Glutathione is one of the body’s most important antioxidants that your body makes on its own. It is a critical ingredient required for detoxification and also to keep your immune system functioning well and kicking in when needed. However, with age your body is not able to make as much glutathione as what is needed for a healthy antioxidant defense and to efficiently remove toxins from the body.

Aging and many other internal and environmental factors can lead to glutathione deficiency in the body. This can cause poor immunity, increased inflammation, accumulation of toxins, and increased risk of disease. Studies show that poor glutathione levels can speed up the rate at which you age and increase your risk of diseases such as heart disease, cancer, lung disease, dementia and more. [1] [2] [3]

In addition, people with chronic disease such as Alzheimer’s, Parkinson’s, fibromyalgia, asthma, AIDS, hepatitis and diabetes are often found to have low glutathione levels.

In this article, we are going to explore the factors that cause glutathione deficiency and what happens when your levels go down? 

What do you need glutathione for?


Glutathione is a naturally occurring molecule made up of three amino acids - cysteine, glycine and glutamine. Every cell of your body makes and needs glutathione. The magic behind its antioxidant and detoxification superpowers lies with the sulphur molecule it contains.

Sulphur is a sticky molecule that binds to various toxins including the free radicals, xenobiotics (drugs and poisons), carcinogens, pesticides, radiation, and heavy metals such as mercury, cadmium and lead.

As explained in this article: “It is a coenzyme in various enzymatic reactions. The most important of these are redox reactions, in which the thiol grouping on the cysteine portion of cell membranes protects against peroxidation; and conjugation reactions, in which glutathione (especially in the liver) binds with toxic chemicals in order to detoxify them. Glutathione is also important in red and white blood cell formation and throughout the immune system.” [4]

A substantial body of research suggests that healthy levels of glutathione are critical to controlling inflammation and premature ageing at a cellular level. These properties make glutathione an essential molecule to keep chronic disease at bay.

Let’s find out how glutathione works hard in keeping you healthy.

1.    Glutathione supports detoxification process

Glutathione is at the centre of how your body eliminates toxins. This is the reason why the liver contains very high amounts of glutathione as it is one of the main organs that help the body remove waste and toxins from the body.   

The process of detoxification is complex and requires all kinds of antioxidants, proteins and enzymes. It is made up of phase 1, phase 2 and phase 3 pathways.

  • Glutathione along with other antioxidants (such as CoQ10, vitamins C, A and E, zinc, and selenium) protect the liver from free radicals that are generated during detoxification.
  • Glutathione has an amazing capability to bind with all kinds of toxins, making them water soluble. This step makes it easier for the body to eliminate toxins through the skin, intestines and kidneys.

2.    Provides strong antioxidant defense

Glutathione, as an antioxidant, cools off free radical molecules by giving them the extra electrons they need to become stable. These highly reactive molecules are known to damage cells and their delicate sub-structures including lipid membranes, proteins, DNA and mitochondria. This oxidative damage and the resulting inflammation can give rise to all kinds of chronic diseases such as heart disease, cancer, obesity, diabetes, arthritis and neurogenerative disease such as Alzheimer’s and Parkinson’s.

But there is a reason why glutathione is called the master antioxidant of the body.

  • As an endogenous antioxidant (produced by the body on its own), it is found within the cells. This means it is always positioned to defend cells and their structures from oxidative damage. 
  • It is regenerated in the liver and recycles other important antioxidants, which prepares your body much better to fight and neutralize free radicals.
  • Protects DNA from oxidative damage when a cell divides.
  • Protects immune cells from the effects of free radicals.
  • Reduces damage caused by UV and other radiation. It also helps in DNA repair, which makes it extremely helpful in protecting cells from exposure to radiation. [5]

3.    Optimizes immune functions

Your body needs sufficient levels of glutathione to maintain healthy immune functions. 

  • Boosts the production as well as functions of white blood cells, particularly T cells
  • Helps T cells to grow and to launch responses [6] required to fight off infections, and even cancer
  • Prevents cellular toxicity, damage and death by getting rid of free radicals and metabolic waste-material usually produced when immune cells are in action.
Studies show that people suffering from chronic diseases such as AIDS, diabetes and cancer have a poor glutathione status. And that it is not surprising. When you are sick or struggling with a long-standing disease, your body needs more antioxidant support than ever to deal with such stress. These conditions not only deplete glutathione but also reduce the levels of other antioxidants such as magnesium, CoQ10 and vitamin D.

What causes glutathione deficiency?


People don’t have healthy glutathione levels for a number of reasons, age being one of the primary reasons. Young people usually have high levels, which diminish as you grow old. Most people lose about half of their natural ability to produce glutathione by the time they reach their 70’s or early 80’s.

In addition, as we just discussed, so many internal processes – including protecting cells from oxidative damage; recycling of other antioxidants such as vitamin C, E and alpha lipoic acid; proper functioning of immune cells especially T cells; DNA synthesis and repair, and of course, detoxifying the body – all require glutathione. These processes take away some glutathione. And then there are other external factors that deplete glutathione, creating additional stress on the body. Check out this long but not exhaustive list:

  1. Exposure to harmful substances such as heavy metals, pesticides, UV rays and ionizing radiation.
  2. Unhealthy diet lacking in enough nutrients and antioxidants, including the cofactors and precursors that you need to make glutathione.
  3. Excessive exercise and strenuous physical activity.
  4. Chronic stress, anxiety and depression.
  5. Smoking and drinking.
  6. Too much exposure to artificial light (called light pollution). This impairs the production of melatonin, a hormone involved in recharging worn-out glutathione after the master antioxidant is depleted from dealing with free radicals.
  7. Presence of chronic conditions such as HIV/AIDS, asthma, fibromyalgia, diabetes, cancer, autism spectrum disorders.
  8. Non-chronic yet stressful situations like burns, surgery or any other physical trauma.
  9. Infections such as cold and flu.
  10. Excessive use of certain medications and antibiotics.
  11. Magnesium deficiency, as magnesium is an important cofactor in the production of glutathione.
All these internal and environmental factors crowd the body and lead to excessive generation of free radicals. To a great extent, your body is very much capable of fighting off free radicals and limiting the oxidative damage. It has usually got all the endogenous (internally produced) and exogenous (obtained through healthy diet and supplements) antioxidant support it needs to limit the side effects of free radicals.

