Theory:ROS may be an essential biological compound

hi,

saw a post by Joao Pedro de Magalhaes on the transhumantech list [originally on the extropy list]

Quote:
"First of all, overexpression of glutamate-cysteine ligase extends lifespan in Drosophila by up to 50%:

http://www.ncbi.nlm....00&query_hl=210

Glutamate-cysteine ligase is involved in glutathione synthesis, that can act as an antioxidant. The highest life-extension was due to overexpression in the brain, which is similar to previous results with SOD. So far, manipulations of the glutathione system in mice have failed to affect aging, but this particular genes has not been tested. In mammals, I believe the glutathione system mostly acts on oxidative defence in erythrocytes--though it has other functions. Mutations in these genes in humans have been associated with anemia but polymorphisms have been linked with myocardial infarction. This system could thus be similar to what we saw with catalase: overexpression leads to life-extension in Drosophila and, in mice, has a protective effect of cardiac disease but does not
impact on the whole aging process. We'll see if they develop some similar model in mice.


In the next paper they created a Drosophila strain with high levels of antioxidants and a lower production of ROS. Interestingly, the animals actually live less than controls:

http://www.ncbi.nlm....61&query_hl=112

This seems to support the idea that ROS are not just damaging compounds, but essential biological molecules used in a myriad of functions. On this subject, I have a paper on ROS that could be of interest to some of you:

http://www.ncbi.nlm....03&query_hl=116

Lastly, here's another recent paper showing that antioxidant protection does not correlate with longevity in rodents, in line with many other results suggesting that antioxidant protection is already optimized in mammals:

http://www.ncbi.nlm....18&query_hl=112
"

Oxidation is a fundamental necessity for life, so it's not surprising that inhibiting it can have both good and bad effects depending on the degree and the situation. I've thought for a long time that the assumption that antioxidants are simple goods regardless of action and magnitude is sure to prove very simplistic. Not that I don't take antioxidants and endogenous antioxidant upregulators. Who knows what the best course is.

Anway, very interesting info. Thanks!

Veyr interesting. I concur with Paul on the fact that free radicals are a necessary part of life (as we know it presently). Where mst people run into troube is by eating too much bad food and ending up with excessive amounts of free radicals and/or unused calories. So I wouldn't be surprised if antioxidant supplementation did not extend the lives of "healthy" people by all that much. However, a daily mutli-vitamin certainly does not hurt.

this thread seemed to catch on quickly:) I have been little supprised that people were not more interested as this is probably one of the most fundamental issues that many people have wrong in their "implicit personal theories of aging" compared to real scientists' view on aging.

anyway, I think this comment sums up the situation at the moment (made in this thread).

The point: as is agreed by everyone actually in biogerontology, "free radicals" do NOT, in general, cause aging. However, there is a GREAT DEAL of evidence that ROS in the mitochondria do. SINCE CR & hardwired longevity do not have a clear-cut effects against "any ol' ROS," "any ol' ROS" are not involved in aging. SINCE CR & hardwired longevity DO have clear-cut effects against *mt* ROS issues, *mt* ROS issues very probably ARE critical to aging.

This is why every supplement that does not specifically fight mitochondrial ROS is doomed to failure (and according to comments by Jaoa, they might even be harmful). This is why most supplements around are just waste of money (marketed by their great "antioxidant" properties, possibly harmful waste of money.

Aubrey commented that essential functioning of ROS has been known for a while:

Thing is, this is not news -- roles of ROS (and not just nitric oxide) in signalling have been kown for over a decade (check out Sue Goo Rhee in PubMed). I have cited this sort of work quite often in my papers as reasons for focusing on removal of accumulating but initially inert molecules and cells rather than removal or bioactive ones.

This is why every supplement that does not specifically fight mitochondrial ROS is doomed to failure (and according to comments by Jaoa, they might even be harmful). This is why most supplements around are just waste of money (marketed by their great "antioxidant" properties, possibly harmful waste of money.

That did not come out right (and the edit fundtion does not work). What I meant was that supplements that are puprported to fight ROS in general but not not specifically mtROS probably don't work and might be harmful. That's why "good antioxidant" properties and "high ORAC values" are meaningless in general. That does not of course mean that supplements that work through another route, such as AGE inhibitors, would not be helpful even though they don't directly counteract mtROS.

opales,

It sounds like based on what you're saying, wouldn't that mean that a type of antioxidant like say, "Protandim", that works from the inside out rather than the outside in, be effective at fighting mitochondrial ROS.

