Glutathione
Glutathione
What is it?
Put simply, glutathione is an antioxidant molecule used by the body to prevent damage from biological stress. It helps neutralise damaging “free radicals” or “Reactive Oxidative Species” (ROS), molecules formed from stressors like exercise, infection – or even day to day process like breathing!
Reactive Glutathione(GSH) is a “tripeptide”- made from three amino acids:
· cysteine
· glutamate
· glycine
Why is it important? Why should I eat to support glutathione metabolism?
Glutathione reduces the damage that occurs from oxidative stress. Reactive oxidants can damage the membranes of cells – the “skin” that holds cells and their components together, as well as the DNA in the cells. This stops a cell carrying out its normal functions efficiently and can lead to the death of the cell.
One of the areas in which glutathione and oxidative stress is particularly important is in the mitochondria – the power plants of the cell. Producing energy for the body’s functions, as well as exercise, causes a lot of oxidation, and could go onto damage these biological batteries! What’s more, not only will damaged mitochondria compromise energy production, but the cell reacts to malfunctions in these energy-factories by effectively committing suicide; sacrificing itself to protect the rest of the body!
However – oxidative stress isn’t a completely unavoidable threat. Although our body’s natural processes produce oxidants, environmental pollutants and an unhealthy; lifestyle can increase this stress on the body. However, tissue-damage from such prevalent toxins as Carbon Monoxide, heavy metals, and pesticides has been demonstrated to be significantly lower in people with adequate Glutathione levels!
The antioxidant for the athlete!
Antioxidants are a controversial area in sports nutrition. On the one hand, you want to limit damage, keep soreness and fatigue in check and perform at a consistently high level in training to get fitter and stronger. On the other hand, too much antioxidant can actually blunt the stress signals your body uses to get stronger and fitter after damaging exercise – no pain, no gain! Supplementation to support glutathione levels is a perfect compromise – it supports your body’sownantioxidant system, rather than excessively mopping up all oxidative stressors, which would throw your body out of balance! Supplementation with high-cysteine proteins which raised glutathione levels after three months actually improved muscular power and muscular endurance in athletes (Lands, Grey et al. 1999)!
As well as supporting training and recovery directly, high glutathione levels provide better immune defences and reduce the likelihood of infection. This will help an athlete undertaking an intense regime to help keep their immune system string – you can’t train and get fitter if you’re laid up in bed!
How to raise Glutathione levels
- Cold Showers + swimming
Taking cold showers and swimming in the cold increases glutathione and helps ‘body hardening’ best to do before you train rather than after you train in general. Many people who live and swim by the sea remark on their incredible wellness from their daily cold bathing.
- N?Acetyl?Cysteine (NAC)
N-acetyl cysteine (NAC) is a modified version of cysteine that’s more bio-available and sold in supplement form. It increases glutathione synthesis only when there is a demand, which is possibly why it doesn’t run the risk of blunting training adaptations like some high-dose antioxidants.
? Whereas other antioxidants may be continually active and interfere with cell signalling needed to adapt to training, NAC seemingly supports the body’s own defences when oxidative stress has surpassed a given threshold.
? 2-3g of NAC taken throughout exercise have been shown to increase endurance capacity by supporting the glutathione anti-oxidant system, however a lower daily dose would appear to be better for longer term adaptation. You need some oxidative stress to kick in the adaptation process. Around 250-500mg would be enough to give some support and not hinder adaptation.
? NAC can regulate inflammation, keeping cytokines at levels appropriate to the situation, while also having demonstrated anti-cancer effects in-vitro.
Other cool things this amino acid does is to help with overcoming addiction and withdrawal, it’s also a major poison detoxifier, being the go to medical treatment for accidental pain killer overdose.
