. I am cutting back to once a week or less for Res.

[markymark]

I found these comments by Bill Sardi and James Betz at nutraingredients.com
mm

http://www.nutraingr...est-researchers

3 comments


Resveratrol does NOT interfere with exercise

At no time did resveratrol significantly increase any health risk in this study. Exercise and exercise+resveratrol produced about the same effects and resveratrol did NOT meaningfully block the effects of exercise. Cholesterol and blood pressure remained within "desirable" and "optimal" ranges as indicated by the American Heart Association and other sources. This study is slanted to unfairly demean resveratrol. Any biologically-trained reporter should be able to ferret this out, but none did. See resveratrolnews.com for a more authoritative report.
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Posted by Bill Sardi
23 July 2013 | 04h58

new res study

This study has been reported in many of the science journals and is well documented. It seems that resveratrol works better on people with health problems than those without. However, there is a chance that that there is an element missing and that is quercetin which is reported necessary for proper function and triggering of the SIRT1 gene. This study was reported on this forum site a few posts under specifically about exercise also. http://www.ncbi.nlm....Pubmed_RVDocSum
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Posted by Ian Liberman
23 July 2013 | 01h57
Flawed study

Given the small study size, its short time frame, and lack of controls for diet, stress, hormonal cycle fluctuations and other relevant factors, and a fundamental protocol short coming I will elaborate on below, I would be very hesitant to attribute much credibility or value to its results.

The amount of resveratrol given the subjects would not be sufficient to neutralise the quantity of reactive oxidative species generated by the exercise undertaken by the subjects, let alone the oxidative species generated within the mitochondria pursuant to normal metabolic, non exercise related daily energy production. It certainly would not be adequate to substantially eliminate the effects of exercise generated Crebs Cycle Mitochondrial ROS production, as the authors claim. Also, given the short half life of resveratrol in whole blood and tissues it is highly unlikely that a single non time-release dose administered once per day could sustain the concentration of Trans-resveratrol within the muscle tissue needed to quench the free radical production created by the high intensity exercise.

Eight weeks is not a sufficiently long duration trial period to investigate cardiovascular fitness, blood pressure or changes in oxygen utilisation capacity.

Furthermore, the long term cardiovascular benefits of chronic resveratrol administration have been reasonably well established, and no significance is accorded these exercise and health benefits in this study.

Also, without actually measuring the miochondrial ROS levels in vivo and relating their concurrent values and variations to the observed whole organism performance parameters it is not possible to conclude that ROS inhibition accounted for the difference in exercise benefits observed between the two groups. This is more supposition than supportable conclusion on the part of the researchers. Many other factors could have accounted for the short term observed effects.

Finally, it is stated that resveratrol "attenuated" the effects of high intensity training but how could this conclusion be made, and how is it quantified given that different subjects were given resveratrol and the placebo, versus a standard protocol in which one group was given supplementation while the control group was given a placebo. Following the exercise phase measurements would be made of each groups response to exercise.

Then, the subjects who were administered Resveratrol would be allowed a period of time to clear the resveratrol and its metabolites from their plasma and tissues. Following the clearance phase, the study would be repeated with the groups swapped. That is, the group which was given resveratrol would become the control group and the group which was given the placebo would be given Resveratrol. At the end of this phase measurements would be made and analysed.

Regrettably, I must conclude that this study was a waste of time and money, and unless its results can be replicated in a more robust investigation utilising the protocol I outlined above it should be disregarded. In any study costs are a huge limiting factor, but when the cost constraints preclude the design and application of a sufficiently valid investigation, the hard decision to abandon the study altogether is the right decision for science and for one's reputation as a scientist.
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Posted by James Betz
22 July 2013 | 19h30

Edited by markymark, 23 July 2013 - 07:35 PM.

[maxwatt]

Agreed, and obviously so, that ROS quenching is not a credible mechanism to explain the results claimed. But the statement by Betz et al. that there was no significant difference between the groups was not significant, is contradicted by this statement from the abstract: "Exercise training lead to a 45% greater (P < 0.05) increase in maximal oxygen uptake in the placebo group than in the resveratrol group..." . Other markers also differed.

