The ultimate guide to glutathione: Benefits, side-effects & research

Do you know that your body produces a powerful antioxidant to protect cells from cellular damage?

Antioxidants are molecules in many plants and trees and have been used for thousands of years to treat different ailments. These are also present in the human body. One of the most potent antioxidants in nature is a substance called glutathione. 

Cells in the body naturally produce glutathione in large amounts, signifying that this has a critical role in cellular health. Its levels are comparable to essential biomolecules such as glucose and cholesterol.

Glucose is an important molecule since it is the body’s primary energy source. Meanwhile, cholesterol is vital since it is the building block of many cellular organelles. 

What is glutathione? 

Glutathione acts as an antioxidant that scavenges free radicals produced during cellular metabolism. Glutathione is a simple protein composed of three amino acids: glutamate, glycine and cysteine [1].

This tripeptide is involved in different cellular pathways and reactions. For example, it is involved in lipid synthesis, breakdown and cellular immunity. Glutathione has two forms: oxidised glutathione (GSSH) and reduced glutathione (GSH). 

To maintain healthy cells and tissues, there must be a balance between the production of antioxidants and free radicals. When there is an imbalance, this can lead to injury of the cells and cellular death called apoptosis and early aging [2]. 

Free radicals play protective roles when produced in appropriate amounts. Here are some examples of their roles in maintaining the integrity of cells, tissues and organs: 

  • Wound healing 
  • Controlling the flow of blood through the arteries 
  • Fighting infection 
  • Keeping the brain sharp and in focus 

However, when free radicals are produced in excess amounts, this can damage the cells. Glutathione is responsible for disabling excess free radicals. However, when glutathione secretion is insufficient to disable excess free radicals, this can lead to oxidative stress. The following are some consequences of oxidative stress [3]: 

  • Inflammatory diseases (adult respiratory disease syndrome; glomerulonephritis; vasculitis; arthritis; lupus erythematosus) 
  • Ischemic diseases (stroke; heart disease)
  • Hypertension 
  • Emphysema
  • Neurological disorders (Alzheimer’s disease; muscular dystrophy; Parkinson’s disease) 

Lipids and proteins are oxidised when oxidative stress occurs, leading to changes in their function and structure. 

Natural sources of glutathione 

Glutathione is naturally produced in the body. However, certain plants and food can raise the level of glutathione in the body.

This is good news as this can help individuals who have low levels of glutathione. For example, as we age, the production of glutathione also reduces. This may explain why older adults are prone to inflammatory diseases associated with oxidative stress. 

Did you know that your body produces antioxidants to combat excess free radicals, protect your cells and tissues from damage, and slow down ageing? 
Photograph: Danijela Maksimovic/shutterstock

Here are some examples of food that you can enjoy while increasing your glutathione levels in the body: 

Avocados 

If you are one of those who love avocados, you are in for a treat! Avocados are one of the foods that contain the rich and powerful antioxidant glutathione

Avocados are eaten raw, which makes them ideal as a natural source of glutathione (4). Cooking and packaging avocados and other fruits and food that naturally contain glutathione can affect the glutathione level in these foods.

High heat can affect glutathione structure and may impair its function. Prolonged cooking of foods rich in glutathione can destroy this protein compound or decrease its concentrations.

Hence, eating avocado raw or as an avocado shake can help maintain its glutathione level. So, when you plan to eat avocado in your next meal, remember to eat it raw. You will not only harvest the benefit of glutathione, but you can also enjoy the other health benefits of avocado. 

Healthy, versatile and delectable – avocados have become a kitchen staple worldwide.

Asparagus

Asparagus is another vegetable that is rich in phytochemicals, which are known antioxidants. Since this vegetable is rich in glutathione, it can naturally increase glutathione levels in the body. If you are interested in whether asparagus is best cooked or eaten raw, a study has demonstrated that eating it raw is better than eating it cooked [4]. 

Since asparagus is often cooked before being eaten, you may reduce the cooking time to retain its glutathione levels. The longer you grill, cook, heat, or boil asparagus, the greater the chances that its glutathione level is reduced or glutathione molecules are destroyed. 

Broccoli 

Broccoli is another popular vegetable that is used to accompany meat dishes. It can also be cooked with other vegetables as part of healthy, vegetarian meals. Furthermore, it is a rich source of glutathione (GSH) and can raise levels of GSH in the body. 

Similar to other food sources of glutathione, it is best eaten raw. For most recipes that include broccoli, heat, bake or boil the vegetable.

