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CategoryAuthorDateTitleCompoundForm, dose, duration, subjectsMain resultsAdverse effectsNAD+ levels
1CNS


Birkmayer et al.2002

Stabilized NADH (ENADA) improves jet lag-induced cognitive performance deficit 


NADH20 mg NADH capsules, one time; 35 subjects
  • performed better on 4 cognitive test measures and reported less sleepiness
  • none reported
  • not measured
2CNSDemarin et al.2004

Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study. 


NADH10 mg capsules, 6 months; 26 subjects 
  • no evidence of progressive cognitive deterioration
  • scored higher on verbal fluency and visual-constructional ability
  • No effect on attention, memory or severity of dementia
  • none reported
  • not measured
3CNSKuhn et al.1996

Parenteral application of NADH in Parkinson's disease: clinical improvement partially due to stimulation of endogenous levodopa biosynthesis 


NADH10 mg i.v. over 30 min for 7 days; 15 subjects
  • Parkinsonian patients showed significant clinical improvement
  • NADH significantly increased the bioavailability of plasma levodopa.
  • none reported
  • not measured
4CNSBirkmayer 1996Coenzyme nicotinamide adenine dinucleotide: new therapeutic approach for improving dementia of the Alzheimer typeNADHAlzheimer patients, 10 mg/day for 8-12 weeks; 17
  • in all patients, an improvement in cognitive dysfunction was observed
  • on the mini-mental state examination, the minimum improvement was 6 points and the maximum improvement 14 points with a mean value of 8.35 points
  • improvement on the basis of the global deterioration scale (GDS) was a minimum of 1 point and a maximum of 2 points with a mean value of 1.82 
  • no side effects or adverse effects have been reported from the patients or their caregivers 
  • not measured
5CNSBirkmayer1993

Nicotinamide adenine dinucleotide (NADH)--a new therapeutic approach to Parkinson's disease. Comparison of oral and parenteral application


NADH1/2 i.v. infusion, 1/2 oral
  • in 80% of the patients, a beneficial clinical effect was observed: 19.3% of the patients showed a very good (30-50%) improvement of disability, 58.8% a moderate (10-30%) improvement. 21.8% did not respond to NADH. 
  • younger patients and patients with a shorter disease duration have a better chance to improve than older patients and patients with longer duration of the disease.
  • oral NADH yielded an overall improvement in the disability which was comparable to that of the parenterally applied form.
  • none reported
  • not measured
6CNSRainer et al.2000No evidence for cognitive improvement from oral nicotinamide adenine dinucleotide (NADH) in dementiaNADHmild to moderate dementia, 10 mg/day; 25 subjects
  • no evidence for any cognitive effect as defined by established psychometric tests
  • none reported
  • not measured
7CVSAlegre et al.2010

Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome 

NADH20 mg oral capsules, 2 months; 77 subjects
  • decreased anxiety and maximum heart rate
  • treatment did not modify other clinical variables 
  • none reported
  • not measured
8Drug addictionO’Hollaren1961Diphosphopyridine Nucleotide in the Prevention, Diagnosis and Treatment of Drug AddictionNAD+500-1000 mg of NAD+ added to 300 cc. normal saline, rate of tolerance varied from 5-35 drops per minute; daily for 4 days, then twice weekly for one month and a maintenance dose twice per month; 100 subjects
  • if administered too rapidly, patients complain of headache and shortness of breath
  • in more than 100 patients, there has been no toxic effect
  • complete, immediate, total and permanent withdrawal can be achieved
  • heroin, opium, morphine, meperidine, codeine, alcohol, methadone, cocaine, amphetamines, barbiturates and tranquilizers
  • craving is completely removed
  • headache and shortness of breath
  • not measured
9Immune systemOsar et al.2004

Nicotinamide Effects Oxidative Burst Activity of Neutrophils in Patients with Poorly Controlled Type 2 Diabetes Mellitus 


NAM50 mg/kg oral capsules, one month; 40 subjects
  • oxidative burst activity in patients receiving NAM was greater when compared with placebo 
  • nausea (25%)
  •  not measured
10KidneyTakahashi et al.2004

