NAD+ and precursors: research

NAD+ helps cells use energy; wellness injection benefits remain unproven.

Also called: NAD+, NAD, nicotinamide adenine dinucleotide, coenzyme I, DPN, NR, nicotinamide riboside, NMN, β-NMN, nicotinamide mononucleotide.

NAD+ and precursors · NAD+ coenzyme and vitamin B3-derived precursors.

Evidence is separated by administered compound. NOPARK tested oral nicotinamide riboside, not injected NAD+. NAD+, NR and NMN have distinct route-specific evidence.

Studies

NOPARK: NR in early Parkinson disease. rct, n=410, Adults with early Parkinson disease. NR did not improve Parkinson outcomes; the main outcome favored placebo. (source)
NAD+ infusion: six-hour pilot. pk-study, n=11, Healthy men aged 30–55. A slow infusion changed blood and urine metabolites; it did not test health benefits. (source)
NAD+ in ischemic heart failure. rct, n=180, Adults with ischemic heart failure; LVEF ≤45%; usual therapy continued. A small improvement in pumping function needs replication. (source)
NAD+ added to hearing-loss care. rct, n=38, Adults with sudden sensorineural hearing loss; several standard treatments continued. One small add-on study reported more hearing recovery. (source)
NAD+ versus NR infusions. cohort, n=14, 14 adults attending a commercial wellness service. NAD+ caused substantially more infusion discomfort than NR. (source)
Single IV dose: 2024 preprint. rct, n=53, Generally healthy adults. Preliminary data suggest different infusion tolerability for NAD+ and NR. (source)
NAD+ and NR shots: 2026 preprint. rct, n=45, Generally healthy adults. Only tiny three-day cohorts have tested NAD+ shots against placebo. (source)
NR shots: 100-day pilot preprint. open-label, n=39, Generally healthy adults. This NR injection study cannot establish NAD+ injection safety. (source)
First NR dose study. crossover-rct, n=12, Healthy adults. Oral NR raises NAD-related blood markers. (source)
NR step-up pharmacokinetics. pk-study, n=8, Healthy adults. Short exposure raised blood NAD+ with large person-to-person variation. (source)
NR in middle-aged and older adults. crossover-rct, n=24, Healthy middle-aged and older adults. NR raised blood NAD+ in a small crossover trial. (source)
NR in men with obesity. rct, n=40, 40 sedentary men with obesity and insulin resistance. NR did not improve insulin sensitivity in this trial. (source)
NR: 100, 300 and 1000 mg. rct, n=140, Overweight, otherwise healthy adults aged 40–60. NR raised NAD+ with similar overall event rates to placebo. (source)
NR in older muscle. crossover-rct, n=12, 12 older men. Higher muscle NAD metabolites did not improve mitochondrial function. (source)
NR in overweight adults. crossover-rct, n=13, 13 overweight or obese adults. Most metabolic benefits seen in animals were absent. (source)
NR in stable systolic heart failure. rct, n=30, Adults with stable reduced-ejection-fraction heart failure. A small safety study did not establish heart-failure benefit. (source)
NADPARK: early Parkinson study. rct, n=30, Newly diagnosed, untreated Parkinson disease. This biomarker study led to the larger negative NOPARK trial. (source)
NR-SAFE: 3000 mg per day. rct, n=20, Adults with Parkinson disease. A high NR dose had only short-term safety testing. (source)
NR and CoQ10 in kidney disease. crossover-rct, n=25, Adults with eGFR <60 mL/min/1.73 m². Changes in blood metabolites did not improve peak exercise capacity. (source)
NICE: walking with artery disease. rct, n=90, Adults with lower-extremity peripheral artery disease. NR modestly improved walking distance in one artery-disease trial. (source)
NR dose escalation in mild cognitive impairment. rct, n=20, Older adults with mild cognitive impairment. Higher NAD+ did not improve cognition. (source)
NR in amnestic mild cognitive impairment. rct, n=42, Older adults with amnestic mild cognitive impairment. This separate trial also found no cognitive benefit. (source)
NR and Alzheimer blood markers. crossover-rct, n=46, Adults over 55 with subjective cognitive decline or mild cognitive impairment. A blood-marker change did not translate into better cognition. (source)
NR in long COVID. rct, n=58, Community-dwelling adults with long COVID. NR raised NAD+ without improving the main symptom outcomes. (source)
NR in COPD. rct, n=40, Adults with stable COPD. NR lowered an airway inflammation marker in one small trial. (source)
NR in Werner syndrome. crossover-rct, n=9, Adults with genetically confirmed Werner syndrome. An extremely small rare-disease trial found exploratory benefits. (source)
NR with exercise for blood pressure. rct, n=54, Sedentary adults aged ≥55 with elevated daytime blood pressure. NR did not improve the blood-pressure effect of exercise. (source)
