Compound

    NADH

    TL;DR

    The reduced form of NAD+, a coenzyme central to cellular energy production. Early research hints at benefits in chronic fatigue and Parkinson's, but evidence is preliminary and NADH's stability and absorption are problematic.

    Ideal For

    • People with chronic fatigue interested in an experimental but plausibly mechanistic option
    • Biohackers exploring mitochondrial support who accept the limited evidence base

    Avoid If

    • Pregnancy and breastfeeding — safety data insufficient
    • People on dopaminergic drugs or with bipolar mania — theoretical caution

    Frequently Asked Questions

    Overview

    NADH (nicotinamide adenine dinucleotide, reduced form) is the electron-carrying coenzyme at the heart of mitochondrial energy production — it donates electrons to the electron transport chain that generates ATP. Supplemental NADH is marketed for fatigue, cognitive performance, and neurodegenerative disease. The clinical evidence is genuinely early-stage: a small randomized trial in chronic fatigue syndrome found that 10-20 mg/day of stabilized oral NADH reduced symptom severity compared with placebo, and open-label Parkinson's studies from the 1990s suggested motor benefits possibly linked to NADH's role as a cofactor for tyrosine hydroxylase (the rate-limiting enzyme in dopamine synthesis). However, these findings await replication in larger modern trials. A practical challenge is that NADH degrades rapidly when exposed to light, heat, and stomach acid, so enteric-coated, stabilized formulations matter considerably.

    How It Works

    • Serves as the primary electron donor to mitochondrial Complex I, driving ATP production
    • Cofactor for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis
    • Participates in redox reactions that regenerate glutathione and other antioxidants
    • May stimulate endogenous dopamine production, hypothesized basis for Parkinson's effects

    Benefits & Outcomes

    Chronic Fatigue Relief

    Energy
    Mixed evidence
    Limited
    Effectiveness 2/5

    NADH shows promise for chronic fatigue in small trials, generally as an adjunct to CoQ10 rather than alone.

    Health Concerns Addressed

    Chronic Fatigue Syndrome (ME/CFS)

    condition
    Mixed evidence
    Limited
    Effectiveness 3/5

    One small randomized trial found that 10-20 mg/day of stabilized NADH reduced chronic fatigue syndrome symptom severity compared with placebo, and NADH is mechanistically plausible given the mitochondrial dysfunction reported in ME/CFS. However, this remains a single small trial awaiting replication.

    Supporting Research
    11 studies

    Nicotinamide adenine dinucleotide precursors in human health and disease: a systematic review of clinical trials

    Score: 7/10
    2022
    systematic_review

    Sharma C, Donu D, Cen Y

    Oral NAD precursors reliably raise blood NAD+ levels, but trials have failed to show consistent functional benefits.

    View source

    Effect of coenzyme Q10 plus NADH supplementation on fatigue perception and health-related quality of life in myalgic encephalomyelitis/chronic fatigue syndrome

    Score: 7/10
    2021
    rct
    n=207

    Castro-Marrero J, Segundo MJ, Lacasa M

    Eight weeks of CoQ10 plus NADH significantly reduced fatigue perception and improved sleep and quality of life.

    View source

    Effect of nicotinamide riboside on skeletal muscle and metabolic health: a randomized, placebo-controlled trial

    Score: 7/10
    2018
    rct
    n=40

    Dollerup OL, Christensen B, Svart M

    An NAD+ precursor did not improve insulin sensitivity, mitochondrial function or body composition over 12 weeks.

    View source

    Coenzyme Q10 plus NADH supplementation in chronic fatigue syndrome: a randomized controlled trial

    Score: 6/10
    2016
    rct
    n=80

    Castro-Marrero J, Saez-Francas N, Segundo MJ

    CoQ10 plus NADH reduced maximum heart rate during exercise and improved fatigue scores versus placebo.

    View source

    The use of stabilized NADH in chronic fatigue syndrome: a randomized, double-blind, placebo-controlled study

    Score: 4/10
    1999
    crossover
    n=26

    Forsyth LM, Preuss HG, MacDowell AL

    31% of chronic fatigue syndrome patients responded to NADH versus 8% on placebo over four weeks.

    View source

    Effects of NAD+ precursor supplementation on glucose and lipid metabolism in humans: a meta-analysis

    Score: 7/10
    2022
    meta_analysis
    n=14750

    Zhong O, Wang J, Tan Y +1 more

    The main research terms of NAD+ precursors were Nicotinamide Riboside (NR), Nicotinamide Mononucleotide (NMN), Nicotinic Acid (NA), Nicotinamide (NAM).

    View source

    NADH in the treatment of Parkinson's disease: an open-label evaluation of oral and parenteral administration

    Score: 2/10
    1993
    observational
    n=885

    Birkmayer JGD, Vrecko C, Volc D +1 more

    About half of treated Parkinson's patients improved in an uncontrolled open-label NADH evaluation.

    View source

    Effects of Nicotinamide Mononucleotide Supplementation on Muscle and Liver Functions Among the Middle-aged and Elderly: A Systematic Review and Meta-analysis of Randomized Controlled Trials

    Score: 6/10
    2025
    meta_analysis
    n=412

    Wang JP, Wang L, Wang T +1 more

    Based on changes in gait speed (SMD: 0.34 m/s, 95%CI [0.03, 0.66] p = 0.033), NMN had significant effects on muscle mass.

    View source

    Nicotinamide riboside supplementation raises NAD+ and affects sirtuin signalling in humans: a randomized trial

    Score: 7/10
    2018
    rct
    n=24

    Martens CR, Denman BA, Mazzo MR +5 more

    Chronic supplementation with the NAD+ precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD+ metabolism in healthy middle-aged and older adults.

    View source

    The Effect of Nicotinamide Mononucleotide and Riboside on Skeletal Muscle Mass and Function: A Systematic Review and Meta-Analysis

    Score: 9/10
    2025
    meta_analysis

    Prokopidis K, Moriarty F, Bahat G +1 more

    Current evidence does not support NMN and NR supplementation for preserving muscle mass and function in adults with mean age of over 60 years.

    View source

    Effects of Nicotinamide Mononucleotide on Glucose and Lipid Metabolism in Adults: A Systematic Review and Meta-analysis of Randomised Controlled Trials

    Score: 8/10
    2024
    meta_analysis
    n=342

    Chen F, Zhou D, Kong AP +1 more

    Short-term supplementation of NMN of 250-2000 mg/d did not show significantly positive impacts on glucose control and lipid profile.

    View source

    Safety Information

    Potential Side Effects

    {"Mild insomnia or jitteriness at higher doses — take in the morning","Unstabilized products degrade rapidly; enteric-coated blister packs matter","Expensive relative to the strength of evidence"}

    Drug Interactions

    • Levodopa and dopaminergic drugs: theoretical additive effects via tyrosine hydroxylase cofactor activity
    • Stimulants: possible additive alerting effects

    Pregnancy & Breastfeeding

    Pregnancy: insufficient_data

    Breastfeeding: insufficient_data

    Dosage Guidelines

    Dosage Used in Studies

    Consult healthcare provider

    Forms Compared

    Standard research form; protection from stomach acid is essential

    Bypasses stomach degradation; used in some fatigue research

    Clinic-administered; not a supplement and outside oral dosing evidence

    Medical Disclaimer

    The information provided on this website is for educational and informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any supplement regimen.

    Individual results may vary. The statements on this website have not been evaluated by the Food and Drug Administration. Products and information are not intended to diagnose, treat, cure, or prevent any disease.