There are chances that GSH levels are reduced or that GSH is destroyed in the cooking process. To minimise the effects of cooking on the vegetable, broccoli should be half-cooked. Reducing the cooking time can help retain the GSH levels in broccoli. 

Okra 

Okra is a green vegetable that is widely grown in temperate countries. This vegetable contains high amounts of glutathione.

However, the exact mechanism of how it can raise glutathione levels in the body has yet to be elucidated. Cooked okra has lower glutathione levels compared with raw okra. Okra must be cooked for a short period to retain most of its glutathione contents. 

Almonds 

Mislabelled as nuts, almonds are fruit seeds of almond trees common in Mediterranean countries. Interest in almonds is high since it has been shown to raise glutathione levels. One study reported that among young male smokers, ingestion of 84 grams of almonds (about ⅔ cup) daily for four weeks led to a significant decrease in smoking-related biomarkers of oxidative stress [5].

Apart from diminished biomarkers, antioxidant activities and antioxidant levels likewise increased significantly. It is well known that smoking increases oxidative stress, damaging lung linings. Eating ⅔ cup of almonds daily may help address the oxidative stress brought on by smoking. 

Research studies on glutathione 

Taking glutathione supplements may help delay ageing and protect you from neurodegeneration. Further, antioxidant supplements such as glutathione can improve your physical and cognitive functioning.

Were you having difficulties climbing the stairs because of arthritis? Do you remember where you just placed your car keys?

The boost of antioxidant supplements can help you remember where you last put your car keys. Since antioxidants have anti-inflammatory properties, they can lessen the inflammation in your joints. This will make walking and climbing stairs easier! 

Glutathione is an antioxidant and anti-aging drug

Glutathione plays a pivotal role in detoxifying xenobiotics and protecting cells against cellar damage due to oxidative stress. When GSH levels are decreased, individuals demonstrate the standard features associated with ageing and other pathological conditions, including neurodegenerative disorders [6]. Notably, patients with Parkinson’s disease tend to exhibit low levels of GSH as the first sign of the disease. 

Although GSH depletion is linked to cellular death, the exact mechanism of how decreased levels lead to cell death remains unclear. Interestingly, while GSH is abundant in the cells, supplements that have GSH tend to be poorly absorbed in the body.

This poor absorption is due to the low bioavailability of GSH in supplements. However, recent research studies have shown that chemical modification of GSH and the addition of N-acetyl cysteine could help improve the absorption of GSH in the body. Hence, when choosing a glutathione supplement, it is best to consider if it is modified or has added precursors such as N-acetyl cysteine to improve its absorption. 

Currently, there is evidence that GHS can delay aging. Aging is a complex process where marked changes are seen in antioxidant enzymes [7].

Most of the antioxidant enzymes affected during ageing include glutathione peroxidase, superoxide dismutase and catalase. All these antioxidant enzymes are naturally produced in the body and play essential roles in reducing the danger posed by free radicals. 

As organisms and cells increase their age, there is a decrease in the respiratory chain, which leads to a reduction in ATP production. ATP is needed for the metabolism of energy. Hence, the ageing process represents an ominous cycle.

Decreased levels of antioxidants lead to reduced production of ATP. When energy production is impaired, it results in increased production of free radicals and mitochondria dysfunction [8]. As the mitochondria lose their function, this sets off a series of events that ultimately lead to cellular death. 

The excellent news is the administration of glutathione precursors such as cysteine and glycine can increase GSH levels and activity. You can take supplements containing glycine and cysteine to help delay the progression of ageing and the destruction of the mitochondria. Consider taking glutathione supplements to counter the effects of ageing. When glutathione is increased in older patients, this helps delay ageing [8]. 

Glutathione as a skin-whitening product 

Studies have been conducted to examine the skin-whitening effects of glutathione. White-skinned individuals often tan their skin, while those who have darker skin tend to do the opposite and brighten their skin with available skin products in the market [9].

Currently, glutathione is one of the more popular skin-whitening products in the market. However, how effective is glutathione in brightening your skin? Can you take glutathione supplements to enjoy fairer skin? 

First, it is crucial to understand what melanin, eumelanin and pheomelanin are. The skin pigment melanin consists of two types of melanin: reddish-yellow pheomelanin and blackish-brown eumelanin. Brighter skin has a higher pheomelanin proportion.

