NR and the Heart: What the Animal, Pharmacokinetic and Human Data Show

This is a Mt. Angel Vitamins company white paper, not a peer-reviewed article. It asks whether nicotinamide riboside (NR) helps the heart. Mouse heart studies are mostly positive. Human trials that measured heart, blood vessel or blood pressure outcomes are small and mostly null, and none tested heart events. NR reliably raises blood NAD in people. Searched PubMed on 22 October 2026.

If you're not a researcher

  • Does NR help the heart? Nobody has shown it in people yet. Mouse heart-failure studies are mostly positive, and small human trials mostly found nothing on heart, blood vessel or blood pressure outcomes [1, 2, 14, 15].
  • The surprise: in one mouse model of artery disease, high-dose NR made plaques bigger, not smaller [4].
  • The larger of the two human heart-failure studies (30 patients, 12 weeks) was built to test safety. Its authors could not draw conclusions about heart function [12].
  • A 6-week blood pressure trial in 54 adults found no extra drop from NR plus walking compared with placebo plus walking [15].
  • Established: NR raises blood NAD in people, and short trials of 100 to 1,000 mg a day have not flagged a major safety problem [5, 7, 8]. Not established: any heart benefit in people.
  • If you have heart failure, peripheral artery disease, or take blood pressure medicine, ask a clinician before you add NR.
  • The full ingredient review, with dosing and forms: the NR monograph.

This is a Mt. Angel Vitamins company white paper. It is not a journal article and has not been through journal peer review. The question is whether nicotinamide riboside (NR), a form of vitamin B3 that the body converts into NAD+, helps the heart. We searched PubMed on 22 October 2026 with ten distinct queries and read more than 100 records. Where an abstract left out participant numbers, we read the full text. We kept 29 studies.

Does the "animal and blood-level data only" claim hold?

No. Some summaries describe NR's heart evidence as animal and blood-level data only, and PubMed does not support that. Ten human NR studies measured a heart, blood vessel or blood pressure outcome, or enrolled people with heart failure or peripheral artery disease. They are small (4 to 90 people) and short (5 days to 52 weeks). Most are null or preliminary. None is powered for heart events, and none reports a clinical outcome such as hospital admission or death.

What the mouse heart studies found

Mouse studies carry the strongest heart signal, and they are still animal evidence. Grade for human benefit: Insufficient.

  • Mice with dilated cardiomyopathy that ate NR in their food developed heart failure more slowly. The effect was strongest in that model and partial in a pressure-overload model [1].
  • In the pressure-overload model, NR started after heart function had already dropped still improved mitochondrial function and slowed the decline. The benefit held in mice without the SIRT3 gene [2].
  • In a Friedreich ataxia model, NMN or NR raised survival and modestly reduced heart-muscle thickening, with limited changes in ejection fraction [3].
  • In mice prone to atherosclerosis, the top NR dose increased aortic plaque, plasma TNF-alpha and IL-6, and LDL cholesterol. The authors advise caution in people with atherosclerosis [4].

What the blood and pharmacokinetic studies found

Blood NAD is the best-established part of the NR record. Grade for NR raising blood NAD metabolites: Strong (several human trials, consistent direction).

  • Single oral doses of 100, 300 and 1,000 mg raised blood NAD metabolites in a dose-dependent way in 12 healthy adults, in randomized sequences with 7-day washouts [5].
  • An open-label study of 8 healthy volunteers titrated NR from 250 mg up to 1,000 mg twice daily and tracked a 24-hour curve. NR and NAD+ rose significantly, and NR was well tolerated [6].
  • Eight weeks of 100, 300 or 1,000 mg daily in 140 enrolled overweight adults raised whole-blood NAD by 22%, 51% and 142%, per the abstract [7]. The body text gives a 14% to 114% range, so read the exact figures with care.
  • In a 14-day study of 65 healthy adults, NR and NMN raised circulating NAD about equally. Nicotinamide did not, at least over chronic dosing [9]. The authors suggest gut microbes convert NR and NMN to nicotinic acid, a step they tested outside the body.
  • Across seven human cohorts, whole-blood NAD did not change with age or lifestyle, but it did change with NR. The authors argue blood NAD is a weak marker of aging [10].

What the human heart-failure studies found

No human NR trial has used heart function as its primary endpoint in heart failure. Two studies enrolled heart-failure patients, and neither was built to measure heart pumping.

