A trendy substance called glutathione

There is currently a big demand for glutathione. It is trendy among people who use it to whiten their skin. Others take it supposedly to cure certain ailments.

Glutathione, also known as L-gamma-glutamyl-L-cysteinylglycine, is a peptide made up of three amino acids: glutamic acid, cysteine and glycine.  It occurs in two forms, such as reduced glutathione (referred to as glutathione or GSH) that is a monomer with a single peptide unit and oxidized glutathione (referred to as glutathione disulfide or GSSG) that is a dimer consisting of two glutathione units joined together. One unit of GSSG can be converted to two units of GSH by the enzyme glutathione reductase.

Glutathione is the biologically active form that has antioxidant property. As a major antioxidant, it is found in virtually all cells and helps protect the cells from oxidative stress. The antioxidant function of glutathione is useful in detoxifying peroxides that the body produces in the course of growth and metabolism, in which GSH is converted to GSSG by the enzyme glutathione peroxidase. Also, glutathione is used in the synthesis of deoxyribonucleotides, the building blocks of deoxyribonucleic acid (DNA).

The blood of healthy pediatric individuals was found to have 90 percent GSH and 10 percent GSSG (Pastore et al., Clinical Chemistry, 2001, vol. 47, pp. 1467-1469). The ratio of glutathione to glutathione disulfide (GSH/GSSG) can be used to evaluate oxidative stress in biological systems. Alterations in this ratio have been shown in aging, cardiovascular disease and cancer.

Healthy people do not need to take glutathione or food supplement that enhances glutathione production. Under normal conditions, the liver produces sufficient glutathione to maintain healthy cells, so glutathione supplement does not provide added benefit. The constituent amino acids of glutathione are considered as non-essential amino acids because they can be made in the body from metabolites of proteins and glucose.

Glutathione is available only as a dietary supplement but there are claims regarding its usefulness for the treatment of various diseases, such as diabetes, hypertension, atherosclerosis, osteoarthritis, Alzheimer’s disease, Parkinson’s disease, autism, cataract, macular degeneration, glaucoma, cancer, heart disease, liver disease, asthma, cystic fibrosis, pulmonary emphysema, chronic fatigue syndrome, and male infertility. So far, there are no wide-ranging scientific evidence and clinical trials to support these claims.

As a side effect, glutathione whitens the skin by inhibiting the enzyme tyrosinase that has a role in the production of melanin. Melanin refers to a group of natural pigments that are present in most living things. It is a derivative of the amino acid tyrosine and is made in specialized cells called melanocytes that are found in the basal layer of the epidermis. The most common type of melanin is eumelanin that is of brown and black subtypes and is the most abundant in humans. The process of melanin production is called melanogenesis; it can be enhanced when skin is exposed to sunlight or indoor UV radiation, causing the skin to tan.

Having dark or fair skin is typically genetically influenced. In various ethnic groups, the melanocytes differently express the melanin-producing genes giving rise to dark or fair skin depending on the amount of melanin produced. Some people have a genetic condition called albinism that is characterized by very little or no melanin production resulting in white skin and hair.

Glutathione is found in skin-whitening products including soap and lotion, and in the forms of pill, nasal spray and injectable product. Glutathione that is applied on the skin is not effectively absorbed by skin cells; it has poor stability of thiol (sulphur-hydrogen part in cysteine) that undergoes rapid autoxidation or formation of disulfide. Taking glutathione orally is not an effective way to get it into the body circulation because glutathione is degraded by enzymes in the gastrointestinal tract and so it is not absorbed as such. The efficacy of glutathione in nasal spray for the treatment of respiratory diseases is uncertain. Intravenous injection is the preferred mode of administering glutathione.

Regular and unregulated injections of glutathione to whiten skin may expose people to potential health risks associated with long-term use of a high dose of the substance. There are biochemical reactions in the body that require oxidation processes. The folding of various proteins into their functional forms involves oxidation in which the cysteine (amino acid) units form disulfide bonds. Flooding the cells with glutathione may cause “reductive stress” (the counterpart of oxidative stress) due to alteration in GSH/GSSG ratio that may adversely affect the protein folding process and may lead to certain degenerative diseases associated with unfolded or misfolded proteins that manifest as protein aggregates. A study has shown that reductive stress due to excessive level of antioxidant, such as glutathione, aggravates protein aggregation that can cause heart disease (Kannan et al., Cardiovascular Research, 2013, vol.100, pp. 63-73). Although there is still scant scientific evidence regarding reductive stress, it may be worthwhile further looking into.

Concerning skin color, I wonder why people would want to change the genetic feature that they have. About 15 years ago when I was in Salt Lake City, Utah, I met a lady who said that she liked my natural tan; she was going to a tanning salon because she said that her white skin looked like that of a fish. In Boracay, I met fair-skinned people who exposed themselves to sunlight at midday to have a tan, unmindful of the risk of developing skin cancer. On the other hand, many brown-skinned people spend resources to whiten their skin. Biologically speaking, a healthy glowing skin, whether it is dark or fair, has a “wow” effect.

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Elsie C. Jimenez, a biochemist and molecular biologist, is professor emeritus at the University of the Philippines Baguio. E-mail at [email protected].