Glutathione and Cancer

What is glutathione?

Glutathione, a sulfur-containing compound, is the master detoxifier and main antioxidant in the body. A combination of three simple building blocks of proteins or amino acids—cysteine, glycine, and glutamine—glutathione is part of a larger family of enzymes comprising the powerful detoxification group called glutathione-S-transferase (GST).

Low levels of glutathione are associated with immune deficiency, progression of chronic diseases, and aging.

What are the potential benefits of glutathione?

• Supports healthy immune function
• Helps control inflammation
• Detoxifies unhealthy substances
• Protects cells
• Aids functional energy metabolism
• Assists amino acid transport¹

Along with antioxidant defense of the cell, glutathione plays a central role in drug detoxification and cell communication impacting the regulation of gene expression, cell death, and cell growth².

What are additional potential benefits of glutathione for some people with cancer?

Studies also suggest that intravenous glutathione protects reduces toxicity, cancer side effects, improves or maintains quality of life, and enhances therapeutic effects in some cancer patients treated with certain chemotherapy agents^3-7.

Glutathione may also help treat cancer cachexia. The progression of cancer cachexia is associated with the depletion of intracellular glutathione (GSH) and increases in markers of oxidative stress due to high levels of toxicity in the body⁸.

Some research indicates contraindications between glutathione and some chemotherapy agents related to antioxidants and their interference. Top Cancer Resources has information about interactions in Cancer Drugs, Herbs, and Supplements. The chapter Nutrient and Herb Interactions with Conventional Cancer Treatments in Definitive Guide to Cancer, 3rd Edition: An Integrative Approach to Prevention, Treatment, and Healing by Lise Alschuler, ND and Karolyn A. Gazella includes references to contraindications between glutathione and specific cancer drugs.

What causes decreases in glutathione?

A poor diet, pollution, toxins, medications, alcohol, smoking, sedentary lifestyle, stress, trauma, aging, infections, radiation, cancer cells, conventional cancer treatments, and other factors produce oxidative stress generating free radicals that may decrease glutathione levels. Free radicals are unstable molecules that play a role in illness. Oxidation involves the loss of an electron from an atom or molecule. Since atoms and molecules want to have a full set of electrons, free radicals that form during oxidative stress search for and combine with other molecules to acquire electrons. In this process, free radicals can damage DNA. Since pieces of DNA are genes telling cells how to work in the body, when to grow, and divide, free radicals can initiate cancer development and growth.

As a master detoxifier and antioxidant in the body, glutathione is responsible for removing excess free radicals. However, if the amount of free radicals is higher than available glutathione, the body’s total level of glutathione will decrease.

What are some strategies to increase glutathione?

Glutathione can be taken orally or intravenously. Research indicates glutathione is not well absorbed orally. Intravenous glutathione delivers the highest levels of the substance with increased absorption.

What are other sources of glutathione?

Some food and supplement sources of glutathione include the following. A qualified integrative cancer care provider can optimally recommend specific supplements for each individual with the right dosages and combinations.

• Sulfur-rich foods—garlic, onions, and cruciferous vegetables
• Bioactive whey protein
• N-acetyl-cysteine
• Alpha lipoic acid
• Methylation nutrients folate and vitamins B6 and B12
• Milk thistle
• Selenium
• Antioxidants such as Vitamin C and E

What is the role of glutathione genetic variations in health conditions such as cancer?

Genes are involved in glutathione metabolism to produce enzymes that allow the body to create and recycle glutathione. These genes have many names such as GSTM1 and GSTP1. Studies suggest that different glutathione-S-transferase (GST) gene abnormalities may correlate with cancer diagnosis, response to cancer therapies, and even survival^9-11. Some health care providers test patients to measure these genes for information about strengths and weaknesses in glutathione metabolism. This customized information about each person provides details about bodily functions and helps direct treatments.

For More Information

• The Definitive Guide to Cancer, 3rd Edition: An Integrative Approach to Prevention, Treatment, and Healing by Lise Alschuler, ND and Karolyn A. Gazella
• Textbook of Functional Medicine

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References

1. Textbook of Functional Medicine
2. Franco R, Schoneveld OJ, Pappa A, Panayiotidis MI. The central role of glutathione in the pathophysiology of human diseases. Arch Physiol Biochem. 2007 Oct-Dec;113(4-5):234-58. Review. PubMed PMID: 18158646.
3. Cascinu S, Cordella L, Del Ferro E, Fronzoni M, Catalano G. Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial. J Clin Oncol. 1995 Jan;13(1):26-32. PubMed PMID: 7799029.
4. Cascinu S, Catalano V, Cordella L, Labianca R, Giordani P, Baldelli AM, Beretta GD, Ubiali E, Catalano G. Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2002 Aug 15;20(16):3478-83. PubMed PMID: 12177109.
5. Milla P, Airoldi M, Weber G, Drescher A, Jaehde U, Cattel L. Administration of reduced glutathione in FOLFOX4 adjuvant treatment for colorectal cancer: effect on oxaliplatin pharmacokinetics, Pt-DNA adduct formation, and neurotoxicity. Anticancer Drugs. 2009 Jun;20(5):396-402. PubMed PMID: 19287306.
6. Smyth JF, Bowman A, Perren T, Wilkinson P, Prescott RJ, Quinn KJ, Tedeschi M. Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomized trial. Ann Oncol. 1997 Jun;8(6):569-73. PubMed PMID: 9261526.
7. Definitive Guide to Cancer, 3rd Edition: An Integrative Approach to Prevention, Treatment, and Healing by Lise Alschuler, ND and Karolyn Gazella
8. Integrative Oncology by Donald Abrams, MD and Andrew Weil, MD
9. Kilburn L, Okcu MF, Wang T, Cao Y, Renfro-Spelman A, Aldape KD, Gilbert MR, Bondy M. Glutathione S-transferase polymorphisms are associated with survival in anaplastic glioma patients. Cancer. 2010 Feb 24. [Epub ahead of print] PubMed PMID: 20187096.
10. Sreeja L, Syamala V, Hariharan S, Syamala VS, Raveendran PB, Sivanandan CD, Madhavan J, Ankathil R. Glutathione S-transferase M1, T1 and P1 polymorphisms: susceptibility and outcome in lung cancer patients. J Exp Ther Oncol. 2008;7(1):73-85. PubMed PMID: 18472644.
11. Kraggerud SM, Oldenburg J, Alnaes GI, Berg M, Kristensen VN, Fossa SD, Lothe RA. Functional glutathione S-transferase genotypes among testicular germ cell tumor survivors: associations with primary and post-chemotherapy tumor histology. Pharmacogenet Genomics. 2009 Oct;19(10):751-9. PubMed PMID: 19741569.