25 replies to this topic

[health_nutty]

http://plaza.ufl.edu...euwen/April.PDF

SUPPLEMENTATION WITH VITAMIN C AND N-ACETYL-CYSTEINE
INCREASES OXIDATIVE STRESS IN HUMANS AFTER AN ACUTE MUSCLE
INJURY INDUCED BY ECCENTRIC EXERCISE
A. CHILDS, C. JACOBS, T. KAMINSKI, B. HALLIWELL, and C. LEEUWENBURGH*
Biochemistry of Aging Laboratory, Center for Exercise Science, College of Health and Human Performance, University of Florida,
Gainesville, FL, USA; and Department of Biochemistry, National University of Singapore, Kent Ridge Crescent, Singapore,
Singapore
(Received 1 May 2001; Accepted 15 June 2001)
Abstract—There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants
vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We
induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized
by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6.
Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10
mg/kg body weight) for 7 d. The resulting muscle injury caused increased levels of serum bleomycin-detectable iron and
the amount of iron was higher in the vitamin C and NAC group. The concentrations of lactate dehydrogenase (LDH),
creatine kinase (CK), and myoglobin were significantly elevated 2, 3, and 4 d postinjury and returned to baseline levels
by day 7. In addition, LDH and CK activities were elevated to a greater extent in the vitamin C and NAC group. Levels
of markers for oxidative stress (lipid hydroperoxides and 8-iso prostaglandin F2a; 8-Iso-PGF2a) and antioxidant enzyme
activities were also elevated post-injury. The subjects receiving vitamin C and NAC had higher levels of lipid
hydroperoxides and 8-Iso-PGF2a 2 d after the exercise. This acute human inflammatory model strongly suggests that
vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative
stress. © 2001 Elsevier Science Inc.
Keywords—Pro-oxidants, Ascorbic acid, Neutrophils, Sepsis, Free radicals, Disease, Antioxidants

[wydell]

So, are spending a bunch of money on antioxidants only to find that we are increasing oxidation? That would be ironic.

[mike250]

yeah that was discussed on a different board. antioxidants shouldn't be used post-workout.

[Shepard]

So, are spending a bunch of money on antioxidants only to find that we are increasing oxidation? That would be ironic.

Redox is terribly complicated. I certainly don't feel qualified to speak as an authority on the matter, but I have finally learned enough to realize how little I know about the subject.

On the topic of antioxidant supplementation around exercise, I have a good bit of data scattered around on the subject. I'm busy studying at the moment, but I can weigh in on it tomorrow. I know there was a discussion on here about it, too. My current position is no significant antioxidant supplementation around intense exercise.

[wydell]

So, are spending a bunch of money on antioxidants only to find that we are increasing oxidation? That would be ironic.

Redox is terribly complicated. I certainly don't feel qualified to speak as an authority on the matter, but I have finally learned enough to realize how little I know about the subject.

On the topic of antioxidant supplementation around exercise, I have a good bit of data scattered around on the subject. I'm busy studying at the moment, but I can weigh in on it tomorrow. I know there was a discussion on here about it, too. My current position is no significant antioxidant supplementation around intense exercise.

Shepard: I would be interested in hearing this info, as I have been supplementing before and after exercise to help prevent exercise induced oxidation.

[wydell]

I am going to look around to see if I can find some studies that point to certain antioxidants reducing oxidation during exercise.

If certain antioxidants are pro-oxidants under exercise conditions, perhaps they are proxidants under many other conditions as well (e.g., where there is inflamation generally)

[mike250]

it’s been shown that damaging eccentric exercise didn’t change the normal levels of our body’s antioxidants (Child et al., 1999). In other words, our body has a natural antioxidant defense capability, and this was not stressed at all despite the exercise and the subsequent muscle damage.

but there is also other data showing that there is an impact of exercise on natural antioxidant levels (Lee et al., 2002; Goldfarb et al., 2005)

anyhow it seems that the the microtrauma experienced by the muscle cells is worse when you use the antioxidants. But if that is indeed the case would it be possible that this increased muscle damage can lead to more growth?

[wydell]

I am going to look around to see if I can find some studies that point to certain antioxidants reducing oxidation during exercise.

