SIRT1 and brain ischemia: However, another study reported the positive effects of nicotinamide, an inhibitor of SIRT1, on the outcome of brain ischemia, and the explanation given is that SIRT1 is a NAD+-dependent enzyme, and therefore in a moment of extreme nutrient deficiency such as stroke, the detrimental effects of its high energy consumption outweigh its aforementioned beneficial effects [135].