Glutathione’s Role

Brain Health

How do low levels of glutathione affect brain and mental health? There is a clear link between low glutathione levels and decreased brain health.

 

As we age, it’s not uncommon to experience a bit of forgetfulness or difficulty concentrating. These are just two examples of neurodegeneration, a process by which the neurons in our brains become damaged and may even die.

 

This leaves us with “shrinking” brains that don’t function to their full capacity. While this process is unavoidable as we age, it can be slowed, or even reversed, and glutathione (GSH) plays an important role.

 

Accelerated neurodegenerative diseases, like Parkinson’s disease and Alzheimer’s diseases  exhibit high levels of oxidative stress damage to the brain as well as low active glutathione (GSH) levels. GSH can ease and decrease the rate of damage to brain tissue.

 

While these results are promising, a 2017 study involving Alzheimer’s patients using intranasal GSH found that GSH and placebo had equally good results — after three months. Glutathione produced positive results. However, so did the placebo.

 

Other neurological illnesses like Lyme disease weaken when your body experiences higher levels of glutathione.

Immune Support

Glutathione helps your immune system stay strong and ready to fight infections. While vitamin C seems to get all the accolades when it comes to immunity, glutathione is the under-recognized supporting actor who deserves the starring role.

 

Research shows that active glutathione (GSH) primes white cells such as natural killer (NK) and T cells, your body’s front-line infection fighters. GSH-enhanced T cells are able to produce more infection-fighting substances, controlling both bacterial and viral infections.

 

One clinical trial in particular found that GSH doubled NK cells’ ability to be cytotoxic (kill invaders) after just six months of use. Glutathione actually has a potent antibacterial effect as it helps the immune cells called macrophages fight the bacterium that causes tuberculosis, Mycobacterium tuberculosis.

 

In another study, researchers found that GSH modulates the behavior of many immune system cells, affecting adaptive immunity and protecting against microbial, viral and parasitic infections.

 

There are many chronic infections such as EBV, hepatitis, herpes viruses and Lyme, to name a few, which can deregulate and suppress the immune system. Glutathione can modulate and reverse this suppression.

 

Autoimmune diseases also appear to be hallmarked by imbalanced glutathione levels.

Athletic Performance

Glutathione can boost athletic performance when used before workouts. Best of all, you don’t have to be an ultramarathoner or a bodybuilder. Anyone from the average runner to the weekend warrior can benefit from this exercise enhancer.

 

In a study of eight men receiving 1,000 milligrams of glutathione before exercise, the glutathione group performed better, felt less fatigued, and had lower blood lactic acid levels than the placebo controlled group.

 

This is key, since increased lactic acid in the body can result in fatigue, low blood pressure, muscle aches, a drop in body temperature, and respiratory problems.

 

Glutathione combined with L-citrulline boosted nitric oxide production (NO) better than placebo or L-citrulline alone. Nitric oxide is well known to dilate blood vessels improving blood flow and oxygen delivery to muscles and tissues. This improves athletic performance and exercise output.

 

Energy production occurs within all cells (except red blood cells) via the mitochondria. Glutathione protects mitochondria from free radicals and the oxidative damage they cause. In this way, glutathione is paramount to energy production. If mitochondria are damaged, they slow down and start to make less energy. The affected  “diseased” mitochondria leads to decreased bodily function and efficiency.

 

To make things worse, damaged mitochondria output more free radicals. In turn, these free radicals cause further mitochondrial damage and create a vicious cycle of less energy and more damage.

 

GSH binds these free radicals and relieves oxidative stress — not just on the mitochondria, but on the rest of the cell.

Nrf2 Activation

Normally within the cell, GSH synthesis increases dramatically in response to oxidative stress through increased GCL (glutamate cysteine ligase) transcription via nuclear factor erythroid 2-related factor 2 (Nrf2), providing availability of rate-limiting cysteine.

 

However, numerous viruses have evolved survival mechanisms that manipulate the Nrf2 pathway by activating or inhibiting it for viral benefit,ranging from inducing cell death and lytic release of virions to the reduction of the inflammatory response to support viral propagation.

 

Indeed, Nrf2 plays a critical role in balancing the intracellular redox state, which is basally maintained at a low level in the cytosol by Kelch-like ECH associated protein 1 (Keap1).

 

Through binding of Nrf2, Keap1 allows for Nrf2 ubiquitylation and subsequent proteasome degradation. However, oxidative stress leads to conformational changes in the Nrf2-Keap1 complex that allow Nrf2 to translocate to the nucleus, where it induces transcription of multiple genes involved in redox regulation, immunity, inflammation, and antiviral mechanisms.

 

Given the role of Nrf2 in protecting against oxidative stress, Nrf2 has been called the master regulator of tissue damage during infection and is essential for the control of inflammation through redox control.

 

Additionally, Nrf2 has been shown to block transcriptional upregulation of proinflammatory cytokine genes through blocking transcription in vitro and was identified as an upstream regulator of cytokine production in murine inflammatory models. This Nrf2-mediated inhibition was independent of redox control and not a secondary consequence of ROS elimination. Therefore, Nrf2 is the key regulator for the two important protective pathways in the cell: anti-inflammation and antioxidation.

Skin Health

Science says that glutathione is an effective answer.  Fortunately, you don’t have to empty your wallet to restore the youth and health of your skin. You can solve the problem from the inside out. Cells can heal and regenerate themselves, thanks to glutathione.