Hyperpigmentation of the skin is due to exposure to ultraviolet radiation and results in the production of free radicals such as nitrogen species and reactive oxygen [10]. When not balanced by antioxidants, these free radicals can lead to skin ageing. When glutathione is present, it converts eumelanin to pheomelanin, thereby leading to brighter skin [11]. 

A literature review examined recent studies on the effectiveness of intravenous glutathione as a whitening agent [12]. A total of three clinical trials were included in the review.

Findings suggested that intravenous glutathione has short bioavailability, with half oxidised or removed from the blood circulation in just 10 minutes. Further, results revealed that glutathione appeared effective only in areas most exposed to the sun. This corroborates earlier reports that glutathione seems effective during new melanogenesis (formation of pigments) and not in areas with existing pigments. 

Interestingly, the literature review demonstrated that glutathione was effective in smoothening skin wrinkles and improving the skin’s elasticity and suppleness, regardless of whether the skin was exposed to the sun or protected from the sun. Hence, when burdened with skin wrinkles in different areas of the body, not only in the face, you should consider taking intravenous glutathione supplements. This could increase the suppleness of your skin while reducing wrinkles in areas exposed to the sun. 

What are the benefits of glutathione? 

As a powerful antioxidant, glutathione has many known benefits in the body. Here are some benefits that might interest you as you consider taking glutathione supplements: 

Increases the effects of vitamins C and E 

Vitamins C and E are regarded as having antioxidant properties. Both vitamins are needed to prevent cell damage while maintaining cellular function and health [13].

Glutathione, a natural antioxidant, increases the therapeutic effects of both vitamins. Together, these vitamins and glutathione help fight oxidative stress and inflammation. 

Do you know that most long-term diseases, such as heart and neurodegenerative diseases, could be due to chronic inflammation? Intake of vitamins C and E and glutathione supplements can help ward off these diseases and keep you healthy and young. 

It helps protect mitochondrial DNA (mtDNA) 

There are markers in the cells or tissues that would indicate longevity. For example, scientists rely on the telomeres of animals and humans to determine long life. Longer telomeres (found at the ends of the chromosomes) are associated with longer life, while shorter telomeres indicate a shorter life span. 

In the cells, mtDNA is a marker of the cell’s longevity or tissues. Glutathione activity and levels would indicate the activity of the mtDNA. Low levels of glutathione are consistent with reduced activity of the mtDNA [14]. 

Neutralises free radicals 

Excess free radicals can destroy cells and lead to rapid ageing in animal studies. In humans, it is well known that free radicals are involved in inflammation, leading to diseases such as arthritis and other neurodegenerative disorders. Further, free radicals also react with other proteins and enzymes, that ultimately leads to cellular death. 

Antioxidants counter the adverse effects of free radicals. As a powerful antioxidant, glutathione helps neutralise free radicals formed in the liver following the detoxification of toxins [14]. It helps protect the liver from free radicals, allowing it to continue detoxifying toxins and metabolites. 

Acts as a cofactor in many enzymes 

Cofactors are proteins or molecules that promote the activity of an enzyme. They are also called helpers of enzymes.

Apart from being an antioxidant, glutathione is a cofactor of many enzymes. When glutathione is in its reduced form, it becomes a crucial cofactor of many antioxidant pathways. Hence, consuming glutathione supplements can help increase antioxidant activities and promote cellular health while preventing early cell death. 

It helps protect brain tissues

Inorganic mercury, a heavy metal, can be ingested through the foods we eat. For example, shellfish and fish containing methylmercury traces can be mercury sources for humans. When eaten, mercury can be stored in the brain. As a lipophilic inorganic metal, mercury can readily pass the blood-brain barrier and be retained in the brain for several years [15]. 

Once stored in the brain tissues, mercury can have harmful effects. For instance, some patients with Alzheimer’s were found to have high levels of mercury in their cerebellum [15].

In turn, the mercury level in the cerebellum led to several changes that ultimately ended in the development of neurodegenerative disease. When glutathione in its reduced form is present in the brain, it will bind with mercury chloride and prevent further damage caused by mercury. 

Regulates growth and death of cells 

Glutathione is critical in regulating the growth and death of cells in the body. During the cell cycle, cells divide and form new cells.

During cell growth, when glutathione activities are stopped, this leads to the suppression of cell division. DNA synthesis is reduced, followed by a reduction of cell growth. 

In addition, glutathione is responsible for the expression of signalling molecules responsible for cellular death. Cells with low glutathione levels are at increased risk of injury and death. 