But continuous, long-term exposure to harmful substances and poor lifestyle choices drain the body of glutathione (and other antioxidants). This weakens your body’s natural defense system that works to rid the body of toxins and keep infections and disease at bay.

In fact, these external factors make the body vulnerable to disease and poor quality of life in two ways. Firstly, you need an increased supply of glutathione and other antioxidants to cope with all the oxidative stress your body is going through. And secondly, you don’t have enough glutathione reserves in the body as most of it is already spent. In this situation, glutathione deficiency develops, leading to low energy levels, impaired immune functions and reduced ability to remove toxins.

What does glutathione deficiency mean for the body?


  • Increased oxidative stress but reduced resources to cope with it
  • Significant reduction in the body’s ability to remove toxins, which translates into poor liver function, and accumulation of toxins and heavy metals.
  • Reduced ability to repair DNA, leading to cellular mutations 
  • Poor immunity

What are the symptoms of low glutathione levels?


Most of the symptoms listed here might not necessarily indicate glutathione deficiency. These symptoms could also be a result of some other underlying condition. However, it means that improving your glutathione levels will greatly help in improving many important body functions, which in turn improves (reduces) these symptoms:

  • Lack of energy and fatigue
  • Headaches
  • Dry skin
  • Confusion and brain fog
  • Joint pains and aches
  • Sleep issues
  • Frequent colds and infections
  • Development of conditions like heart disease, cancer and diabetes
Symptoms like depression, confusion and brain fog are not surprising as glutathione is the main antioxidant in the brain. And oxidative damage in the mitochondria is believed to be the underlying reason for bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). [7] This study also found lower levels in psychiatric illness.

Patients suffering from Parkinson’s and Alzheimer’s disease also have low levels of glutathione in their body. Oxidative stress and inflammation have been strongly implicated in the development of many chronic diseases including neurological disorders.

Glutathione deficiency and genetic factors


There are certain genes involved in glutathione production. Basically, these genes contain instructions for making and activating enzymes involved in the production and recycling of glutathione. Genetic mutations or absence of these genes in some people can lead to glutathione deficiency.

For example, there is a family of enzymes called Glutathione S-transferases or GSTs. These enzymes play a very important role in phase 2 of the detoxification process, also known as the conjugation pathway. GST enzymes catalyze conjugation reactions that bind glutathione to various toxins to make them water soluble. Besides playing a critical role in detoxification, these enzymes also have antioxidant functions.

There are different types of genes that contain instructions for creating these enzymes, such as GSTM1, GSTM2 and GSTP1. These genes are also involved in the metabolism of cysteine, folic acid and B family of vitamins, which work as cofactors in producing glutathione. [8] It appears that most of the people who are suffering from chronic disease lack the GSTM1 gene, leading to reduced production of glutathione.

In another example, a gene called the GSS gene is involved in making the enzyme glutathione synthetase, which you need to create glutathione. Mutations in this gene can cause glutathione deficiency. Glutathione synthetase deficiency is a very rare disorder and can be mild, moderate or severe – leading to a wide range of symptoms ranging from premature destruction of red blood cells (Hemolytic anemia), increased acidity in the blood and tissues to neurological symptoms such as delayed physical reactions, slowed speech, loss of co-ordination, intellectual disability, seizures, tremors and muscle stiffness. You can find more information of this rare disorder here.  

It appears that maintaining optimum glutathione levels help to stay in good health when it comes to reducing your risk of chronic disease, inflammation and premature ageing. But can glutathione supplements really help with raising your glutathione levels? Can diet help? What role does a healthy lifestyle, such as healthy sleeping patterns and exercise, play here?  

It is generally believed that regular oral supplements may not be very helpful in increasing your levels naturally, mostly because of bioavailability and absorption challenges. But liposomal glutathione supplements have changed the game as they can improve the absorption as they by-pass the digestion route. In addition, there are certain foods that provide the raw materials needed to make glutathione in the body.

References:

  1. N Ballatori et al. Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem. 2009
  2. Chava B. Pocernich. D. Allan Butterfield. Elevation of glutathione as a therapeutic strategy in Alzheimer disease. 2012. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
  3. Townsend et al. The importance of glutathione in human disease. Biomed Pharmacother. 2003
  4. Glutathione. PubChem.
  5. Anupam Chatterjee. Reduced Glutathione: A Radioprotector or a Modulator of DNA-Repair Activity? Nutrients. 2013.
  6. T W Mak et al. Glutathione Primes T Cell Metabolism for Inflammation. Immunity. April 2017.
  7. Glutathione deficiency. Immune Health Science.com.
  8. Gawryluk et al. Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. International Journal of Neuropsychopharmacology, Volume 14, Issue 1, 1 February 2011.