 

Glutathione not only decreases the melanin (pigmentation) in your skin, but has also been found to decrease wrinkles and increase skin elasticity.

 

Glutathione works on the skin pigment production by inhibiting tyrosinase, an enzyme involved in making melanin.

 

In one study, both GSH and GSSG achieved a skin lightening effect — though it takes a few weeks to develop. The effect on pigmentation is transient, so you would need to continue using glutathione to maintain the skin-whitening effect.

 

scientific review of multiple studies confirmed that the use of glutathione results in skin lightening.

 

Glutathione has also been shown to decrease psoriasis. The glutathione levels in this clinical trial were increased by consumption of whey protein, which contains glutamylcysteine, a precursor to GSH.

 

The same studies also show that glutathione doesn’t just lighten skin, but it improves skin elasticity and decreases wrinkles.

Aging

Many people know the chef’s trick of sprinkling a little lemon juice over fruit to keep it from turning brown. Antioxidants are like that lemon juice. By consistently “sprinkling” your body with antioxidants like glutathione, you can prevent your body from “browning” or “oxidizing” which causes damage and aging of cells. Antioxidants are the “anti-agers” of the nutrient world, working to protect your body from free radicals, and the oxidative damage they cause.

 

Every time you eat, breathe, or move, your body uses fuel created from the food you eat to produce energy. But just as a car releases harmful byproducts as exhaust, so too does your own body’s energy-producing efforts produce a dangerous byproduct:  free radicals.

 

Free radicals are highly reactive forms of oxygen that are missing an electron. When they come into contact with normal molecules, they steal an electron, damaging the healthy cell and its DNA.

 

In fact, some estimates show that your DNA takes 10,000 oxidative hits daily. Antioxidants work to counteract the damage caused by free radicals.

 

Glutathione is the “master” antioxidant, directly binding to oxidative compounds that damage cell membranes, DNA, and energy production. It directly neutralizes a wide range of oxidants, including superoxide, nitric oxide, carbon radicals, hydroperoxides, peroxynitrites, and lipid peroxides.

 

Glutathione offers the all-important antioxidant defense like few others can.

Publications

  1. Competent and Reliable Scientific Evidence: Sinha-Hikim I, Shen R, Paul Lee WN, Crum A, Vaziri ND, Norris KC. Effects of a novel cystine-based glutathione precursor on oxidative stress in vascular smooth muscle cells. Am J Physiol Cell Physiol. 2010 Sep;299(3):C638-42. doi: 10.1152/ajpcell.
  2. Competent and Reliable Scientific Evidence: The American Chemical Society, August 21, 2007, Boston, MA. Author: Crum, Albert. Overcoming the Intracellular Synthesis Impasse of Glutathione—the “Master Antioxidant” of the Immune 1 System. Subtitle: The unique and vital delivery role of Cystine/Cysteine coupling and the importance of the sulfhydryl (SH) in detoxifying oxyradicals to preserve cell, gene, and immune health.

  3. Crum, A, Nutritional or Therapeutic Composition to Increase Bodily Glutathione Levels, Patent No. US 6,592,908 B1, July 15, 2003. Amendment Patent: US RE 39734, July 17 2007. https://patents.google.com/patent/USRE42645E1/en

  4. N Tareen, J Lee, SB Nicholas, D Martins, Sinha-Hikim, KC Norris, Charles R. Safety and Efficacy of a Novel Oxidative Stress Modulator (OSM), Drew University (NT, SBM, DM, KCN); Jackson State University, University of California, Los Angeles (SBN, KCN).

  5. Bains VK, Bains R. The antioxidant master glutathione and periodontal health. Dent Res J (Isfahan). 2015 Sep-Oct;12(5):389-405. doi: 10.4103/1735-3327.166169. PMID: 26604952; PMCID: PMC4630702

  6. Dringen R, Hirrlinger J. Glutathione pathways in the brain. Biol Chem. 2003 Apr;384(4):505-16. doi: 10.1515/BC.2003.059. PMID: 12751781.

  7. Morris D, Khurasany M, Nguyen T, Kim J, Guilford F, Mehta R, Gray D, Saviola B, Venketaraman V. Glutathione and infection. Biochim Biophys Acta. 2013 May;1830(5):3329-49. doi: 10.1016/j.bbagen.2012.10.012. Epub 2012 Oct 23. PMID: 23089304.

  8. Weschawalit S, Thongthip S, Phutrakool P, Asawanonda P. Glutathione and its antiaging and antimelanogenic effects. Clin Cosmet Investig Dermatol. 2017;10:147-153. Published 2017 Apr 27. doi:10.2147/CCID.S128339

  9. Adeoye O, Olawumi J, Opeyemi A, Christiania O. Review on the role of glutathione on oxidative stress and infertility. JBRA Assist Reprod. 2018;22(1):61-66. Published 2018 Mar 1. doi:10.5935/1518-0557.20180003

  10. Jahoor F, Taffet GE, Sekhar RV. GLUTATHIONE DEFICIENCY AND OXIDATIVE STRESS IN AGING: METABOLIC MECHANISM AND TARGETED INTERVENTION. Innov Aging. 2019;3(Suppl 1):S416. Published 2019 Nov 8. doi:10.1093/geroni/igz038.1551

  11. Sekhar RV, Patel SG, Guthikonda AP, et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Am J Clin Nutr. 2011;94(3):847-853. doi:10.3945/ajcn.110.003483