NR and exercise in Friedreich ataxia. rct, n=66, Patients aged 10–40 with Friedreich ataxia; half were adults. The combination beat placebo, but adding NR to exercise did not. (source)
Single-dose NR brain scan. open-label, n=10, 10 healthy adults. A scan detected more brain NAD+ after a single dose. (source)
NR versus NMN blood and brain kinetics. pk-study, n=12, 6 healthy adults and 6 adults with Parkinson disease. The blood NAD pool changes more slowly than precursor drug levels. (source)
First NMN single doses. pk-study, n=10, 10 healthy Japanese men. Single NMN doses were tolerated in a very small study. (source)
NMN in women with prediabetes. rct, n=25, Postmenopausal women with overweight or obesity and prediabetes. One small trial improved a muscle insulin-response measure. (source)
NMN with running training. rct, n=48, Recreational runners; 10 men and 2 women per group. Some exercise thresholds improved; maximum oxygen uptake did not. (source)
NMN morning versus evening. rct, n=108, Older Japanese adults. Sleep and fatigue findings were mixed and timing-dependent. (source)
NMN: 1000 or 2000 mg per day. rct, n=32, Overweight or obese adults aged 55–80. A specific NMN formulation raised blood NAD over two weeks. (source)
NMN in older men. rct, n=42, Healthy older Japanese men. Small exploratory muscle findings need replication. (source)
NMN 250 mg: 12-week safety. rct, n=30, Healthy adults. NMN raised blood NAD with no clear short-term safety signal. (source)
NMN 1250 mg safety study. rct, n=31, Healthy adults aged 20–65. 1250 mg daily had only four weeks of safety testing. (source)
NMN intravenous pilot. single-arm, n=10, 10 healthy volunteers. A tiny IV NMN study found biomarker changes. (source)
NMN: 300, 600 and 900 mg. rct, n=80, Healthy middle-aged adults. NMN raised NAD; health and longevity benefits remain unproven. (source)
NMN in older men with diabetes. rct, n=14, Men aged ≥65 with diabetes and weak grip or slow walking. NMN did not improve strength or walking speed. (source)
NMN 2000 mg in older adults. rct, n=30, Overweight or obese adults aged ≥45. Short-term changes in weight and pressure need larger confirmation. (source)
NMN and artery stiffness. rct, n=36, Healthy middle-aged adults. A favorable trend did not establish an artery benefit. (source)
NMN, walking and sleep. rct, n=60, Older adults. The primary test was negative; some secondary measures improved. (source)
NMN eight-week open-label study. open-label, n=11, Healthy middle-aged Japanese men. No controlled clinical benefit can be inferred. (source)
NMN and post-meal insulin. open-label, n=11, 11 healthy adults. A rise in NAD did not consistently mean better glucose regulation. (source)
NMN in COVID with kidney injury. rct, n=42, Adults hospitalized with COVID-19 and acute kidney injury. Raising NAD did not improve measured kidney or disease outcomes. (source)
NR, NMN and nicotinamide compared. rct, n=65, 65 healthy adults. NR and NMN showed similar blood-marker effects. (source)
NMN after muscle-damaging exercise. crossover-rct, n=11, 11 untrained young men. Lower inflammatory signals did not mean better muscle repair. (source)
NMN in immune thrombocytopenia. open-label, n=25, Adults with steroid-refractory or steroid-dependent immune thrombocytopenia. One uncontrolled disease-specific trial needs confirmation. (source)
NMN under the tongue versus swallowed. crossover-rct, n=14, 14 healthy adult men. Faster breakdown products do not prove better NAD delivery or benefit. (source)
Formulated oral NAD+ pilot. rct, n=60, Healthy adults aged 45–75. One formulation changed blood NAD without proven health benefit. (source)
NR plus pterostilbene in older adults. rct, n=120, Adults aged 60–80. The combination raised NAD; this was not an NR-only trial. (source)
NR plus pterostilbene in kidney injury. rct, n=24, Hospitalized adults with acute kidney injury. The tiny safety cohorts did not establish kidney benefit. (source)
NR plus pterostilbene in fatty liver. rct, n=111, Adults with nonalcoholic fatty liver disease. The primary liver-fat outcome was negative. (source)
NR plus pterostilbene after muscle injury. rct, n=32, Adults aged 55–80. The combination did not speed muscle repair. (source)
NR plus pterostilbene in menopause. open-label, n=40, 40 women over 35; 32 with menopause-transition symptoms. One week of open-label reports cannot establish benefit. (source)
NR combination in ALS. rct, n=32, Adults with amyotrophic lateral sclerosis. A small combination study needs larger independent replication. (source)
Early NAD report in drug addiction. case-series, Patients with drug or alcohol dependence. A historical clinician described IV dosing; controlled evidence for addiction benefit is lacking. (source)