Nicotinamide suppresses hyperphosphatemia in hemodialysis patients 


NAM1080 mg/day mean dose oral capsules, 12 weeks; 65 subjects
  • serum high-density lipoprotein (HDL) cholesterol concentrations increased from 47.4 ± 14.9 mg/dL to 67.2 ± 22.3 mg/dL
  • serum low-density lipoprotein (LDL) cholesterol concentrations decreased from 78.9 ± 18.8 mg/dL to 70.1 ± 25.3 mg/dL
  • serum triglyceride levels did not change significantly.
  • diarrhea (5), thrombocytopenia (1)
  • baseline: 9.3 +/- 1.9 (nmol / 10*exp5 RBC)
  • 12 weeks: 13.2 +/- 5.3
11KidneyMehr et al.2018De novo NAD+ biosynthetic impairment in acute kidney injury in humansNAMplacebo, 1g or 3 g per day; once daily by mouth or orogastric tube on days −1, 0, and +1 relative to surgery; 329 subjects
  • phase I pilot study of oral Nam administration among adults undergoing cardiac surgery
  • NAM administration significantly increased blood and urine NAM
  • NAM administration at the 3 gm/day regimen increased NMN whereas both Nam regimen increased MeNAM relative to placebo
  • NAM treatment was associated with lower blood levels of the cardiac injury marker troponin T

  • NAM was associated with better estimated renal function compared to placebo 

  • AKI events were significantly lower with NAM treatment than placebo

  • NAM administration was not associated with increased adverse events compared to placebo
  • not measured
12MetabolismDollerup et al.2018

A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects 


NR2000 mg orally capsules, 12 weeks; 40 subjects
  • no effect on insulin sensitivity, endogenous glucose production, and glucose disposal and oxidation
  • no effect on resting energy expenditure, lipolysis, oxidation of lipids, or body composition. 
  • no serious adverse events
  • pruritus, excessive sweating, bloating, and
    transient changes in stool
  • all NAD metabolites were significantly increased
13Muscle




Castro-Marrero et al.2016

Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome - A randomized, controlled, double-blind trial. 


NADH CoQ10 or placebo5 mg NADH, 50 mg CoQ10, 8 weeks; 80 subjects
  • significant reduction in max HR during a cycle ergometer test at week 8 versus baseline
  • perception of fatigue also showed a decrease
  • pain and sleep did not improve in the active group
  • none reported
  • not measured
14MuscleSantaella et al.2004

Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome 


NADH5-10 mg for 2 years; 31 subjects
  • dramatic reduction of the mean symptom score in the first trimester (fatigue, sleep disturbance, myalgia, lymphadenopathy)
  • symptom scores in the subsequent trimesters of therapy were similar in both treatment groups
  • none reported



  • not measured
15MuscleForsyth et al.1999

Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome


NADH10 mg capsules, 4 weeks plus crossover 4 weeks; 26 subjects
  • 31% responded favorably to NADH in contrast to (8%) to placebo decrease in symptoms: fatigue, neurocognitive difficulties, sleep disturbance, postexertional malaise headaches, muscle weakness, arthralgia, myalgias, history of allergy, swelling and tenderness of lymph nodes
  • mild GI symptoms
  • not measured
16MuscleMero et al.2008

Effects of nicotinamide adenine dinucleotide hydride on physical and mental performance 


NADH30 mg capsules, 4 weeks; 8 subjects
  • no effects on V_ O2max, maximal anaerobic running time or mental performance
  • none reported
  • not measured
17MuscleDolopikou et al.2019

Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. 


