Introduction
Why NAD+?
NAD+ boosting strategies: preclinical evidence
Exercise and caloric restriction induce nicotinamide phosphoribosyltransferase expression through AMPK
NAD+ precursors increase NAD+ bioavailability and activate SIRTs
Inhibition of NADases increases NAD+ bioavailability and SIRT1 activity
How to boost NAD+ in humans?
Increasing NAD+ bioavailability through exercise and caloric restriction
Supplementation of NAD+ precursors
Inhibition of NAD+ consumers
Future perspective
ClinicalTrials.gov registration no. | Title | Disease/condition | Interventions | Outcome measures | Sex | Participant age (years) and number | Study design |
---|---|---|---|---|---|---|---|
NCT03540758 | Regulation of endogenous glucose production by central KATP channels | T2D; glucose metabolism disorders; high BG | Drugs: diazoxide ± nicotinic acid or placebo | EGP | M and F | 21–65 (adult, older adult) n = 45 | Randomised, SGA, single maskeda, for basic science purposes |
NCT03432871 | Nicotinamide riboside and mitochondrial biogenesis | Mitochondrial diseases | Dietary supplement: nicotinamide riboside | Bioavailability; safety (treatment-related AEs, blood analytes, temperature, BP, pulse); mitochondrial biogenesis (MRI, respiratory chain enzyme analysis, mitochondrial DNA quantification); mitochondrial disease symptoms (dynamometric measure of muscle strength, 6 minute walk test, QOL [SF-36; qualitative], TUG) | M and F | 18–70 (adult, older adult) n = 15 | SGA, no masking (open label), for treatment purposes |
NCT03310034 | NAD supplementation study (NADS) | Ageing | Dietary supplement: NAD+ precursors (nicotinic acid, nicotinamide and Trp) or control | Ex vivo mitochondrial respiration; basal metabolic rate; in vivo mitochondrial capacity; submaximal exercise energy expenditure; glucose tolerance; ectopic lipid accumulation; acetylcarnitine levels; physical function | M and F | 65–75 (older adult) n = 14 | Randomised, crossover assignment, double maskingb, for basic science purposes |
NCT03151707 | The effects of nicotinamide riboside supplementation on NAD+/NADH ratio and bioenergetics | Healthy | Drug: nicotinamide riboside | Brain NAD+/NADH ratio; brain PCr/ATP ratio; creatine kinase enzyme rate | M and F | 18–65 (adult, older adult) n = 60 | SGA, no masking (open label), for treatment purposes |
NCT03151239 | Effect of ‘nicotinamide mononucleotide’ (NMN) on cardiometabolic function | Glucose metabolism disorders | Dietary supplement: NMN or placebo | Insulin sensitivity; beta cell function | F | 55–75 (adult, older adult) n = 50 | Randomised, parallel assignment, triple maskingc, for basic science purposes |
NCT02950441 | Nicotinamide adenine dinucleotide and skeletal muscle metabolic phenotype (NADMet) | Ageing | Dietary supplement: nicotinamide riboside or placebo | Mitochondrial function in skeletal muscle (high resolution respirometry); skeletal muscle NAD+ levels in vastus lateralis biopsy (targeted metabolomics); response to OGTT/HOMA-IR; lipid profile; muscle arterio-venous difference (tissue-specific metabolite trafficking, O2 consumption, CO2 production); muscle biopsy (adaptive expression profile [genomic]); RMR (indirect calorimetry); NAD+ metabolomics, changes in steroid ratios in 24 h urine collection (GC/MS); muscle strength (grip testing) | Male | 70–80 (older adult) n = 12 | Randomised, crossover assignment, quadruple maskingd, for treatment purposes |
NCT02835664e | Nicotinamide riboside and metabolic health | Obesity; insulin resistance | Dietary supplement: nicotinamide riboside or placebo | Muscle and liver insulin sensitivity; ex vivo muscle mitochondrial function; ectopic lipid accumulation; BAT activity; cardiovascular risk variables; whole body EE; body composition; acetylcarnitine levels | M and F | 45–65 (adult, older adult) n = 15 | Randomised, crossover assignment, quadruple maskingd, for treatment purposes |
NCT02689882e | Pharmacokinetic study of nicotinamide riboside | Metabolic disturbance | Dietary supplement: nicotinamide riboside | Average Css of nicotinamide riboside and NAD following up-titration to 1000 mg by mouth twice daily; serum levels of K+, creatine kinase, glucose, uric acid and ALT | M and F | 21–50 (adult) n = 8 | SGA, no masking (open label) |
NCT02303483e | The effect of vitamin B3 on substrate metabolism, insulin sensitivity, and body composition in obese men | Obesity | Dietary supplement: nicotinamide riboside or placebo | Insulin sensitivity; substrate metabolism; body composition; activation of satellite cells; lipid accumulation in liver and skeletal muscle; glucose turnover; insulin signalling in skeletal muscle and adipose tissue biopsies; palmitate turnover; gut microbiota; incretin hormone secretion | M | 40–70 (adult, older adult) n = 40 | Randomised, parallel assignment, quadruple maskingd, for treatment purposes |
NCT02300740e | Pharmacokinetic analysis of nicotinamide riboside | Healthy | Dietary supplement: nicotinamide riboside | Serum nicotinamide riboside; metabolites of nicotinamide riboside; AUC for serum nicotinamide riboside; T1/2, Cmax and Tmax of serum nicotinamide riboside | M | 18–30 (adult) n = 12 | Randomised, crossover assignment, no masking (open label), for treatment purposes |
NCT01321034e | Effect of niacin in the lipoprotein (a) concentration | Hypercholesterolaemia | Drug: niacin/laropiprantf | Absolute and relative Lp(a) lowering effect of niacin/laropiprant at 1 g/20 mg and 2 g/40 mg per day in participants with normal, high and very high Lp(a) (<1.07 μmol/l, 1.07–2.14 μmol/l and > 2.14 μmol/l, respectively) and depending on number of KIV-2 repeated copies on the apo(a) gene | M an F | 18–80 (adult, older adult) n = 90 | SGA, no masking (open label), for treatment purposes |
NCT01216956e | Metabolic effects of an 8 week Niaspan treatment in patients with abdominal obesity and mixed dyslipidemia | Obesity and dyslipidaemia | Drug: ER nicotinic acid or placebo | NEFA and triacylglycerol concentrations over time; insulin sensitivity; lipoprotein metabolism; lipid profile | M | 18–65 (adult, older adult) n = 24 | Randomised, crossover assignment, double maskingb, for treatment purposes |
NCT00618995e | A study to evaluate the effects of ER niacin/laropiprant, laropiprant, ER niacin, and placebo on urinary prostanoid metabolites (0524A-079) | T2D | Drug: ER niacin + laropiprantf or ER niacin or laropiprantf or placebo | 11-dTxB2; PGIM | M and F | 18–65 (adult, older adult) n = 26 | Randomised, crossover assignment, double maskingb, for treatment purposes |
NCT00485758e | Extended niacin/laropiprant in patients with type 2 diabetes (0524A-069) | T2D | Drug: ER niacin/laropiprantf or placebo (unspecified) | LDL-c; HDL-c; triacyclglycerol | M and F | 18–80 (adult, older adult) n = 796 | Randomised, parallel assignment, double maskingb, for treatment purposes |