  • Zhou and colleagues drew blood from patients with stage D heart failure and gave oral NR for 5 to 9 days. In 4 patients, immune-cell mitochondrial respiration rose and inflammatory gene expression fell [11]. The abstract describes a before-and-after design with no placebo arm.
  • Wang and colleagues randomized 30 people with stable heart failure with reduced ejection fraction, 2 to 1, to NR or placebo for 12 weeks. NR was raised to 1,000 mg twice daily by week 3 [12]. Whole-blood NAD roughly doubled, and the rise tracked with better immune-cell respiration and lower NLRP3 expression. The trial was safe and well tolerated. Ejection fraction on echocardiogram, a six-minute walk test and a heart-failure questionnaire were prespecified exploratory outcomes, and the authors state the trial could not draw positive or negative conclusions about them.
  • HF-AF ENERGY is a separate trial of NR for atrial fibrillation in heart-failure patients with defibrillators. Its design paper describes a 4-month observation period and a 4-month intervention [13]. We found no results paper in PubMed as of 22 October 2026.

Grade: Insufficient for a heart-function effect. Preliminary for short-term safety in stable heart failure with reduced ejection fraction.

Blood pressure, blood vessels and heart function in human trials

Martens and colleagues' 2018 crossover trial is the first place to look. Over two 6-week periods in healthy middle-aged and older adults, NR lowered systolic pressure by 3.9 mmHg and diastolic pressure by 2.0 mmHg, neither significant after correcting for multiple comparisons. A follow-up analysis found the trend most pronounced in people with baseline systolic pressure of 120 to 139 mmHg [8]. Grade for blood pressure: Insufficient to Preliminary.

Study Who, and how many Design and dose Endpoint Result Main limit
Martens 2018 [8] 30 randomized healthy adults (24 completed) Double-blind crossover, 2 × 6 weeks, NR 1,000 mg a day Systolic and diastolic BP, carotid-femoral pulse wave velocity (PWV) SBP -3.9 mmHg and DBP -2.0 mmHg, both not significant after correction; PWV trended lower Small; subgroup finding is post hoc
Remie 2020 [14] 13 overweight or obese adults Double-blind placebo crossover, 6 weeks, NR 1,000 mg a day Cardiac ejection fraction, cardiac energy status, ambulatory BP No change in any of the three 13 people; not heart patients
Lin 2025 [15] 54 randomized adults aged 55 or older with daytime systolic BP of 130 or higher (49 completed) Double-blind, 6 weeks: NR plus three 30-minute walks a week, against placebo plus walks, and against NR alone Daytime systolic BP (primary), PWV, nighttime BP NR plus walking: mean change +5.19 mmHg. Placebo plus walking: -2.71 mmHg. No added drop from NR. PWV trended down, -0.31 m/s Pilot; nighttime finding is post hoc
Martens 2026 [17] 52 randomized adults with amnestic mild cognitive impairment (42 completed) Double-blind, 12 weeks, NR 1,000 mg a day; capsules supplied by Niagen Bioscience Cognition (primary); cerebral blood flow, BP and PWV (secondary) No change in cognition, total cerebral blood flow, BP or PWV. An exploratory aortic augmentation index fell with NR and rose with placebo Brain-focused trial; BP was not the target
Szarvas 2025 [18] 8 adults with peripheral artery disease Open-label pilot, 4 weeks, NR (dose not stated in the abstract) Peripheral endothelial function, cerebrovascular response, cognition Endothelial function trended up; one cerebrovascular measure rose significantly; cognition improved in several domains Open-label, 8 people
Shoji 2025 [19] 11 enrolled and 9 randomized adults with Werner syndrome Double-blind crossover, 26 weeks per arm, NR 1,000 mg a day Safety (primary); cardio-ankle vascular index (arterial stiffness) No serious adverse events; CAVI improved Rare genetic disease; very small
McDermott 2024 [20] 90 adults with peripheral artery disease Double-blind, 6 months, NR with or without resveratrol against placebo Six-minute walk distance NR added 17.6 m against placebo (90% lower bound +1.8 m); resveratrol added nothing Walking outcome, not a vessel measure
Ahmadi 2023 [21] 25 adults with chronic kidney disease Randomized crossover, 6 weeks each, NR 1,000 mg a day against CoQ10 and placebo Peak oxygen uptake (VO2 peak) No change in VO2 peak; NR lowered submaximal VO2 at 30 W (P=0.03) Kidney patients; not heart
Lin 2026 [22] 66 randomized people aged 10 to 40 with Friedreich ataxia and ejection fraction of 45% or higher Randomized 2 by 2 factorial, 12 weeks, weight-based NR (300 to 900 mg) with or without exercise Peak oxygen uptake during exercise testing NR plus exercise beat control by 0.21 L/min (95% CI 0.05 to 0.36; P=0.03). NR added nothing to exercise alone (P=0.49) Neurological disease; fitness outcome, not heart function

