How To Boost Your Glutathione Levels Naturally
Alittle tri-peptide molecule present in every cell in our body is being revealed by science to be the most potent anticancer, anti-aging component of human health. And now the latest research suggests it may also be the “critical link” in building muscle and enhancing athletic performance.
Natures most potent anti-aging, antioxidant compound may also be the key to muscle growth and athletic performance.
Glutathione (GSH) is the centerpiece of all antioxidant defense systems within the body.1 It is the front-line of cellular defense against toxins, infection, UV exposure, generation of free radicals, and cancer-forming compounds.1,2 It also serves to regenerate other critical antioxidants like vitamins C & E.1 However, as we age our glutathione levels diminish and these low levels are directly linked to the many diseases of aging such as Alzheimer’s, Parkinson’s, and various forms of cancer.(See previous article on GSH) As an added complication, GSH is useless to take in supplement form because it cannot be transported into our cells.1,2
A regular structured exercise program is shown to be invaluable in forming optimal GSH levels and free radical protection within our cells. However, up-to-date reviews by world-renowned antioxidant and muscle metabolism scientists indicate that intense training programs actually deplete GSH levels.1,2 This not only impairs performance, but it results in an increase in free radical damage to organs and tissues. This excessive free radical production is the suspected culprit of accelerated aging! (see previous article on GSH)
It appears the increased demands of muscle imposed by frequent and strenuous exercise deprives the immune cells of optimal GSH levels, a prerequisite to proper immune function.1 An undesirable competition arises between muscle tissue and the immune system for the limited sources of GSH.1 This metabolic struggle is a bad one and you are the one that loses. At the very least, low GSH levels lead to infection, muscle loss, and prolonged poor performance.1 More serious repercussions are Chronic Fatigue Syndrome and numerous other serious illnesses.1
The good news is, research clearly demonstrates that when you provide your body with the right nutritional substrates, cellular GSH levels dramatically increase.3,4,5 The impact of replenishing GSH levels with the right supplements is phenomenal. It reverses muscle loss and enhances the health and immune function of clinically ill people.3,4 And what is relevant to most everyone reading this is that supplementing with specific nutritional substrates to replenish GSH levels builds muscle and enhances athletic performance in healthy individuals even before any type of training.5
This is uncharted territory in the nutrition world and the emerging research is incredible.
Building or Losing Muscle?
It all has to do with cyst(e)ine.
Cancer, HIV, Crohnes disease, Over training, and Chronic Fatigue Syndrome are all completely unrelated conditions. However, they all demonstrate conspicuously similar blood amino acid profiles and significant muscle loss.6
Studies clearly demonstrate that blood levels of the amino acid cysteine (and its di-bonded residue cystine) appears to be the critical indicator of any change in lean body mass.6,7 Cysteine levels are shown to be a physiological regulator of nitrogen balance and body cell mass.7 Cystine levels are so reliable that scientists can now analyze them to predict muscle loss.7,8 Low cystine and glutamine levels in blood and muscle, along with increased glutamate and urea production characterize and forecast dramatic loss of muscle tissue.6,7,8 These “biochemical symptoms” appear way before weight loss becomes detectable. It doesn’t matter whether you are a super athlete or have a clinical illness, if your body’s ravenous cysteine demands are not met you lose muscle.6,7,8
This new research is beginning to shed light on why some people just can’t seem to gain appreciable muscle size no matter how intensely they train. It’s also underscoring the importance of intelligent supplementation. You can take all the protein and creatine you want, but if you are not specifically addressing GSH replenishment by using the right kind of protein and specific GSH supporting substrates, then your gains (if there are any) will be slow.
Training Induced Muscle Loss.
If you think you have to be an elite athlete performing super training schedules to be at risk of losing muscle and overtraining, you’re wrong. One study of 46 healthy and fit males shows the subjects lost large amounts of muscle while eating their normal diet and training only 1 hour, 3 times a week! This loss was evident within 4 weeks of training.8
With every passing decade on this planet each of us lose the ability to process cysteine correctly.7 This is thought to place an increasing burden on muscle glutamine stores to meet metabolic demands. This decline in cysteine production results in muscle loss that is usually assumed to be an uncontrollable part of the aging process.7 Wrong! If you structure a supplement program that allows you to maintain or enhance cystine levels, and weight train regularly, you’ll forgo the normal age related muscle loss! You’ll enhance body composition in favor of lean body mass.
Why Do We Lose Muscle So Easily?
