L-Glutathione News

By Kimberly Pryor

Glutathione is the king of all antioxidants. It rules our body’s cells, for without it, they would be helpless during the fatal onslaught of free radicals.

Glutathione plays a prominent role in regulation of cellular events including gene expression, DNA and protein synthesis, cell proliferation and apoptosis (programmed cell death), and immune response. Glutathione deficiency contributes to oxidative stress, which is involved in aging and the development of such diseases as Alzheimer’s, Parkinson's, liver disease, cystic fibrosis, sickle cell anemia, HIV and AIDS, cancer, strokes—even H. pylori infections.1-2

Recently, an abundance of research has emerged on glutathione’s role in health.

Cardiovascular Disease
Researchers studied the association between fasting plasma total glutathione levels and cardiovascular disease among 134 cardiovascular disease cases and 435 healthy control subjects.3 Mean total glutathione concentrations were lower in all cardiovascular disease cases than in control subjects.

Among subgroups of subjects with different types of cardiovascular disease, both the cerebral infarction cases and cerebral hemorrhage cases had significantly lower glutathione levels than the corresponding control groups. After adjustment for other confounding factors, the risk of cardiovascular disease was significantly lower in the subjects with the highest glutathione levels compared to the subjects with the lowest levels. This association was most prominent in patients with lacunar infarction or cerebral hemorrhage.

According to the study authors, “These findings suggest that reduced plasma total glutathione levels are a risk factor for CVD, especially for cerebral small vessel disease.”

Australian researchers established a similar link between glutathione and cardiovascular health.4 When the researchers caused a drop in glutathione levels in the mitochondria of cultured brain cells, the cells became more vulnerable to damage by nitric oxide or peroxynitrite.

The same researchers conducted an in vivo study and determined that a partial loss of glutathione occurs during cerebral ischemia (stroke) and persists during reperfusion (the reintroduction of blood into the blocked area). Furthermore, infusion of glutathione monoethylester, a compound that can increase mitochondrial glutathione, decreased the volume of the area deprived of blood.4

The researchers concluded, “Together these recent findings indicate that alterations in mitochondrial glutathione are likely to contribute to the severity of tissue damage in stroke and possibly other neurological disorders.”

Cancer
Free radicals are involved in the processes leading to cancer. Unfortunately, glutathione, which could normally help mount a defense against the free radicals, is often depleted in patients with cancer.

In one study of 52 bladder cancer patients and 24 healthy adult controls, levels of malondialdehyde, a free-radical promoting substance, were significantly higher and glutathione levels significantly lower in cancer patients compared to controls.5

In other studies of lung6 and breast cancer7, levels of glutathione-dependent enzymes were markedly altered, depending on the disease stage.

Animal studies also have indicated that glutathione deficiency is linked to DNA damage.8

H. Pylori
Helicobacter pylori is the primary cause of gastritis and peptic ulcer disease and can lead to the onset of gastric cancer. Previous studies have shown that H. pylori infection causes increased production of reactive oxygen species within the gastric mucosa, possibly leading to the H. pylori associated diseases.

One group of researchers, after reviewing the medical literature, proposed that the severity of inflammation and damage associated with H. pylori infection is dependent on stomach cells’ ability to counteract the increased reactive oxygen species load. They hypothesized that glutathione availability is important in mounting an adequate defense against the reactive oxygen species generated by the H. pylori infection.2 The researchers suggested that increasing glutathione availability could provide a novel method for preventing or reducing the damage caused by H. pylori.

HIV
Studies have shown that reduced levels of glutathione and its precursor cysteine play a role in HIV’s progression to AIDS.9 In one study, researchers analyzed blood samples from healthy volunteers and HIV positive patients undergoing different antiretroviral regimens. The study authors then determined the viral load in the HIV patients and levels of cysteine and glutathione.

The results indicated that a decrease in glutathione and cysteine levels was associated with disease progress. In fact, the greater the viral load, the lower the level of glutathione and cysteine.

