Glutathione and Neurodegenerative Disease

It’s well known that our risk of developing chronic diseases increases as we age. The reasons behind this are incredibly complex, but one of the most widely accepted explanations is called the “free radical theory of aging” ^[1].  First conceived in 1956, it is one of the most thoroughly researched theories known and, although not fully proven, is the best theory so far. It provides conclusive evidence that oxidative stress is intimately involved in aging.

As our lifespan increases, we become more susceptible to chronic disease. Especially those brought on by oxidative stress, like neurodegenerative diseases ^[2] which insidiously affect our brain and cognition.

A compromised glutathione (GSH) system in the brain has a strong correlation with oxidative stress and has been shown to be implicated in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, progressive supranuclear palsy, Huntington’s disease and multiple sclerosis ^[3-5].

It is now possible to determine the concentration of glutathione (GSH) in living human brains using magnetic resonance spectroscopy (MRS), with multiple MRS studies showing depleted brain glutathione (GSH) levels in all the major neurodegenerative diseases ^[6-9].

Strategies to increase neuronal or brain glutathione (GSH) as a potential treatment have been proposed by many researchers. However, none of the therapeutic candidates have been successful so far ^[10-12], with the major impediment for most being a failure to cross the blood-brain barrier. As yet, there is no available evidence to suggest that orally administered gamma-glutamylcysteine (GGC) can reach the human brain, but there are several theories that indicate it may well do so. An animal study was able to demonstrate that intravenously administered gamma-glutamylcysteine (GGC) did cross the blood-brain barrier and increased glutathione (GSH) in the brain ^[31]. A MRS human clinical study is underway to determine if oral supplementation with gamma-glutamylcysteine (GGC) can increase brain glutathione (GSH) levels.

References

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