Read as a pattern, blood pressure barely moved. The signals that did appear were walking distance and single arterial-stiffness measures, in small or unusual groups. Freeberg and colleagues registered a 3-month trial of NR 500 mg twice daily in 94 adults aged 50 and older with systolic pressure of 120 to 159 mmHg, with casual systolic pressure as the primary endpoint [16]. That paper describes the protocol. We found no results paper.

Grades, per outcome: blood pressure Insufficient to Preliminary; arterial stiffness and vessel function Preliminary; heart pumping Insufficient; exercise fitness Preliminary (one trial, one population).

What about NMN?

NMN is a different molecule with its own trials, and its human heart data are also thin. We found no human NMN trial in heart failure. The NMN monograph covers the ingredient in full.

  • A 28-day trial of MIB-626, a microcrystalline form of beta-NMN, in 30 overweight or obese adults found diastolic pressure 7.01 mmHg lower than placebo (95% CI -13.44 to -0.59; P=0.034). The abstract's wording puts the dose at two 500 mg tablets twice daily [23].
  • A 12-week trial of 250 mg a day in 36 healthy middle-aged adults found pulse wave velocity tended to fall, with no significant difference from placebo [24].
  • Six weeks of NMN with training in 48 amateur runners raised relative oxygen-uptake measures in the 600 and 1,200 mg groups. Absolute peak oxygen uptake did not change [25].
  • Single oral doses of 100, 250 or 500 mg in 10 healthy men changed neither heart rate nor blood pressure [26].

Grade: Preliminary.

Is NR safe for the heart?

Short human trials have not flagged a major heart-safety problem. None was designed to detect cardiovascular events, and most ran for weeks, not years.

  • In 140 enrolled overweight adults, 8 weeks of NR up to 1,000 mg a day caused no flushing and did not raise LDL cholesterol [7].
  • In 20 people with Parkinson disease, 1,500 mg twice daily for 4 weeks caused no moderate or severe adverse events. Serum homocysteine rose slightly early on. The trial did not test heart outcomes, so the rise is a flag for future trials, not a finding about the heart [27].
  • The longest human study in this search ran two years, in ataxia telangiectasia. It was open-label and single-arm, and its participant count and dose are not in the abstract. NR was well tolerated [28].
  • The mouse plaque result is the main caution. High-dose NR raised plaque and inflammation markers in that model [4].

Grade: Preliminary.

What the evidence review says

Gallagher and colleagues (2026) screened 113 NAD studies: 33 in people, 28 of those randomized, and 80 in rodents. Human NR and NMN reliably raised circulating NAD metabolites and were generally well tolerated. Functional and vascular outcomes were heterogeneous and often null [29].

What is established, what is proposed, and what would settle it

  • Established: NR raises blood NAD in people at doses from 100 to 1,000 mg a day, and short human trials report it is generally well tolerated. In mice, NR protects heart function in some heart-failure models.
  • Proposed: NR could help heart failure through NAD-dependent mitochondrial and immune effects. That idea rests on mechanism and on 4 to 30 patients.
  • What would settle it: a randomized trial in heart-failure patients with a heart-function primary endpoint and clinical follow-up, the HF-AF ENERGY results, and longer cardiovascular safety data that address the mouse plaque result.

Glossary

  • NAD+: a coenzyme that carries electrons in energy metabolism and cell signaling.
  • Nicotinamide riboside (NR): a form of vitamin B3 that the body converts into NAD+.
  • Nicotinamide mononucleotide (NMN): a precursor one step closer to NAD+ than NR, studied as a separate supplement.
  • Mitochondria: the structures inside cells that make most of their usable energy.
  • Heart failure with reduced ejection fraction (HFrEF): heart failure in which the left ventricle pumps out 40% or less of its blood with each beat.
  • Ejection fraction: the share of blood in the left ventricle that is pumped out with each heartbeat.
  • Pulse wave velocity (PWV): how fast the pressure wave travels along the large arteries, a standard arterial stiffness measure.
  • Cardio-ankle vascular index (CAVI): an arterial stiffness measure that combines pressure and wave speed from the ankle to the heart.
  • Peak VO2: the most oxygen a person can use during exercise, a fitness measure.
  • PBMC (peripheral blood mononuclear cells): immune cells drawn from a blood sample and used as a stand-in for tissue mitochondria.
  • Pharmacokinetics (PK): how a dose is absorbed, distributed and cleared over time.
  • Crossover trial: each participant gets both the active and placebo periods, in a set order.
  • NLRP3: an inflammation signaling protein measured in some heart-failure studies.
  • Homocysteine: an amino acid whose blood level is tracked in cardiovascular research.

