Objective: The main objective was to determine if α-synuclein could be modulated by niacin supplementation, contributing to improved Parkinson’s disease (PD) symptoms.

Background: Niacin supplementation increases NAD and, thus, ATP levels in the body. This version of vitamin B3 is anti-inflammatory, acting on its receptor, GPR109A. Previous studies found that GPR109A is upregulated in PD patients.Moreover, blood levels of niacin and NAD were lower than age-matched controls. Clinical trials exhibit improved NAD and niacin levels of PD patients after daily niacin supplementation. The literature also reveals an antioxidant capacity of niacin. Since niacin supplements can alter NAD levels, inflammation, and oxidative stress, it is critical to determine if PD symptom improvement may also be attributed to modulation of α-synuclein levels.

Method: Forty-seven patients enrolled in a randomized clinical trial took either 250mg of daily niacin or a placebo for six months. The subsequent six months permitted all remaining subjects to take daily niacin in an open-label portion of trial, allowing every patient to try the supplement. Electrochemiluminescent (ECL) or Enzyme-linked immunosorbent assays (ELISAs) determined the levels of plasma α-synuclein in PD patients before and after niacin. Total α-synuclein was measured by ECL assay from Meso Scale Discovery. α-synuclein phosphorylated at serine residue 129 (pS129) and oligomers, were measured by ELISA.

Results: Interestingly, pS129 α-synuclein plasma levels decreased by 6.7 ng/ml in the niacin group at six months (CI 0.4548 to 12.89; p=0.03) and at one year by 6.2 ng/ml (CI 1.589 to 10.74; p=0.01). The placebo group displayed higher plasma levels than the niacin-treated at six months. Levels of α-synuclein in plasma exosomes were also measured. Oligomers decreased by 1.6 ng/ml from baseline to six months in the placebo group (CI 0.1284 to 3.122; p=0.03). Additionally, an increase of 0.19 ng/ml was found in exosome levels of pS129 from six months to one year in the niacin group (CI -0.3661 to -0.01161; p=0.04). In contrast, levels decreased by 0.98 ng/ml from baseline to one year in the placebo group (CI 0.06209 to 1.896; p=0.04).

Conclusion: These findings indicate the therapeutic potential of niacin in altering α-synuclein plasma levels in PD patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/phosphorylated-%ce%b1-synuclein-at-serine-residue-129-decreased-in-parkinsons-disease-patients-taking-250mg-of-daily-niacin-for-six-months/