- Foods That Boost Glutathione Levels
Whey
Foods which contain high levels of sulphur?containing amino acids help to maintain optimal glutathione levels. The study cited previously on muscular endurance used a whey-derived supplement, as dairy and whey are particularly good sources. Some researchers have suggested that undenatured forms of whey stimulate the body to produce more glutathione due to the particular shape of the sulfur-containing peptides in the isolates (alpha?lactalbumin). Some people are milk intolerant or follow a vegan path so in this case mixed aminos are a viable vegan friendly alternative. The best ones are NAC, cysteine, glutamine
- Natural foods
Eggs are also extremely high in sulphurous aminos, while other foods that may help support glutathione metabolism include garlic, broccoli, avocado and spinach
- Milk Thistle,
Milk thistle is a powerful antioxidant and supports the liver by supporting glutathione levels. Several studies on rodents have shown a glutathione-mediated effect helping to protect the liver and kidneys in our little furry friends after milk-thistle supplementation (Das and Vasudevan 2006; Vessal, Akmali et al. 2010).
- Alpha Lipoic Acid
ALA increases the levels of glutathione, and is a natural antioxidant which reduces free radicals. Supplementation has increased glutathione levels and reduced oxidative stress in animals (Jones, Li et al. 2002; Wollin and Jones 2003; Chae, Shin et al. 2008).
- Turmeric (curcumin)
Long term consumption has been shown to increase glutathione and reduce oxidative stress in Parkinson’s patients – keeping your brain resisting the ravages of age (Mythri, Veena et al. 2011)! These antioxidant effects extend the uses of this spice to helping to improve fat metabolism, blood sugar regulation and chronic disease (Madkor, Mansour et al. 2011)!
- Selenium
Glutathione peroxidase, the major enzyme responsible for the body’s own anti-oxidant actions, depends on the presence of selenium. Supplementation has boosted the immune system and helped reduce the incidence of illness in children (Liu, Yin et al. 1997).
Other helpful supplements include SAME but this is regulated in Europe. Methionine is another viable amino which should support glutathione levels. Glycine is also a building block for glutathione and another useful addition to your supplement regime. Just 3 grams can also support deeper REM sleep.
You’ll notice if you read through the referenced ingredients inclusions for the R5 aminos, that all of the glutathione building element are in place to aid glutathione production. In addition the other antioxidant support enzyme minerals are there, for SOD and sleep support is covered alongside tissue re-synthesis OAKG. Go ahead and read about it here.
Chae, C. H., C. H. Shin, et al. (2008). "The combination of alpha-lipoic acid supplementation and aerobic exercise inhibits lipid peroxidation in rat skeletal muscles." Nutr Res28(6): 399-405.
We investigated the effect of DL-alpha-lipoic acid (LA) supplementation and regular aerobic exercise on the concentrations of malondialdehyde (MDA) and vitamin E, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and the levels of glutathione (GSH) in rat skeletal muscles (soleus and red gastrocnemius). For 8 weeks, rats (n = 7 per group) were (1) exercised on a treadmill for 30 min d(-1), (2) treated with supplemental LA, or (3) exercised and treated with supplemental LA. Control rats (n = 7) did not receive LA and were not exercised. DL-alpha-lipoic acid (100 mg kg(-1)) was administered daily as an oral supplement. The rats were exercised in a graded manner for 5 d wk(-1). The concentration of MDA in the soleus and red gastrocnemius was significantly lower in rats that exercised and received LA than in the other groups. Compared with the other groups, rats that exercised and received LA had a significantly higher vitamin E concentration in the soleus. The SOD and GPx activities in the soleus and red gastrocnemius were significantly higher in rats that exercised and received LA. These results suggest that LA supplementation combined with aerobic treadmill exercise inhibits lipid peroxidation in skeletal muscles. This effect was especially remarkable in the soleus, which is particularly sensitive to oxidative stress, as revealed by the increased vitamin E level and SOD and GPx activities.
Das, S. K. and D. M. Vasudevan (2006). "Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver." Indian J Biochem Biophys43(5): 306-311.