References

Citation records were retrieved from PubMed on 22 October 2026 (According to PubMed). Each DOI links to the publisher record. Participant counts and doses come from the abstract unless the text says otherwise.

  1. Diguet N, et al. Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy. Circulation. 2017. PMID 29217642. DOI
  2. Walker MA, et al. Raising NAD Level Stimulates Short-Chain Dehydrogenase/Reductase Proteins to Alleviate Heart Failure Independent of Mitochondrial Protein Deacetylation. Circulation. 2023. PMID 37965787. DOI
  3. Perry CE, et al. NAD+ precursors prolong survival and improve cardiac phenotypes in a mouse model of Friedreich's Ataxia. JCI Insight. 2024. PMID 39171530. DOI
  4. Wang YJ, et al. NAD boosting increases atherosclerotic plaques and inflammation in Apoe knockout mice. Atherosclerosis. 2025. PMID 40215896. DOI
  5. Trammell SA, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature Communications. 2016. PMID 27721479. DOI
  6. Airhart SE, et al. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers. PLoS One. 2017. PMID 29211728. DOI
  7. Conze D, et al. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Scientific Reports. 2019. PMID 31278280. DOI
  8. Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications. 2018. PMID 29599478. DOI
  9. Christen S, et al. The differential impact of three different NAD boosters on circulatory NAD and microbial metabolism in humans. Nature Metabolism. 2026. PMID 41540253. DOI
  10. Trętowicz MM, et al. Human whole-blood NAD levels do not vary with age or lifestyle interventions. Nature Metabolism. 2026. PMID 42135539. DOI
  11. Zhou B, et al. Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure. Journal of Clinical Investigation. 2020. PMID 32790648. DOI
  12. Wang DD, et al. Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction. JACC Basic to Translational Science. 2022. PMID 36644285. DOI
  13. Pool L, et al. The HF-AF ENERGY Trial: Nicotinamide Riboside for the Treatment of Atrial Fibrillation in Heart Failure Patients. Cardiovascular Drugs and Therapy. 2022. PMID 36227441. DOI
  14. Remie CME, et al. Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans. American Journal of Clinical Nutrition. 2020. PMID 32320006. DOI
  15. Lin Y, et al. Nicotinamide riboside combined with exercise to treat hypertension in middle-aged and older adults: a pilot randomized clinical trial. GeroScience. 2025. PMID 40770531. DOI
  16. Freeberg KA, et al. Nicotinamide Riboside Supplementation for Treating Elevated Systolic Blood Pressure and Arterial Stiffness in Midlife and Older Adults. Frontiers in Cardiovascular Medicine. 2022. PMID 35620522. DOI
  17. Martens CR, et al. A phase-II randomized controlled pilot study of nicotinamide riboside supplementation in older adults with amnestic mild cognitive impairment. Alzheimer's and Dementia. 2026. PMID 42478598. DOI
  18. Szarvas Z, et al. Effects of NAD supplementation with oral nicotinamide riboside on vascular health and cognitive function in older adults with peripheral artery disease: Results from a pilot 4-week open-label clinical trial. Journal of Pharmacology and Experimental Therapeutics. 2025. PMID 40479886. DOI
  19. Shoji M, et al. Nicotinamide Riboside Supplementation Benefits in Patients With Werner Syndrome: A Double-Blind Randomized Crossover Placebo-Controlled Trial. Aging Cell. 2025. PMID 40459998. DOI
  20. McDermott MM, et al. Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial. Nature Communications. 2024. PMID 38871717. DOI
  21. Ahmadi A, et al. Randomized crossover clinical trial of coenzyme Q10 and nicotinamide riboside in chronic kidney disease. JCI Insight. 2023. PMID 37159264. DOI
  22. Lin KY, et al. Safety and efficacy of individualised exercise and NAD precursor supplementation in patients with Friedreich's ataxia in the USA: a single-centre, 2 × 2 factorial, randomised controlled trial. Lancet Neurology. 2026. PMID 42009009. DOI
  23. Pencina KM, et al. Nicotinamide Adenine Dinucleotide Augmentation in Overweight or Obese Middle-Aged and Older Adults: A Physiologic Study. Journal of Clinical Endocrinology and Metabolism. 2023. PMID 36740954. DOI
  24. Katayoshi T, et al. Nicotinamide adenine dinucleotide metabolism and arterial stiffness after long-term nicotinamide mononucleotide supplementation: a randomized, double-blind, placebo-controlled trial. Scientific Reports. 2023. PMID 36797393. DOI
  25. Liao B, et al. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. Journal of the International Society of Sports Nutrition. 2021. PMID 34238308. DOI
  26. Irie J, et al. Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocrine Journal. 2019. PMID 31685720. DOI
  27. Berven H, et al. NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease. Nature Communications. 2023. PMID 38016950. DOI
  28. Presterud R, et al. Long-Term Nicotinamide Riboside Use Improves Coordination and Eye Movements in Ataxia Telangiectasia. Movement Disorders. 2023. PMID 37899683. DOI
  29. Gallagher C, et al. NAD+ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence. Ageing Research Reviews. 2026. PMID 41655607. DOI