Also, if some ROS is helpful wouldn't the seemingly small dose Protandim delivers possibly be better than a higher dose?

In advance, sorry i mentioned the P word again

Many essential vitamins are also antioxidants. They are helpful in many ways in maintaning health. If your diet isn't well rounded enough to get all the vitamins your body needs (for whatever reason), then I can't see how a multivitamin is a waste of money.

Also, I can't see the harm in having extra antioxidants roaming around the body of someone who is overweight or over-eats from time to time. If antioxidants are neutralizing excess and useless ROS, I don't see how that can be a bad thing.

Again, for a healthy person with a good diet, maybe there isn't a lot of life extension to be gained from pure antioxidant supplementation, but there is no way you are going to tell me that essential vitamins are bad for health.

i think antioxidant fanatics are going about it the wroing way. obviously, if oxidation was a huge factor in aging cyclists would be dead at 20.

"That did not come out right (and the edit fundtion does not work). What I meant was that supplements that are puprported to fight ROS in general but not not specifically mtROS probably don't work and might be harmful."

A familiar tune I don't buy it.

Many essential vitamins are also antioxidants. They are helpful in many ways in maintaning health. If your diet isn't well rounded enough to get all the vitamins your body needs (for whatever reason), then I can't see how a multivitamin is a waste of money.

Also, I can't see the harm in having extra antioxidants roaming around the body of someone who is overweight or over-eats from time to time. If antioxidants are neutralizing excess and useless ROS, I don't see how that can be a bad thing.

Again, for a healthy person with a good diet, maybe there isn't a lot of life extension to be gained from pure antioxidant supplementation, but there is no way you are going to tell me that essential vitamins are bad for health.

It may be heresy here, but I'm much more concerned with disease prevention/amelioration then life extension and e.g. given that oxidized cholesterol is what is damaging to arteries (to name one obvious example) I think the baby is being thrown out with the bathwater.

" i think antioxidant fanatics are going about it the wroing way. obviously, if oxidation was a huge factor in aging cyclists would be dead at 20."

uh the body can cope to some degree and undoubtedly revs up production of endogenous antioxidants.

I meatn obviously to agree with mind, and should have phrased things better then the bathwater bit, but I know better then to try to edit the post.

Oh and with the cyclist, just because the body copes e.g. revs up endogenous antioxidants does not mean it does so optimally.

Edited by scottl, 07 May 2006 - 10:26 AM.

Many essential vitamins are also antioxidants. They are helpful in many ways in maintaning health. If your diet isn't well rounded enough to get all the vitamins your body needs (for whatever reason), then I can't see how a multivitamin is a waste of money.

Also, I can't see the harm in having extra antioxidants roaming around the body of someone who is overweight or over-eats from time to time. If antioxidants are neutralizing excess and useless ROS, I don't see how that can be a bad thing.

Again, for a healthy person with a good diet, maybe there isn't a lot of life extension to be gained from pure antioxidant supplementation, but there is no way you are going to tell me that essential vitamins are bad for health.

No of course I am not saying that just because some substance happens to have antioxidant properties (say a vitamin) that it is a waste to get vitamin the recommended amount, that's absurd. Most likely, the RDAs for known antioxidants like C or E contain some "antioxidant" effect in addition to their essential functions in maintaining essential processes for life. For example, the RDA 90mg/day for C is a whole lot more than what is needed to keep scurvy away. The question is, what happens after we go beyond those RDA amounts.

Your commentary on being overweight etc. might be appealing, but I am not sure on what evidence it is based on. I have not seen positive trials with antiox supplementation decreasing mortality in obese persons, I am sure such would have been conducted if it was as obvious theoretical possibility as you portray it.