Agreed that 8 weeks is too short a time frame, but not too short to see improvements from exercise in untrained men. (The trained semi-pro cyclists informally reported on in this group took three months to see an improvement from resveratrol.) I recall a rodent study showing no exercise improvement with resveratrol, whereas other studies had shown a marked improvement. It turned out to be a question of motivation: The mice would not expend effort on a treadmill unless their tails were electro-shocked if they stopped running; with the shocks the rats showed a market improvement with resveratrol over controls. Without, they did less well. So perhaps motivation is a factor? The abstract gives no details on the exercise protocol, and I suspect it was a rather mild form of exercise for untrained older men. Treadmills are somewhat easy to "game" your performance by leaning on the hand supports, for instance. I would hope the experimenters could' control for this, but perhaps they did not ... particularly if the lead authors wanted to obtain a spectacular and publicity-generating result, and their students perhaps unconsciously fudged things to this end. But this is speculation, that the exercise-plus-resveratrol group did not work as hard.

Also noted was a difference in blood lipid levels, and blood glucose. If someone taking resveratrol were to buy a glucose meter, or get lab work for lipids, then cease taking resveratrol for two months, then remeasure--- that would be an interesting data point. Or get the labs done, then take resveratrol....

Edited by maxwatt, 23 July 2013 - 08:10 PM.

[maxwatt]

Another study, this one showing runners more prone to oxidative damage, and even more so with resveratrol. Sedentary subjects did not show pro-oxidant effects from resveratrol in this study. Nothing about dose in the abstract.

Med Food. 2012 May;15(5):441-7. doi: 10.1089/jmf.2011.0173. Epub 2012 Mar 22.

Double-face activity of resveratrol in voluntary runners: assessment of DNA damage by comet assay.

Tomasello B, Grasso S, Malfa G, Stella S, Favetta M, Renis M.

Source

Department of Drug Sciences, University of Catania, Catania, Italy.

Abstract


Voluntary runners are subjected to a massive increase in reactive oxygen/nitrogen species production, which can promote different oxidative stress-related diseases such as premature aging, neurodegenerative disorders, and cancer. The aims of this work were to evaluate the following in peripheral blood cells of voluntary runners: (i) DNA status; (ii) susceptibility to the in vitro insult induced by hydrogen peroxide (H(2)O(2)) as a breaking agent; (iii) capabilities of 3,5,4'-trihydroxystilbene (RESV) in counteracting DNA damage. Twenty-five male voluntary runners were compared with 20 sedentary men, as age-matched controls, and DNA status was evaluated with different versions of comet assay: alkaline, neutral, and Fpg enzyme-modified version to measure 8-OH-deoxyguanosine (8-oxo-dG) levels. The H(2)O(2) and/or RESV treatments were performed directly on agarose-embedded cells (atypical comet assay). The results evidenced DNA damage and levels of 8-oxo-dG higher in runners than in sedentary control subjects. The runners' DNA was more prone to the in vitro-induced oxidative insult (200 μM H(2)O(2)) than that of the control group. Resveratrol (100 μM), depending on the individual basal DNA status, was able to switch from antioxidant to pro-oxidant. Our results, on the one hand, validated the proposed in vitro experimental protocol in order to measure individual DNA status. On the other hand, our data point out the importance of monitoring the athletes' redox status before subjecting them to dietary supplementation treatment.

[balance]

When a new miracle supplement comes along, better hurry and take it while it still works.

Well said, gave me a chuckle.

[markymark]

Although coming from a pro-TRESV site, this one is a well written critique of the "study" in question:

http://www.resveratr...y-exercise/805/

[maxwatt]

but Saardi's critique, linked one post above, does not address the 45% increase in oxygen uptake in exercise alone vs. no change in res plus exercise group. It sounds significant in the abstract, but could it be another red herring or straw man perhaps intended to mislead?

[markymark]

hm, first of all, I did not read the paper.

However, did the resveratrol group "deliver" the same (increase) in workload (in watts) as the execise-only group?
If so, didn't they (the resveratrol group) "need" less (45 %, relative) oxygene for the same workload?

[Hebbeh]

hm, first of all, I did not read the paper.

However, did the resveratrol group "deliver" the same (increase) in workload (in watts) as the execise-only group?
If so, didn't they (the resveratrol group) "need" less (45 %, relative) oxygene for the same workload?

That was my take on it from my own and others I know experiences. My exercise capacity increases with resveratrol which could only be explained by improved.oxygen utilization. I need less oxygen....get less winded and less tired. It's a positive not a negative. This study was obviously biased for a negative conclusion even though the data indicates otherwise. Looks pretty shady.

