This paper offers some ideas for increasing cellular [NAD+].Houtkooper, Riekelt H., and Johan Auwerx. "Exploring the therapeutic space around NAD+." The Journal of cell biology 199.2 (2012): 205-209.
Brief literature searches offer these possible interventions:Precursors:
diet/supplements: nicotinamide, nicotinamide riboside, nicotinic acid, tryptophan
experimental: nicotinamide mononucleotideAMPK inducers:
lifestyle: caloric restriction, fasting, endurance exercise
diet/supplements: aspirin, berberine, resveratrol, quercetin, anthocyanins, genistein, EGCG, capsaicin, curcumin, garlic oil, hispidulin (Snow Lotus), glabridin (deglycyrrhizinated licorice), gelegine (goats rue)
prescription drugs: metformin, phenformin, rosiglitazone, pioglitazone, troglitazone, salsalate, phenobarbital
experimental: 5-aminoimidazole-4-carboxamide riboside (Acadesine, AICAR), dinitrophenol, oligomycin, 2-deoxyglucose, A23187, A769662, PT1poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors:
experimental: H2O2, 3-aminobenzamide, 1,5-dehydroxyisoquinoline, 5-aminoisoquinolinone, 1,5-isoquinolinediol, N-(6-oxo-5,6-dihydro-phenanthridin-2-yl) -N,N-dimethylacetamide (PJ-34), 5-iodo-6-amino-1,2-benzopyrone; thieno[2,3-c]isoquinolin-5-one, BGP-15, GPI 6150, INO-1001, L-2286 Sirtuin inhibitors
(on balance, maybe not a good idea):
supplements: nicotinamide, nicotinamide riboside
experimental: NADH, carbamido-NAD, dihydrocoumarin, splitomicin, 2-OH-napthaldehyde, sirtinol, M15
Another useful review is:Bogan, Katrina L., and Charles Brenner. "Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition." Annu. Rev. Nutr. 28 (2008): 115-130.
High dose nicotinic acid used to treat dyslipidemia has well known skin flushing side effect. Nicotinamide doesn't cause flushing, but lacks the lipid benefits
, and may be hepatotoxic at high doses
. Nicotinamide riboside shouldn't cause flushing, and has much greater potential to increase [NAD+] in neurons, but its potential for high-dose hepatoxicity has not been evaluated, and like nicotinamide, its also a potential inhibitor of sirtuins:Sasaki, Yo, Toshiyuki Araki, and Jeffrey Milbrandt. "Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy." The Journal of neuroscience 26.33 (2006): 8484-8491.Belenky, Peter, et al. "Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD." Cell 129.3 (2007): 473-484.
I suspect one could achieve fairly high [NAD+] with far less than 500 mg/kg of a research reagent by combining high-dose nicotinic acid (if the flushing is tolerable) or more moderate-dose nicotinamide riboside (superior for brain [NAD+], but I'd like to see if it inhibits Sirt1), intermittent fasting + endurance exercise, a high polyphenol diet, aspirin (at AMPK activating dosages
), and optionally, berberine or metformin.
Edited by Darryl, 21 December 2013 - 02:10 AM.