Can Oral Glutathione Supplements Work?

DHM

New Member
Thread starter #1
Anyone had experience with this (Shots, inhaler, orals)?

I was listening to the Joe Rogan podcast with Dr. Gordon and they had discussed glutathione supplementation mainly to avoid hangovers, I myself am interested in overall liver health.

Ive only read about its clinical applications and how some individuals have overdosed during skin whitening procedures.

Thanks for your insight.
 
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#2
Glutathione.jpg
Hey DHM. We see Glutathione mainly dispensed as an Intramuscular or Intravenous Injection for liver detoxification and cancer prevention as it is a potent antioxidant. If administering Glutathione intravenously it is recommended to be under the guidance of a doctor or registered nurse. I've never heard of a patient overdosing if supervised by a licensed physician. I recommend contacting Defy Medical as they are experts in this field.
 
#5
Glutathione is best administered via injection. It absorbs very poorly when administered orally, only a small fraction would be bio-available. Im not too familiar with the inhalers. Glutathione is very fragile so it must be stored in the fridge and used within the listed shelf-life (usually 90 days with the injectable).

Here is another fact sheet for injectable glutathione: http://defymedical.com/resources/health-articles/162

It can certainly help with alcohol toxicity and "hang-over" symptoms as GSH binds to alcohol converting it to compounds which are easily excreted from the body. This excerpt from Life Extension regarding GSH and alcohol says it best:
"Glutathione.
Oxidative stress combined with acetaldehyde causes a profound impairment of the body's natural antioxidant systems, by depleting stores of a compound called glutathione (McKillop 2005). Restoring cellular healthy glutathione levels, therefore, seems to be a natural strategy to prevent alcohol-related cancers.
Glutathione, one of the body's most important natural antioxidants, plays a key role in alcohol detoxification. In the liver, glutathione binds to toxins and transforms them into compounds that can be excreted in the bile or urine. The liver's supply of glutathione may be exhausted by binding to carcinogens produced during alcohol detoxification by the liver. The direct conjugation of acetaldehyde and glutathione has been observed in acute models of alcohol ingestion. When depleted by chronic alcohol ingestion, glutathione becomes unavailable for ordinary regulatory processes.
These findings should not surprise anyone who understands that the ingestion of alcohol inflicts massive free-radical damage throughout the body. When a person is exposed to a known toxic substance (such as alcohol), it makes sense to take an antidote (antioxidants) to provide at least partial protection against the short-term (hangover) and long-term (degenerative disease) effects."

Another good treatment for alcohol toxicity is oral supplementation of N-Acetyl-Cysteine (NAC). NAC is a precursor to glutathione and appears to absorb well orally. In addition, NAC can bind directly to alcohol reducing the effects of alcohol on surrounding tissues.

N-acetyl cysteine (NAC) powerfully replenishes glutathione levels in tissues, helping to fend off the consequences of acute oxidative stress (Pascale 1989; Novitskiy 2006). Rats supplemented with NAC prior to treatment with acetaldehyde are potently protected against toxicity and death; the effect is even more powerful when combined with vitamin C and thiamine (Novitskiy 2006). Independently, NAC binds acetaldehyde directly, further preventing its damaging effects (Vasdev 1995).

Protocol:

Injectable GSH: Take 1000mg-1600mg per week (spread out, for example 2.5cc two to three times per week for 30-90 days (for acute detox). When drinking alcohol, take one dose prior to drinking and another the day after. Try supplementing with 600mg of NAC orally on the same days.
 
#8
Thank you Jason.. I would love to try defy glutithone but i can't deal with so many IM injections..can it go subQ? also i dont drink having had hep C in 1997 but was in intereferon therapy as a trial then for a full year and it is like my body never recovered from the interferon it was worse than the Hep c. wondering how/ if the glutatione may help with that or if i just stick to the NAC? thanks for your support!
 
#9
You can definitely inject GSH subq, I personally take it this way (or IV) as I also don't like taking so many IM injections. 1ML daily SC for 30-90 days will work.

Just be aware that GSH can be slightly irritating at the injection site so you may experience a little bruising and soreness which occurs after the injection. It should not be anything that you cannot tolerate, but its good to know ahead of time. Make sure you keep it stored in your fridge and do not combine GSH with any other solution as it can degrade rather quickly due to its fragility.
 
#10
I forgot to mention that it is still good to supplement the oral NAC in between (and during) especially if you have a higher level of toxicity and/or low GSH levels due to illness etc. It will help maintain levels.
 