If certain antioxidants are pro-oxidants under exercise conditions, perhaps they are proxidants under many other conditions as well (e.g., where there is inflamation generally)

well, here is number one. This looks good to me as polyphenols are a major part of my supplementation

http://www.nutraingr...s-sports-drinks

Flavonoids reduce exercise-induced oxidative stress

By Stephen Daniells



Get the latest Market Reports on
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1/30/2006 - Sports drinks rich in antioxidants could reduce exercise-induced oxidative stress (EIOS), reports new research.

High intensity exercise can bring on oxidative stress, where free radicals attack tissue and increase ageing. Oxidative stress has been linked to an increased risk of various diseases including cancer, Alzheimer's, and cardiovascular disease.

The researchers, from San Antonio Catholic University in Spain, showed that a drink containing black grape, raspberry and red currant concentrates reduced protein oxidation by 23 per cent. Similar tests for a placebo crossover showed protein oxidation increased by 12 per cent.

[wydell]

one more for the night, though this may be contrary to the original cited study. I will leave it you biochem types to explain it to me.


http://www.atypon-li...ournalCode=cclm


L-Cysteine supplementation prevents exercise-induced alterations in human erythrocyte membrane acetylcholinesterase and Na+,K+-ATPase activities

P.S. You guys are starting to make me rethink my NAC supplementation

[health_nutty]

I'm really hoping to hear from Zoolander on this one.

[mike250]

well personally I use BCAAs during workouts and waxy maize/liquid nutrition post-workout. I don't use anti-oxidants if at all.

[lucid]

Well, just from looking at what you guys have posted (I am certainly not an expert).

It seems that since Vit C gets recycled, I believe that I have read that it can cause more damage to a cell where as it is easier for Vit C to cross various membranes than the oxidant. Once Vit C has neutralized an oxidant, it will go on to oxidize something else.

There are some non cycling anti-oxidants. I believe that lycopene and melatonin are non-cycling, someone should check me on that. I believe flavanoids cycle though. But they may not pass through the same membranes as Vit C.

Cheers.

[Matt]

I always drinks green tea before and after exercise...

[Brainbox]

Lets stir up the issue a bit more. This is a study I showed in a separate topic about a month ago. It didn't raise to much attention nor comment at that time.

Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process.Close GL, Ashton T, Cable T, Doran D, Holloway C, McArdle F, MacLaren DP.
Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK. gclose@liv.ac.uk

Exercise involving lengthening muscle actions, such as downhill running, results in delayed onset muscle soreness (DOMS), which may be attributable to reactive oxygen species (ROS). Although exercise causes oxidative stress, any link between ROS and DOMS remains speculative. There is emerging evidence to suggest that ROS play an important physiological role, assisting in the recovery process and protecting the cell from future damage; however, this has not been fully established. Despite this uncertainty as to the precise role of ROS, attempts to prevent post-exercise ROS production through antioxidant intervention are still common. The study investigated the effects of ascorbic acid supplementation on ROS production and DOMS following downhill running. Subjects were assigned to two groups. The ascorbic acid group (group AA) received 1 g ascorbic acid 2 h pre-, and for 14 d post-downhill running, whilst the placebo group (Pl group) received a placebo. Blood samples were drawn pre-supplement, pre- and post-exercise, and then 1, 2, 3, 4, 7 and 14 d post-exercise for analysis of ascorbate, malonaldehyde and total glutathione. DOMS was assessed using a visual analogue scale and pressure algometry. Muscle function was assessed using isokinetic dynamometry. Plasma ascorbate was elevated throughout in group AA compared with the Pl group. Downhill running resulted in DOMS in both groups. Muscle function was impaired post-exercise in both groups, although a delayed recovery was noted in group AA. Malonaldehyde increased 4 d post-exercise in the Pl group only. Ascorbic acid supplementation attenuates ROS production following downhill running, without affecting DOMS. Furthermore, ascorbic acid supplementation may inhibit the recovery of muscle function.

PMID: 16611389 [PubMed - indexed for MEDLINE]

[health_nutty]

Yes, I remember that one too brainbox.

Here is one for vitamin C:

http://www.nutraingr...gh-dose-vitamin

[Brainbox]

Yes, I remember that one too brainbox. 

Here is one for vitamin C:

http://www.nutraingr...gh-dose-vitamin

Yes, it's certainly not all bad, on the contrary. I will keep taking my gram of C a day.

[mike250]

well inhibiting the recovery of muscle tissue is not a good thing.

[zoolander]

In the presence of iron the detrimental effects of superoxide and hydrogen peroxide are amplified by the subsequent formation of the hydroxyl radical which has been implicated in damaging several biomolecules such as DNA, proteins and lipids.