Early pyridine-nucleotide report in alcohol use. case-series, Patients with drug or alcohol dependence. Historical reports do not establish efficacy or an exact modern regimen. (source)
NAD-containing infusion in substance use. case-series, n=50, 50 people with mixed substance use disorders. Uncontrolled combination infusions cannot establish NAD-only benefit. (source)
NAD+ skin patch plus naltrexone. open-label, n=36, Adults with persistent fatigue after COVID-19. A combined uncontrolled intervention cannot isolate NAD+ effects. (source)
Metabolic mixture in COVID: phase 2. rct, n=93, Ambulatory adults with COVID-19. Any benefit belongs to the mixture, not NR alone. (source)
Metabolic mixture in COVID: phase 3. rct, n=304, Ambulatory adults with COVID-19. Any benefit belongs to the mixture, not NR alone. (source)
Metabolic mixture in Alzheimer disease. rct, n=69, Adults over 50 with mild or moderate Alzheimer disease. Within-group improvement did not establish overall superiority to placebo. (source)
Metabolic mixture in Parkinson disease. rct, Adults with Parkinson disease. The multi-ingredient trial does not establish an NR-only treatment. (source)
Two-year NR in ataxia telangiectasia. open-label, Children and adults with ataxia telangiectasia. A rare-disease uncontrolled study does not prove general longevity benefit. (source)
NMN metabolic outcomes: eight trials. meta-analysis, n=342, 342 mainly nondiabetic middle-aged or older adults. Short NMN trials did not establish broad metabolic benefit. (source)
NR/NMN and older muscle. meta-analysis, Adults with study mean ages 60.9–83 years. Pooled evidence does not support preserving muscle mass or function. (source)
Wellness evidence review through 2025. systematic-review, Human and rodent intervention literature. Biochemical effects are clearer than health or longevity benefits. (source)
NR and tumor spread in mice. animal, Triple-negative breast-cancer mouse model. This is a cancer-risk signal in mice, not proof that NR causes cancer in humans. (source)
NR in Li-Fraumeni syndrome. single-arm, n=1, Cancer. Registry results add information beyond published abstracts. (source)
NR in severe COVID with kidney injury. rct, n=28, SARS-CoV-2 Infection. This tiny, severely ill cohort had numerically more deaths with NR; cause is uncertain. (source)
NR in chemotherapy neuropathy. single-arm, n=5, Chemotherapy-induced Peripheral Neuropathy. Registry results add information beyond published abstracts. (source)
NR and heart-failure muscle function. single-arm, n=2, Heart Failure. Registry results add information beyond published abstracts. (source)
NR and small skin nerves. rct, n=45, Small Fiber Neuropathy. Registry results add information beyond published abstracts. (source)
NR before LVAD surgery. single-arm, n=5, Heart Failure，Congestive. Registry results add information beyond published abstracts. (source)
NR and immune-cell response. crossover-rct, n=38, Atherosclerosis. Registry results add information beyond published abstracts. (source)
NR brain-energy pilot. single-arm, n=11, Healthy. Registry results add information beyond published abstracts. (source)
NMN metabolism: 12-study review. meta-analysis, n=513, Adults in NMN trials. Review results vary with endpoints, methods and included trials. (source)
NMN muscle/liver review. meta-analysis, n=412, Adults in NMN trials. Review results vary with endpoints, methods and included trials. (source)
NMN blood-pressure review. meta-analysis, n=349, Adults in NMN trials. Review results vary with endpoints, methods and included trials. (source)
1966 NAD alcohol-withdrawal study. rct, Men with acute alcohol-related brain syndrome. A controlled historical IM NAD study exists, but its full dosing/results were not recovered. (source)
NMN 300 mg: 60-day trial. rct, n=66, Healthy adults aged 40–65. The study did not measure lifespan or establish an anti-aging effect. (source)
NMN with or without PQQ before exercise. rct, n=60, 60 adult exercise-study participants. The study does not establish a performance benefit from NMN. (source)
NR and vascular/cognitive tests in PAD. open-label, n=8, 8 older adults with peripheral artery disease. Before/after changes in eight people cannot establish benefit. (source)
NR with exercise in cancer survivors. rct, n=20, Adult survivors of childhood cancer with prediabetes. The pilot established feasibility, not NR efficacy. (source)
NR in ataxia telangiectasia. open-label, n=24, 24 people with ataxia telangiectasia. The uncontrolled rare-disease signal needs confirmation. (source)
NR in one young child with ataxia. case-report, n=1, One child aged 3 years 6 months with ataxia telangiectasia. A single developing child cannot establish pediatric efficacy or safety. (source)