There is no way denying that unlike previously held, ROS are involved in many beneficial processes so randomly counteracting them might not be optimal strategy. Of all micronutrients, I think antioxidants have received most trials and fairly systematically they have been failures. I think the reason might be the simplistic theory the trials are built upon. Here is fresh from the oven another failed antiox-trial from NEJM. Note that antioxidant supplementation was associated with non-significant harmful effects:

http://content.nejm....ort/354/17/1841

Unfortunately that 100 "abstract" does not tell much, here is a synopsis by a NEJM subsriber MD:

Text is available on-line only to subscribers of NEJM.
Dosage was 1000 mg vitamin C and 400 IU vitamin E daily.
Women in the vitamin group had a higher incidence of abnormal LFTs and
hypertension, but "because multiple comparisons were made, the findings of
potential harm could be explained by chance alone."

It may be heresy here, but I'm much more concerned with disease prevention/amelioration then life extension and e.g. given that oxidized cholesterol is what is damaging to arteries (to name one obvious example) I think the baby is being thrown out with the bathwater.

I am interested in disease prevention as long as it enhances overall life-extension. ok, lets work from the assumption oxidized cholesterol is damaging to arteries, although I am not sure it is. My logic here applies to other similar phenomenon too. First question is, can dietary antioxidants (say above RDAs) do jack to prevent cholesterol from oxidizing, maybe the phenomenon is under very strict genetical control? Second, even if it does, could the disturbed cell signalling be enough to counteract the benefits from total LE perspective, say by increasing cancer incidence?

Or maybe the body has tight genetical control for antioxidants in general, and the excess amounts are just pissed away, giving the body perhaps a little extra stress. We know almost all vitamin C is pissed away after certain fairly small amount:
http://www.cron-web....fs.html#_edn147
http://www.cron-web....fs.html#_edn148

I don't know the answers to these questions, I am just providing other plausible scenarios.

Opales,

You have referenced a study on pregnant women:


"Antioxidants and the Prevention of Preeclampsia — Unresolved Issues"

"Preeclampsia is a pregnancy-specific, multisystem disorder... "


Since it is unlikely that you or I will be pregnant in this lifetime this aricle has no relevance to you or I--except it fits your pre-concieved notion of anti-oxidants being harmful (I'm taking your word, I ain't gonna read it).

I totally agree that ROS probably serve vital functions and that more anti-oxidants are not necessarily better. However there is no shortage of studies done badly, or studies done on patient populations that are not relevant to you, I or most people here. It would make your case more credible if you would pick your ammo more carefully.

The question is, what happens after we go beyond those RDA amounts.

The question to be asked before this one might be:
"On what recently discovered facts are the RDA's based upon?"

Back then, the anti-oxidant world was simple. Nobody heard of them or in case they were heard of were not taken seriously.

Could this early approach have resulted in reasonable educated RDA guesses by just looking at the net, externally visible effects?

And do we presently posses sufficient knowledge to change the RDA’s on a scientific basis?

Opales,

You have referenced a study on pregnant women:

"Antioxidants and the Prevention of Preeclampsia — Unresolved Issues"

"Preeclampsia is a pregnancy-specific, multisystem disorder... "

Since it is unlikely that you or I will be pregnant in this lifetime this aricle has no relevance to you or I--except it fits your pre-concieved notion of anti-oxidants being harmful (I'm taking your word, I ain't gonna read it).

I totally agree that ROS probably serve vital functions and that more anti-oxidants are not necessarily better.  However there is no shortage of studies done badly, or studies done on patient populations that are not relevant to you, I or most people here.  It would make your case more credible if you would pick your ammo more carefully.

Well the study once again showed that possibility of anti-oxidant having harmful effects, did not think I drew any further results than that.

Speaking of which, here is a study of common antioxidants featuring carcinogenic and pro-oxidant activities in certain situations. These are the reasons I'd rather wait for actual animal and human trials with clinical endpoints (preferaby total mortality) rather than engage in wild optimistic experimentation with substances with only mechanistic logic with in vitro results accompanied perhaps by weak animal studies. The list of possibly carcinogenic substances reads like directly from Joe Lifeextensionist's regime.