Glutathione also can protect against the free radical damage that occurs as the result of standard treatments used in AIDS patients.10

Liver Health
Hepatitis C is characterized by decreased mitochondrial glutathione and increased mitochondrial susceptibility to free radicals.11 Furthermore, glutathione deficiency is common in liver cirrhosis patients and hepatitis patients.12

Cystic Fibrosis and Lung Health
New findings suggest that cystic fibrosis mutations lead to glutathione deficiency in the epithelial lining fluid of the lung and in immune system cells and the gastrointestinal tract.13 This deficiency increases over time as the higher-than-normal oxidant burden of cystic fibrosis leads to successively larger glutathione decrements without the normal opportunity to fully recover physiologic levels. This glutathione deficiency may be the trigger for initial depletion of other antioxidants and may also initiate the excessive inflammation found in cystic fibrosis.

According to the researchers, “In a way, cystic fibrosis may be thought of as the first identified disease with glutathione system dysfunction.”

Researchers have noted glutathione depletion in lung epithelial lining fluid in other respiratory diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and adult respiratory distress syndrome. The study authors concluded, “Therapies to augment glutathione may also be contemplated in these diseases.”

Glutathione and Vitamin C
As glutathione absorbs free radicals, it becomes oxidized and loses its antioxidant properties. Vitamin C helps to recycle the oxidized glutathione back to its reduced form so that it can continue to act as a powerful free radical quencher.

References
1. Shekhar R, Walimbe V, Raja S, Zagrodsky V, Kanvinde M, Wu G, Bybel B.
Glutathione metabolism and its implications for health. J Nutr. 2004 Mar;134(3):489-92.
2. Matthews GM, Butler RN. Cellular mucosal defense during Helicobacter pylori infection: a review of the role of glutathione and the oxidative pentose pathway. Helicobacter. 2005 Aug;10(4):298-306.
3. Shimizu H, Kiyohara Y, Kato I, Kitazono T, Tanizaki Y, Kubo M, Ueno H, Ibayashi S, Fujishima M, Iida M. Relationship between plasma glutathione levels and cardiovascular disease in a defined population: the Hisayama study. Stroke. 2004 Sep;35(9):2072-7.
4. Sims NR, Nilsson M, Muyderman H. Mitochondrial glutathione: a modulator of brain cell death. J Bioenerg Biomembr. 2004 Aug;36(4):329-33.
5. Arikan S, Akcay T, Konukoglu D, Obek C, Kural AR. The relationship between antioxidant enzymes and bladder cancer. Neoplasma. 2005;52(4):314-7.
6. Kaynar H, Meral M, Turhan H, Keles M, Celik G, Akcay F. Glutathione peroxidase, glutathione-S-transferase, catalase, xanthine oxidase, Cu-Zn superoxide dismutase activities, total glutathione, nitric oxide, and malondialdehyde levels in erythrocytes of patients with small cell and non-small cell lung cancer. Cancer Lett. 2005 Sep 28;227(2):133-9. Epub 2005 Jan 8.
7. Yeh CC, Hou MF, Wu SH, Tsai SM, Lin SK, Hou LA, Ma H, Tsai LY. A study of glutathione status in the blood and tissues of patients with breast cancer. Cell Biochem Funct. 2005 Sep 2; [Epub ahead of print].
8. Reliene R, Schiestl RH. Glutathione depletion by buthionine sulfoximine induces DNA deletions in mice. Carcinogenesis. 2005 Sep 14; [Epub ahead of print].
9. Sbrana E, Paladini A, Bramanti E, Spinetti MC, Raspi G. Quantitation of reduced glutathione and cysteine in human immunodeficiency virus-infected patients. Electrophoresis. 2004 Jun;25(10-11):1522-9.
10. Mondal D, Pradhan L, Ali M, Agrawal KC. HAART drugs induce oxidative stress in human endothelial cells and increase endothelial recruitment of mononuclear cells: exacerbation by inflammatory cytokines and amelioration by antioxidants. Cardiovasc Toxicol. 2004;4(3):287-302.
11. Korenaga M, Okuda M, Otani K, Wang T, Li Y, Weinman SA. Mitochondrial dysfunction in hepatitis C. J Clin Gastroenterol. 2005 Apr;39(4 Suppl 2):S162-6.
12. Onoda H, Takahashi H, Osada M, Saito A, Zeniya M, Toda G. [The relationship between the intracellular redox status of immune cells and progression of hepatitis C virus related chronic liver disease] [Article in Japanese] Nihon Rinsho Meneki Gakkai Kaishi. 2004 Oct;27(5):315-21.
13. Hudson VM. New insights into the pathogenesis of cystic fibrosis: pivotal role of glutathione system dysfunction and implications for therapy. Treat Respir Med. 2004;3(6):353-63.

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