Next reads

The Bottom Line

No human trial has shown that NR improves heart function. The larger of the two heart-failure studies was built to test safety, and the mouse heart data are mostly positive. Human NR raises blood NAD reliably at 100 to 1,000 mg a day, and short trials have not flagged a major heart-safety problem. If you have heart failure, peripheral artery disease, or take blood pressure medicine, ask your clinician before you add NR. The NR monograph covers dosing and forms.

FAQ

Does NR help the heart?

No human trial has shown that NR improves heart function. Mouse studies found that NR in food slowed the development of heart failure, and that NR started after heart function had already dropped still helped. Human trials that measured blood pressure, arterial stiffness or heart pumping were small, mostly short, and mostly null. So the honest answer is that a heart benefit in people is still an open question, not a yes or no.

Does nicotinamide riboside help heart failure?

The evidence cannot answer that yet. One trial gave NR or placebo to 30 people with reduced ejection fraction for 12 weeks. NR was safe and roughly doubled whole-blood NAD, but the authors could not draw conclusions about heart function. A second study gave NR to 4 patients for 5 to 9 days and measured immune cells rather than the heart. As of 22 October 2026, no heart failure trial with a heart-function primary endpoint had been published.

Is there human evidence that NR supports heart function?

Some, and most of it is small and null. Ten human NR studies measured a heart, blood vessel or blood pressure outcome, or enrolled people with heart failure or peripheral artery disease. In 13 adults, 6 weeks of NR did not change ejection fraction or ambulatory blood pressure. In 54 adults with high blood pressure, NR plus walking did not lower daytime systolic pressure more than placebo plus walking. The positive signals were walking distance and one arterial stiffness measure, in small groups.

What did the NR heart studies in mice find?

Mice that ate NR in their food developed heart failure more slowly, and the effect was strongest in a dilated cardiomyopathy model. In a pressure-overload model, NR started after heart function had dropped still improved mitochondrial function and slowed the decline. In a Friedreich ataxia model, NMN or NR raised survival and modestly reduced heart muscle thickening. The counterweight: in mice prone to atherosclerosis, the top NR dose increased artery plaque. All of this is animal evidence, and mouse doses do not map directly onto human doses.

Is NR safe for the heart?

Short human trials have not flagged a major heart-safety problem, but none was built to detect heart events. In 140 overweight adults, 8 weeks of NR up to 1,000 mg a day caused no flushing and did not raise LDL cholesterol. In 20 people with Parkinson disease, 1,500 mg twice daily for 4 weeks caused no moderate or severe adverse events, though homocysteine rose slightly early on. The longest human study found ran two years and reported NR well tolerated.

Does NMN help heart function?

The human data are small and mixed. In a 28-day trial of an NMN form called MIB-626, 30 overweight or obese adults had diastolic blood pressure 7 mmHg lower than placebo (P=0.034). In a 12-week trial of 250 mg a day, 36 healthy adults had arterial stiffness that tended to fall, not significantly. We found no human NMN trial in heart failure. NMN and NR are different molecules, so NR results do not carry over automatically.

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