How do NMN and NR become NAD+? In human trials, both raised blood NAD+
How do NMN and NR become NAD+? In human trials, both raised blood NAD+
What happens to NMN and NR once swallowed? In human trials both raised blood NAD+, comparably in a 2026 head-to-head, and two NMN trials also found better walking results.
Article info
How we made this. Made with AI and checked against every study we cite. It is not medical advice.
Updated:
How we check · Methodology · Is NMN legal in US supplements? · Corrections · How we’re funded
Evidence: 13 studies, 13 in humans.
65
healthy adults took NR, NMN or nicotinamide in a 2026 head-to-head
Two common ways to raise the energy molecule NAD+ are nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR). The useful version is not the molecule you swallow, but the NAD+ it becomes inside the body. In people, both precursors raise the blood NAD+ level, and a 2026 head-to-head found the two did it comparably. Two NMN trials also found better walking results, and one found better sleep scores. Whether a higher blood level shows up as more energy or faster recovery is still an open question.
The short version
- Your cells rebuild most of their own NAD+ from recycled parts. NAD+ cannot be taken directly from food, and one enzyme, NAMPT, is the key step in rebuilding it (Navas 2021, a review; Zhang 2025, a review).
- NMN and NR are two NAD+ precursors. In human trials, both raise the blood NAD+ level (Yi 2023, Pencina 2023, Orr 2024).
- In a 2026 randomized head-to-head of 65 healthy adults, 14 days of NR or NMN raised blood NAD+ by a comparable amount, while plain nicotinamide did not (Christen 2026).
- Two NMN trials also found functional gains over placebo: longer six-minute walks in 80 middle-aged adults (Yi 2023), and a faster 4-meter walk and better sleep scores in 60 older adults (Morifuji 2024). Two NR trials in people with mild cognitive impairment raised blood NAD+ but did not improve cognition (Orr 2024, Martens 2026).
- A review of the human trials finds the effect is smaller than earlier lab work predicted, and the gut makes it more complicated (Yaku 2023).
Show the scienceHow it works
How it works
NAD+ sits at the center of energy metabolism. NAD+ and its partner NADH are swapped back and forth in the cell’s main energy-making reactions, such as glycolysis, the TCA cycle and oxidative phosphorylation (Navas 2021, a review). The enzyme NAMPT is a key rate-limiting step in rebuilding a cell’s NAD+ pool (Zhang 2025, a review).
The cell recycles rather than imports. NAD+ cannot be taken directly from food. Instead, NAMPT recovers NAD+ from nicotinamide, and this recycling generates most of the cell’s NAD+ (Navas 2021, a review). That is why precursors are the way supplements try to raise it.
The two precursors can take different routes. NR and NMN both end up as NAD+, but they can behave differently in the body, and where each one goes depends on the tissue and on the enzymes and transporters it has (Yoshino 2018, a review).
- NMN itself reaches the blood: in a trial of 32 adults aged 55 to 80, 1,000 mg of NMN once or twice a day for 14 days raised blood NMN, and blood NAD+ rose in a dose-related way (Pencina 2023).
- The gut adds a second route. In the 2026 head-to-head, lab tests with human gut bacteria found that NR and NMN both give rise to nicotinic acid, and nicotinic acid was a potent NAD+ booster in blood samples. The authors propose that NR and NMN raise blood NAD+ mainly through this gut-dependent route, the Preiss-Handler pathway, rather than the recycling loop (Christen 2026). That route has been shown in the lab, not yet inside the body.
Why the tissue matters. The NAMPT recycling loop helps sustain NAD+ especially in high-energy tissues such as skeletal muscle, and a review discusses exercise and NAD+ boosters as ways to support it (Su 2024). The level the trials measure, however, is the blood.
Figure 1. NMN sits one step from NAD+ in the salvage pathway, the main route cells use to keep NAD+ topped up.
Source: Covarrubias et al., Nature Reviews Molecular Cell Biology, 2021 (PubMed 33353981).
What the trials measured
Blood NAD+ is the reliable finding. In a randomized trial of 80 healthy middle-aged adults taking 300, 600 or 900 mg of NMN by mouth for 60 days, blood NAD+ rose at every dose versus placebo at days 30 and 60, highest at 600 and 900 mg (Yi 2023). In the same trial, six-minute walking distance rose more than with placebo at every dose, general health scores were better, and a blood-based biological age measure stayed unchanged with NMN while it rose with placebo (Yi 2023). In 32 overweight or obese adults aged 55 to 80, 1,000 mg of NMN once or twice a day for 14 days brought substantial, dose-related rises in blood NAD+ (Pencina 2023).
