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What Is NMN?
NMN (Nicotinamide Mononucleotide) is a nucleotide derived from ribose and nicotinamide. It is a direct and potent precursor to NAD+ (nicotinamide adenine dinucleotide), requiring only one enzymatic step for conversion. NMN is found naturally in small amounts in various foods including broccoli, cabbage, cucumber, edamame, and avocado.
NMN has become one of the most studied compounds in longevity research, particularly through the work of Dr. David Sinclair at Harvard Medical School and Dr. Shin-ichiro Imai at Washington University.
Key Characteristics
- Bioavailability: Rapidly absorbed and converted to NAD+
- Transport: Uses Slc12a8 transporter in gut
- Safety: Well-tolerated in human trials to date
- Research Status: Multiple ongoing clinical trials
How NMN Works
NAD+ Biosynthesis Pathway
NMN is converted to NAD+ through the salvage pathway:
- NMN is absorbed in the gut (or enters cells)
- NMNAT enzymes (NMNAT1, 2, 3) convert NMN to NAD+
- NAD+ is then available for cellular processes
- NAD+ is consumed, producing nicotinamide (NAM)
- NAM is recycled back to NMN via NAMPT enzyme
Tissue Distribution
Studies show NMN supplementation increases NAD+ in multiple tissues:
- Liver — highest accumulation
- Skeletal muscle
- Brain (crosses blood-brain barrier)
- Heart
- Kidney
- White adipose tissue
Research Findings
Animal Studies
Extensive preclinical research has demonstrated:
Metabolic Benefits
- Improved insulin sensitivity in aged and diabetic mice
- Enhanced glucose tolerance
- Reduced weight gain on high-fat diets
- Increased energy expenditure
Physical Function
- Improved exercise capacity and endurance
- Enhanced muscle function in aged animals
- Better mitochondrial function
- Increased blood flow via improved vascular function
Cognitive Function
- Preserved memory in aging models
- Protected against neurodegeneration
- Improved cerebral blood flow
- Reduced neuroinflammation
Cardiovascular
- Protected against heart failure in mouse models
- Improved cardiac function after ischemia
- Reversed vascular aging
Human Clinical Trials
NMN has moved into human research with promising early results:
| Study | Participants | Findings | Year |
|---|---|---|---|
| First-in-human safety | 10 healthy men | Safe, well-tolerated single doses up to 500mg | 2020 |
| Washington Univ. | 25 postmenopausal women | Improved muscle insulin sensitivity | 2021 |
| Exercise study | 48 runners | Enhanced aerobic capacity | 2021 |
| Sleep study | 108 adults | Reduced drowsiness, improved physical performance | 2022 |
Key Published Research
| Year | Focus | Key Finding | Reference |
|---|---|---|---|
| 2016 | Long-term effects | 12-month NMN improved health in aged mice | Mills et al., Cell Metabolism |
| 2018 | Vascular aging | NMN reversed vascular dysfunction | Das et al., Cell |
| 2019 | Transport | Identified Slc12a8 as NMN transporter | Grozio et al., Nature Metabolism |
| 2021 | Human muscle | Improved muscle insulin action | Yoshino et al., Science |
| 2022 | Bioavailability | Confirmed NAD+ increase in humans | Multiple studies |
NMN vs Other NAD+ Precursors
Comparison
- NMN vs NR: NMN is one step closer to NAD+; may have different tissue distribution
- NMN vs Niacin: Niacin causes flushing; NMN does not
- NMN vs Nicotinamide: High-dose nicotinamide may inhibit sirtuins; NMN doesn't
- Stability: NMN is relatively stable in proper storage conditions
Dosing in Research
Typical doses used in human studies:
- Range: 250mg - 1200mg daily
- Common dose: 250-500mg daily
- Timing: Often taken in the morning
- Duration: Studies range from single dose to 12+ weeks
Regulatory Status
NMN is sold as a dietary supplement in many countries. The FDA has raised questions about its supplement status in the US due to ongoing drug investigations. NMN is not approved as a drug for any condition. Long-term safety in humans is still being established through ongoing research.
Summary
NMN represents one of the most exciting and well-researched compounds in the longevity field. Its ability to raise NAD+ levels, combined with promising data from both animal studies and early human trials, has generated significant scientific and public interest. As more clinical trials complete, we'll gain clearer understanding of NMN's potential benefits and optimal use in humans.