Nelson Vergel

Founder, ExcelMale.com
#13
Factors Affecting Glutathione Status

Your body's natural glutathione levels fluctuate constantly throughout the day, are lowest in the morning and decrease as you age. Exposure to toxins, ingested and environmental chemicals and even things as healthy as exercise can all increase free radicals and ramp up your body's need for glutathione.

Time of Day: According to researchers at Emory University, levels of glutathione vary over a 24-hour period, spiking about six hours after each meal and hitting their lowest point in the morning hours.
Age: Young, healthy people tend to have enough glutathione. However, glutathione levels start to decline at around age 45 and continue to decline until death.
Health Conditions: Glutathione status may be depleted by a variety of different health conditions.
Diet: The best dietary sources of glutathione are freshly prepared meats and fresh fruits and vegetables (both raw and cooked). Most processed foods have little to no glutathione.
Glutathione Antagonists: Some foods - such as cereals, bread, and dairy products - are not only lacking glutathione, they actually act as glutathione antagonists. Common beverages such as tea and coffee also contain glutathione -destroying compounds, although in lower concentrations.
Lifestyle Factors: Because cigarette smoking and excessive alcohol intake cause an increase in free radical production, both habits deplete glutathione levels.
Medications: Both prescription and over-the-counter drugs can lower glutathione status.
Weight: People who are overweight tend to have lower glutathione levels than those who are within normal weight range because excess fat is correlated with oxidative (free radical-induced) stress.
 

Nelson Vergel

Founder, ExcelMale.com
#14
European Journal of Nutrition
March 2015, Volume 54, Issue 2, pp 251–263 | Cite as
Randomized controlled trial of oral glutathione supplementation on body stores of glutathione


Abstract

Purpose

Glutathione (GSH), the most abundant endogenous antioxidant, is a critical regulator of oxidative stress and immune function. While oral GSH has been shown to be bioavailable in laboratory animal models, its efficacy in humans has not been established. Our objective was to determine the long-term effectiveness of oral GSH supplementation on body stores of GSH in healthy adults.

Methods

A 6-month randomized, double-blinded, placebo-controlled trial of oral GSH (250 or 1,000 mg/day) on GSH levels in blood, erythrocytes, plasma, lymphocytes and exfoliated buccal mucosal cells was conducted in 54 non-smoking adults. Secondary outcomes on a subset of subjects included a battery of immune markers.

Results

GSH levels in blood increased after 1, 3 and 6 months versus baseline at both doses. At 6 months, mean GSH levels increased 30&#8211;35 % in erythrocytes, plasma and lymphocytes and 260 % in buccal cells in the high-dose group (P < 0.05). GSH levels increased 17 and 29 % in blood and erythrocytes, respectively, in the low-dose group (P < 0.05). In most cases, the increases were dose and time dependent, and levels returned to baseline after a 1-month washout period. A reduction in oxidative stress in both GSH dose groups was indicated by decreases in the oxidized to reduced glutathione ratio in whole blood after 6 months. Natural killer cytotoxicity increased >twofold in the high-dose group versus placebo (P < 0.05) at 3 months.

Conclusions

These findings show, for the first time, that daily consumption of GSH supplements was effective at increasing body compartment stores of GSH.


From paper:

There is less data on the bioavailability of oral GSH in humans. While GSH was found to be absorbed and transported in human intestinal epithelial cells in vitro [30] and in buccal mucosal cells in vivo [23], results from a clinical study of oral GSH, administered as a single dose (150 &#956;mol/kg) to 7 healthy adults, showed no significant effect on plasma GSH levels during a 4.5 h period [31]. However, the rapid turnover of GSH in human plasma would likely make it difficult to detect an increase in plasma after a single oral dose. Thus, our current objectives were to determine the long-term effects of daily oral GSH supplementation on GSH levels in different body stores. We conducted a randomized, double-blinded, placebo-controlled trial of oral GSH at two doses, 250 and 1,000 mg/day, administered for 6 months in healthy adults on the levels of GSH in different blood compartments and exfoliated buccal mucosal cells. GSH oxidation products, GSH disulfide (GSSG) and GSH protein mixed disulfides (GSSP), are commonly used biomarkers of oxidative stress [32]; thus, we also examined the effects of oral GSH on GSSG/GSH and GSSP/GSH ratios in blood. Since intracellular GSH plays a key role in the maintenance and regulation of certain immunological functions [33, 34] including the activation of lymphocytes and functional activity of NK cells [35, 36, 37], secondary endpoint analysis included the assessment of hematologic measurements of immune function including neutrophil phagocytosis, neutrophil respiratory burst, lymphocyte proliferation and natural killer (NK) cell cytotoxicity in a subset of subjects."