Both precursors, about equal. The 2026 head-to-head is the closest thing to an NR-versus-NMN answer yet. In 65 healthy adults over 14 days, NR and NMN raised blood NAD+ comparably; nicotinamide did not raise it over the two weeks, and only nicotinamide had a short-lived effect on the blood NAD+ profile right after it was taken (Christen 2026).
Walking and sleep. A randomized trial of 60 older adults found 250 mg of NMN a day for 12 weeks raised blood NAD+, gave a faster 4-meter walk than placebo and improved sleep quality scores; a stepping test did not differ (Morifuji 2024).
Higher doses of NR. In 20 older adults with mild cognitive impairment, NR built up to 1 gram a day for 10 weeks raised blood NAD+ 2.6-fold, and an exploratory analysis found a modest drop in epigenetic age; cognition stayed stable (Orr 2024). In 42 adults with amnestic mild cognitive impairment, 12 weeks of NR raised blood NAD+ twofold but did not improve cognitive function, total blood flow to the brain or blood pressure (Martens 2026). In a four-week safety trial in 20 people with Parkinson’s disease, 1,500 mg of NR twice a day raised blood NAD+ up to fivefold, with no moderate or severe adverse events (Berven 2023).
Muscle. In a five-month study of 20 identical twin pairs, NR at 250 to 1,000 mg a day raised muscle mitochondrial number and changed NAD+ metabolism and gut bacteria, but did not improve body fat or metabolic health (Lapatto 2023).
One caveat. Across the field, oral NR and NMN are safe and raise NAD+ in people, but the effect has been smaller than the earlier lab work predicted, and the gut microbiome adds complexity (Yaku 2023).
Figure 2. NAD+ is a helper molecule for energy metabolism and a fuel for enzymes that maintain cells; several of those enzymes use it up as they work.
Source: Covarrubias et al., Nature Reviews Molecular Cell Biology, 2021 (PubMed 33353981).
Next step
If you would rather see the numbers for yourself, the dose story walks through how far blood NAD+ rose with each dose the trials tested. Read Does a bigger NMN dose raise NAD+ more? next.
Blood NAD+, walking and sleep in human NR and NMN trials
- Blood NAD+ (NR)Large improvement · Orr 2024
- Walking distance (NMN)Unclear · Yi 2023
- Sleep quality (NMN)Unclear · Morifuji 2024
Figure 3. What the trials found for each outcome, as each study's abstract reports it. A bar to the right of the centre line shows the size of the improvement the study reported; a dot on the line means no measurable change.
Source: Healthspan Post summary of the cited studies (PubMed).
Show the scienceStudy-by-study table: 13 studies, design, dose and grade
The evidence
Every study cited in this article. Grades: A human RCT or meta-analysis; B small, pilot or observational human study; C animal or cell study.
| Study | Design | People | Dose / duration | Result | Grade | Source |
|---|---|---|---|---|---|---|
| Christen 2026[1] | RCT | 65 healthy adultsn = 65 | NR, NMN or nicotinamide; amounts not reported14 days | NR and NMN, but not nicotinamide, comparably raised blood NAD+; only nicotinamide had a short-lived acute effect. In lab tests with human gut bacteria, NR and NMN gave rise to nicotinic acid, a potent NAD+ booster in blood samples. | A | PubMed 41540253 |
| Yi 2023[2] | RCT | 80 healthy middle-aged adultsn = 80 | 300, 600 or 900 mg NMN/day60 days | Blood NAD+ rose in every NMN group versus placebo at days 30 and 60, highest at 600 and 900 mg; six-minute walking distance and general health scores rose versus placebo; blood biological age rose with placebo and stayed unchanged with NMN; no HOMA-IR change; well tolerated. | A | PubMed 36482258 |
| Morifuji 2024[3] | RCT | 60 older adultsn = 60 | 250 mg NMN/day12 weeks | Blood NAD+ and its metabolites were higher at 12 weeks; the 4-meter walk was faster and sleep quality improved versus placebo; the stepping test did not differ. | A | PubMed 38789831 |
| Berven 2023[4] | RCT | 20 people with Parkinson's diseasen = 20 | 1500 mg NR twice daily4 weeks | Blood NAD+ rose up to fivefold; well tolerated, with no moderate or severe adverse events. | A | PubMed 38016950 |
| Orr 2024[5] | RCT | 20 older adults with mild cognitive impairmentn = 20 | NR escalated to 1 g/day10 weeks | Blood NAD+ rose 2.6-fold; cognition (MoCA) and other neurocognitive and psychometric measures stayed stable; an exploratory analysis found a modest drop in epigenetic age. | A | PubMed 37994989 |