http://www.ncbi.nlm....3&dopt=Abstract

Antioxidants are considered as the most promising chemopreventive agents against various human cancers. However, some antioxidants play paradoxical roles, acting as "double-edged sword." A primary property of effective and acceptable chemopreventive agents should be freedom from toxic effects in healthy population. Miscarriage of the intervention by beta-carotene made us realize the necessity for evaluation of safety before recommending use of antioxidant supplements for chemoprevention. We have evaluated the safety of antioxidants on the basis of reactivity with DNA. Our results revealed that phytic acid, luteolin, and retinoic acid did not cause DNA damage under the experimental condition. Furthermore, phytic acid inhibited the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an indicator of oxidative DNA damage, in cultured cells treated with a H(2)O(2)-generating system. Thus, it is expected that these chemopreventive agents can safely protect humans against cancer. On the other hand, some chemopreventive agents with prooxidant properties (alpha-tocopherol, quercetin, catechins, isothiocyanates, N-acetylcysteine) caused DNA damage via generation of reactive oxygen species in the presence of metal ions and endogenous reductants under some circumstances. Furthermore, other chemopreventive agents (beta-carotene, genistein, daidzein, propyl gallate, curcumin) exerted prooxidant properties after metabolic activation. Therefore, further studies on safety should be required when antioxidants are used for cancer prevention. Antioxid. Redox Signal. 7, 1728-1739.

"We have evaluated the safety of antioxidants on the basis of reactivity with DNA."

MEANS ISLATED IN VITRO which is even less relevant to me then pregnant women.

in the presence of metal ions...

...endogenous reductants ***under some circumstances***.

Again, no way to quote opales given the way he writes:

"Well the study once again showed that ***possibility** of anti-oxidant having harmful effects, did not think I drew any further results than that.

The possiblity is irrelevant given that the population is pregnant women, and not only pregnant women, but pregnant women with a disease only pregnant women get.

Opales your posts are biased and clearly you continue to see out stuff to back your postion. I'm certainly willing to look at opposing views, but again, it would be helpful if you picked your examples better. There are tons on in vitro stuff about potential harm which does not pan out in vivo

I'm aware that my scientific knowledge about specific studies is not up to par with the most of you, but the bigger picture seems to suggest that the LE features anti oxidant were supposed to have several years ago are not being backed up with scientific studies (yet).

So, regardless the presence of even harmful effects, it is also not been proven that they have significant positive effect for LE.

Furthermore, regarding the general health benefits in preventing general decease (where aging is not seen as simply being a decease) , they do have proven positive effects, although in this area the synergistic effects are outperforming the effects of single substances alone. I'm not referring to situations were deficiency plays a major role.

So the question might be whether a megadose of a few substances might be better that just eating healthy food. Where the problem that our current way of processing food diminishes the anti oxidant features just cannot be compensated by taking supplements.

There's a lot of hypothesis in this, but I would like to hear your opinions on this.

I have now seen more support for this theory in the form of a reversal of doctrine regarding the underlying premise for the role of lactic acid in mitochondrial function. We apparantly are still building that model folks.

please reference this thread too:
http://www.imminst.o...ST&f=44&t=10559

Vol. 96, Issue 3, 1129-1134, February 2, 1999
http://www.pnas.org/...tract/96/3/1129
Role of mitochondrial lactate dehydrogenase and lactate oxidation in the intracellular lactate shuttle
George A. Brooks*, Hervé Dubouchaud, Marcia Brown, James P. Sicurello, and C. Eric Butz
Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, CA 94720-3140

Communicated by Howard A. Bern, University of California, Berkeley, CA, December 4, 1998 (received for review August 26, 1998)

To evaluate the potential role of mitochondrial lactate dehydrogenase (LDH) in tissue lactate clearance and oxidation in vivo, isolated rat liver, cardiac, and skeletal muscle mitochondria were incubated with lactate, pyruvate, glutamate, and succinate. As well, -cyano-4-hydroxycinnamate (CINN), a known monocarboxylate transport inhibitor, and oxamate, a known LDH inhibitor were used. Mitochondria readily oxidized pyruvate and lactate, with similar state 3 and 4 respiratory rates, respiratory control (state 3/state 4), and ADP/O ratios. With lactate or pyruvate as substrates, -cyano-4-hydroxycinnamate blocked the respiratory response to added ADP, but the block was bypassed by addition of glutamate (complex I-linked) and succinate (complex II-linked) substrates. Oxamate increased pyruvate (10-40%), but blocked lactate oxidation. Gel electrophoresis and electron microscopy indicated LDH isoenzyme distribution patterns to display tissue specificity, but the LDH isoenzyme patterns in isolated mitochondria were distinct from those in surrounding cell compartments. In heart, LDH-1 (H4) was concentrated in mitochondria whereas LDH-5 (M4) was present in both mitochondria and surrounding cytosol and organelles. LDH-5 predominated in liver but was more abundant in mitochondria than elsewhere. Because lactate exceeds cytosolic pyruvate concentration by an order of magnitude, we conclude that lactate is the predominant monocarboxylate oxidized by mitochondria in vivo. Mammalian liver and striated muscle mitochondria can oxidize exogenous lactate because of an internal LDH pool that facilitates lactate oxidation.

