For a generally healthy adult who runs regularly, does supplementation with NAD+ (nicotinamide adenine dinucleotide) precursors such as nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN) improve endurance or performance, and what safe dosing regimen is recommended?

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NAD+ Supplementation for Running Performance

Based on current evidence, NAD+ precursor supplementation (NMN or NR) shows limited and inconsistent benefits for running performance, and you should prioritize proven nutritional strategies like carbohydrate intake (30-60g/hour during runs >1 hour) and proper hydration instead. 1

Evidence for Performance Benefits

Mixed Research Findings

  • One 2021 study in amateur runners showed that NMN supplementation at 600-1200 mg/day for 6 weeks improved aerobic capacity (VO2 and ventilatory thresholds) when combined with regular training, though VO2max itself did not change 2

  • However, a contradictory 2021 study found that 7 days of NR supplementation (1000 mg/day) did not alter substrate metabolism, mitochondrial function, or exercise-induced signaling pathways in skeletal muscle during or after endurance exercise 3

  • The evidence is fundamentally inconsistent, with no clear consensus on whether NAD+ precursors actually improve running performance in healthy adults 4

Mechanism Uncertainty

  • While NAD+ levels decline with age and supplementation can raise NAD+ metabolites in tissues, the clinical evidence that raising NAD+ concentrations improves physiological function remains unclear 4

  • NAD+ depletion is associated with mitochondrial dysfunction and cellular energy deficits, particularly relevant in aging populations 5, but this does not necessarily translate to performance benefits in healthy runners

Safety Concerns

Cardiovascular Risk Signal

  • A 2025 study in atherosclerosis-prone mice found that NMN (300 mg/kg) and NR (230 mg/kg) improved dyslipidemia and fatty liver but promoted atherosclerosis progression 6

  • Lower doses around 100 mg/kg had minimal harmful effects, suggesting dose-dependent cardiovascular risks 6

  • This raises significant safety concerns that have not been adequately addressed in human trials, particularly for long-term use

Tolerability Data

  • Short-term supplementation (6-8 weeks) with NR at 1000 mg/day appears well-tolerated in middle-aged and older adults 7

  • Standard dosing from available formulations: NR 1-2 tablets once or twice daily 8, NMN 2 capsules daily 9

Proven Alternatives for Running Performance

Carbohydrate Strategy (Evidence-Based Priority)

  • Consume 30-60g of carbohydrates per hour during runs exceeding 1 hour through sports drinks, gels, or other sources 1

  • Pre-run: 1-3 g/kg body weight of carbohydrates 3-4 hours before exercise for optimal glycogen availability 1

  • For events >90 minutes: 10-12 g/kg/day carbohydrate loading for 36-48 hours before the event 1, 10

  • Habitual intake of 7-10 g/kg/day maintains fully repleted glycogen stores for regular training 1

Hydration Management

  • Aim to lose no more than 2-3% of body weight during exercise 5, 11

  • Measure body weight before and after long training runs to establish individual hydration needs 5

  • Hypertonic fluids with carbohydrates and sodium improve water absorption efficiency 11

Clinical Recommendation

Do not supplement with NAD+ precursors for running performance. The evidence is too inconsistent to justify use, potential cardiovascular risks exist, and proven nutritional strategies (carbohydrate intake and hydration) have far stronger evidence for improving endurance performance. 1, 2, 3, 6

If You Choose to Supplement Despite Limited Evidence

  • Use the lowest effective dose based on the single positive study: 600 mg/day NMN 2

  • Avoid doses >1000 mg/day given atherosclerosis concerns in animal models 6

  • Supplement for at least 6 weeks while maintaining regular training 2

  • Monitor for any cardiovascular symptoms and discontinue if concerns arise 6

Common Pitfalls to Avoid

  • Do not expect NAD+ supplementation to replace proper carbohydrate fueling strategies 1

  • Do not assume that benefits seen in aging or diseased populations translate to healthy athletes 5, 4

  • Do not ignore the inconsistent research findings—one positive study does not establish efficacy 2, 3

  • Be aware that supplement contamination is a significant concern, with 15-25% of sports supplements potentially containing undeclared substances 11

References

Guideline

Carbohydrate Intake for Endurance Performance

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions.

The journals of gerontology. Series A, Biological sciences and medical sciences, 2023

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Carbohydrate Loading for Marathon Runners

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Beta-Alanine Supplementation for Muscle Endurance

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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