| Pencina 2023[6] | RCT | 32 overweight or obese adults, 55-80 yearsn = 32 | 1000 mg NMN (MIB-626) once or twice daily14 days | Blood NMN rose, blood NAD+ showed substantial dose-related increases and blood NAD metabolites rose; very little unmodified NMN was excreted in the urine; well tolerated. | A | PubMed 35182418 |
| Martens 2026[7] | RCT | 42 adults with amnestic mild cognitive impairmentn = 42 | not reported12 weeks | Blood NAD+ rose twofold in the NR group; no improvement in cognitive function, total cerebral blood flow or blood pressure. | A | PubMed 42478598 |
| Lapatto 2023[8] | pilot | 40 adults (20 BMI-discordant identical twin pairs)n = 40 | 250 to 1000 mg NR/day, escalating5 months | NR improved systemic NAD+ metabolism, muscle mitochondrial number, myoblast differentiation and gut microbiota in both twins; it did not improve adiposity or metabolic health. | B | PubMed 36638183 |
| Navas 2021[9] | review | not reportedn = not reported | not reportednot reported | NAD+ and NADH work together in energy metabolism; because NAD+ cannot be taken directly from food, NAMPT recovers it from nicotinamide and generates most of the cell's NAD+. | B | PubMed 33384409 |
| Zhang 2025[10] | review | not reportedn = not reported | not reportednot reported | NAMPT is a key rate-limiting enzyme in NAD+ synthesis and regulates how the cell regenerates NAD+. | B | PubMed 40775221 |
| Yoshino 2018[11] | review | not reportedn = not reported | not reportednot reported | NMN and NR can behave differently; their fates depend on the tissue and its NAD+-making enzymes, nucleotidases and transporters. | B | PubMed 29249689 |
| Su 2024[12] | review | not reportedn = not reported | not reportednot reported | The NAMPT-driven salvage pathway helps sustain NAD+ especially in high-energy tissues such as skeletal muscle; the review discusses exercise and NAD+ boosters as ways to enhance it. | B | PubMed 39372950 |
| Yaku 2023[13] | review | not reportedn = not reported | not reportednot reported | Oral NR and NMN are safe and significantly raise NAD+ in people, but the effect is lower than preclinical results predicted, and host-gut microbiota adds complexity. | B | PubMed 37335049 |
References
- Christen S, Redeuil K, Goulet L, et al. (2026). The differential impact of three different NAD+ boosters on circulatory NAD and microbial metabolism in humans. Nat Metab. PubMed 41540253
- Yi L, Maier AB, Tao R, et al. (2023). The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Geroscience. PubMed 36482258
- Morifuji M, Higashi S, Ebihara S, et al. (2024). Ingestion of β-nicotinamide mononucleotide increased blood NAD levels, maintained walking speed, and improved sleep quality in older adults in a double-blind randomized, placebo-controlled study. Geroscience. PubMed 38789831
- Berven H, Kverneng S, Sheard E, et al. (2023). NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease. Nat Commun. PubMed 38016950
- Orr ME, Kotkowski E, Ramirez P, et al. (2024). A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment. Geroscience. PubMed 37994989
- Pencina KM, Lavu S, Dos Santos M, et al. (2023). MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults. J Gerontol A Biol Sci Med Sci. PubMed 35182418
- Martens CR, Decker KP, DeConne TM, et al. (2026). A phase-II randomized controlled pilot study of nicotinamide riboside supplementation in older adults with amnestic mild cognitive impairment. Alzheimers Dement. PubMed 42478598
- Lapatto HAK, Kuusela M, Heikkinen A, et al. (2023). Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study. Sci Adv. PubMed 36638183
- Navas LE, Carnero A (2021). NAD+ metabolism, stemness, the immune response, and cancer. Signal Transduct Target Ther. PubMed 33384409
- Zhang W, Ren H, Chen W, et al. (2025). Nicotinamide phosphoribosyltransferase in NAD+ metabolism: physiological and pathophysiological implications. Cell Death Discov. PubMed 40775221
- Yoshino J, Baur JA, Imai SI (2018). NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metab. PubMed 29249689
- Su M, Qiu F, Li Y, et al. (2024). Mechanisms of the NAD+ salvage pathway in enhancing skeletal muscle function. Front Cell Dev Biol. PubMed 39372950
- Yaku K, Nakagawa T (2023). NAD+ Precursors in Human Health and Disease: Current Status and Future Prospects. Antioxid Redox Signal. PubMed 37335049