This study suggests that vitamin C is pro-oxidant because is can reduced Fe3+ (iron) into Fe2+ in vitro. It is the Fe2+ that then reacts with superoxide and hydrogen peroxide to generate the hydroxyl radical that causes the damage. Hence, vitamin C is acting indirectly. They also point out that thiols and transistional metal mixtures also promote hydroxyl radical generation and hence are also damaging to cells. This is where NAC comes into the equation because essentially it is a thiol/sulfur compound.

So what's the big deal here?......well in the presence of iron both vitamin C and NAC can form these reactive mixtures (ascorbate-iron/thiol-iron) that promote hydroxyl radical formation.

They comment....

Inflammation can be induced by acute exercise in unadapted subjects and can increase free levels of iron

hence, supplementation with vitamin C and/or NAC under inflammatory conditions (eg. intense exercise to the beginner or intense intense exercise for trained) is not advisable if one is prevent hydroxyl radical formations and damaged to biomolecules such as DNA, proteins and lipids.

The following sums up

it has been suggested that under certain conditions, vitamin C may act as a pro-oxidant due to the high reactivity of vitamin C with transitional metals, including iron. ....................increases in free metals, immediate intake of supplements, and activation of peroxide-producing cells could be responsible for the increased levels of oxidative stress and cell damage in subjects receiving the supplement...........

Under normal conditions supplementing with vitamin C and/or NAC should not set up a reactive (prooxidation) situation that damages cells because in normal non-inflammatory conditions we have a series of proteins that bind iron such as transferrin, ferritin and albumin.

Once again for clarity......

Intake of these supplements for long periods of time may have harmful effects in certain chronic disease conditions characterized by increased free levels of iron and inflammation

Taking the supplements in inflammatory conditions or elevated iron may have harmful effects. So we're talking about eccentric exercise in untrained---->inflammation or other situations such as dietary iron overload, haemochromatosis as well as using these supplements with medications that can cause elevated iron (eg. thyroxine).

closing comment from the paper that essentially answers the the initial question

This study does not argue to discontinue supplementation with either vitamin C or NAC in healthy humans, however, further studies are required to study the effects of chronic use of these supplements with disease conditions characterized by increased levels of free iron and inflammation

[health_nutty]

"hence, supplementation with vitamin C and/or NAC under inflammatory conditions (eg. intense exercise to the beginner or intense intense exercise for trained) is not advisable if one is prevent hydroxyl radical formations and damaged to biomolecules such as DNA, proteins and lipids."

What would be considered intense intense exercise? I'm nearly always pushing myself to improve the amount of weight I lift. I guess this is another reason not to go the extreme?

[mike250]

I would believe it would be if you're in an over-trained mode.

[zoolander]

No. Progessive overload is a very important aspect of training. Note that they used untrained to eccentric (lengthening) failure. Traditional training with weights usually only takes you to concentric (Shortening/contraction) failure because the concentric is weaker when compared to the eccentric. Eccentric training is a lot more damaging because you're at the extreme. You'll need assistance to go to eccentric failure.

We've done muscle damage studies in our lab and they're really intense. Traditionally you find the 1-RM for the exercise and then use a weight that is 110-120% greater than the subjects 1-RM. You assist with the concentric phase but let the subject take the entire load on the eccentric (down/lengthening) phase. You usually only damage 1 side as well and use the contra-lateral as the control. Well at least with leg biopsies. I was involved in a muscle damage study and walking around with a damaged left hamstring is almost as weird as having you're left butt check full of stanazol

[zoolander]

I think if you really listen to your body you'll know when your working under inflammatory conditions. The muscle is tender to touch and slightly swollen/inflammed.

[health_nutty]

Thanks, Zoo!

[zoolander]

No problemo

[lynx]

This and other studies like it argue for spin trapping radicals rather than using
conventional chain reacting antioxidants.
PBN and NtBHA quench radicals without becoming radicals.

Edited by lynx, 06 June 2007 - 11:00 PM.

[PWAIN]

Zoolander,

you said:
"because in normal non-inflammatory conditions we have a series of proteins that bind iron such as transferrin, ferritin and albumin. "

What happens to those protiens under inflammatory conditions? Do they get used up, stop working? If a way could be found to increase the amount of these proteins, might that be beneficial especially for times of inflammation?

Although I suspect we couldn't supplement for them directly, might there be a way of getting the body to produce more?