NAD+ and precursors dosage

Typical reported dose: 25 mg three times a week, building up to 100 mg

NR: 500 mg: NR 500 mg twice daily. twice daily, by mouth. Studied in a trial. Studied in: Adults with early Parkinson disease. (source)
NAD+: 750 mg: NAD+ 750 mg once over 6 hours. 750 mg total in saline over 6 hours. once over 6 hours, into a vein. Studied in a trial. Studied in: Healthy men aged 30–55. (source)
NAD+: 750 mg: NAD+ 750 mg once over 6 hours. once over 6 hours, into a vein. Clinician-published. Studied in: Healthy men aged 30–55. (source)
NAD+: 10 mg: NAD+ 10 mg IV daily for 7 days, in 100 mL glucose or saline. once daily, into a vein. Studied in a trial. Studied in: Adults with ischemic heart failure; LVEF ≤45%; usual therapy continued. (source)
NAD+: 5 mg: NAD+ 5 mg once daily during hospitalization. once daily during hospitalization, into muscle. Studied in a trial. Studied in: Adults with sudden sensorineural hearing loss; several standard treatments continued. (source)
Observed NAD+ IV 500 mg course: NAD+ 500 mg once daily. once daily, into a vein. Clinician-published. Studied in: 14 adults attending a commercial wellness service. (source)

Highest studied: One 14-person crossover trial tested a single 250 mg sublingual NMN tablet..

These are doses reported in labels, trials or user reports, not a personal plan. Check the source behind each one.