Intra- and extra-cellular lactate shuttles.
http://www.ms-se.com/pt/re/msse/abstract.0...#33;8091!-1
Medicine & Science in Sports & Exercise. 32(4):790-799, April 2000.
BROOKS, GEORGE A.
Abstract:
BROOKS, G. A. Intra- and extra-cellular lactate shuttles. Med. Sci. Sports Exerc., Vol. 32, No. 4, pp. 790-799, 2000. The "lactate shuttle hypothesis" holds that lactate plays a key role in the distribution of carbohydrate potential energy that occurs among various tissue and cellular compartments such as between: cytosol and mitochondria, muscle and blood, blood and muscle, active and inactive muscles, white and red muscles, blood and heart, arterial blood and liver, liver and other tissues such as exercising muscle, intestine and portal blood, portal blood and liver, zones of the liver, and skin and blood. Studies on resting and exercising humans indicate that most lactate (75-80%) is disposed of through oxidation, with much of the remainder converted to glucose and glycogen. Lactate transport across cellular membranes occurs by means of facilitated exchange along pH and concentration gradients involving a family of lactate transport proteins, now called monocarboxylate transporters (MCTs). Current evidence is that muscle and other cell membrane lactate transporters are abundant with characteristics of high Km and Vmax. There appears to be long-term plasticity in the number of cell membrane transporters, but short-term regulation by allosteric modulation or phosphorylation is not known. In addition to cell membranes, mitochondria also contain monocarboxylate transporters (mMCT) and lactic dehydrogenase (mLDH). Therefore, mitochondrial monocarboxylate uptake and oxidation, rather than translocation of transporters to the cell surfaces, probably regulate lactate flux in vivo. Accordingly, the "lactate shuttle" hypothesis has been modified to include a new, intracellular component involving cytosolic to mitochondrial exchange. The intracellular lactate shuttle emphasizes the role of mitochondrial redox in the oxidation and disposal of lactate during exercise and other conditions.

http://intl-jap.phys...tract/92/4/1573
J Appl Physiol 92: 1573-1584, 2002. First published January 18, 2002; doi:10.1152/japplphysiol.01069.2001
8750-7587/02  Vol. 92, Issue 4, 1573-1584, April 2002

Changes in MCT 1, MCT 4, and LDH expression are tissue specific in rats after long-term hypobaric hypoxia
Grant B. McClelland and George A. Brooks
Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, California 94720

Little is known about the effect of chronic hypobaric hypoxia on the enzymes and transporters involved in lactate metabolism. We looked at the protein expression of monocarboxylate transporters MCT 1, MCT 2, and MCT 4, along with total lactate dehydrogenase (LDH) and LDH isozymes in skeletal muscle, cardiac muscle, and liver. Expression of these components of the lactate shuttle affects the ability to transport and oxidize lactate. We hypothesized that the expression of MCTs and LDH would increase after acclimation to high altitude (HA). The response to acclimation to HA was, however, tissue specific. In addition, the response was different in whole muscle (Mu) and mitochondria-enriched (Mi) fractions. Heart, soleus, and plantaris muscles showed the greatest response to HA. Acclimation resulted in a 34% increase in MCT 4 in heart and a decrease in MCT 1 (47%) and MCT 4 (47%) in plantaris Mu. In Mi fractions, the heart had an increase (,40%) and soleus a decrease (40%) in LDH. HA also had a significant effect on the LDH isozyme composition of both the Mu and Mi fractions. Mitochondrial density was decreased in both the soleus (17%) and plantaris (44%) as a result of chronic hypoxia. We conclude that chronic hypoxia had a tissue-specific effect on MCTs and LDH (that form the lactate shuttle) but did not produce a consistent increase in these components in all tissues.

