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Review
. 2020 May 14;9(5):425.
doi: 10.3390/antiox9050425.

Sobriety and Satiety: Is NAD+ the Answer?

Nady Braidy  1 , Maria D Villalva  1 , Sam van Eeden  2
Affiliations
Review

Sobriety and Satiety: Is NAD+ the Answer?

Nady Braidy et al. Antioxidants (Basel). .

Abstract

Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that has garnered considerable interest in the last century due to its critical role in cellular processes associated with energy production, cellular protection against stress and longevity. Research in NAD+ has been reinvigorated by recent findings that components of NAD+ metabolism and NAD-dependent enzymes can influence major signalling processes associated with the neurobiology of addiction. These studies implicate raising intracellular NAD+ levels as a potential target for managing and treating addictive behaviour and reducing cravings and withdrawal symptoms in patients with food addiction and/or substance abuse. Since clinical studies showing the use of NAD+ for the treatment of addiction are limited, this review provides literature evidence that NAD+ can influence the neurobiology of addiction and may have benefits as an anti-addiction intervention.

Keywords: NAD+, cocaine; addiction; alcohol; cellular energetics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
NAD+ biosynthesis pathways. The kynurenine pathway represents the de novo pathway of NAD+ is synthesis from catabolism of the amino acid tryptophan. NAD+ can also be synthesised via salvage of nicotinamide, nicotinic acid, nicotinic acid riboside and nicotinamide riboside form of vitamin B3. Abbreviations: NR kinase, nicotinamide riboside kinase; NAMPT, nicotinamide phosphoribosyltransferase; NMNAT, nicotinamide mononucleotide adenyltransferase; NAPRT, nicotinic acid phosphoribosyltransferase; PNP, purine nucleoside phosphorylase.
Figure 2
Figure 2
Circadian rhythms are regulated by the availability of NAD+. NAMPT is a SIRT1/CLOCK/BMAL1-regulated circadian gene. SIRT1 and NAMPT and NMNAT form part of a circadian regulatory feedback loop, regulating the availability of NAD+. NAD+ regulates SIRT1, SIRT3 and SIRT6 activities. SIRT1 also regulates CLOCK/BMAL1 expression in the suprachiasmatic nucleus. SIRT6 regulates chromatin recruitment of CLOCK/BMAL1. SIRT3 regulates oxidative phosphorylation and fatty acid oxidation in the mitochondria via circadian deacetylation of mitochondrial enzymes. Abbreviations: NAD+, nicotinamide adenine dinucleotide; NAMPT, nicotinamide phosphoribosyltransferase; NMNAT, nicotinamide mononucleotide adenyltransferase; SIRT, sirtuins.
Figure 3
Figure 3
NAD+ regulates oxytocin activity via CD38 and cADPR. Social behaviour is regulated by the amount of central OXT released due to NAD-dependent calcium release by CD38 activity and cADPR generation. Abbreviations: NAD+, nicotinamide adenine dinucleotide; NADP, nicotinamide adenine dinucleotide phosphate; CD38, NAD+ glycohydrolase; cADPR, cyclic adenosine diphosphoribose; OXT, oxytocin; NAADP, nicotinic acid adenine dinucleotide phosphate; Ryr, ryanodine receptor.
Figure 4
Figure 4
NAD+ regulates Drp1 associated in mitochondrial homeostasis. CLOCK/BMAL1 modulated mitochondrial biogenesis and mitophagy via NAD-dependent SIRT1. Deacetylation of the transcription factor PGC1A by SIRT1 regulates mitochondrial biogenesis. Drp1-mediated mitochondrial fission precedes mitophagy leading to formation of fragmented mitochondria that are taken up by autophagosomes. Abbreviations: NAD+, nicotinamide adenine dinucleotide; NAMPT, nicotinamide phosphoribosyltransferase; SIRT1, sirtuin-1; OPA1, mitochondrial dynamin like GTPase; MFN1/2, mitofusin-1/2; FIS1, mitochondrial fission 1 protein; DRP1, dynamin-related protein-1; PINK1, PTEN-induced kinase 1; BNIP1, BCL-2 interacting protein 1; PARKIN, E3 ubiquitin-protein ligase parkin.
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