[maxwatt]

Yes, I too find my workouts are too easy when I take resveratrol. I will definitely cut back to make them harder, so I can get more benefit from my training. :P

FWIW, if you google the lead author, Lasse Gliemann, he seems to be a triathlete a well as a PhD candidate. Perhaps he is trying to gain a competitive advantage by discouraging others from taking it. (Tongue firmly in cheek)

Edited by maxwatt, 24 July 2013 - 09:14 PM.

[balance]

Less muscle soreness from a resveratrol metabolite:

http://www.ncbi.nlm....pubmed/20558128

[malbecman]

Here is another story about the original article in Journal of Physiology:

http://www.nlm.nih.g...ory_139052.html

[maxwatt]

One thing I've not seen mentioned in the writeups on Gliemann's paper, is time-of-day of administration,

Resveratrol agonizes CLK1 and CLK2, biological clock genes. These are normally activated late at night, or very early in the morning. Sunlight resets the clock, and these genes' expression drops.

I used to recommend that resveratrol be taken in the morning, but in view of the clock gene action, I would suggest either very late at night or before dawn. I had been taking it at breakfast, and notice it seemed more effective in winter when my breakfast was before sunrise. I am now taking it at bedtime in the summer. Seems to improve workout quality.

Anyway, I wonder if the paradoxical studies control for time of day of administration, and if this accounts for the failure to replicate positive studies.

[balance]

That is an excellent observation maxwatt, regardless if it is the reason for the above study's results, I will incorporate that in my advice and regimen. Thanks

[geo12the]

Just saw this:

Int J Sport Nutr Exerc Metab. 2013 Aug 5. [Epub ahead of print]

Effects of Resveratrol in Patients With Type 2 Diabetes Mellitus on Skeletal Muscle SIRT1 Expression and Energy Expenditure.

Goh KP, Lee HY, Lau DP, Supaat W, Chan YH, Koh A FY.

Source

Division of Endocrinology, Khoo Teck Puat Hospital, Alexandra Health, Singapore.

Abstract


Objectives: The primary aims of the study were to examine the effect of resveratrol on skeletal muscle SIRT1 expression and energy expenditure in subjects with type 2 diabetes mellitus (T2DM). Background: Animal and in vivo studies indicate that resveratrol increases SIRT1 expression that stimulates PGC1α activity. Subsequent upregulation of AMPK and GLUT4 expression are associated with improved insulin sensitivity in peripheral tissues. Methods: Ten subjects with T2DM were randomized in a double-blind fashion to receive 3g resveratrol or placebo daily for 12 weeks. Secondary outcomes include measures of AMPK, p-AMPK and GLUT4 expression levels, energy expenditure, physical activity levels, distribution of abdominal adipose tissue and skeletal muscle fiber type composition, body weight, HbA1c, plasma lipid subfraction, adiponectin levels and insulin sensitivity. Results: There was a significant increase in both SIRT1 expression (2.01 vs 0.86 arbitrary units [AU], P=0.016) and p-AMPK to AMPK expression ratio (2.04 vs 0.79 AU, P=0.032) in the resveratrol group compared to the placebo group. Although the percentage of absolute change (8.6 vs -13.9 %, P=0.033) and percentage of predicted resting metabolic rate (RMR) (7.8 vs -13.9 %, P=0.013) were increased following resveratrol, there was a significant reduction in average daily activity (-38 vs 43.2%, P=0.028) and step counts (-39.5 vs 11.8%, P=0.047) when compared to placebo. Conclusions: In patients with T2DM, treatment with resveratrol regulates energy expenditure through increased skeletal muscle SIRT1 and AMPK expression. These findings indicate that resveratrol may have beneficial exercise-mimetic effects in patients with T2DM.

[cudBwrong]

Yes, I too find my workouts are too easy when I take resveratrol. I will definitely cut back to make them harder, so I can get more benefit from my training. :P

Maxwatt is making a joke, but this may be a key to understanding what is going on. The study is measuring maximal oxygen uptake, which is oxygen into the body. Other studies show resveratrol improving the efficiency or rate of the processing of oxygen by mitochondria. One assumes that these are all stages on the same assembly line conveyor belt, but the relationships are complex.

If mitochondria are less efficient, perhaps the body is required to consume more oxygen in order to accomplish an equivalent amount of work. Perhaps this extra oxygen "leaks" away from useful work, on other pathways where it causes damage in the form of oxidative stress. Think of it as analogous to a machine that wastes energy due to friction, energy which is dissipated as heat. It takes energy to damage cells.

