Glutathione: Source, supplementation and side-effects

Are you interested in boosting your immune system, delaying aging, and protecting yourself from cardiovascular and neurodegenerative diseases? Why not consider taking glutathione supplements to improve your health.

Glutathione serves many purposes in the body and is known as one of the most potent antioxidants. It has been shown to have protective effects against many diseases common today.

For example, there is evidence that it can help protect you or delay the progression of Alzheimer’s disease. When levels are low, this can cause a cascade of events that ultimately lead to health conditions.

However, when glutathione levels are sufficient, you enjoy protection from various diseases and can also benefit from detoxification. Excess free radicals produced during cellular metabolism can destroy cells and are removed from the body. Not to forget, you can also enjoy glowing skin.

Glutathione increases the suppleness and strength of your skin and brightens skin parts exposed to the sun. You can also live a longer life with adequate amounts of glutathione.

What is glutathione? 

Glutathione is a potent antioxidant naturally produced in the cells of your body. It is naturally found in nerve and liver cells and cells of the nervous system. This molecule is called a tripeptide and comprises three amino acids: L-cysteine, glycine and glutamate. 

Interest in glutathione has increased in the past years due to its antioxidant and anti-inflammatory properties. It is also called GSH and is available in an inactive state as oxidised glutathione (GSSG) and, in the active form, reduced glutathione (L-glutathione or GSH). Called a powerful antioxidant, it boosts the regeneration or recycling of other antioxidants in the body, such as alpha-lipoic acid, vitamins C and E and coQ10 [1]. 

Glutathione exists in two forms: L-glutathione or GSH, known as the active form of glutathione and the inactive form called oxidised glutathione (GSSG). Active GSH plays a role in scavenging excess free radicals in the body. It disables free radicals, but in the process, it turns into oxidised glutathione, the inactive form. 

Antioxidants are molecules in many plants and trees and have been used for thousands of years to treat different ailments
Photograph: Thongden Studio/Shutterstock

The oxidised form is turned back into the active state through the glutathione reductase enzyme. So, you don’t have to worry that you will have insufficient amounts of active glutathione. If glutathione reductase enzymes are present, you can continue to enjoy the benefits of GSH. 

The challenge arises when the enzyme glutathione reductase cannot cope with the demands of converting reduced glutathione to active GSH. Once this occurs, GSSG accumulates, leading to cellular damage. 

What is the role of glutathione in the mitochondria? 

Mitochondria are organelles of the cells that are composed of two layers. They are vital since they convert glucose into adenosine triphosphate (ATP) – cellular energy – and for this reason mitochondria are considered the powerhouse of the cell.

However, when the mitochondria stop producing energy (ATP), cells in the body also die since all cells require ATP for metabolism. 

The role of mitochondria is not only limited to the production of ATP. It also has its own DNA, and mitochondria send out information and can communicate with other parts of the cell.

These mitochondria even send signals or messages for a cell to undergo apoptosis or cell death. Cells that undergo apoptosis are beyond repair. Once they die, their organelles and other parts are recycled to become new cells. 

Glutathione plays a vital role in protecting the mitochondria. For example, glutathione scavenges or neutralises free radicals produced during glucose metabolism to ATP. It also ensures that toxins and heavy metals are removed from the ATP. 

Recycling of glutathione 

Converting oxidised glutathione to its active form would take a lot of energy! However, don’t worry as GSH is typically produced in large amounts in the cells. The GSH levels in our cells are as high as those of cholesterol and glucose [2]. The high amounts of GSH in the cells signify that it is crucial to cellular function and health. 

What are the roles of glutathione in the body? 

Glutathione participates in many cellular activities and is the body’s active component of different metabolic pathways. Hence, it is unsurprising that it has significant roles in maintaining overall health. Here are GSH’s most essential functions [2]: 

  • Antiaging 
  • Energy production 
  • Antioxidant 
  • Detoxification 

In addition, GSH also takes an active role in cellular and metabolic pathways: 

  • Expression of genes 
  • Co-factor of enzymes 
  • Cell communication and signalling 
  • Differentiation and proliferation of cells 

What happens when GSH is depleted? 

Depleting GSH will make cells and tissues susceptible to inflammation and oxidative stress. Both can lead to chronic conditions and accelerate ageing [3].

When your GSH levels are low, the mitochondria cannot effectively convert glucose to ATP. As a result, the mitochondria get oxidised. When the mitochondria are oxidised, inflammatory cells are activated to clean up the free radical damage.

Hence, it is no surprise that when you have depleted GSH, you can develop conditions such as heart disease and type 2 diabetes. It is now established that both type 2 diabetes and heart disease are due to chronic inflammation [4]. 

What are the natural sources of glutathione? 

If you are worried about depleting GSH levels, you can always boost this naturally through eating foods high in GSH or those that can increase GSH levels in your body. These are some examples of food that can help you raise your GSH levels: 

  • Avocado
  • Asparagus
  • Almonds 
  • Baru almonds 
  • Okra 
  • Broccoli 
  • Spinach 
  • Peas
  • Tomatoes
  • Peas 
  • Brussels sprouts 
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

Glutathione supplementation 

The good news is some supplements can help replenish GSH. These supplements include the following: 

  • Liposomal glutathione forms
  • Transdermal and lotions
  • Inhaled GSH 
  • Intravenous GSH 
  • Oral tablets

Common side effects when taking glutathione supplements 

Glutathione is considered generally safe [5]. Intake of supplements at 1500 mg/day has been recorded to be safe for adults. Children with cystic fibrosis treated with GSH received a daily dose of 65 mg/kg/day. If a child is 40 kg, they can take 2600 mg/day divided into three doses. Even at this dose, there were no reported side effects or adverse events. 

But in some cases, some individuals can experience adverse events after consuming glutathione supplements. One point showed that inhalation of glutathione exacerbated asthma. Hence, if you have a history of asthma, always ask your doctor if it is safe to take glutathione. However, it is better to avoid glutathione therapy if you have a history of asthma. 

Another isolated case revealed that an individual developed a hepatic injury after administering intravenous glutathione [5]. Although the damage was reversible, this rare adverse event should be considered for those with prior liver disease. 

Despite being generally safe, other reported side effects include the following: 

  • Increased flatulence 
  • Loose stools 
  • Abdominal cramps
  • Allergic reactions 
  • Rashes 

Allergic reactions to glutathione are a medical concern as this can lead to bronchoconstriction. Once your airways are constricted, you will have difficulty breathing. Always inform your physician of any allergic reactions to medications or supplements before planning to take glutathione. 

Drug-to-drug interactions between glutathione and other medications might also lead to adverse events. For example, when taken in high amounts, acetaminophen can impair the effects of glutathione.

Although this might not lead to adverse reactions, impairment of glutathione during intake of acetaminophen might lower your glutathione levels. In turn, this could have adverse effects on your overall health. 

Finally, choosing the most appropriate glutathione supplement will depend on your current needs, whether to prevent heart disease or achieve glowing skin. Always consult your physician, who will help you monitor your reaction to glutathione. 

[1] https://pubmed.ncbi.nlm.nih.gov/3657365/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684116/
[3] https://pubmed.ncbi.nlm.nih.gov/26467067/
[4] https://pubmed.ncbi.nlm.nih.gov/35308180/
[5] https://www.drugs.com/npp/glutathione.html

Photograph: Yury1964/Shutterstock
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