The production of reactive oxygen species (ROS) is considered to be a major factor in oxidative cell injury. The antioxidant activity or the inhibition of the generation of free radicals is important in providing protection against such hepatic damage. Silymarin, derived from the milk thistle plant, Silybium marianum, has been used in traditional medicine as a remedy for diseases of the liver and biliary tract. In the present study, the effect of hepatoprotective drug silymarin on body weight and biochemical parameters, particularly, antioxidant status of ethanol-exposed rats was studied and its efficacy was compared with the potent antioxidant, ascorbic acid as well as capacity of hepatic regeneration during abstention. Ethanol, at a dose of 1.6 g/kg body wt/day for 4 wks affected body weight in 16-18 week-old male albino rats (Wistar strain weighing 200-220 g). Thiobarbituric acid reactive substance (TBARS) level, superoxide dismutase (SOD), and glutathione-s-transferase (GST) activities were significantly increased, whereas GSH content, and catalase, glutathione reductase (GR) and GPx (glutathione peroxidase) activities significantly reduced, on ethanol exposure. These changes were reversed by silybin and ascorbic acid treatment. It was also observed that abstinence from ethanol might help in hepatic regeneration. Silybin showed a significant hepatoprotective activity, but activity was less than that of ascorbic acid. Furthermore, preventive measures were more effective than curative treatment.
Jones, W., X. Li, et al. (2002). "Uptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cells." Free Radic Biol Med33(1): 83-93.
Alpha-lipoic acid, which becomes a powerful antioxidant in its reduced form, has been suggested as a dietary supplement to treat diseases associated with excessive oxidant stress. Because the vascular endothelium is dysfunctional in many of these conditions, we studied the uptake, reduction, and antioxidant effects of alpha-lipoic acid in cultured human endothelial cells (EA.hy926). Using a new assay for dihydrolipoic acid, we found that EA.hy926 cells rapidly take up and reduce alpha-lipoic acid to dihydrolipoic acid, most of which is released into the incubation medium. Nonetheless, the cells maintain dihydrolipoic acid following overnight culture, probably by recycling it from alpha-lipoic acid. Acute reduction of alpha-lipoic acid activates the pentose phosphate cycle and consumes nicotinamide adenine dinucleotide phosphate (NADPH). Lysates of EA.hy926 cells reduce alpha-lipoic acid using both NADPH and nicotinamide adenine dinucleotide (NADH) as electron donors, although NADPH-dependent reduction is about twice that due to NADH. NADPH-dependent alpha-lipoic acid reduction is mostly due to thioredoxin reductase. Pre-incubation of cells with alpha-lipoic acid increases their capacity to reduce extracellular ferricyanide, to recycle intracellular dehydroascorbic acid to ascorbate, to decrease reactive oxygen species generated by redox cycling of menadione, and to generate nitric oxide. These results show that alpha-lipoic acid enhances both the antioxidant defenses and the function of endothelial cells.
Lands, L. C., V. L. Grey, et al. (1999). "Effect of supplementation with a cysteine donor on muscular performance." Journal of Applied Physiology87(4): 1381-1385.
Oxidative stress contributes to muscular fatigue. GSH is the major intracellular antioxidant, the biosynthesis of which is dependent on cysteine availability. We hypothesized that supplementation with a whey-based cysteine donor [Immunocal (HMS90)] designed to augment intracellular GSH would enhance performance. Twenty healthy young adults (10 men, 10 women) were studied presupplementation and 3 mo postsupplementation with either Immunocal (20 g/day) or casein placebo. Muscular performance was assessed by whole leg isokinetic cycle testing, measuring peak power and 30-s work capacity. Lymphocyte GSH was used as a marker of tissue GSH. There were no baseline differences (age, ht, wt, %ideal wt, peak power, 30-s work capacity). Follow-up data on 18 subjects (9 Immunocal, 9 placebo) were analyzed. Both peak power [13 ± 3.5 (SE) %,P < 0.02] and 30-s work capacity (13 ± 3.7%, P < 0.03) increased significantly in the Immunocal group, with no change (2 ± 9.0 and 1 ± 9.3%) in the placebo group. Lymphocyte GSH also increased significantly in the Immunocal group (35.5 ± 11.04%,P < 0.02), with no change in the placebo group (?0.9 ± 9.6%). This is the first study to demonstrate that prolonged supplementation with a product designed to augment antioxidant defenses resulted in improved volitional performance.