Product used: https://setriaglutathione.com/glutathione-studies
 

Nelson Vergel

Founder, ExcelMale.com
#15
GLUTATHIONE
Pharmacologic Category: Supplement

General Information: Glutathione (GSH) is composed of three amino acids combined to produce a peptide that is both a powerful antioxidant and performs several critical roles in the body. According to researchers this peptide is so essential to optimum health that the level of GSH in our cells could possibly be used to predict how long we’ll live (1, 2).

While GSH is vitally essential to maintaining a healthy immune system, it isn’t classified as an essential nutrient; this is because the body does create its own supply from the amino acids:


  • L-cysteine
  • L-glutamic acid
  • Glycine

One of the reasons why GSH is so important for optimum health is that it’s present in every cell in the body. One way antioxidants like glutathione help maintain good physical health is by neutralizing free radicals, which can cause cellular damage through oxidation. Since glutathione is naturally present within all types of cells, it is in a prime position to do this. It’s considered one of the most important antioxidants in the human body (3).

Glutathione and immune function: Glutathione plays a significant role in immune function (4). It encourages the T-cell function that’s essential for a healthy immune system (5), Protects from environmental toxins, and could possibly fight cancer (6).

Additionally, glutathione is essential in a broad range of metabolic processes: (6, 7)


  • It links together (conjugates) with many drugs to make it easier for the body to digest them


  • Glutathione acts to neutralize a toxic metabolic byproduct: Methylglyoxal


  • GSH is involved in the protein disulfide bond rearrangement that is necessary for the synthesis of one third of all the body’s proteins


  • It protects the body from the oxidative damage caused by glutathione peroxidase by acting as a helper molecule for certain enzymes


  • Glutathione plays an important role in stimulating cancer cell death (apoptosis)



  • The liver uses GSH to help detoxify fats before the gallbladder emits bile, supporting healthy digestion


GSH to remove and detoxify carcinogens: GSH is also crucial in the removal and detoxification of carcinogens, and according to recent studies (8) alterations in this metabolic pathway, can influence cell survival profoundly. Glutathione is responsible for several vital roles within a cell besides antioxidation (8):


  • Maintenance of the redox state(chemical reactions in which the oxidation state of atoms are modified)
  • Modulation of the immune response
  • Detoxification of foreign bacteria and viruses

Glutathione and chronic disease: Research has demonstrated that glutathione deficiency is a factor in many chronic conditions; HIV/AIDS, Alzheimer’s, Parkinson’s disease, asthma, different cancers, cataracts, macular degeneration, open angle glaucoma, diabetes, and many diseases of the liver, kidneys, lungs, and digestive system (9).

Glutathione depletion due to aging and alcohol consumption: Glutathione plays a major role in the detoxification of ethanol (consumed as alcoholic beverages) and people who routinely drink will experience GSH depletion (10). Aging is another factor; as the body ages glutathione levels will drop below the level necessary to maintain healthy immune function (among other processes) (10).

Glutathione depletion is also caused by other factors: Besides alcohol consumption and the aging process, there are other factors that can deplete levels of Glutathione (11, 12, 13, 14):


  • Acetaminophen
  • Aspartame
  • Benzopyrenes (tobacco smoke, fuel exhaust, etc.)
  • Many household chemicals (detergents, fabric softeners, air fresheners, mothballs, cleaners, bleach, etc.)

Glutathione for male fertility: In a study of eleven infertile men, suffering from dyspermia associated with various andrological pathologies - Glutathione was observed to exert a significant effect on sperm motility. Glutathione appeared to have an observable therapeutic effect on certain andrological pathologies that cause male infertility (15).

GSH and artherosclerosis: In one study, ten patients with artherosclerosis were administered glutathione which resulted in a significant increase in blood filtration, in addition to a significant decrease in blood viscosity and platelet aggregation. Consequently, GSH infusion was determined to be an effective method of decreasing blood viscosity while increasing blood filtration (16).

Glutathione has anti-aging properties: In a three-month study of female subjects, the women taking GSH showed significantly improved skin elasticity and amelioration of wrinkles compared to test subjects who received a placebo (17).

