Glutathione: the unsung hero of antioxidants

Article | 0 comments

Glutathione is considered by scientists to be one of most powerful antioxidants, yet remains relatively unknown, compared to other nutrients.  Manufactured in every cell in the body, but produced in large amounts by the liver, glutathione is made from three building blocks of protein, the amino acids cysteine, glycine and glutamine.1,2  At this time of year, when many of us feel more exposed to stress, infection, reduced sleep, alcohol and other toxins, due to end of year events and Christmas parties, it is interesting to understand how nutrients such as glutathione are working away in the background to protect us from the damage these factors can cause.

Glutathione is one of the key nutrients found in many green vegetables, which can help to speed up phase II detoxification in the liver.6

The liver processes a wide variety of potentially harmful substances, including alcohol, steroid hormones, medication and toxic metals, in two stages, known as phase I and phase II detoxification.3 Most chemicals, either produced by the body or to which we are exposed through our diet and environment, first undergo phase I detoxification, which produces highly reactive and carcinogenic by-products.  In other words, the products our body is trying to eliminate, are temporarily converted into substances which are potentially even more harmful than they were originally. These by-products are then further processed in phase II and rendered less harmful, into a state in which they can be removed from the body, excreted in bile and urine.

liverThe timing of these processes in the liver is critical and if phase I reactions happen too fast for phase II to deal with the toxic by-products, they can promote the development of cancer.4 For example, cigarette smoke speeds up phase I, which can lead to a build-up of highly toxic substances waiting to be removed via phase II.  Meanwhile, the beneficial properties of broccoli and other cruciferous vegetables help to speed up phase II detoxification and thereby contribute to cancer prevention.5 Glutathione is one of the key nutrients found in many green vegetables, which can help to speed up phase II detoxification in the liver.6

Our ability to protect our body against major disease such as cancer or heart disease is closely related to the balance between our exposure to harmful free radicals and our intake of protective antioxidant nutrients.3 To explain this in more detail, we need to understand that oxygen underpins all plant and animal life and is required by every human cell to release energy from food, which subsequently drives all our body functions.  However, oxygen is chemically reactive, highly unstable and can oxidise other molecules, meaning that it steals part of other atoms and compounds.  Classic examples are rusty iron and browned fruit, whereby oxygen has stolen an electron, the outer part of the iron or fruit atoms and the resulting oxidation reaction causes the original compounds to be damaged. Now imagine that this is going on inside you!  Free radical is another name for a damaged atom or group of atoms, which has a missing electron and ‘attacks’ neighbouring atoms, in an attempt to steal an electron back.  This in turn damages the neighbouring atom and the cycle continues.

…damage caused to body cells by free radicals triggers inflammation, cancer, arterial damage and ageing.2,8

Free radicals are produced by all combustion processes which involve oxygen, such as smoking, the burning of petrol to create exhaust fumes; frying or barbecuing food; radiation (including sunlight); and even by many normal body processes such as converting food to energy, or exercising.7 Collectively, we refer to these damaging factors as oxidative stress and the damage caused to body cells by free radicals triggers inflammation, cancer, arterial damage and ageing.2,8 The liver is an organ which is particularly susceptible to damage caused by oxidative stress.8

sunburn             bbq-meat      exercise

While we can limit our exposure to some free radicals, it is impossible to avoid them completely and therefore the role of antioxidants is crucial for maintaining the balance which promotes good health.  Antioxidant nutrients such as vitamins A, C and E, beta carotene, zinc, selenium and co-enzyme Q10 work as a team to disarm free radicals, by sharing and donating electrons, which then repair the oxidised or damaged free radical and prevent further damage to cells.  Various warning signs indicate that we don’t have the balance right and that our antioxidant intake is insufficient, compared to our level of free radical exposure.  These include recurrent or difficulty in shaking off infections; slow skin healing; excessive wrinkles for your age; or inability to detoxify after exposure to free radicals, such as feeling groggy or achy after exercise, or being exposed to pollution. Do any of these issues sound familiar?electron-donation

This brings us back to glutathione, which works very closely with other antioxidant nutrients such as vitamins A, C and E and in turn is used to produce the body’s most powerful antioxidant enzyme, glutathione peroxidase.  It is this enzyme which enables the liver to protect us from oxidative stress in the form of car exhaust fumes, cigarette smoke, radiation and other carcinogens, infections, excessive alcohol and toxic metals.9  Although it is made in every cell in the body, the liver has the greatest capacity to produce and store glutathione and levels of this important antioxidant are seen to increase significantly when a cell is exposed to oxidative stress.10  So what can we do to assist the production of glutathione? Production requires the amino acids cysteine, glycine and glutamine and therefore ensuring adequate intake of these precursors, or building blocks, along with nutrients to support liver function, is the best approach to promoting adequate glutathione.

Foods to eat:

Sulphur-containing foods which are high in the sulphurous amino acids cysteine and methionine.  Diets low in sulphur-containing amino acids are shown to have a negative impact on glutathione levels.10 Broccoli, kale, cabbage, Brussels sprouts, cauliflower, bok choy, watercress, radish, turnip, onion, garlic, leek, eggs, fish.

Selenium-rich foods. Selenium helps the body to produce and recycle glutathione 4 and is required to make the important antioxidant enzyme glutathione peroxidase.  Brazil nuts, fresh tuna, beef, poultry, egg, spinach, mushrooms, brown rice, chia, flax and sesame seeds.

Brightly coloured fruit and vegetables, plus nuts and seeds which contain vitamins A, C and E.  These work as a team with other antioxidants, to recycle glutathione and prevent cell damage by free radicals. Tomatoes, peppers, melon, pumpkin, butternut squash, sweet potato, spinach, carrots, berries, oranges, kiwi fruit, avocado, almonds, sunflower seeds.