NR500 mg capsules, 2 days separated by washout and crossover; 24 subjects
  • increased NADH (51% young; 59% old)
  • increased NADPH (32% young 38% old)
  • decreased F2-isoprostanes by 18%
  • did not affect VO2max and concentric peak torque
  • improved isometric peak torque by 8% and the fatigue index by 15% in the old
  • did not exert any redox or physiological effects in the young
  • none reported
  • not measured
18Musclevan de Weijer et al.2015

Evidence for a Direct Effect of the NAD+ Precursor Acipimox on Muscle Mitochondrial Function in Humans 


Acipimox750 mg oral capsules, 2 weeks; 21 subjects
  • mitochondrial respiration in skeletal muscle increased
  • elevated expression of nuclear-encoded mitochondrial gene sets
  • mitonuclear protein imbalance, which may indicate activation of the mitochondrial unfolded protein response
  • none reported
  • not measured 
42MuscleElhassan et al.2019Nicotinamide riboside augments the human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures in aged subjects: a placebo-controlled, randomized trialNR1g per day orally for 21 days, 12 males, aged 70-80
  • 33% self-reported increased in libido
  • 2-fold increase in muscle NAAD
  • no increase in muscle NAM
  • 5 fold increase in muscle MeNAM, 2-PY, 4-PY
  • increased NMN 1.4 fold in blood
  • no effect on NAM in blood
  • urinary NAM clearance pathways highly active with a marked excess of MeNAM, 2-PY, 4-PY
  • NAAD 4.5 fold
  • urinary NAR 20-fold increase
  • NAM was elevated 2.5 fold in urine
  • NR downregulates gene sets associated with energy metabolism in muscle
  • NR upregulates cell adhesions, cytoskeleton organization, and cell motility genes
  • NR did not change glycolysis in muscle
  • NR does not alter skeletal muscle mitochondrial bioenergetics or handgrip strength
  • oral NR doesn't alter systemic cardiometabolic parameters (no change in body weight, blood pressure, lipid profile, fasting glucose, and insulin) 
  • NR does not alter skeletal muscle blood flow or substrate utilization
  • the downregulation of mitochondrial and glycolysis genes in undetectable when considered at a functional level
  • NR depresses circulating levels of inflammatory cytokines (IL-6,5,2, and TNF-a)
  • NAD+ content in skeletal muscle and brain does not decline with age
  • no adverse effects
  • no increase in muscle NAD+ levels
  • 2-fold increase in blood NAD+ levels 
19Pharmacokinetic

Dellinger et al. 2017

Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study

NR+ PT 250-500 mg and 50-100 mg pterostilbene, capsules, 8 weeks; 120 subjects 
  • decreased liver enzymes at the recommended dose but not at higher dose
  • decreased diastolic pressure at the recommended dose
  • increased muscle strength in the high dose group
  • increased LDL slightly
  • 48 adverse events reported
  • pruritis, nausea, fatigue, headache, dyspepsia, abdominal discomfort, diarrhea
  • increased NAD+ levels 40% at 30 days at the recommended dose, increased NAD+ levels 90% in the 2x the recommended dose but slipped to 55% at 60 days
20PharmacokineticAirhart et al.2017

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.


NR250-1000 mg capsules, 8 days; 8 subjects
  • increases observed for both NR and NAD+
  • the latter increased by 100%.
  • absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly 
  • may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases.
  • no adverse events
  • decrease of 0.4 mEq/L Potassium, Hematocrit, Hb, platelet count
  • baseline: 27±5 uM
  • peak: 50±20 uM
21PharmacokineticMartens et al.2018

Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults.


NR1000 mg capsules, 6 weeks then cross over; 24 participants
  • chronic supplementation is well tolerated and effectively stimulates NAD+ metabolism in healthy middle-aged and older adults
  • potential benefits of NR for reducing blood pressure and arterial stiffness in this group
  • nausea (1), skin rash (1), flushing (1), leg cramps (1), increased bruising (1)
  • peak: 16.2 (pmol/mg pr)
  • baseline :10 (pmol/mg pr)
22PharmacokineticTrammell et al.2016

Nicotinamide riboside is uniquely and orally bioavailable in mice and humans


NR100-1000 mg capsules, 3 test days separated by 7 days each; 12 subjects
  • oral NR increases blood NAD+ with a 45-fold elevation of NAAD 
  • NAD+ increased by 2.7 fold
  • Me-2PY increased by 8.4 fold
  • none reported
  • 2.7 fold higher
23PharmacokineticDragovic et al.1995

Nicotinamide pharmacokinetics in patients.

