A clinical trial on the effectiveness of niacin supplementation in Parkinson’s disease patients has recently been published in Frontiers in Aging Neuroscience.
The link between niacin and Parkinson’s disease
Niacin is a form of vitamin B3 that is commonly manufactured as a dietary supplement. Patients with Parkinson’s have considerably lower levels of vitamin B3 compared to controls. They also present with multiple symptoms consistent with vitamin B3 deficiency, including fatigue, disrupted sleep, and mood changes. Several known mechanisms of Parkinson’s disease interfere with vitamin B3 production and metabolism. Furthermore, niacin impacts anti-aging pathways, such as DNA repair, metabolism, and NAD+ levels. As a disease of aging, many of these same pathways contribute to the development and progression of Parkinson’s disease. Animal studies have also supported evidence that niacin may be beneficial for Parkinson’s disease.
The clinical trial design
32 men and 15 women with an average age of 62 years and a diagnosis of Parkinson’s disease were enrolled in this double-blind study.  Along with their regular medications, they took daily supplements of either a placebo, 100 mg of niacin, or 250 mg of slow-release niacin. Each patient was assessed before treatment and after three months. Clinical assessments were carried out including disease-specific measures, such as the Unified Parkinson’s Disease Rating Scale III (UPDRS) and more general quality of life measures, such as the Fatigue Severity Scale. Blood was also collected from the patients and analyzed for niacin plasma levels and inflammatory cytokines.
80% of subjects receiving 100 mg experienced flushing, a common side effect of niacin supplementation, compared to only 5% of the 250-mg slow-release group. Following the results of the 3 month study, all subjects began taking 250 mg of slow-release niacin daily. If they were already on that regimen, they remained so for 9 more months for a total of one year. Those in the placebo and 100 mg groups took the 250 mg supplement for 12 more months. All measures were taken again after 12 months of 250 mg slow-release niacin.
Did niacin help Parkinson’s disease patients?
The study’s primary endpoint, the UPDRS, showed a high amount of variability at 3 months, but it improved from baseline at 12 months. Although there was no control group at the 12-month time point, scores improved by 3.5 points, while a decline of 5.5 points would have been expected over the same time period in a similar study population.
Many secondary measures also improved, including handwriting, perception of fatigue, mood, postural control, and frontal EEG rhythm. Several other measures, such as quality of sleep, did not change after 12 months of niacin treatment. These may or may not represent benefits, since declines might reasonably be expected based on disease progression. Only one measure was poorer compared to baseline, an assessment of visual attention and task switching known as the Trail Making Test.
As expected, niacin levels increased with niacin supplementation. At 12 months, niacin levels were approximately 34% higher in plasma than at baseline. GPR109A, a receptor for vitamin B3, decreased in peripheral blood mononuclear cells with niacin supplementation. This effect has been previously reported to contribute to niacin’s anti-inflammatory mechanisms. However, of the 12 inflammatory cytokines measured, only one anti-inflammatory (IL-10) increased while two pro-inflammatory cytokines also increased (MIP-1a and IL-1ß).
We have demonstrated the potential effectiveness of over-the-counter niacin enhancement as a proof of concept to support the well-being of individuals with PD. Vitamin B3 augmentation has the potential to maintain or improve symptoms. Based on the results of this effectiveness exploratory trial, a larger multicenter RCT is warranted.
Clinical studies on niacin, NMN, NAD+, etc. are difficult to fund and research since they cannot be patented. Because of their expense, clinical trials such as this one are often done in a small number of patients, and they require some creative study designs to achieve the desired statistical power. In this study, all of the participants were placed in the 250 mg experimental niacin group after their 3-month follow-up.
The effects that niacin supplementation had on these Parkinson’s disease patients were interesting, clinically meaningful, and statistically significant. However, nearly all of these effects were seen at 12 months of supplementation, where there was no longer a blinded placebo group to compare to. It’s true that the effects of niacin were impressive, especially for a supplement with a very high safety profile, but the placebo effect is no joke. It is difficult to interpret the results of this study without a proper control group.
Studies like this one are incredibly important, especially when considering the poor translatability of many findings in mouse studies into humans. In the end, the limitations of this study unfortunately do not permit it to prove whether niacin can slow or partially reverse the progression of Parkinson’s disease. However, it does suggest that it might and convincingly demonstrates the need for a larger scale, placebo-controlled, double-blind clinical trial.
 Chong, R., Wakade, C., … & Purohit, S. Niacin enhancement for Parkinson’s disease: an effectiveness trial. Frontiers in Aging Neuroscience (2021). https://doi.org/10.3389/fnagi.2021.667032