Work out syringe units with the dosing calculator

NAD+ and precursors side effects and risks

Reported side effects

Stomach upset with oral NR: In an 8 week trial: 20.0%, 14.3%, 11.4% at 100, 300, 1000 mg/day vs 14.3% placebo., mild. Review persistent symptoms and other supplements; rates vary widely across populations. (source)
Diarrhea with NR or an NR combination: PAD trial: NR 39.3%; NR plus resveratrol 54.6%; placebo 27.6%., moderate. Assess ongoing diarrhea and hydration. The combination may be less tolerable. (source)
NAD+ infusion cramps, nausea and chest pressure: All 6 NAD+ clients in a small retrospective series reported symptoms; this is not a general incidence estimate., moderate. Pause the infusion and alert clinical staff. Chest pain, breathlessness or fainting needs urgent assessment. (source)
Severe chills, shaking, vomiting or fatigue after injections: unknown, serious. Get urgent assessment; FDA reports were consistent with excessive endotoxin contamination. (source)
Injection pain and local irritation: NR shot preprint: pain >2 minutes 45.9%; soreness/tightness 43.2%. NAD+ route specific rates were not published there., moderate. Persistent redness, warmth, swelling or fever needs assessment. (source)
Headache or nausea with high-dose NR: NR 3000 mg/day: 3 headache events and 2 nausea events vs 0 and 0 placebo, in 10 people per arm., mild. These are small-study event counts, not a reliable population frequency. (source)
Poor sleep, jitteriness or anxiety: unknown, moderate. Reported online with NR/NMN or NAD+ shots; causal links and rates are unproven. (source)
Iontophoresis patch skin irritation: 25% in the uncontrolled NAD+ plus naltrexone study., mild. Stop applying to irritated skin and have the reaction assessed. (source)

Stop and get help if

Severe chills, shaking, repeated vomiting or sudden illness after an injection: Stop administration and get urgent medical assessment; contamination or endotoxin is possible.
Chest pain, breathlessness, fainting or a sustained racing heart during an infusion: Stop the infusion and seek urgent assessment; do not assume it is a normal NAD+ sensation.
Spreading redness, marked warmth, swelling or fever after an injection: Get prompt medical assessment for infection or a serious reaction.
Face or tongue swelling, wheezing or trouble breathing after administration: Stop administration and seek emergency care for a possible severe reaction.
Sudden severe vomiting, diarrhea, agitation or confusion after starting naltrexone in the NAD+ combination: Seek urgent medical care for possible opioid withdrawal triggered by naltrexone.

Who should avoid it

pregnant: This is an editorial screen, not an FDA NAD+ label.
breastfeeding: This is an editorial screen, not an FDA NAD+ label.
tryingToConceive: This is an editorial screen, not an FDA NAD+ label.
under18: Some rare-disease studies enrolled children; they do not establish routine wellness use under 18.
activeCancer: Animal NR data show a tumor-growth/spread signal. Human risk is unknown; review any NAD booster with the oncology team.
cancerHistory: Cancer recurrence risk has not been tested adequately; animal findings cannot quantify human risk.
kidneyDisease: Small kidney-disease trials do not establish safe self-dosing, particularly during acute illness.
liverDisease: Liver safety needs individual review. A negative liver-fat trial of an NR combination is not proof of liver treatment.
heartCondition: NAD+ infusions can cause chest pressure and faster heart rate. Heart-failure trials used monitored care.
diabetes: NMN may change insulin responses. Review glucose monitoring and medicines; a hypoglycemia interaction is not established.
testedAthlete: IV fluid volume can breach WADA M2.2 even when the infused substance is not prohibited.
other: The large NR Parkinson trial found worse clinical scores than placebo; discuss supplementation with the treating neurologist.
other: Do not repeat exposure after a serious reaction until the ingredient, excipients and possible contamination are assessed.
other: For the naltrexone combination only: opioid analgesics, current opioid dependence or acute withdrawal contraindicate naltrexone. It can trigger severe withdrawal.

Interactions

Other NAD+ boosters or high-dose vitamin B3: Duplicate exposure has no proven extra benefit. NR, NMN, NAD+ and niacin are not interchangeable milligram for milligram.
Insulin and sulfonylureas: A direct interaction is unproven. Because NMN changed insulin sensitivity in one trial, discuss extra glucose checks when medicines lower blood sugar.
Levodopa and Parkinson medicines: NR-SAFE had changes in movement symptoms and levodopa use. NOPARK found worse scores; a direct drug interaction remains unproven.
Cancer treatment and NAD-pathway drugs: NAD supports DNA-repair pathways used in cancer biology. Clinical interaction effects are unknown; review with the oncology team.
Opioids, only when naltrexone is included: NAD+–naltrexone combination only: opioid use or dependence contraindicates naltrexone and can cause severe withdrawal. Assess recent use before starting.