NAMblood samples of patients undergoing treatment with NAM, hyperthermia and radiation therapy for a variety of recurrent/metastatic cancers; 12 subjects
  • escalating oral doses of 3,4,5,6 and 10 g of NAM showed a linear relationship between maximum recorded plasma concentrations and the dose in grams 
  • maximum plasma levels were observed by 30 min in most patients ingesting up to 6 g of NAM.
  • five out of six patients ingesting 10 g of NAM demonstrated increasing plasma levels at least up to 3 h post-ingestion.
  • doses up to 6 g were well-tolerated 
  • doses of 10 g were generally not well tolerated, 
  • nausea and vomiting over 6 g
  • not measured
24PharmacokineticTian et al.2013Excess nicotinamide increases plasma serotonin and histamine levelsNAM

urine and blood samples from healthy males, 100 mg NAM;
9 subjects

  • plasma MeNAM level and the urinary excretion of 2-Py significantly increased after oral loading with 100 mg NAM, which was accompanied by a decrease in the methyl-group donor betaine.
  • plasma serotonin and histamine levels significantly increased.
  • excess NAM may disturb monoamine-neurotransmitter metabolism.
  • significance in understanding the etiology of monoamine-related mental diseases, such as schizophrenia and autism (a neurodevelopmental disorder).
  • none reported
  • not measured
25PharmacokineticConze et al.2019Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight AdultsNRurine and blood samples from healthy, overweight, males and females aged 40-60; 140 subjects, 100,300, or 1000 mg/day
  • significantly increased concentrations of MeNAM and 2PY (1000 mg group by more than 10 times baseline, 300 mg group by 3 times)
  • no change in LDL-C - PT was likely responsible in the other study
  • no change in homocysteine levels in contrast to prior studies
  • no difference between the number of adverse events in placebo and test groups
  • blood NAD+ levels in PBMCs peak 8 hours after administration of 300 or 1000 mg 
  • blood levels of NAD+ increased by 22, 51, 142 % with respect to baseline after 2 weeks
  • after 8 weeks, the levels were maintained
26Skin







Damian et al.2008

Ultraviolet radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide


NAM topical, 5 %, irradiated daily for 3 days; 70 participants
  • suberythemal UV caused significant immunosuppression, although component UVB and UVA doses delivered independently did not.
  • men were immunosuppressed by UV doses three times lower than those required to immunosuppress women.
  • topical NAM prevented immunosuppression
  • mechanisms of protection may include alterations in complement, energy metabolism, and apoptosis pathways. 
  • no adverse effects
  • not measured
27SkinYiasemides et al. 2008

Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans

NAMoral 500-1500 mg/day, 7 days, 61 subjects
  • reduced UV immunosuppression with no immune effects in unirradiated skin (-7,14,33%)
  • low dose group also showed protection
  • did not alter susceptibility to sunburn
  • no adverse effects 
  • increased blood levels of NAD+ by 30% after one hour 
  • 90 min, no difference from baseline 
28SkinChen et al.2015

A phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention 


NAM1000 mg/day, 12 months, 386 participants 
  • decreased rate of new nonmelanoma skin cancers by 23% 
  • decreased actinic keratoses 20% 
  • no benefit after discontinuation
  • no serious adverse effects
  •  not measured
29SkinDrago et al.2017

Prevention of non-melanoma skin cancers with nicotinamide in transplant recipients: a case-control study


NAM750 mg/day, 6 months, 38 participants
  • treatment: AKs decreased in size in 18/19 patients (88%)
  • seven patients (42%) had shown complete clinical regression
  • no patient developed new AKs
  • controls: 91% showed an increase in AK size and/or developed new AKs; seven pre-existing AKs progressed to squamous-cell carcinoma
  • diarrhea (1)
  • not measured
30SkinJacobson et al.2007

A topical lipophilic niacin derivative increases NAD, epidermal differentiation and barrier function in photodamaged skin


MN1-5%, 0.5 mL per day, 12-18 weeks; 16 participants
  • increased stratum corneum thickness by approximately 70%

  • increased epidermal thickness by approximately 20%

  • increased rates of epidermal renewal by 6% to 11%

  • increased the minimal erythemal dose by 8.9 and 10% relative to placebo.

