Part of the paper I found most interesting was the "Human Trials" section that includes research in progress:
NAD+ boosters have shown efficacy in a variety of mouse models of human disease (Figure 4), prompting numerous clinical trials of NAD+ boosters in humans (Table 1). The most studied of the NAD+ precursors in humans is NA (niacin). In large doses, greater than a gram, NA is an effective way to treat hypercholesterolemia, as it lowers LDL and is one of the few drugs that significantly raises HDL (Altschul et al., 1955; Garg et al., 2017; Rivin, 1962). It is commercially available either as compressed NA (Niacor) or extended-release to prevent the flushing caused by prostaglandin release (Niaspan, Advicor, Simcor). Niaspan was first approved for several indications by the FDA in 1997 and later used in combination with statins for the treatment of primary hyperlipidemia and mixed dyslipidemia. NA and NAM have been or are currently being evaluated for other health benefits, including treatments for acne, kidney diseases, lupus, AD, schizophrenia, diabetes mellitus, non-small-cell lung carcinoma, obesity, HIV-induced dyslipidemia, NAFLD, sickle cell disease, and others. Though NA has been shown to raise NAD+ levels in rodents (Canto´ et al., 2012; Santidrian et al., 2013), the possibility that NA improves cholesterol profiles in humans, at least in part by raising NAD+ levels (Gariani et al., 2016), is generally not discussed in the literature.
In rodents, NAD+ boosters such as NR and NMN appear to raise NAD+ to greater levels than NA and NAM, though no head-to-head study has yet been performed. NR is currently sold by companies such as Elysium Health and HPN as a supplement, either alone or in combination with methylated resveratrol, that typically contains ‘‘Niagen’’. Research into the effects of NR and NMN in humans is gaining considerable traction, with a number of registered clinical trials being recently completed or currently underway (see Clinicaltrials. gov). For example, a randomized, double-blind, three-arm crossover pharmacokinetic study in 12 human subjects showed that NR raises NAD+ by as much as 2.7-fold in human blood with a single oral dose of 1,000 mg, with NAAD emerging as a sensitive biomarker (Trammell et al., 2016a). Researchers at the University of Washington completed a clinical trial with 140 participants showing that orally administered NR gives a dose-dependent increase in NAD+ from 250 to 1,000 mg/day, plateauing at a 2-fold increase in NAD+ at day 9 (Airhart et al., 2017). Another study reported positive effects of NR on vascular endothelial function in healthy middle-aged and older adults, with further investigations of motor and cognitive changes to come (Heilbronn, 2017). At least seven other studies are now underway assessing the effects of NR on such parameters as muscle mitochondrial function, cognition, immune function, kidney function, TBI, brown fat activity, lipid accumulation, energy metabolism, cardiovascular risk, body composition, and acetylcarnitine levels.
An international collaborative team between Keio University in Tokyo and Washington University School of Medicine in St. Louis is running a phase I human clinical study of NMN in Japan (Tsubota, 2016). Clinical trials examining the safety and efficacy of NMN are also currently being run at Washington University, investigating the effect on insulin senstivity, endothelial function, lipids, body and liver fat, and markers of cardiovascular and metabolic health. MetroBiotech, a Boston-based company, has generated a pipeline of novel NAD+ precursors, the first of which, MIB-626, is being tested in clinical trials in Boston. Calico has a program to develop NAMPT activators, but the program is on hold. Luteolin, a CD38 inhibitor, had positive neuroprotective effects on children with autism, but whether NAD+ is responsible for the benefit was not investigated (Tsilioni et al., 2015). SARM1, a promising therapeutic target for axonopathies (Essuman et al., 2017) is in preclinical development at Disarm Therapeutics.
PARP1/2 inhibitors improve the health of mice on a HFD (Cerutti et al., 2014). Although their toxicity may preclude them from use in chronic diseases, there are others with fewer side effects in development (Malyuchenko et al., 2015).