NAD+

NMN, NAD+ &
Aging

NMN supplementation significantly increases NAD+ levels in postmenopausal women, improving muscle insulin sensitivity and energy markers, published in Science.

Study
summary

This pioneering study by Yoshino et al. (2021), published in Science, one of the most prestigious journals in the world, is the first randomized scientific trial to demonstrate in humans that oral supplementation with NMN (nicotinamide mononucleotide) significantly increases NAD+ levels in muscle tissue.

NAD+ (nicotinamide adenine dinucleotide) is a fundamental coenzyme present in all living cells, central to energy metabolism, DNA repair and the regulation of sirtuins, proteins linked to longevity. Its levels decline by 40 to 60% between ages 20 and 60.

This trial represents a decisive human proof of concept after years of promising results in animal models, paving the way for targeted supplementation strategies to counteract age-related energy decline.

Bibliographic information
  • Journal Science (impact factor 63)
  • Authors Yoshino et al. (Washington Univ.)
  • Year 2021
  • DOI 10.1126/science.abe9985
  • Type Double-blind randomized controlled trial
Natural NAD+ decline
-40 to -60%
Drop in NAD+ levels between ages 20 and 60, one of the major causes of age-related energy decline
Methodology

Study design

Design & population

Double-blind placebo-controlled RCT. 25 postmenopausal women (55–70 years) slightly overweight with prediabetes. 2 arms: NMN 250 mg/day for 10 weeks vs identical placebo. Muscle biopsies before and after.

Metabolic measurements

NAD+ levels and metabolites by mass spectrometry in muscle biopsies. Hyperinsulinemic-euglycemic clamp to measure insulin sensitivity. DXA scan for body composition. VO2max by ergospirometry.

Genomic analyses

RNA-seq on muscle tissue to analyze transcriptomic changes induced by NMN. Identification of activated metabolic pathways: SIRT1/SIRT3, PGC-1α, mitochondrial respiratory chain, insulin/IGF-1 signaling pathways.

Safety & tolerance

Weekly monitoring: CBC, hepatic, renal, lipid panels. Digestive tolerance questionnaires. No discontinuation of treatment due to side effects. Safety profile evaluated in all 25 participants.

Results

Key results

+38%
Increase in intramuscular NAD+ levels after 10 weeks of NMN supplementation 250 mg/day
+25%
Improvement in muscle insulin sensitivity measured by euglycemic clamp, improved glucose metabolism
SIRT1↑
Activation of sirtuin 1 (SIRT1), enzyme of longevity and DNA repair, confirmed by RNA-seq
PGC-1α↑
Activation of PGC-1α, master regulator of mitochondrial biogenesis, increased number of muscle mitochondria
0 serious AE
No serious adverse events reported, excellent tolerance of NMN at 250 mg/day over 10 weeks

Scientific relevance
for our patients

This study published in Science marks a turning point in preventive aging medicine. For the first time in humans, it is demonstrated that simple oral supplementation can significantly raise NAD+ levels in target tissues, translating concretely into an improvement in energy metabolism comparable to that observed with regular physical exercise.

The 25% improvement in muscle insulin sensitivity is particularly important for our patients aged 45+: muscle insulin resistance is one of the first signs of metabolic aging, preceding type 2 diabetes by several decades. By correcting it via the restoration of NAD+, we act on a fundamental mechanism of aging, not on a symptom.

Activation of SIRT1 and PGC-1α is the signal that NMN does not just "fill" the NAD+ reservoir, it activates a cascade of cellular maintenance processes: DNA repair, mitochondrial biogenesis, epigenetic regulation. These mechanisms are at the heart of our regenerative medicine approach.

We integrate NMN into our micronutrition protocols after a complete biological assessment (NAD+ measurement, metabolic panel, epigenetic biological age) to personalize dosage and optimize efficacy according to each patient's profile.

Patient profiles concerned
  • Women and men 45+ seeking to slow metabolic aging
  • Patients with prediabetes or insulin resistance
  • Unexplained chronic fatigue of metabolic origin
  • Athletes wanting to optimize recovery and endurance
  • Preventive approach to age-related cognitive and physical decline
Micronutrition protocol
NMN 250–500 mg/day
Personalized dosage after NAD+ assessment. Take in the morning on an empty stomach for optimal absorption. Biological follow-up at 3 months.
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