Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial.

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• As we age, NAM levels decline, which could have a negative effect on cardiovascular health.
• Middle-aged adults may like to consider NMN supplementation to improve NAM metabolism and arterial stiffness.
• However, without data on CVD events, it is difficult to determine actual risk reductions.

Introduction

• Nicotinamide adenine dinucleotide (NAD+) is a coenzyme involved in metabolism. When we age, NAD+ levels decline resulting in poorer metabolism and age-related disease such as cardiovascular disease (CVD). Nicotinamide mononucleotide (NMN) is a precursor in the biosynthesis of NAD+.
• This double-blind, randomised control trial aimed to determine the effect of supplementing NMN on NAD+ levels, CVD risk factors and sirtuin 1 (SIRT1) expression, which relies on NAD+ for adequate functioning.

Methods

• 36 healthy male and female individuals aged between 40-65 years of age were assigned to either NMN (125mg/day) or placebo for 12 weeks.
• One capsule was taken twice per day after meals.
• Serum nicotinamide (NAM), NAD+, NMN, advanced glycation end products (AGES), 8-hydroxydeoxyguanosine (8-OHdG) and SIRT1 mRNA expression were measured.
• The condition of blood vessels (arterial stiffness) was also assessed using the ankle brachial index (ABI).
• In a sub-analysis, individuals with hypertension, above average body mass index (BMI), or blood glucose level were also assessed for blood vessel condition using the ABI.

Results

• The results showed that from baseline serum NAM decreased in the placebo group (P=0.014), whereas it increased in the NMN group (P=0.006). This resulted in an increase in the NMN group compared to placebo (P=0.037).
• Interestingly serum NAM was lower in the NMN group compared to placebo at baseline (P=0.001).
• There was no statistically significant difference in ABI with NMN supplementation.
• Amongst those with hypertension there was also no change in ABI. However, those with high BMI or blood glucose, there was an improvement in vascular condition compared to placebo (P=<0.007 and P=0.019 respectively).
• 8-OHdG, SIRT1 mRNA and AGEs remained unchanged by NMN supplementation

Conclusion

• NMN supplementation enhanced NAD+ metabolism in middle-aged adults.
• It also relieved arterial stiffness and reduced CVD risk factors.

• Apparently healthy middle-aged adults who would like to activate NAD metabolism and decrease their risk for CVD, should consider 12-week supplementation with NMN (125mg/day).
• ABI should be monitored to ensure desired effects.
• It is unclear as to the effects of NMN supplementation after 12-weeks.

• Future research should consider longer supplementation duration and/or adding in a follow-up period to determine duration of effect.
• Different supplemental doses should also be researched to determine an optimal dose.