In this study, we used macrophage RAW264.7 cells to elucidate the molecular mechanism underlying the anti-inflammatory actions of niacin. Anti-inflammatory actions of niacin and a possible role of its receptor GPR109A have been studied previously. However, the precise molecular mechanism of niacin’s action in reducing inflammation through GPR109A is unknown. Here we observed that niacin reduced the translocation of phosphorylated nuclear kappa B (p-NF-κB) induced by lipopolysaccharide (LPS) in the nucleus of RAW264.7 cells. The reduction in the nuclear translocation in turn decreased the expression of pro-inflammatory cytokines IL-1β, IL-6 in RAW264.7 cells. We observed a decrease in the nuclear translocation of p-NF-κB and the expression of inflammatory cytokines after knockdown of GPR109A in RAW264.7 cells. Our results suggest that these molecular actions of niacin are mediated via its receptor GPR109A (also known as HCAR2) by controlling the translocation of p-NF-κB to the nucleus. Overall, our findings suggest that niacin treatment may have potential in reducing inflammation by targeting GPR109A.

Dysbiosis is implicated by many studies in the pathogenesis of Parkinson’s disease (PD). Advances in sequencing technology and computing have resulted in confounding data regarding pathogenic bacterial profiles in conditions such as PD. Changes in the microbiome with reductions in short-chain fatty acid (SCFA)-producing bacteria and increases in endotoxin-producing bacteria likely contribute to the pathogenesis of PD. GPR109A, a G-protein coupled receptor found on the surface of the intestinal epithelium and immune cells, plays a key role in controlling intestinal permeability and the inflammatory cascade. The absence of GPR109A receptors is associated with decreased concentration of tight junction proteins, leading to increased intestinal permeability and susceptibility to inflammation. In inflammatory states, butyrate acts via GPR109A to increase concentrations of tight junction proteins and improve intestinal permeability. Niacin deficiency is exacerbated in PD by dopaminergic medications. Niacin supplementation has been shown to shift macrophage polarization from pro-inflammatory to an anti-inflammatory profile. Niacin and butyrate, promising nutrients and unique ligands for the G protein-coupled receptor GPR109A, are reviewed in this paper in detail.

A six-month double-blind, placebo-controlled randomized study was conducted to ascertain whether low-dose daily niacin supplementation would improve motor symptoms in Parkinson’s disease (PD) patients. A total of 47 PD patients were assigned to receive low-dose niacin or a placebo. At the end of the double-blind phase, all participants received open-label niacin for the next six months. All patients were evaluated at baseline, after six months, and after one year of treatment. The primary outcome measure was the Unified Parkinson’s Disease Rating Scale III (UPDRS III) scores. Secondary outcome measures were depression, sleep quality, mental flexibility and cognition, and physical fatigue. Niacin treatment was well-tolerated by forty-five subjects. The mean [95% CI] change in UPDRS III scores at six months of placebo was −0.05 [95% CI, −2.4 to 2.32], and niacin was −1.06 [95% CI, −3.68 to 1.57]. From six to twelve months when both groups received open-label niacin supplementation, the average UPDRS III scores significantly decreased for the placebo group by 4.58 [95% CI, −0.85 to 8.30] and the niacin group by 4.63 [95% CI, 1.42 to 7.83] points. Low-dose niacin supplementation is a well-tolerated adjunct therapy and may improve motor function in PD when taken over a longer period.