Product quality risks

FDA reports of severe reactions to NAD+ injections were consistent with endotoxin contamination.
A study tested 18 NMN products. NMN deviations from adjusted label claims ranged from −100% to +11.2%.
An oral purity result cannot establish injectable sterility, endotoxin safety or correct dose.
A 2026 FDA warning identified NAD+ bulk compounding outside 503B eligibility and major sterile-manufacturing failures.

How NAD+ and precursors works

NAD+ helps cells move energy from food and supports enzymes that repair DNA. NR and NMN are building blocks used to make it. Swallowing a precursor, infusing NAD+ and injecting it under the skin are different exposures. A higher blood level does not show that organs work better.

NAD+/NADH redox pair: Transfers electrons during energy production.
Sirtuins and PARPs: Use NAD+ in stress responses and DNA repair.
NRK and NMNAT pathways: Convert NR and NMN into NAD+; gut metabolism also contributes.

Half-life: NR was about 2.7 hours in four volunteers. A reliable human terminal half-life for infused NAD+ is not established.

Gaps: No human lifespan trial establishes that NAD+, NR or NMN slows aging. No reliable long-term safety, efficacy or pharmacokinetic map for home NAD+ SC or IM use. No modern society-endorsed wellness, microdose or cycling schedule was found. Oral precursor data do not establish NAD+ injection, infusion or patch benefits. Pregnancy, breastfeeding, fertility, drug interactions and uncommon harms remain poorly studied. Detailed adverse-event tables and exact schedules could not be recovered for several historical or paywalled trials. Community prevalence is qualitative within searched threads; independent users and product contents were not verified. No final NAD-specific 503A bulks approval or PCAC decision was located. FDA’s 2026 enforcement letter says NAD bulk is not 503B-eligible. EU/UK NMN market authorization and Australian injectable scheduling need a further jurisdiction-specific check. Several minor studies lack complete arm-level event rates in accessible records; no missing numbers were inferred. The human-study count is an inventory of reported studies/cohorts, not a proven count of independent participants; historical overlap is uncertain.

Related to NAD+ and precursors

MOTS-c: A peptide the body makes; injection benefits and safety remain unproven.
SS-31 (elamipretide): A peptide approved for Barth syndrome muscle strength; benefit needs confirmation and broader energy benefits remain unproven.

NAD+ and precursors: the short version

Sources

GenoGenix LLC - 718739 - 01/20/2026, FDA · FDA · 2026
Safety of beta-nicotinamide mononucleotide (β-NMN) pursuant the regulation (EU) 2015/2283 and the bioavailability of nicotinamide from this source in the context of Directive 2002/46/EC., Turck et al. · EFSA journal. European Food Safety Authority · 2026
The 2026 Prohibited List, World Anti-Doping Agency · WADA · 2026
503A Categories Update for September 2024, FDA · FDA · 2025
DailyMed - NALTREXONE HYDROCHLORIDE tablet, film coated, DailyMed · 2023
Safety of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of nicotinamide from this source, in the context of Directive 2002/46/EC., Turck et al. · EFSA journal. European Food Safety Authority · 2019
FDA reminds compounders to use ingredients suitable for sterile compounding, FDA
FDA to Compounders: Know Your Bulks and Excipients Suppliers, FDA
Item: /regulated-product-applications/id/application/RP-2116, Food Standards Agency
Nicotinamide riboside chloride, Food Standards Agency
NMN 500 (531006), Therapeutic Goods Administration
Product information, Health Canada
Re: Docket Number FDA-2023-P-0872, FDA
Submitted 75-Day Premarket Notifications for New Dietary Ingredients, FDA
TUE Physician Guidelines: Intravenous infusions and/or injections, World Anti-Doping Agency

Sources checked: 2026-10-18.

Information only, not medical advice. Peptifacts does not sell anything and does not link to sellers.