Updated on February 8, 2023
- Glutathione deficiency is prevalent in Parkinson’s disease patients, potentially contributing to neurological damage and disease progression.
- Glutathione supplementation could compensate for diminished glutathione levels, thereby supporting healthier function and reducing disruptive symptoms.
- Although research is ongoing, in vitro and clinical studies offer compelling evidence that glutathione can produce significant benefits for patients.
Does glutathione help Parkinson’s disease? That was the question posed by experts from the University of Medicine and Dentistry of New Jersey in a 2008 review paper. By the time of the study, the data supporting a potential role for glutathione supplements as an alternative therapy in Parkinson’s disease had been mounting for almost two decades, piquing the interest of researchers, patients, and practitioners alike. Although the antioxidant activity of glutathione was well-established at the time, the reviewers highlighted more recent evidence of the functional role of glutathione in a variety of additional processes in the central nervous system. These processes include the removal of peroxides and other toxins, the regulation of protein function and synthesis, the modulation of DNA synthesis and repair, the transportation of amino acids, and the cellular communications facilitated by glutamate receptors and hormonal signaling. The authors of the review believe these factors, taken together, might account for the consistent demonstration that the glutathione levels in the substantia nigra (a part of the brain with a role in reward and movement) were 40-50 percent lower in Parkinson’s disease patients. Replenishing and maintaining glutathione levels through supplementation, they suggest, could therefore provide therapeutic benefit in Parkinson’s disease patients.
In the 14 years since that review was published, the in vitro evidence that a glutathione supplement could make a positive difference for Parkinson’s disease patients has only grown stronger. Not only have cell-based studies continued to support the hypothesis that glutathione can play a functional role in opposing the pathophysiological processes associated with Parkinson’s disease, there are also new studies that combine lab-based evidence with measurements of patient outcome measures to solidify the connection between glutathione levels and disease symptoms. As yet, there have only been a few direct clinical trials on glutathione supplements for Parkinson’s disease patients, and they have not produced definitive evidence. However, a 2017 trial highlights some of the opportunities for future exploration and suggests that patients could realize therapeutic benefits.
Glutathione Supplements for Parkinson’s
Over the last decade, researchers have been building a solid case for the potential benefits of glutathione supplements for Parkinson’s disease. One of the most recent contributions came from researchers at Thomas Jefferson University in Philadelphia, who in 2016 published a relevant study in the journal PLoS One. These researchers were focusing on the role of n-acetyl-cysteine (NAC), a precursor to glutathione, in protecting midbrain dopamine neurons. They found that in a tissue culture model of Parkinson’s disease, exposure to NAC led to higher levels of dopamine transmitter binding in two parts of the brain involved in Parkinson’s disease pathophysiology: the caudate and the putamen. Specifically, the glutathione level was 4.4 percent higher in the caudate and 7.8 percent higher in the putamen, both of which are considered to be statistically significant improvements. This suggests that the conversion of NAC to glutathione supports the functioning of the dopamine system in Parkinson’s disease patients, which has been associated with both the physical and the motor effects of the condition.
Another relevant contribution came out of a collaboration by researchers at the University of Washington, Washington State University, and the Bastyr University Research Institute. Building on previous cellular-level research linking oxidative stress to the development of Parkinson’s disease progression, the researchers sought to describe associations between glutathione status, age, and Parkinson’s disease severity, in an attempt to establish a more solid connection between glutathione status and patient symptoms.
In a study of blood samples from 58 Parkinson’s disease patients, they found that glutathione levels not only declined with age, they were also correlated with statistically significant improvements in scores on the Unified PD Rating Scale (UPDRS), which is commonly used to measure Parkinson’s disease severity based on patients’ symptoms, as well as the Patient-Reported Outcomes in PD, another symptom-based scale. This evidence supports their conclusion that serum levels of glutathione can serve as an effective biomarker for Parkinson’s disease. Moreover, the data suggests that glutathione status could be a “modifiable risk factor” for Parkinson’s disease, warranting future clinical trials on glutathione supplementation.
Clinical Trials: Mixed Evidence and Opportunities for Future Design Enhancements
Although there is now three decades’ worth of solid laboratory evidence suggesting that glutathione supplementation can address symptoms in Parkinson’s disease patients, the results from the few clinical studies that have been conducted are somewhat less convincing. So far, only four clinical trials have been published, with the most recent coming in 2017 from the same research group that published the previously-discussed investigation on using glutathione as a biomarker for Parkinson’s disease. This time, they conducted a double-blind, placebo-controlled trial, in which 45 individuals with mild-to-moderate Parkinson’s disease receive intranasal glutathione supplementation.
The participants were assigned to one of three groups: a control group, in which participants received a placebo, or one of two treatment groups, in which participants received intranasal glutathione supplements of either 100 mg or 200 mg, three times daily for three months. To measure the effects, the UPDRS was again used to quantify patient outcomes. In the low-dose treatment group, the researchers reported score improvements, but they were not statistically significant. In the high-dose treatment group, they reported statistically significant improvements in the total score, the motor subscore, and the non-motor subscore. However, it is important to note that their statistical analysis indicated that the statistical significance of the score improvements was stronger in the placebo group than it was in either of the treatment groups. Therefore, although the researchers were able to demonstrate that intranasal glutathione supplementation could have a positive impact on patient symptoms, they failed to demonstrate these effects were distinct from a placebo effect.
The results from the other three clinical trials have been similarly mixed, and because they did not use the rigorous, controlled-trial methodology used in the 2017 study, it is unwise to integrate or compare results. Nevertheless, it is clear that a placebo effect might be impacting the clarity of the results in each of the studies. For instance, in both the 2017 study and an open-label 1996 study, there was a heavy emphasis on the ritual of glutathione administration (which, for the 2017 study, involved tilting the head back and inhaling deeply). These types of administration rituals are well-known to be associated with placebo effects, since regular rituals associated with medication administration can have psychological impacts on patients. For this reason, more researchers are looking to tweak the methodology of future studies to obtain more conclusive, reliable results on the potential effectiveness of glutathione supplementation.
Evidence from NAC Supplementation Studies
Currently, researchers are looking to preliminary studies on NAC to justify ongoing clinical trials of glutathione supplementation because NAC is converted to glutathione in the body. Alongside their in vitro study, the Thomas Jefferson University-based research group also conducted a randomized trial in which patients were treated with either NAC for three months or received no treatment. This precluded a placebo effect, and it produced promising results. Overall, the researchers found that the intervention led to a rise in dopamine transmitter binding and a 13-percent improvement on UPDRS rating scale scores. Although they could not provide definitive proof these findings were linked, their data offers further support for additional clinical trials on both NAC and glutathione supplementatnio that could prove beneficial for Parkinson’s disease patients.
In the coming years, it will be revealing for researchers to build on lab-based evidence in well-designed, large-scale clinical trials. For patients and practitioners today, it could still be worth considering a glutathione supplement as an alternative therapy for Parkinson’s disease patients. Although the evidence from clinical trials remains inconclusive, the strong evidence from the lab suggests that the effects could be significant for some patients.
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Works Cited
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Mischley LK, Standish LJ, Weiss NS, et al. 2016. Oxidative Medicine and Cellular Longevity.
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Monti DA, Zabrecky G, Kremens D, et al. PLoS One. 11(6):e015702.
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