http://ajpendo.physi...act/290/6/E1237
Am J Physiol Endocrinol Metab 290: E1237-E1244, 2006. First published January 24, 2006; doi:10.1152/ajpendo.00594.2005 0193-1849/06

Colocalization of MCT1, CD147, and LDH in mitochondrial inner membrane of L6 muscle cells: evidence of a mitochondrial lactate oxidation complex Takeshi Hashimoto, Rajaa Hussien, and George A. Brooks
Department of Integrative Biology, University of California, Berkeley, California

Submitted 30 November 2005 ; accepted in final form 18 January 2006

Results of previous studies suggested a role of mitochondria in intracellular and cell-cell lactate shuttles. Therefore, by using a rat-derived L6 skeletal muscle cell line and confocal laser-scanning microscopy (CLSM), we examined the cellular locations of mitochondria, lactate dehydrogenase (LDH), the lactate-pyruvate transporter MCT1, and CD147, a purported chaperone protein for MCT1. CLSM showed that LDH, MCT1, and CD147 are colocalized with the mitochondrial reticulum. Western blots showed that cytochrome oxidase (COX), NADH dehydrogenase, LDH, MCT1, and CD147 are abundant in mitochondrial fractions of L6 cells. Interactions among COX, MCT1, and CD147 in mitochondria were confirmed by immunoblotting after immunoprecipitation. These findings support the presence of a mitochondrial lactate oxidation complex associated with the COX end of the electron transport chain that might explain the oxidative catabolism of lactate and, hence, mechanism of the intracellular lactate shuttle.

Lactate and glucose interactions during rest and exercise in men: effect of exogenous lactate infusion

"We have evaluated the safety of antioxidants on the basis of reactivity with DNA."
MEANS ISLATED IN VITRO which is even less relevant to me then pregnant women.
in the presence of metal ions...
...endogenous reductants ***under some circumstances***.

Opales your posts are biased and clearly you continue to see out stuff to back your postion. I'm certainly willing to look at opposing views, but again, it would be helpful if you picked your examples better. There are tons on in vitro stuff about potential harm which does not pan out in vivo.

The fact is that antioxidants have been failing in large human studies (mortality, CVD, cancer) despite very promising in vitro and even animal studies.

http://www.americanh...identifier=4452

Until recently, it was thought that LDL cholesterol lipoprotein oxidation and its biological effects could be prevented by using antioxidant supplements. However, more recent clinical trials have failed to demonstrate a beneficial effect of antioxidant supplements. Some studies even suggest that antioxidant supplement use could have harmful effects.

http://www.cancer.go...es/antioxidants

Considerable laboratory evidence from chemical, cell culture, and animal studies indicates that antioxidants may slow or possibly prevent the development of cancer. However, information from recent clinical trials is less clear. In recent years, large-scale, randomized clinical trials reached inconsistent conclusions.

Thus I think it is important to ask why is that. In that context even a mere in vitro study providing MECHANISM for harmful effects may give valuable knowledge.

You make it sound like I am challenging these awesome antioxidant study results through mere weak in vitro hypothesises, when in fact I am working the other way around.

Lazarus I have read with interest your quotes on lactic acid and the mitochondria. There is one point, well known for some time, about metabolic speed. When glucose is converted to lactic acid to produce ATP, we can get ATP faster that when glucose is converted to CO2 and water with the help of the mitochondria. However, fermentation is not efficient because only two ATP molecules are obtained from each glucose instead of the 38 ATPs per glucose molecule given by the mitochondria. In yeast, which granted are very simple organisms, a sort of aging has been described. Yeasts growing and fermenting glucose into ethanol age faster than yeast growing on glycerol, which is used only by the mitochondria. Th current beleive is that ROS, which indeed accumulated at higher levels when yeast are growing in glucose, reduce life span. However, antioxidants can not extend sinificantly the life of these yeasts but mutations in genes that control glucose metabolism do (i. e sch9 or sck2). In addition, ethanol (the yeast version of lactic acid) has been blamed for yeast aging even if we know that ethanol can be also burned by the mitochondria. I wonder whehter something fundamental about cell metabolism and the speed of biochemical reactions contains a hidden varaible in these problems.

Edited by ferbeyre, 26 July 2006 - 04:52 PM.

uh the body can cope to some degree and undoubtedly revs up production of endogenous antioxidants.

ROS raise every time after exercise.