Unfortunately, doctors and nutritionists have not accepted the fact that building muscle requires a very particular biochemical environment within the body that can not be achieved via a normal diet. At the hub, the epicenter of this optimal biochemical environment is the amino acid cysteine. Our body’s demand for this sulfur containing amino acid is so extensive that it easily exceeds the supply present in the average diet.1,4 In virtually every case as soon as an effective cysteine supplement is introduced lean muscle mass, immune function, health, and GSH levels improve.
With every passing decade on this planet each of us lose the ability to process cysteine correctly.7 This is thought to place an increasing burden on muscle glutamine stores to meet metabolic demands. This decline in cysteine production results in muscle loss that is usually assumed to be an uncontrollable part of the aging process.7 Wrong! If you structure a supplement program that allows you to maintain cystine levels, and weight train regularly, you’ll forgo the normal age related muscle loss! You’ll enhance body composition in favor of lean muscle mass.
Cysteine is the rate limiting amino acid in the formation of GSH.1,2 If the body does not have enough cystine to go around, GSH levels plummet and so does the strength of your immune system, 1,4 your athletic performance,2 and your hard-earned muscle.8 Now to exciting news. Research has shown three nutritional supplements to be extremely effective at boosting cell GSH to optimum levels.
By systematically introducing these key nutritional substrates into your daily schedule you will see dramatic improvements in your ability to enhance muscle growth while minimizing body fat. And the great thing about this is it’s all backed by solid scientific research. You not only will be targeting what research is showing to be the biochemical marker for optimum muscle growth, but you will be supporting and enhancing your immune system.
NAC – N-acetyl-cysteine
The supplement N-acetyl-L-cysteine (NAC) is the cysteine amino acid with a CH3CO (acetyl group) bonded at the N terminal. Its GSH replenishing and sparing aspects have been extensively documented.2,8,9 NAC’s potent antioxidant and nucleophilic properties produce little or no side effects in humans,2,10 and reduce viral replication while increasing plasma cysteine and glutamine levels in Hepatitis B and HIV patients.11,12
It is suspected that NAC supplementation works by either providing cysteine for GSH formation and/or directly scavenging reactive oxygen species itself.9 Research on rodents and humans using real-life dosages confirms the free radical scavenging effects of NAC. In fact, NAC’s free radical scavenging effect prevents the usual decline in GSH levels seen as a result of intense exercise.13
An observation of humans undertaking anaerobic threshold training (an intense form of exercise), exhibited marked declines in blood GSH levels.13 Now here are some exciting results discovered in this research. One group also supplemented with 4 x 200 mg of NAC for two days prior to testing and then took an additional 800 mg on the morning of the testing. This supplementation with NAC completely prevented the oxidation of GSH and maintained optimum GSH levels during and after intense exercise.13 NAC supplementation resulted in an increase in free radical scavenging capacity in the blood therefore preserving valuable GSH levels.13
The results of another double blind placebo controlled trial of 46 athletic men further demonstrate the regulatory role of cysteine and the potent effects of NAC supplementation.8
In this study a 4-week training program consisting of only three 1 hour sessions a week of weight lifting and sprints produced a loss in muscle mass, and an increase in body fat in the placebo group.8 Here’s the eye opening part, these effects were completely prevented by taking 2 x 200 mg capsules of NAC daily.8 The NAC-fed group built muscle and lost fat. Also, the placebo group produced a decrease in their CD4+ immune cells, the NAC-treated group did not.8 Although GSH was not monitored, the scientists that conducted this and other studies on muscle loss commented that the results with NAC supplementation are characteristics of its effect on the GSH depletion/preservation gradient. NAC maintains GSH levels in blood, muscle, and liver. And this preservation of GSH is a prerequisite of building muscle.6,7,8
The results of several double blind placebo controlled studies show NAC supplementation preserves critical glutathione levels while increasing the body’s scavenging capacity for the high amount of free radicals produced during intense exercise.
R-ALA – Alpha Lipoic Acid
Another supplement that has the remarkable ability to increase cell GSH levels is the nutrient called R a-Lipoic acid (R-ALA). It is shown to be safe for human use (it is also made within the body), and may prove to be even more potent than NAC at boosting GSH levels.2,14 R-ALA is also known as thioctic acid (a sulfur containing molecule) and at physiologic pH R-ALA becomes an anion; lipoate.
