NADH and NAD+ are two forms of the same molecule, nicotinamide adenine dinucleotide. One takes up electrons, the other gives them away: this exchange powers energy production in every cell. NADH is also sold as a supplement, often with promises broader than the evidence. Here is what distinguishes NAD+ from NADH, what their ratio reveals and what NADH supplement studies actually show.
Key takeaways
- NADH is the reduced form of NAD+: it carries two electrons, delivering them to mitochondria to make ATP.
- The NAD+/NADH ratio indicates the cell's state; alcohol, for example, lowers it in the liver.
- NADH is fragile: degradation speeds up as conditions become more acidic or warmer.
- Small, short NADH supplement trials mainly involved chronic fatigue, with inconsistent results.
NAD+ and NADH: two forms of one molecule
NAD+ is the oxidised form, ready to accept electrons. Receiving two electrons and one proton turns it into NADH, the reduced form. NADH then transfers those electrons to another molecule, becoming NAD+ again.
Both coexist and continuously interchange: together they make up the cell's NAD pool. Other roles, synthesis and age-related changes are explained in our article on what NAD+ is and why it declines with age.
What does “NADH + H+” mean?
During the reaction, the molecule broken down (a sugar, fatty acid…) loses two electrons and two protons. NAD+ takes up both electrons and only one proton; the other remains free. That is why textbooks often write “NADH + H+”: it is the same NADH molecule.
What about NADPH?
Around 10% of NAD+ is converted into NADP+, whose reduced form NADPH has other tasks. It provides electrons for synthesis and antioxidant defences, particularly recycling glutathione, for which NAC is a precursor. NADH and NADPH are not interchangeable.
| Feature | NAD+ | NADH |
|---|---|---|
| Form | Oxidised | Reduced |
| Role | Accepts two electrons | Donates them |
| Where it acts | Glycolysis, Krebs cycle, fat breakdown | Mitochondrial respiratory chain |
| Used by sirtuins and PARPs | Yes | No |
| As a supplement | Through precursors (NR, NMN, B3) | NADH capsules or tablets |
What is NADH's role in energy production?
NADH transports electrons released by food breakdown to the machinery making ATP. For one glucose molecule, glycolysis produces two NADH in the cytoplasm. Pyruvate conversion and the Krebs cycle then produce eight in mitochondria, ten in total.
NADH delivers electrons to respiratory chain complex I. Their passage between complexes pumps protons across the mitochondrial membrane, and this flow drives ATP synthase. Each NADH thereby enables around 2.5 ATP molecules to be made.
Two special cases: shuttles and lactate
NADH made in the cytoplasm cannot cross the inner mitochondrial membrane. Only its electrons pass via two shuttles: malate–aspartate transfers them to mitochondrial NADH, glycerol-3-phosphate to FADH2, yielding less ATP.
When glycolysis runs faster than mitochondria, lactate dehydrogenase reoxidises NADH to NAD+ by converting pyruvate to lactate. This allows glycolysis to continue.
The NAD+/NADH ratio: an indicator of cellular state
The ratio indicates whether the cell leans towards oxidation or reduction. It varies by compartment. In well-fed rat liver, around 725 free NAD+ molecules occur per free NADH in cytoplasm, versus around eight to one in mitochondria.
These figures concern free forms: much NADH is protein-bound, complicating measurements. The ratio changes with metabolic state. It falls during fasting in rat liver and during alcohol breakdown, whose enzymes convert NAD+ into NADH. In the human brain, it declines with age while NADH increases.
NADH supplements: how strong are claimed benefits?
A fragile molecule
NADH tolerates acidity poorly. Laboratory measurements show faster degradation in more acidic and warmer conditions. Stomach passage is therefore an obstacle, explaining forms designed to limit acid exposure, enteric-coated or delayed-release, whose technologies we compare in our article on capsules and their shells. Hexagon® NADH 25mg is offered as delayed-release capsules.
Absorption remains scarcely documented in humans. Food NAD and NADP are known to be transformed into nicotinamide in the intestine before absorption. Some swallowed NADH probably undergoes the same process, but to our knowledge the proportion reaching cells intact has never been measured.
Human trials
A handful of trials tested 10 to 20mg NADH daily, almost all in patients. The table summarises the main ones.
| Trial | Participants | Dose and duration | Main result |
|---|---|---|---|
| Forsyth, 1999 | 26 patients, chronic fatigue | 10mg/day, 4 weeks | 31% responders versus 8% with placebo |
| Alegre, 2010 | 77 patients, chronic fatigue | 20mg/day, 2 months | No difference on most outcomes |
| Castro-Marrero, 2015 | 73 patients, chronic fatigue | 20mg + 200mg CoQ10, 8 weeks | Fatigue reduced compared with placebo |
| Castro-Marrero, 2021 | 207 patients, chronic fatigue | 20mg + 200mg CoQ10, 12 weeks | Fatigue: progression parallel to placebo |
| Demarin, 2004 | 26 patients, Alzheimer's disease | 10mg/day, 6 months | Better global score, memory unchanged |
These trials share limitations: small samples, short durations, questionnaires sometimes designed by the researchers themselves, and results not confirmed across trials. In the largest, only 144 of 207 participants completed it. Tablets were manufactured and supplied by a company paying the lead author, while placebo contained vitamin C and phosphatidylserine, potentially clouding comparison according to the authors.
