Nicotinamide riboside and pterostilbene reduces frequency and severity of undesirable symptoms of the menopause transition: an open-label, pilot clinical trial

Introduction Nicotinamide adenine dinucleotide (NAD+) is a metabolite of vitamin B3 necessary for the production of key hormones like estradiol. Both NAD+ and estradiol levels decrease with age. Reduced estradiol levels have been associated with undesirable symptoms of the menopause transition. Previous clinical trials have demonstrated that oral supplementation with NRPT, a combination of the NAD+ precursor nicotinamide riboside (NR) plus pterostilbene (PT), significantly increases NAD+ levels. In the present study, the effects of a 7-day supplementation of NRPT on undesirable symptoms of the menopause transition were examined. Methods An open-label, pilot clinical trial ( ClinicalTrials.gov identifier NCT04841499) was conducted to assess the efficacy of NRPT supplementation (commercially known as Basis; a combination of nicotinamide riboside and pterostilbene) in 40 healthy women over 35 years of age, 32 of which self-reported symptoms associated with the menopause transition (MS group) and eight women who were not experiencing any (or minimal) symptoms associated with menopause (No-MS group). All 40 women were given the recommended dose of NRPT (250 mg NR and 50 mg PT) daily for 7 days. A menopausal symptom survey was taken at baseline and at the end of the 7-day intervention. Urine was also collected at baseline and after 7 days to assess levels of estrone (E1) and estradiol (E2) and the changes in the vitamin B3 catabolome stemming from NRPT supplementation. Results At the end of the study, significant decreases in both the frequency and magnitude of bloating, hot flashes, and poor sleep were reported in the MS group as compared to baseline. This was accompanied by a significant increase in the E2/E1 ratio. The No-MS group did not report any significant changes in these endpoints. As anticipated NRPT intake significantly increased urinary levels of methyl-nicotinamide (Me-NAM) as well as the methylated pyridone carboxamides (Me-PYs) in all groups. A significant time x menopausal status interaction was observed for nicotinuric acid (NUA). No other significant changes occurred for the other nicotinamide catabolites, such as nicotinamide N-oxide (NAM-N-Oxide), and a newly characterized NAD + catabolite, N-methyl-nicotinuric acid (Me-NUA). Discussion This study demonstrates that NRPT is effective in significantly decreasing the frequency and magnitude of undesirable symptoms of the menopause transition and significantly increases the E2/E1 ratio in menopausal women.