Liu, X., S. Yin, et al. (1997). "[Effects of selenium supplement on acute lower respiratory tract infection caused by respiratory syncytial virus]." Zhonghua Yu Fang Yi Xue Za Zhi31(6): 358-361.
An intervention study was conducted in 75 young children under one year hospitalized with pneumonia or bronchiolitis caused by respiratory syncytial virus (RSV) to evaluate therapeutic effectiveness of selenium (Se) supplement on acute respiratory lower tract infection caused by RSV with randomly controlled and double-masked method. Trial subjects were divided into two groups, one with 37 children in routine treatment and the other with 38 children in routine treatment plus Se supplement. The control group derived from 35 normal children during their physical check-up in the out-patient department. Sodium selenite was supplemented orally with 1 mg on the second day of hospitalization. Results showed that days needed for their relief of symptoms and signs were fewer in Se supplement group than that in controls and recovery in indicators of cell immune was better in the former than that in the latter. Levels of Se and glutathione peroxidase in plasma and white cells could be increased by Se supplement. It suggests that Se supplement can promote recovery from RSV infection.
Madkor, H. R., S. W. Mansour, et al. (2011). "Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats." Br J Nutr105(8): 1210-1217.
Spices which show hypoglycaemic, hypolipidaemic and antioxidant activities may have a role in the treatment of diabetes and its complications. The present study aimed to compare the modulatory effects of garlic, ginger, turmeric and their mixture on the metabolic syndrome and oxidative stress in streptozotocin (STZ)-nicotinamide diabetic rats. Diabetes was induced in overnight fasted rats by a single intraperitoneal injection of STZ (65 mg/kg body weight) and nicotinamide (110 mg/kg body weight, 15 min before STZ injection). Diabetic rats orally received either distilled water (as vehicle) or 200 mg/kg body weight of garlic bulb, ginger rhizome or turmeric rhizome powder suspension separately or mixed together (GGT mixture) for twenty-eight consecutive days. The results showed that these spices and their mixture significantly alleviated (80-97 %, P < 0.05-0.001) signs of the metabolic syndrome (hyperglycaemia and dyslipidaemia), the elevation in atherogenic indices and cellular toxicity in STZ-nicotinamide diabetic rats by increasing the production of insulin (26-37 %), enhancing the antioxidant defence system (31-52 %, especially GSH) and decreasing lipid peroxidation (60-97 %). The greatest modulation was seen in diabetic rats that received garlic and the GGT mixture (10-23 % more than that in the ginger and turmeric groups). In conclusion, garlic or the mix including garlic appears to have an impact on each of the measures more effectively than ginger and turmeric and may have a role in alleviating the risks of the metabolic syndrome and cardiovascular complications.
Mythri, R. B., J. Veena, et al. (2011). "Chronic dietary supplementation with turmeric protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-mediated neurotoxicity in vivo: implications for Parkinson's disease." Br J Nutr106(1): 63-72.
Multiple pathways including oxidative stress and mitochondrial damage are implicated in neurodegeneration during Parkinson's disease (PD). The current PD drugs provide only symptomatic relief and have limitations in terms of adverse effects and inability to prevent neurodegeneration. Therefore, there is a demand for novel compound(s)/products that could target multiple pathways and protect the dying midbrain dopaminergic neurons, with potential utility as adjunctive therapy along with conventional drugs. Turmeric is a spice used in traditional Indian cuisine and medicine with antioxidant, anti-inflammatory and potential neuroprotective properties. To explore the neuroprotective property of turmeric in PD, mice were subjected to dietary supplementation with aqueous suspensions of turmeric for 3 months, mimicking its chronic consumption and challenged in vivo with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Brain samples from untreated and treated groups were characterised based on mitochondrial complex I (CI) activity, protein nitration and tyrosine hydroxylase immunoreactivity. Chronic turmeric supplementation induced the enzyme activity of gamma-glutamyl cysteine ligase, which in turn increased glutathione levels and protected against peroxynitrite-mediated inhibition of brain CI. These mice were also protected against MPTP-mediated protein nitration, CI inhibition and degeneration of substantia nigra neurons in the brain. We conclude that chronic dietary consumption of turmeric protects the brain against neurotoxic insults, with potential application in neurodegeneration. Further characterisation of the active constituents of turmeric that potentially promote neuroprotection could improve the utility of dietary turmeric in brain function and disease.