What is this medicine used for? Glutathione may be taken to (4, 11, 12, 13, 14, 15, 16, 17) :


  • Stimulate the immune function
  • Make skin look younger
  • For increased male fertility
  • Decrease blood viscosity
  • Increase lower than optimal levels of glutathione in the body due to aging and environmental stressors

Who shouldn’t take this supplement? Due to a lack of studies on the safety of glutathione during pregnancy and breastfeeding it would be best for women who are pregnant or nursing to avoid using it.

What are the precautions when taking this medicine? Nitric oxide could react with glutathione to create s-nitrosoglutathione, a molecule that can act as a vasodilator. Vasodilation can lead to lowered blood pressure. This side effect may not be safe for people who have hypotension (18).

What are some possible side effects of this medicine? Studies haven’t shown any side effects when supplementing with Glutathione.

How is it best taken? Glutathione can be taken either orally, with a transdermal patch or by intramuscular injection. Studies show that the most effective way to increase glutathione levels is by transdermal patch or by injection (19).

What do I do if I miss a dose? If you do miss a dose; it’s best to take it as soon as you remember. Although, if it’s almost time for the next dose, just skip the missed one and take your next scheduled dose. Don’t take two doses at the same time.

How should I store this medicine? Store Glutathione at between 68°F to 77°F (20°C to 25°C) and keep it away from heat, moisture, and light. Keep all medicines out of the reach of children. Throw away any unused medicine after the expiration date. Do not flush unused medications or pour down a sink or drain.

General statements: Do not share or take anyone else's medicine. Talk with your healthcare provider before starting any new medicine, including over-the-counter, natural products, or vitamins. This patient information summarizes the most important information about your medication; if you would like more information, talk with your doctor.



1) Richie JP Jr, Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA. Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J. 1994 Dec;8(15):1302-7.

2) Cascella R, Evangelisti E, Zampagni M, Becatti M, D'Adamio G, Goti A, Liguri G, Fiorillo C, Cecchi C. S-linolenoyl glutathione intake extends life-span and stress resistance via Sir-2.1 upregulation in Caenorhabditis elegans. Free Radic Biol Med. 2014 Aug;73:127-35. doi: 10.1016/j.freeradbiomed.2014.05.004. Epub 2014 May 15.

3) Lu, Shelly C. “REGULATION OF GLUTATHIONE SYNTHESIS.” Molecular aspects of medicine 30.1-2 (2009): 42–59. PMC. Web. 2 Oct. 2017.

4) Dröge W, Breitkreutz R. Glutathione and immune function. Proc Nutr Soc. 2000 Nov;59(4):595-600.

5) Chang WK, Yang KD, Chuang H, Jan JT, Shaio MF. Glutamine protects activated human T cells from apoptosis by up-regulating glutathione and Bcl-2 levels. Clin Immunol. 2002 Aug;104(2):151-60.

6) Oxidative Medicine and Cellular Longevity.Volume 2013 (2013), Article ID 972913, 10 pages http://dx.doi.org/10.1155/2013/972913.

7) pubchem.ncbi.nlm.nih.gov/compound/124886?from=summary#section=Related-Compounds

8) Balendiran GK1, Dabur R, Fraser D. The role of glutathione in cancer. Cell Biochem Funct. 2004 Nov-Dec;22(6):343-52.


9) Ballatori, Nazzareno et al. “Glutathione Dysregulation and the Etiology and Progression of Human Diseases.” Biological chemistry 390.3 (2009): 191–214. PMC. Web. 2 Oct. 2017.

10) Vogt, Barbara L., and John P. Richie. “Glutathione Depletion and Recovery After Acute Ethanol Administration in the Aging Mouse.” Biochemical pharmacology 73.10 (2007): 1613–1621. PMC. Web. 2 Oct. 2017.

11) Dimova S, Hoet PH, Dinsdale D, Nemery B. Acetaminophen decreases intracellular glutathione levels and modulates cytokine production in human alveolar macrophages and type II pneumocytes in vitro. Int J Biochem Cell Biol. 2005 Aug;37(8):1727-37. Epub 2005 Apr 26.

12) Abhilash, M., Varghese, M.V., Paul, M.V.S. et al. Comp Clin Pathol (2015) 24: 927. https://doi.org/10.1007/s00580-014-2013-8

13) Romero DL, Mounho BJ, Lauer FT, Born JL, Burchiel SW. Depletion of glutathione by benzo(a)pyrene metabolites, ionomycin, thapsigargin, and phorbol myristate in human peripheral blood mononuclear cells. Toxicol Appl Pharmacol. 1997 May;144(1):62-9.

