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    Antioxidant Craze: Too Much Resveratrol May Block Benefits Of Exercise In Older Men
    By News Staff | July 21st 2013 10:10 PM | 8 comments | Print | E-mail | Track Comments

    Resveratrol, a natural antioxidant compound found in red grapes and other plants, has received widespread attention for being a possible anti-aging compound and is now widely available as a dietary supplement; many claims have been made about its role in explaining the cardiovascular health benefits of red wine, and other foods.

    New research in The Journal of Physiology instead suggests that eating a diet rich in antioxidants may actually block or counteract many of the health benefits of exercise, including reduced blood pressure and cholesterol. This is in contrast to studies in animals where resveratrol improved the cardiovascular benefits of exercise.

    At least in older men, too much resveratrol has the opposite effect, the work from the University of Copenhagen found.

    Antioxidants are not a fix for everything. Some degree of oxidant stress may be necessary for the body to work correctly. This study suggests that reactive oxygen species, generally thought of as causing aging and disease, may be a necessary signal that causes healthy adaptations in response to stresses like exercise. So too much of a good thing (like antioxidants in the diet) may actually be detrimental to our health.

    Lasse Gliemann, a PhD student who worked on the study at The University of Copenhagen, explains how they conducted the research, and the results they found: "We studied 27 healthy, physically inactive men around 65 years old for 8 weeks. During the 8 weeks all of the men performed high-intensity exercise training and half of the group received 250 mg of resveratrol daily, whereas the other group received a placebo pill (a pill containing no active ingredient). The study design was double-blinded, thus neither the subjects nor the investigators knew which participant that received either resveratrol or placebo.

    "We found that exercise training was highly effective in improving cardiovascular health parameters, but resveratrol supplementation attenuated the positive effects of training on several parameters including blood pressure, plasma lipid concentrations and maximal oxygen uptake."

    Ylva Hellsten, the leader of the project, says, "We were surprised to find that resveratrol supplementation in aged men blunts the positive effects of exercise training on cardiovascular health parameters, in part because our results contradict findings in animal studies.

    "It should be noted that the quantities of resveratrol given in our research study are much higher than what could be obtained by intake of natural foods."

    This research adds to the growing body of evidence questioning the positive effects of antioxidant supplementation in humans.

    Michael Joyner, from The Mayo Clinic USA, says how the study has wider implications for research: "In addition to the surprising findings on exercise and resveratrol, this study shows the continuing need for mechanistic studies in humans. Too often human studies focus on large scale outcomes and clinical trials and not on understanding the basic biology of how we adapt."


    Comments

    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.

    Hank
    If the study were a one-off, I'd be inclined to agree. Instead, resveratrol has become the poster child for "artifactual findings". Sinclair's SIRT compounds were a $750 million fiasco for Glaxo. Even as far back as 2009 we were making fun of the 'miracle of the week' claims, when it isn't even clear that is the compound in red wine that brings benefit. That's without getting into the antioxidant hype.
    UvaE
     It certainly would not be adequate to substantially eliminate the effects of exercise generated Crebs Cycle Mitochondrial ROS production, as the authors claim.
    You mean the Kreb's cycle 's ROS (reactive oxygen species) production. 

    Furthermore, the long term cardiovascular benefits of chronic resveratrol administration have been reasonably well established.
    Are you sure about that?  Most medical sites report something along the lines of:


    Because there have been very few studies conducted on resveratrol in humans, doctors still can't confirm any benefits, and they don't know what effects these supplements might have on people over the long term. 

    You are right. I meant Krebs cycle, and meant to correct it but could not edit the comment.

    Yes, I am sure of the CVD benefits. I own a patent on one such application, and have collaborated on several clinicals that have not yet been published which will better elucidate these effects.

    Thanks for taking the time to comment.

    I have just started taking daily Ateronon tablets which are supposed to have a similar effect only the source is antioxidants found in tomato skins. One pill is apparently the equivalent of eating twenty tomatoes in terms of antioxidants.
    Would appreciate if anyone has a view on the effectiveness of this supplement?

    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.

    John Hasenkam
    Why do people even assume reducing oxidation is a good thing? The more critical protective issue here might be the induction of Heat Shock Factor which promotes heat shock proteins. Intense exercise, especially endurance exercise, damages proteins, sometimes this is reversible. More importantly, by inducing hsps these damaged proteins can be recovered or via chaperone mediated autophagy degraded. 
    Numerous studies now conflict with that concept and numerous studies indicate antioxidants do not inhibit the oxidation events in exercise. 
     2010 Jul;42(7):1388-95. doi: 10.1249/MSS.0b013e3181cd76be.

    Antioxidant supplementation does not alter endurance training adaptation.



     2011 Jun;93(6):1373-83. doi: 10.3945/ajcn.110.009266. Epub 2011 Apr 20.

    No effect of antioxidant supplementation on muscle performance and blood redox status adaptations to eccentric training.



     2005 Oct;15(5):480-92.

    Exercise and mononuclear cell DNA damage: the effects of antioxidant supplementation.

    Davison GWHughes CMBell RA.

    Source

    School of Health Sciences, University of Ulster Jordanstown, Newtownabbey, Northern Ireland, UK.


    Abstract

    The purpose of this investigation was to determine the effects of antioxidant supplementation on DNA damage following exercise. Fourteen subjects were randomly assigned to one of two groups and required to ingest either antioxidants (400 mg alpha-lipoic acid, 200 mg co-enzyme Q10, 12 mg manganese, 600 mg vitamin C, 800 mg N-acetyl cysteine, 400 microg selenium, and 400 IU alpha-tocopherol per day) or placebos for 7 d. Exercise increased DNA damage, PS, FRAP, and LDH (P < 0.05), but not selectively between groups. LDH and PS concentration decreased 1 h post-exercise (P < 0.05), while LH concentration decreased 1 h post-exercise in the antioxidant group only (P < 0.05). The antioxidant group had a higher concentration of LH (P < 0.05), perhaps due to a selective difference between groups post-exercise (P < 0.05). The main findings of this investigation demonstrate that exhaustive aerobic exercise induces DNA damage, while antioxidant supplementation does not protect against damage.



    PMID:
     
    16327031
     
    [PubMed - indexed for MEDLINE]




    I am an 80 year old board certified medical doctor and have taken resveratrol for 5 years. Five years ago, before resveratrol supplement, I could hardly play one hole without riding on golf cart. Now I am enjoying golf by walking 18 holes without any physical strain. Most of my colleagues have been telling me to do exercise with moderation, saying to keep my heart rate at 80 percent of my biological age which is 80 percent of 140 (220-80=140). That is to say I can only let my pulse go up to 112/minute. But I let my pulse run up to 160/minute for a couple minutes with no cardiopulmonary problem when I workout my elliptical machine.
    I think that the study needs to be improved in many ways, including the sample size, test duration and control for the specific effects or non-effects of resveratrol.

    I think that there are definite benefits to resveratrol and encourage each person to try and evalute its benefits for themself.