Vessal, G., M. Akmali, et al. (2010). "Silymarin and milk thistle extract may prevent the progression of diabetic nephropathy in streptozotocin-induced diabetic rats." Ren Fail32(6): 733-739.
OBJECTIVES: To investigate the effect of silymarin and milk thistle extract on the progression of diabetic nephropathy (DN) in rats. METHODS: Diabetes was induced with a single intraperitoneal (IP) injection of streptozotocin (STZ) (60 mg/kg). Silymarin (100 mg/kg/d) or the extract (1.2 g/kg/d) was gavaged for 4 weeks. Blood glucose (BS), serum urea (S(u)), serum creatinine (S(cr)), and 24-h urine protein (Up) were measured and glomerular filtration rate (GFR) was calculated. Concentration of thiobarbituric acid reactive species (TBARS) and activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were evaluated in the renal tissue. RESULTS: Data were expressed as mean +/- SEM. Silymarin or the extract had no significant effect on BS, S(cr), and GFR. Both milk thistle extract and silymarin, respectively, decreased S(u) (mg/dL) (87.1 +/- 7.78, p < 0.001; 84.5 +/- 7.15, p < 0.001), Up (mg) (5.22 +/- 1.56, p = 0.014; 5.67 +/- 0.86, p = 0.034), and tissue TBARS (nmol/mg protein) (0.67 +/- 0.04, p < 0.001; 0.63 +/- 0.07, p < 0.001) in diabetic rats, compared to diabetic control (DC) (S(u): 131.0 +/- 4.55, Up: 8.3 +/- 0.84, TBARS: 0.94 +/- 0.06). Both the extract and silymarin could increase the activity of CAT (IU/mg protein) (25.5 +/- 4.0, p = 0.005; 20 +/- 1.8, p = 0.16) and GPx (IU/mg protein) (0.86 +/- 0.05, p = 0.005; 0.74 +/- 0.04, p = 0.10), respectively, in diabetic rats compared to DC (CAT = 14.4 +/- 2.0, GPx = 0.57 +/- 0.02). CONCLUSION: Milk thistle extract, to a lesser extent silymarin, can attenuate DN in rats possibly by increasing kidney CAT and GPx activity and decreasing lipid peroxidation in renal tissue.
Wollin, S. D. and P. J. Jones (2003). "Alpha-lipoic acid and cardiovascular disease." J Nutr133(11): 3327-3330.
Alpha-lipoic acid (ALA) has been identified as a powerful antioxidant found naturally in our diets, but appears to have increased functional capacity when given as a supplement in the form of a natural or synthetic isolate. ALA and its active reduced counterpart, dihydrolipoic acid (DHLA), have been shown to combat oxidative stress by quenching a variety of reactive oxygen species (ROS). Because this molecule is soluble in both aqueous and lipid portions of the cell, its biological functions are not limited solely to one environment. In addition to ROS scavenging, ALA has been shown to be involved in the recycling of other antioxidants in the body including vitamins C and E and glutathione. Not only have the antioxidant qualities of this molecule been studied, but there are also several reports pertaining to its blood lipid modulating characteristics, protection against LDL oxidation and modulation of hypertension. Therefore, ALA represents a possible protective agent against risk factors of cardiovascular disease (CVD). The objective of this review is to examine the literature pertaining to ALA in relation to CVD and describe the most powerful actions and potential uses of this naturally occurring antioxidant. Despite the numerous studies on ALA, many questions remain relating to the use of ALA as a supplement. There is no consensus on dosage, dose frequency, form of administration, and/or preferred form of ALA. However, collectively the literature increases our understanding of the potential uses for supplementation with ALA and identifies key areas for future research.