The effects of exercise on various markers of cardiac health, such as blood lipids, and blood pressure, may depend upon factors associated with the extra oxygen consumption -- for example, respiration rates and blood flow. If the need for oxygen intake is reduced, these markers might not improve to the same degree, or even at all. However, that does not mean that resveratrol is not good for the heart, with or without exercise.

So it may not be correct to speak of "negative effects of resveratrol" in the larger sense or to conclude that it is a bad idea to take resveratrol.

I have read only the abstract, but I do not share the criticisms of the study design that others have expressed. I have respect for the power of a double blind randomized trial. It would be interesting to have the experimental and control groups switch protocols after a rest period, but the statistics tell me that this would be unlikely to show a different result. I think it is more likely that there is something real and interesting going on here which can lead us to new knowledge. I suspect that eventually we will learn that these results support, rather than diminish, a cardiovascular benefit for resveratrol.

[hav]

I only just now got a chance to read this study and it just doesn't look like a very exhausting workout they were measuring. The only test they did that might be much of a cardiovascular workout was the 5-k walk but they don't tell us how they did it... individually or as a group. The times for the 5-k walk are so identical, both in the before and after treatment measurements, I suspect they did it as a single group en mass with everyone doing roughly the same pace. The results suggest the resveratrol group was probably coasting, breathing less hard, and thus consuming 45% less oxygen. Maybe the only surprises are 1) that with significantly less exertion the resveratrol group's beneficial markers after the 8 weeks were very close to those of the placebo group, and 2) that only 250 mg/day of resveratrol had such a significant measure of effect on oxygen consumption. Perhaps someone should consider an exercise effects study where oxygen consumption and/or exhaustion levels are held constant and see what happens to the markers... more like what real people do in a real life. And maybe see if there is a dosage effect.

Howard

Edited by hav, 11 August 2013 - 04:51 PM.

[cudBwrong]

The results suggest the resveratrol group was probably coasting, breathing less hard, and thus consuming 45% less oxygen.

[...]
Perhaps someone should consider an exercise effects study where oxygen consumption and/or exhaustion levels are held constant
Howard

Howard and some of the other contributors and I are thinking along similar lines. There is an interesting series of studies which show that the arteries dilate under exercise to match oxygen supply with demand. Here's one of several reports by MJ Joyner et. al:

http://www.ncbi.nlm....pubmed/23887898

This fits with the finding in the Gliemann et al study referenced in the original post that the resveratrol group had lower vasodilation, more TBX synthase, and less prostacyclin. Thromboxane and prostacyclin form a homeostatic system to regulate vascular diameter, again, matching supply and demand.

One way to look at this is that you can't have oxidative stress without oxygen. If one group is consuming more oxygen, that might not be a good thing.

Other things being equal, the capacity for higher oxygen consumption is a marker of good cardiac health. However, the need to consume more oxygen for the same unit of work might be a negative finding, indicating that some of this additional oxygen is winding up in places where it does damage.

This makes us wonder about what we would learn from additional studies along the lines suggested by Howard and others. I find this study to be valid within its limits and suggestive of some new areas of research. However, I would not conclude that it shows that resveratrol is bad for the heart; in fact, it may lead to other results which show just the opposite.

[hallucinogen]

I believe it is COMMON SENSE not to take ANY Vasoconstrictive/Anti-Inflammatory substance within at least half a day, a good 10 hours before or after exercise...

that include Resveratrol, Vitamin C, lame Avocadoes, Fish, Fish oil, WHATEVER ,

first of all, you wont be able to exercise nearly as hard, as far, or as much as you could otherwise, you will get ZERO vasodilation/Pump which is the cornerstone of the whole Exercise which follows much better nutrient exchange,
and you will put MUCH Greater, incredible strain on your whole Body and circulatory system, because even thought your heart tries to pump, the blood simply does not get everywhere and does not facilitate nutrient exchange effectively

Your Recovery will also be NON-EXISTENT and you will do more harm than good exercising like this

Eating right to exercise daily is one of the most complex and difficult sciences which I had to research and experiment with in my Life

The only acceptable time to take Vitamin C or Reservartol would be right before bed-time,
and if you have any sense left at all, you wont exercise after 4pm or you wont sleep and recover as well as you should


I got a big can of 500mg Res sitting around and it is not likely that I will be taking any of it anytime soon now

Edited by hallucinogen, 13 September 2013 - 11:49 AM.

[APBT]

I’m bumping this thread based on the comment here

 

Here is the full text of this thread topic Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men

 

See also this