Glutathione and Depression: Correlation Through Science

Prolonged bouts of sadness, loss of interest in activities, and negative feelings are just some of the signs that you may have Major Depressive Disorder (Depression). Depression is one of the most prevalent diagnoses in the United States, affecting anywhere from 15 to 20 million people yearly. Traditional treatments for depression involve treating the symptoms of depression but are largely unsuccessful in treating the underlying cause. New data suggests that oxidative stress and lower Glutathione (GSH) levels play a larger role in depression than was once thought.

It’s difficult to put your finger on just what it is that is making you sad, but you know for certain that you are sad. You are unable to enjoy activities that once were your most favored pastimes. So, what changed?

You make this inquiry of your doctor, and in the traditional practice of clinicians he offers to start you on anti-depressant medications targeting serotonin/dopamine levels. Far from guaranteeing to work, these medications can cause all sorts of unwanted side effects that can have debilitating effects on your wellbeing. Weight gain, sleep disturbance, feelings of being sick, are all side effects that can be triggered by starting a regimen of prescription anti-depressant medications.

Studies published by the National Institute of Health indicate lower levels of glutathione may be an early marker of depression. Glutathione (GSH) is the major free radical scavenger in the brain, lower levels of this antioxidant elevate cellular vulnerability to oxidative stress. Malondialdehyde (MDA) levels are used as a biomarker to measure oxidative stress.

The brain, in particular, due to its higher oxygen consumption and weaker antioxidant defense, is more vulnerable to oxidative stress. Treating these characteristics of the brain with suitable antioxidants such as glutathione can be an effective strategy in combating major depressive disorder.

Glutathione (GSH), being the most powerful of antioxidants, is able to cross the blood-brain-barrier, where it protects against oxidative stress by playing an antioxidative role. Whereas glutathione prevents cell damage, having insufficient levels of this antioxidant will lead to the onset and progression of many diseases. Lower levels of glutathione remain one of the primary markers of individuals who have neurogenerative diseases.

“OS (oxidative stress) is a main cause of neurodegeneration and its involvement in the pathogenesis of major depressive disorder is unequivocally established (PubMed.ncbi.nlm.gov).” You’re probably thinking, “Okay, I have seen a glutathione supplement at my local grocery store, I’ll just pick that up.” According to PubMed, Glutathione has a “very low bioavailability,” meaning that it is not easily absorbed through oral supplementation.

During the digestion process, the stomach churns and mixes food with acids and enzymes, breaking down content into ever smaller pieces. This acidic environment, although ideal for digestion, causes the bonds between the three amino groups of glutathione to dissolve, resulting in the remints being excreted.

Glutathione via injection or intravenous therapy (IV) bypasses the digestive system and allows for the benefits of glutathione to be felt more quickly and in higher concentrations. Taken through injection or IV infusion therapy, glutathione directly enters the bloodstream without any degradation of the bonds holding the tripeptide together.

In summary, oxidative stress has been established as a cause of depression. Glutathione is able to cross the blood-brain-barrier, where it protects against oxidative stress by playing an antioxidative role. Injection and IV infusion therapy is the most effective route of administration for Glutathione with regards to positive changes in mood and depression.

Further Reading and References

Enjoyed this month blog? There’s more where that came from. 

Role of oxidative stress in depression https://pubmed.ncbi.nlm.nih.gov/32404275/#:~:text=The%20brain%20is%20more%20vulnerable,(MDD)%20is%20unequivocally%20established

Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536296/

Gawryluk, J.W., et al. “Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders”. The International Journal of Neuropsychopharmacology Vol. 14, No. 1 (2011): 123–130