  • reductions in the rates of transepidermal water loss (TEWL) of approximately 20%

  • correlation between increased skin NAD content and resistance to changes in TEWL

  • Rates of TEWL changed more rapidly and to a greater extent in atopic subjects compared with normal subjects

  • no adverse effects
  • increased NAD+ levels in the skin by 25%
31SkinWozniacka et al.2006

In Search for New Antipsoriatic Agents: NAD+ Topical Composition


NAD+

0.3-1% topical, 4 weeks; 37

participants

  • reduction in erythema, infiltration, and desquamation
  • antipsoriatic 
  • none reported
  • not measured
32Skin

Sivapirabu et al. 

 
2009

Topical nicotinamide modulates cellular energy metabolism and provides broad‐spectrum protection against ultraviolet radiation‐induced immunosuppression in humans


NAM0.2-5% topical, 3 days; 70 participants
  • reduced immune suppression by 50% in both low and high doses
  • none reported
  • not measured
33SkinBisset et al.2006

Niacinamide: A B vitamin that improves aging facial skin appearance


NAM5% topical, 12 weeks; 50 participants
  • skin appearance improvement: reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, and skin sallowness, elasticity
  • none reported
  • not measured
34SkinShahmoradi et al.2013

Comparison of topical 5% nicotinamide gel versus 2% clindamycin gel in the treatment of the mild-moderate acne vulgaris: A double-blinded randomized clinical trial


NAM5% topical, 8 weeks; 60 participants
  • reduction in acne severity by 87.72% 
  • none reported
  • not measured
35SkinDraelos et al.2006

The effect of 2% niacinamide on facial sebum production


NAM2% topical, 4-6 weeks; 130 participants
  • reduced sebum excretion
  • none reported
  • not measured
36SkinSurjana et al.2012

Oral Nicotinamide Reduces Actinic Keratoses in Phase II Double-Blinded Randomized Controlled Trials


NAM500-1000 mg daily, oral, 4 months; 76 participants
  • RR reduction of 29-35% in AK
  • RR reduction new skin cancer 76%
  • none reported
  • not measured
37SkinIraji & Banan 2010

The efficacy of nicotinamide gel 4% as an adjuvant therapy in the treatment of cutaneous erosions of pemphigus vulgaris.


NAM4% topical, 30 days; 8 participants 
  • epithelialization index in the NAM group was significantly higher than that in the placebo group 
  • the average diameter of erosions after treatment in the NAM group was lower than that in the placebo group (1.30 vs. 1.75 mm)
  • local flushing and burning sensation 
  • no systemic complications
  • not measured
38SkinWozniacka et al.2005

Topical application of 1-methylnicotinamide in the treatment of rosacea: a pilot study


MeNAM0.25% topical, applied twice daily, 4 weeks; 34 patients
  • improvement was observed in 26 ⁄ 34 cases
  • improvement was good in 9 ⁄ 34 and moderate in 17 ⁄ 34, but no clinical effect was noted in seven subjects
  • itching, burning, skin irritation (1)
  • not measured
39SkinShalita et al.1995

Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris


NAM4% topical, twice daily for 8 weeks; 76 participants 
  • 82% of the patients treated with NAM gel and 68% treated with clindamycin gel were improved.
  • both treatments produced statistically similar reductions in acne lesions (papules/pustules; -60%, NAM vs. -43%, clindamycin and acne severity (-52% NAM group vs. -38% clindamycin group)
  • none reported
  • not measured 
40SkinNavarrete-Solıs et al. 2011

A Double-Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma



NAM4% topical, 8 weeks; 27 patients
  • good to excellent improvement was observed with niacinamide in 44% of patients
  • reduced the mast cell infiltrate and showed improvement of solar elastosis in melasma skin
  • side effects were present in 18% with niacinamide 
  • none reported
  • not measured
41SkinWozniacka et al.2003

Topical application of NADH for the treatment of rosacea and contact dermatitis


NADHointment, 19 patients; 2 weeks
  • 50-75% improvement
  • none reported
  • not measured
  • No labels