Side effects of glutathione 

Glutathione is generally safe and effective to use. There have been no reported side effects with the available doses of glutathione supplements. These supplements contain, on average, 1500 mg/day of reduced glutathione.

Since it is generally recognised as safe (GRAS), it can be used as a supplement to optimise your health. However, few people can develop adverse reactions to glutathione. Some reported adverse reactions include weight gain, loose stools and increased flatulence.

Once you develop these symptoms or side effects, immediately contact your doctor. Your doctor will give you appropriate advice on how to take glutathione safely. Your doctor might advise you to lower the dosage or to take an alternative supplement. 

Despite the safety record of glutathione, there have been few reported rare effects [16]. A case study revealed that intravenous glutathione led to severe hepatic injury. However, the effects of the infusion therapy were reversible. Another case study reported that inhaled glutathione resulted in asthma exacerbations in a patient with a history of asthma. 

To date, there are no contraindications to the intake of glutathione. However, there have been reports that glutathione may interact with acetaminophen in the liver, causing it to lose its function [16]. 

There are limited studies examining the effects of glutathione on particular population groups, such as older adults, those with kidney and liver failure and patients who are lactating and pregnant. Older adults with kidney and liver failure would have difficulties eliminating the supplement. Hence, for this group of individuals, seeking advice from a healthcare professional is necessary to maintain patient safety. 

Appropriate dose of glutathione 

If you are ready to take glutathione supplements to benefit your health or to whiten your skin, it is always best to consult a doctor. This is necessary to determine the most appropriate dosage for your health goal! You can start reaping the benefits of glutathione supplements as soon as you are ready. 

Can children take glutathione to treat diseases? Research showed that children with cystic fibrosis were treated safely with glutathione for six months using a total dosage of 65 mg/kg/day [16]. For a 30 kg child, this translates to 1950 mg/day divided into three doses at mealtimes. Another clinical study showed that glutathione was safe for patients with Parkinson’s disease treated with 1400 mg of the supplement three times per week for four weeks. 

Since glutathione has many uses and benefits, the recommended dosage will depend on your usage. There have been no reported adverse effects following the intake of glutathione at levels as high as 65/mg/kg/day or 1950 mg/day.

However, if you are taking acetaminophen in high doses, consider taking glutathione, as acetaminophen disables glutathione in the liver. Further, there are still no studies investigating the safety and efficacy of glutathione in pregnant women. Hence, when you are planning to become pregnant or are currently pregnant, talk to your doctor if you plan to take glutathione. 

Meanwhile, high doses of glutathione are recommended for those who want to brighten their skin. However, low doses might equally work to brighten those sunspots or skin exposed to the study. A study of patients treated with glutathione at doses of 250 mg/d for 12 weeks demonstrated improvements in skin elasticity and wrinkles, age spots and melanin index in skin areas exposed to the sun [17].

Although this study was small, it provided evidence of the effectiveness of low doses of glutathione in reducing wrinkles and brightening skin areas exposed to the sun. Hence, when considering glutathione for wrinkle reduction and skin brightening, you can start with lower doses of the supplement and gradually increase this under the supervision of your doctor. 

Finally, glutathione remains a powerful antioxidant and is readily available in oral or intravenous form. Talk to your doctor now to start enjoying this natural antioxidant’s benefits.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684116/
[2] https://pubmed.ncbi.nlm.nih.gov/10693912/
[3] https://pubmed.ncbi.nlm.nih.gov/9266153/
[4] https://www.sciencedirect.com/science/article/pii/S1756464614003636
[5] https://pubmed.ncbi.nlm.nih.gov/18029489/
[6] https://pubmed.ncbi.nlm.nih.gov/26467067/
[7] https://pubmed.ncbi.nlm.nih.gov/19679169/
[8] https://www.mdpi.com/2073-4409/11/3/552
[9] https://www.tandfonline.com/doi/full/10.3109/09546631003801619
[10] https://linkinghub.elsevier.com/retrieve/pii/S0923181110000782
[11] https://ijdvl.com/glutathione-as-a-skin-whitening-agent-facts-myths-evidence-and-controversies/
[12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196133/
[13] https://pubmed.ncbi.nlm.nih.gov/12614841/
[14] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523540/
[15] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882944/
[16] https://www.drugs.com/npp/glutathione.html
[17] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413479/

Photograph: Thongden Studio/Shutterstock
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