Niacin for Treatment of Nonalcoholic Fatty Liver Disease (NAFLD): Novel use for an old drug?

Abstract Niacin has been widely used clinically for over half a century for dyslipidemia. Recent new evidence indicates that niacin may be useful in the treatment of nonalcoholic fatty liver disease (NAFLD) and its sequential complications including nonalcoholic steatohepatitis (NASH), and fibrosis. There is an urgent unmet need for a cost-effective solution for this public health problem affecting nearly one in three adults. Niacin inhibits and reverses hepatic steatosis and inflammation in animals and liver cell cultures. It prevents liver fibrosis in animals and decreases collagen in cultured human stellate cells. Its mechanism of action is by oxidative stress reduction and inhibition of diacylglycerol acyltransferase 2 (DGAT2) and other possible targets. An uncontrolled clinical trial in 39 hypertriglyceridemic patients with steatosis showed reduction of liver fat by 47% and reductions in liver enzymes and C-reactive protein from baseline when treated with niacin extended-release for 6 months This hypothesis generating data indicates a novel repurposed use of niacin for NAFLD. Niacin beneficially affects NAFLD at 3 major stages directly and, by affecting steatosis, it indirectly decreases the cascade effect on inflammation and fibrosis. It offers the advantage potentially of combination with other drugs in development for evolving synergistically more intense and broader efficacy. In select patients it may benefit frequently associated atherogenic dyslipidemia. A randomized placebo controlled double-blind parallel trial (with niacin alone or in combination with another drug in development) to assess the safety and efficacy of niacin on steatosis, inflammation and fibrosis in patients with NASH/NAFLD is warranted.