14) National Research Council (US). Multiple Chemical Sensitivities: A Workshop. Washington (DC): National Academies Press (US); 1992. Considerations for the Diagnosis of Chemical Sensitivity.
15) Lenzi A1, Lombardo F, Gandini L, Culasso F, Dondero F. Glutathione therapy for male infertility. Arch Androl. 1992 Jul-Aug;29(1):65-8.

16) Coppola L, Grassia A, Giunta R, Verrazzo G, Cava B, Tirelli A, D'Onofrio F. Glutathione (GSH) improved haemostatic and haemorheological parameters in atherosclerotic subjects. Drugs Exp Clin Res. 1992;18(11-12):493-8.

17) Weschawalit, Sinee et al. “Glutathione and Its Antiaging and Antimelanogenic Effects.” Clinical, Cosmetic and Investigational Dermatology 10 (2017): 147–153. PMC. Web. 2 Oct. 2017.

18) AbhiramPrasadMBBS, MRCPaNeil PAndrewsMBBS, MRCPaFeroz Padder, MBBSa, Mohsin HusainBS, aArshed AQuyyumiMD, MRCP, FACC. Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability. Journal of the American College of Cardiology Volume 34, Issue 2, August 1999, Pages 507-514.

19) Pizzorno, Joseph. “Glutathione!” Integrative Medicine: A Clinician’s Journal 13.1 (2014): 8–12. Print.
 

Nelson Vergel

Founder, ExcelMale.com
#17
Am J Clin Nutr. 2007 Oct;86(4):1016-23.
Diurnal variation in glutathione and cysteine redox states in human plasma.


Abstract

Background: Plasma glutathione/glutathione disulfide (GSH/GSSG) and cysteine/cystine (Cys/CySS) couples are oxidized in humans in association with oxidative stress and cardiovascular disease risk. Animal studies show that both pools undergo diurnal variations associated with dietary intake of sulfur amino acids.

Objective: The objective of this study was to determine whether the redox state of GSH, Cys, GSH/GSSG, or Cys/CySS undergoes diurnal variation in healthy adults.

Design: Plasma samples were collected every hour for 24 h from 63 persons aged 18–86 y who were consuming normal food (protein, 0.8 g · kg−1 · d−1; sulfur amino acids, 20 mg·kg−1·d−1) at standardized mealtimes. Measurements of Cys, CySS, GSH, and GSSG were used with the Nernst equation to calculate the redox states.

Results: Plasma Cys and GSH concentrations varied with the time of day. The highest values for plasma Cys occurred ≈3 h after meals. Glutathione was maximal 6 h after peak plasma Cys. The calculated redox states of the GSH/GSSG and Cys/CySS couples varied in association with the concentrations of the thiol forms. Maximal reduction and oxidation of the Cys/CySS couple occurred at 2130 and 0630, whereas the respective values for the GSH/GSSG couple occurred at 0330 and 1330. The mean diurnal variation for Cys/CySS redox in persons aged ≥60 y was 1.8-fold that in persons aged <40 y.

diurnal variations of glutathione.jpg

Conclusions: Cys/CySS and GSH/GSSG redox states in human plasma undergo diurnal variation with an increased magnitude of variation in Cys/CySS redox state in older persons. This variation could alter sensitivity to oxidative stress over a course of hours.
 
#19
I used NAC Sustain for 20 years, and never used Glutathione due to the conventional wisdom that orally it is not absorbed. But then I saw the same study that Nelson posted in the thread, proving efficacy for oral Glutathione. So, I tried Jarrow Glutathione "Reduced" and it works well enough for me to stop NAC altogether. I have also tried Setria Glutathione Reduced (by Healthy Origins), and it seemed to me somewhat less effective than the Jarrow, but, the Jarrow test was during a period of time with nothing going on, and the results seemed clear to me. The later Setria test was less clear.
 
#20
I used NAC Sustain for 20 years, and never used Glutathione due to the conventional wisdom that orally it is not absorbed. But then I saw the same study that Nelson posted in the thread, proving efficacy for oral Glutathione. So, I tried Jarrow Glutathione "Reduced" and it works well enough for me to stop NAC altogether. I have also tried Setria Glutathione Reduced (by Healthy Origins), and it seemed to me somewhat less effective than the Jarrow, but, the Jarrow test was during a period of time with nothing going on, and the results seemed clear to me. The later Setria test was less clear.
How could you tell that gluthatione was working? I've got a free sample from Bulk Supplements.
 
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