A 2017 systematic review concluded that evidence remains insufficient to use supplements, including NADH, for chronic fatigue symptoms. In Parkinson's disease, small case series sparked interest, but a placebo-controlled trial showed no clear benefit and a review considered recommendations premature.
NADH has no authorised EU health claim; only niacin (vitamin B3), from which it derives, has claims such as “niacin contributes to normal energy-yielding metabolism”. These results in patients at 10 to 20mg daily apply neither to a specific supplement nor healthy people.
NADH or NAD+ precursors: two different approaches
Taking NADH directly supplies the reduced form in the hope it reaches cells. NAD+ precursors such as nicotinamide riboside follow a different approach: supplying building blocks for cells to make their own NAD+, which they reduce into NADH as needed.
To our knowledge, no trial directly compared the approaches. More extensive precursor data appear in our guide on studied ways to increase NAD+.
Frequently asked questions
Is NADH an oxidant or reductant?
A reductant. A reductant donates electrons, which is NADH's role. In the NAD+/NADH pair, NAD+ is the oxidant because it accepts them: this is oxidation–reduction.
Why is one NADH sometimes said to yield three ATP?
This is an older rounded value still in some textbooks. The most reliable measurements give around 2.5 ATP per NADH, as making one ATP requires a non-integer number of protons. A slightly lower value, around 2.3, is even possible.
What is the difference between NADH and FADH2?
Both are electron carriers produced by food breakdown. NADH supplies respiratory complex I; FADH2 supplies complex II, bypassing I. Its electrons therefore pump fewer protons: around 1.5 ATP per FADH2 versus 2.5 per NADH.
When was NADH taken in trials?
In the 1999 trial, 10mg was taken fasting with water forty-five minutes before breakfast. To our knowledge, no study compared intake times: following the label remains the rule.
Is NADH dangerous?
Trials identified no danger at studied doses, but are small. The 1999 trial reported no serious adverse effects at 10mg daily. In 2021, withdrawals for adverse effects, mainly stomach pain and dizziness, were slightly more frequent with placebo (11) than NADH plus coenzyme Q10 (8). Long-term safety data remain very limited.
Should NADH and coenzyme Q10 be combined?
Several chronic fatigue trials tested the duo without determining which acted because both were given together. The combination is theoretically coherent, both participating in the respiratory chain, but no clear benefit has been proved.
Does NADH raise NAD+?
It is not really known. In the 2015 trial, the blood-cell NAD+/NADH ratio was higher after eight weeks of NADH plus coenzyme Q10 than placebo. But to our knowledge no study showed swallowed NADH raising tissue NAD+.
Conclusion
NAD+ and NADH are two sides of the same system: NAD+ accepts electrons released by food breakdown, NADH delivers them to mitochondria to make ATP. Their ratio reflects cellular state and varies with compartment, fasting, alcohol or age. As a supplement, NADH remains fragile, with poorly understood absorption and small, mainly chronic-fatigue trials producing inconsistent results.
Sources
- Xie N et al. (2020). NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduction and Targeted Therapy, 5(1), 227. doi:10.1038/s41392-020-00311-7
- Hinkle PC (2005). P/O ratios of mitochondrial oxidative phosphorylation. Biochimica et Biophysica Acta, 1706(1-2), 1-11. doi:10.1016/j.bbabio.2004.09.004
- Williamson DH, Lund P, Krebs HA (1967). The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver. Biochemical Journal, 103(2), 514-527. doi:10.1042/bj1030514
- Zhu XH et al. (2015). In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proceedings of the National Academy of Sciences, 112(9), 2876-2881. doi:10.1073/pnas.1417921112
- Wu JT, Wu LH, Knight JA (1986). Stability of NADPH: effect of various factors on the kinetics of degradation. Clinical Chemistry, 32(2), 314-319. doi:10.1093/clinchem/32.2.314
- NIH Office of Dietary Supplements (2022). Niacin – Fact Sheet for Health Professionals. ods.od.nih.gov
- Regulation (EU) No 432/2012 establishing a list of permitted health claims made on foods. eur-lex.europa.eu
- Forsyth LM et al. (1999). Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Annals of Allergy, Asthma & Immunology, 82(2), 185-191. doi:10.1016/S1081-1206(10)62595-1
- Alegre J et al. (2010). Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome (article in Spanish). Revista Clínica Española, 210(6), 284-288. doi:10.1016/j.rce.2009.09.015
- Castro-Marrero J et al. (2015). Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? Antioxidants & Redox Signaling, 22(8), 679-685. doi:10.1089/ars.2014.6181
- Castro-Marrero J et al. (2021). 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: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients, 13(8), 2658. doi:10.3390/nu13082658
- Campagnolo N et al. (2017). Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review. Journal of Human Nutrition and Dietetics, 30(3), 247-259. doi:10.1111/jhn.12435
- Demarin V et al. (2004). Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study. Drugs under Experimental and Clinical Research, 30(1), 27-33. PubMed 15134388
- Swerdlow RH (1998). Is NADH effective in the treatment of Parkinson's disease? Drugs & Aging, 13(4), 263-268. doi:10.2165/00002512-199813040-00002
Food supplements do not replace a varied, balanced diet or a healthy lifestyle. Ask a healthcare professional for advice if you are taking medication, pregnant or breastfeeding.