Bone broth is rich in the amino acids glycine and glutamine, which are both required for glutathione production (as well as providing the building blocks to repair damaged cells which line the digestive tract).

Vitamins B6, B12 and folic acid for methylation.  Methylation is a process which occurs more than a billion times per second in every cell of the human body and determines how the cell develops, as well as influencing our overall health.11 Among many other functions, the process of methylation regulates the use of sulphur-containing substances in the body, which includes glutathione.  The specific B vitamins needed for methylation are found in beans, chickpeas, lentils, black eyed peas, asparagus, spinach, broccoli, avocado, nuts, nutritional yeast, poultry and organ meat such as beef liver.

Supplement silymarin, which is extracted from seeds of the milk thistle plant.  Silymarin has been shown to regulate the availability of sulphur-containing amino acids such as cysteine in the liver, thus ensuring that adequate levels are accessible for the liver to produce glutathione. 4, 8

milk-thistle

Aside from its antioxidant mechanisms, glutathione plays other roles in the body, as it supports our immune system in various ways; links together with drugs to aid their removal from the body; assists with the creation of new proteins12; protects us from environmental toxins; and is involved in the process of apoptosis, or programmed cell death, of cancer cells.13

Some scientists speculate that glutathione status is one of the most important indicators of health, having studied how levels decline as we age and drop significantly in patients with various diseases.14 The good news is that it is simple to help our body maintain production of this vital but unacclaimed antioxidant, by eating the foods outlined above and by supporting our precious liver, which bears the load of glutathione production.  So give a little love to your liver:  go easy on the alcohol over the festive season; load your plate with brightly coloured vegetables; sip on bone broth, or use it in soups and gravies; and consider taking a liver support supplement which contains milk thistle, B vitamins and sulphur-containing amino acids such as N-acetyl cysteine or methionine.

View List of References

    1. Shang, Y, Siow Y L, Isaak C K, Karmin O (2016) Downregulation of Glutathione Biosynthesis Contributes to Oxidative Stress and Liver Dysfunction in Acute Kidney Injury. Oxidative Medicine and Cellular Longevity, 2013. [Online] PubMed Central (www.ncbi.nlm.nih.gov/pmc).
    2. Traverso N, Ricciarelli R, Nitti M, Marengo B, Furfaro A L, Pronzato M A, Marinari U M, Domenicotti C (2013) Role of glutathione in cancer progression and chemoresistance. Oxidative Medicine and Cellular Longevity, 2013. [Online] Hindawi Publishing Corporation (www.hindawi.com/journals).
    3. Jamison J (2003) Clinical Guide to Nutrition & Dietary Supplements in Disease Management. Churchill Livingstone, London.
    4. Hodges R E, Minich D M (2015) Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application. Journal of Nutrition and Metabolism, 2015. [Online] Hindawi Publishing Corporation (www.hindawi.com/journals).
    5. Walters D G, Young P J, Agus C, Knize M G, Boobis A R, Gooderham N J, Lake B G (2004) Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazol pyridine (PhIP) in humans. Carcinogenesis, 25 (9): 1659–1669. [Online] Carcinogenesis (www.carcin.oxfordjournals.org).
    6. Lampe J W, Chen C, Li S, Prunty J, Grate M T, Meehan D E, Barale K V, Dightman D A, Feng Z, Potter J D (2000) Modulation of Human Glutathione S-Transferases by Botanically Defined Vegetable Diets. Cancer Epidemiology, Biomarkers & Prevention, 9 (8). [Online] American Association for Cancer Research Journals (www.cebp.accrjournals.org).
    7. Lobo V, Patil A, Phatak A, Chandra N (2010) Free radicals, antioxidants and functional foods: Impact on human health. Pharmacognosy review, 4 (8): 118-126. [Online] PubMed Central (www.ncbi.nlm.nih.gov/pmc).
    8. Kim S H, Oh D S, Oh J Y, Son T G, Yuk D Y, Jung Y S (2016) Silymarin Prevents Restraint Stress-Induced Acute Liver Injury by Ameliorating Oxidative Stress and Reducing Inflammatory Response. Molecules, 21 (4): 443. [Online] Multidisciplinary Digital Publishing Institute (www.mdpi.com).
    9. Lubos E, Loscalzo J, Handy D E (2011) Glutathione Peroxidase-1 in Health and Disease: From Molecular Mechanisms to Therapeutic Opportunities. Antioxidants & Redox Signaling, 15 (7): 1957-1997. [Online] PubMed Central (www.ncbi.nlm.nih.gov/pmc).
    10. Taniguchi M, Mori N, Iramina C, Yasutake A (2016) Elevation of Glucose 6-Phosphate Dehydrogenase Activity Induced by Amplified Insulin Response in Low Glutathione Levels in Rat Liver. Scientific World Journal, 2016. [Online] PubMed Central (www.ncbi.nlm.nih.gov/pmc).
    11. Crider K S, Yang T P, Berry R J, Bailey L B (2012) Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate’s Role. Advances in Nutrition, 3: 21-38. [Online] Advances in Nutrition (www. advances.nutrition.org).
    12. Glutathione compound. Open chemistry database. [Online] (https://pubchem.ncbi.nlm.nih.gov/compound/124886?from=summary#section=Top)
    13. Franco R, Cidlowski J A (2009) Apoptosis and glutathione: beyond an antioxidant. Cell Death and Differentiation, 16: 1303–1314. [Online] Cell Death and Differentiation (http://www.nature.com/cdd/journal).
    14. Kharb S, Singh V, Ghalaut P S, Sharma A, Singh G P (2000) Glutathione levels in health and sickness. Indian Journal of Medical Science, 54 (2): 52-54. [Online] PubMed Central (www.ncbi.nlm.nih.gov/pmc).