Vitamin

NADH

Nicotinamide adenine dinucleotide (reduced form)

Evidence TierCWADA NOT PROHIBITED

tuneTypical Dose

5–20 mg per day

watchEffect Window

2-4 weeks for chronic fatigue. Acute (hours) for sleep deprivation claims (poorly validated).

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

NADH is the reduced form of NAD, central to mitochondrial energy production and redox balance. It is used for fatigue and mental energy complaints, particularly in chronic fatigue-related contexts.

Small trials suggest reduced fatigue and improved certain cognitive measures in chronic fatigue syndrome and some neurologic settings. Mechanistically, NADH supports electron transport and may influence dopamine synthesis. Minority claims include benefits for jet lag and mood, but data are limited and inconsistent. Effects depend on formulation stability and bioavailability, and replication is limited.

Primary electron donor in mitochondrial Complex I, directly facilitating ATP production via oxidative phosphorylation. Also stimulates endogenous dopamine, norepinephrine, and serotonin synthesis.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Reduced CFS symptom severity in small crossover trial (Forsyth 1999, 31% response vs 8% placebo)

Secondary Outcomes

  • Theoretical cognitive enhancement via mitochondrial ATP production (poorly supported)
  • Parkinson's symptom improvement with IV NADH only (Birkmayer 1993, not translatable to oral)

Safety

Contraindications and Interactions

Contraindications

  • Active mania (theoretical catecholamine overstimulation)

Side effects

  • Nausea
  • GI upset
  • Restlessness
  • Insomnia (if taken late in day)

Interactions

  • Partially redundant with NMN/NR (all boost NAD+ pool)
  • Theoretical additive effect with MAOIs

Avoid if

  • Active mania or severe anxiety states

Evidence

Study-level References

nadh-SRC-001RCT Crossover
Sourceopen_in_new

Forsyth LM, et al. "Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome." Ann Allergy Asthma Immunol. 1999.

Population: Adults with Chronic Fatigue Syndrome

Dose protocol: 10 mg/day

Key findings: 31% of patients responded favorably to NADH (10mg) vs 8% for placebo, showing a significant reduction in CFS symptoms. No adverse effects were reported.

Paper content

31% of patients responded favorably to NADH (10mg) vs 8% for placebo, showing a significant reduction in CFS symptoms. No adverse effects were reported.

nadh-pmid-34444817Prospective, randomized, double-blind, placebo-controlled trial.
Sourceopen_in_new

Castro-Marrero J, Segundo MJ, Lacasa M, Martinez-Martinez A, Sanmartin Sentanes R, Alegre-Martin J. Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Nutrients. 2021;13(8):2658. doi:10.3390/nu13082658. PMID:34444817.

Population: Adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Dose protocol: 200 mg CoQ10 + 20 mg NADH daily for 12 weeks

Key findings: In 207 ME/CFS patients, the combination significantly reduced cognitive fatigue (P<0.001) and overall fatigue (P=0.022), and improved quality of life (P<0.05). Sleep duration and efficiency also improved early.

Notes: Largest placebo-controlled trial of CoQ10+NADH in CFS. Combined formulation prevents isolating NADH-specific contribution.

Paper content

This double-blind RCT enrolled 207 adults with ME/CFS and randomized them to 200 mg CoQ10 plus 20 mg NADH daily or placebo for 12 weeks. The active treatment group showed significant reductions in cognitive fatigue (P<0.001) and overall fatigue (P=0.022) compared with placebo. Health-related quality of life improved on the SF-36 scale (P<0.05), and early improvements in sleep duration (week 4, P=0.018) and sleep efficiency (week 8, P=0.038) were observed. This is the largest placebo-controlled trial of CoQ10 plus NADH in CFS to date. A limitation is that the combined formulation makes it impossible to attribute effects to NADH alone.

nadh-pmid-25386668Randomized, double-blind, placebo-controlled trial.
Sourceopen_in_new

Castro-Marrero J, Cordero MD, Segundo MJ, Saez-Frances N, Calvo N, Roman-Malo L, Aliste L, Fernandez de Sevilla T, Alegre J. Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? Antioxid Redox Signal. 2015;22(8):679-85. doi:10.1089/ars.2014.6181. PMID:25386668.

Population: Spanish adults with chronic fatigue syndrome.

Dose protocol: 200 mg CoQ10 + 20 mg NADH daily for 8 weeks

Key findings: In 73 CFS patients, the combination improved fatigue scores (P<0.05), NAD+/NADH ratio (P<0.001), ATP levels (P<0.05), and reduced lipoperoxides (P<0.05).

Notes: Earlier proof-of-concept trial from the same group. Combined formulation limits attribution to NADH alone.

Paper content

This double-blind RCT enrolled 73 Spanish CFS patients and randomized them to 200 mg CoQ10 plus 20 mg NADH daily or placebo for 8 weeks. The active group showed significant improvement in the fatigue impact scale (P<0.05), NAD+/NADH ratio (P<0.001), ATP levels (P<0.05), citrate synthase activity (P<0.05), and reduced lipoperoxides (P<0.05). This earlier and smaller trial from the same research group provided the initial proof-of-concept data for the CoQ10+NADH combination in CFS. As with the larger follow-up trial, the combined formulation prevents isolating NADH-specific effects.

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