Nicotinamide (Vitamin B3) Deficiency in Follicular Fluid of Patients With Ovarian Ageing

Nicotinamide is an essential precursor of NAD involved in energy metabolism. A decline in NAD levels across tissues during ageing is well-documented, and NAD metabolism has been implicated in ovarian ageing. We investigated the relationship between ovarian ageing and the levels of nicotinamide (NAM) and its metabolite 1-methylnicotinamide (MNA) in follicular fluid (FF) and blood of IVF patients. FF was obtained from 86 patients with ovarian ageing and 82 controls. Serum samples were collected from 24 and 29 patients, respectively. Nicotinamide and 1-methylnicotinamide levels were quantified by HPLC-MS/MS. Nicotinamide concentration was significantly decrease in the FF of patients with ovarian ageing (p < 0.01), associated by an increase in 1-methylnicotinamide concentration (p = 0.01), leading to a sharp increase of the MNA/NAM ratio (p < 0.001). This ratio negatively correlated with antral follicle count, anti-Mullerian hormone level and the number of oocytes retrieved, while positively correlating with age. Additionally, there was a positive correlation between the ratio values in FF and serum. Our results suggest an imbalance towards the nicotinamide degradation pathway in ovarian ageing, potentially impairing the NAD salvage pathway. They argue in favour of using nicotinamide to counteract ovarian ageing in patients and suggest the assessment of MNA/NAM ratio as a biomarker.