L-Glutathione and its Potential Benefits in the Liver, Brain, and Skin

L-Glutathione is a tripeptide made from the amino acids glycine, cysteine, and glutamine. It is naturally found in humans, animals, plants, fungi, and bacteria.

In humans, it is produced by the liver and plays a central protective role against oxidative stress from heavy metals, free radicals, reactive oxygen species, peroxides, and many others.

It is also essential for tissue building and repair, protein synthesis, and immune system function. Reduced levels of Glutathione are considered to play a role in autoimmune diseases, metabolic conditions such as insulin resistance, and many more conditions.

Despite the body constantly producing Glutathione, studies show that the supplementation of exogenous L-Glutathione may hold potential for managing various conditions and provide a wide range of benefits.

The peptide may also potentially support the management of certain neurological diseases and even affect skin aging and melanogenesis.

Research

L-Glutathione and the Liver

L-Glutathione peptide shows potential as a potent antioxidant that can play a significant defensive role in protecting the liver against oxidative stress and injury.

According to animal research, low L-Glutathione levels lead to spontaneous liver pathologies characteristic of various clinical stages of liver injury.^[1]

This has led to the investigation of L-Glutathione as a potential therapy for various liver conditions, such as alcohol-related liver disease and non-alcoholic fatty liver (NAFLD).

According to one study of 33 chronic alcoholics, L-Glutathione for just two weeks during their detox treatment significantly improved their liver enzyme levels, such as AST and ALT.^[2] Researchers also report improvement in other hepatic tests, such as bilirubin, GOT, GPT, and GT.^[3] L-Glutathione may also combat the disease-associated reduction in intracellular Glutathione levels, which occurs in most liver diseases.

L-Glutathione and the peripheral nervous system

One of chemotherapy’s most common long-term side effects is neurotoxicity, manifested by peripheral neuropathies, including polyneuropathy. It is widespread in therapies that involve the use of platinum-based antineoplastic drugs or “platins.”

Studies show that L-Glutathione may have protective effects on peripheral nerves and prevent the occurrence of this side effect during chemotherapy.

One study in patients undergoing cisplatin therapy reports that “after the 15th week, four of 24 assessable patients in the GSH (L-Glutathione) arm suffered from neurotoxicity versus 16 of 18 in the placebo arm.”^[4]

Other studies also show that L-Glutathione significantly reduces neurotoxicity during oxaliplatin and carboplatin therapy.^[5,6] Furthermore, all studies reported that L-Glutathione did not decrease the effectiveness of the chemotherapy.

Besides the fact that L-Glutathione may protect the nervous tissue thanks to its potent antioxidative and radical-scavenging effects, studies show that it also activates the so-called nerve growth factor (NGF).^[7] NGF is a neuropeptide with various beneficial effects for nerve tissue, including the stimulation of peripheral nerve growth.

Considering these beneficial effects and their plausible mechanisms, L-Glutathione is under investigation for its potential to reduce chemotherapy-induced peripheral neuropathy.

L-Glutathione and skin tone

L-Glutathione may have anti-melanogenic properties, first reported by in vitro studies. According to these laboratory experiments, L-Glutathione is tightly related to melanogenesis and exerts anti-melanogenic effects due to various mechanisms.^[8] These mechanisms induce a shift towards pheomelanin synthesis rather than eumelanin production. Pheomelanin is a lighter form of melanin with a yellow–red color compared to the darker eumelanin, which is brown–black.

Furthermore, this research indicates that L-Gluthathione’s antioxidant effects, as well as its interference with the intracellular trafficking of melanogenic enzymes, can contribute to its anti-melanin effects.^[9,10]

Clinical studies show that L-Glutathione can significantly reduce skin hyperpigmentation. One trial reported that 6 weeks of L-Glutathione led to significantly lower skin tone, especially at body sites such as the upper inner arm below the axilla and the upper outer thigh.^[11] Yet, it is important to note that the effects of L-Glutathione in these studies were not permanent. Once the therapy is stopped, the skin tone gradually returns to its initial state.

L-Glutathione and Parkinson’s disease

Research reveals that oxidative stress in the nervous system plays a large role in the pathophysiology and progression of Parkinson’s disease.^[12] One of the antioxidants significantly reduced in those patients’ brains is Glutathione, which may lead to increased oxidative toxicity.

Glutathione deficiency has been identified as an early event in the progression of Parkinson’s disease.^[13] Therefore, scientists are investigating the potential of L-Glutathione for improving some of the aspects of Parkinson’s disease in affected patients.

According to the meta-analysis in a study analyzed by Wang et al., there is “a statistically significant difference between the GSH and control groups, in terms of the Unified Parkinson’s Disease Rating Scale (UPDRS) III.”^[14] The researchers reported that the pooled data show L-Glutathione may mildly improve motor scores in patients with Parkinson’s disease. They found that it does not cause increased adverse events compared to a placebo.

Therefore, L-Glutathione administration may potentially improve the symptoms or slow down the progression of the disease in individuals suffering from Parkinson’s disease, although more research is needed.

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References

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2. Nardi EA, Devito R, Tiburzi F, Ceccanti M. Il glutatione ridotto ad alte dosi nella terapia dell’epatopatia alcolica [High-dose reduced glutathione in the therapy of alcoholic hepatopathy]. Clin Ter. 1991 Jan 15;136(1):47-51. Italian. PMID: 1826873.
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