Without getting too heavily into the biochemistry (believe me, you don’t want to go there on this one) R-ALA appears to have a clear advantage over NAC because unlike NAC, R-ALA can be rapidly reduced to dihydrolipoate (DHLA) at the expense of cellular reducing equivalents.2,14 This actually harnesses the metabolic power of the cell to continuously regenerate its own active dithiol form.2,14,15 The cell’s energy maintains the lipoate in a favorable redox state. This is a very efficient recycling mechanism. It is thought to be a beneficial cellular condition for diseases such as diabetes.2 Where as NAC serves as a one time cysteine donor, R-ALA has the ability to serve as a continuous supplier of cysteine!2,14
R-ALA supplementation may prove even more potent than NAC at increasing glutathione levels. R-ALA has the ability to serve as a continuous supplier of cysteine by harnessing the metabolic power of the cell and regenerate its own active form!
Understanding GSH is essential to nutritionally manipulate its production. The trouble with GSH is that it cannot be transported into the cell.1,2 The selective ingredients essential to GSH formation can and have to be transported into the cell before there is any chance of GSH synthesis. Low concentrations of supplemented lipoate (R-ALA) have been shown to increase cellular GSH levels.16,17 Because R-ALA can be recycled from its oxidized form to the potent DHLA by enzymes in the human cell and NAC cannot, lower concentrations of R-ALA have often been found to be more potent than NAC at increasing GSH levels.18,19
While most of the information on R-ALA’s GSH boosting properties have been obtained from invitro studies (in the lab), one recent study14 using oral R-ALA supplementation on rodents produced very favorable results. Oral R-ALA supplementation increased the level of free R-ALA in muscle tissue and increased total GSH levels in blood and liver. Exercise-induced reduction of heart GSH levels was prevented by R-ALA supplementation.14 In this study ALA supplementation protected against oxidative lipid damage in the heart, liver, and muscle. This is a very favorable influence on antioxidant defense systems. 14 As you read this, further research is in progress.
Hydrolyzed Whey Isolate
The most exciting GSH boosting effects belong to whey protein. A recent study5 demonstrates that correctly processed whey protein not only boosts GSH levels, but it builds muscle and enhances athletic performance without any training!5
This study is an important one because it is the first to demonstrate a direct improvement in athletic performance from enhancing the body’s own antioxidant defenses.5 Whey protein’s ability to boost GSH levels and lean body weight in animals and humans was reported a long time ago,3,4 yet very little follow up work has been properly documented until now.
Eighteen healthy subjects completed this double blind placebo controlled three-month study.5 This is the first study to demonstrate an improvement in muscular performance and reduced oxidative stress (cell damage) with any oral supplement. The low temperature, microfiltration processed whey proved to be a superior supplement to casein (the other major milk protein) at decreasing sprint times and increasing power output.5 By the end of the study the subjects taking the whey protein supplement actually lost body fat but weighed the same. This equates to an increase in lean body weight, and with no weight training!5
This study on whey protein is an important one. It was the first to demonstrate an improvement in muscular performance and reduced oxidative stress (cell damage) with any oral supplement!
In this study, blood lymphocyte GSH content was assessed in both groups. The whey supplemented group increased GSH levels by 35% while casein group (skim milk powder) did not.5 This was an excellent study as it examined two quality proteins and clearly demonstrated not all dietary proteins are the same. Whey protein is 3.5% cysteine while casein (the other milk protein) is only 0.3%.5 The whey supplemented group increased cell GSH levels, power output, and lean body mass.5 The casein supplemented group did not.5 Upon examination of the results, it appears the whey supplementation effectively reversed the biochemical profile that produces muscle loss. When this optimal muscle building environment is created, as the scientists commented, the results are staggering!
Tying It All Together.
These are some fascinating breakthroughs in muscle metabolism and the identifying bio-markers of muscle breakdown. With this research we have identified some very key markers to lean muscle preservation and growth as well as enhancement of athletic performance.
By correctly deciphering this research we are now able to construct a supplementation program designed to enhance GSH production within the muscle cell. As the research indicates, this will have a significant and positive impact on muscle growth, fat loss, and athletic performance.
Suggested Supplementation Program.
I am going to recommend four supplements that will positively impact GSH production and increase your body’s ability to develop lean muscle growth. This is new territory with the potential to have a major impact on muscle growth in the likes that have previously been unavailable through nutritional manipulation.
By supplementing with these key substrates you will be enhancing the key components that control the anabolic gradient in muscle tissue. This is an exciting and new approach that effectively “patches” a genetic flaw when it comes to manipulating your body’s ability to build muscle.
VP2 Whey Isolate
Take 1 serving in the morning for breakfast.
Take 1 serving 1 hour after training.
VP2 Whey Isolate
Take 1 serving immediately after training.
Take 1 serving before bed.
Take 2 capsules immediately after training.
Take 1 capsule in the morning.
Take 1 capsule 30 minutes before training.
Take 1 capsule before bed.
A New Era In Muscle Growth.
So there you have it. I truly believe this is the next frontier in performance nutrition. And AST Sports Science has been on the leading edge of this science for many years now. AST has been instrumental in introducing to the athletic community the three most potent compounds for GSH production – VP2 – Hydrolyzed Whey Isolate, NAC 500, and R-ALA 200.
Interpreting this science does not happen by accident. Most supplement companies exist either on copying the innovations of other companies with low grade knockoffs or they hype ineffective, low grade supplements through editorial support of the magazines which they own or through blatant misleading marketing practices. AST Sports Science is committed to bringing you cutting edge, scientifically supported sports nutrition designed to improve physical performance. AST is also committed to bringing the science behind the supplements to help you understand the physiological mechanisms behind nutritionally supported performance enhancement.
Bounous G, Molson J. 1999 Competition for glutathione precursors between the immune system and the skeletal muscle: pathogenesis of chronic fatuge syndrome. Med Hypothesis 53;(4): 347-349.
Sen CK. 1999 Glutathione homeostasis in response to exercise training and nutritional supplements. Molecular & Cellular Biochemistry. 196:31-42.
Bounous G et al. 1992 Whey proteins as a food supplement in HIV-seropostive individuals. Clin.Invest. Med. Vol 16:3 p204-209.
Bounous G et al.1991 The biological activity of undenatured dietary whey proteins: role of glutathione.Clin.Invest.Med. Vol 14:4.p296-309.
Lands LC, Grey VL and Smountas AA.1999 Effect of a cysteine donor on muscular performance.J Appl Physiol. 87 (4):1381-1385.
Droge.W. and Holm.E.1997 Role of cystine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction. FASEB J.11:1077-1089
Hack.V et al. 1997 Cystine levels, cystine flux, and protein catabolism in cancer cachexia, HIV/SIVinfection and senescence. FASEB J. 11:84-92
Kinscherf.R et al. 1996 Low plasma glutamine in combination with high glutamine levels indicate risk for loss of body cell mass in healthy individuals: the effect of N-acetyl-cysteine. J.Mol.Med. vol 74:393-400.
Ruffman R and Wendel A. 1991 GSH rescue by N-acetylcysteine. Klin Wochenschr.69:857-862.
Aruoma O,et al.1989 The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide and hypochlorous acid. Free Radical Biol.Med.6:593-597.
Weiss L; Hildt E; Hofschneider PH 1996 Anti-hepatitis B virus activity of N-acetyl-L-cysteine (NAC): new aspects of a well-established drug. Antiviral Res, 32(1):43-53.
Akerlund B; Jarstrand C; Lindeke B; Sonnerborg A; Akerblad AC; Rasool O. 1996 Effect of N-acetylcysteine (NAC) treatment on HIV-1 infection: a double-blind placebo-controlled trial. Eur J Clin Pharmacol, 50(6):457-61.
Sen CK,Ranken T,Vaisanen S, Rauramaa R. 1994 Oxidative stress after human exercise: effect of N-acetylcysteine supplementation. J.Appl.Physiol.76(6):2570-2577.
Khanna S et al. 1999 Alpha lipoic acid supplementation: Tissue glutathione homeostasis at rest and following exercise. J.Appl.Physiol.86(4):1191-1196
Packer L, Roy S,Sen CK. 1997 Alpha lipoic acid: A mrtabolic antioxidant and potential redox modulator of transcription. Adv Pharmacol 38: 79-101
Sen CK, Roy S,Han D,Packer L.1997 Regulation of cellular thiols in human lymphocytes by alpha lipoic acid. A flow cytometric analysis. Free Radical Biol.Med. 22:1241-1257
Han D,Handelman G, Marcoocci L, Sen CK et al. 1997 Lipoic acid increases de novo synthesis of cellular cysteine utilization. Biofactors 6:321-33890
Sen CK,Roy S, Packer L. 1997 Therapeutic potential of the antioxidant and redox properties of alpha lipoic acid. In: L Montagnier,R Oliver, C Pasquier (eds). Oxidative Stress Cancer, AIDS and Neurodegenerative Diseases. Marcel Dekker Inc., New York: 251-267
Merin JP et al. 1996 Alpha lipoic acid blocks HIV-1 LTR-dependant expression of hygromcin resistance in THP-stable transformants. FEBS Lett 394:9-13