Science of NAD
How are your NAD levels today?
Nerve health impacts how we think and how we move, but replenishing NAD in nerve cells is peculiarly difficult because the metabolic pathway used by niacin is not active in neurons. And yet degenerative nerve disorders and dementia are when we most might most need to maintain our NAD levels.
Here are the studies:
Feb 6, 2023
Neurons - Brain - Parkinson's
Could Vitamins Have a Positive Impact on the Treatment of Parkinson’s Disease?
"...Vitamin B3 supplementation has been shown to alleviate various symptoms associated with PD...Mechanistically, vitamin B3 promotes the biosynthesis of the classical enzyme cofactor nicotinamide adenine dinucleotide (NAD) and mediates the release of nicotinamide by poly-ADP ribosylation. This generates an anti-inflammatory response, which alleviates DA-ergic neurodegeneration caused by neuroinflammation. These findings suggest that dietary supplementation with vitamin B3 may ameliorates oxidative stress and neuroinflammation, which would therefore prevent the death of DA-ergic neurons..."
Jan 19, 2023
Neurons - Spinal Cord Injury
Elevation of NAD+ by nicotinamide riboside spares spinal cord tissue from injury and promotes locomotor recovery
Administration of the NAD+ precursor, NR, to elevate NAD+ within the injured spinal cord mitigates the tissue damage and functional decline that occurs following spinal cord injury….administration of NR enhances NAD+ levels within the injured rat spinal cord, reduces tissue damage, and improves locomotor recovery after a thoracic spinal cord contusion injury in rats. Collectively, the results show that NR is a safe and effective bioavailable agent that can mitigate spinal cord damage.
Jan 13, 2023
Neurons - Neurodegeneration - Parkinsons - Alzheimer's - Huntington's Disease - ALS
International Journal of Molecular Sciences
A Promising Strategy to Treat Neurodegenerative Diseases by SIRT3 Activation
Dec 26, 2022
Neurons - Neurodegeneration - Alzheimer's Disease - Parkinson's Disease
Combined metabolic activators improve metabolic functions in the animal models of neurodegenerative diseases
We showed that combined metabolic activators [including nicotinamide riboside] administration significantly improved behavioural scores in parallel with the neurohistological outcomes in the Alzheimer's Disease and Parkinson's Disease animal models and is a promising treatment for improving the metabolic parameters and brain functions in neurodegenerative diseases.
Dec 14, 2022
Brain - Neurons - Neurodegeneration - Inflammation - Alzheimer's
Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin
We report the first study examining [extracellular vesicles enriched for neuronal origin or "NEV"] NEV biomarkers in response to oral NR supplementation. Our primary analysis of NAD+ and NADH in NEVs suggests an increase in neuronal NAD+ concentration in response to oral NR supplementation....We demonstrate that oral NR supplementation [in humans] increases NAD+ levels in NEVs ...These findings support the ability of orally administered NR to augment neuronal NAD+ levels and modify biomarkers related to neurodegenerative pathology in humans.
Jul 25, 2022
Neurons - Leigh Syndrome - Mitochondrial Dysfunction
Clinical and Translational Medicine
Metabolic rescue ameliorates mitochondrial encephalo-cardiomyopathy in murine and human iPSC models of Leigh syndrome
Our study reveals direct mechanistic explanations of the observed cardiac bradyarrhythmia, diastolic dysfunction and neuronal apoptosis in mouse and human induced pluripotent stem cells (iPSC) models of Leigh Syndrome….Metabolic rescue by nicotinamide riboside (NR) supplementation increased intracellular NAD+/ NADH, restored metabolic derangement, reversed protein hyperacetylation through NAD+‐dependent Sirtuin deacetylase, and ameliorated cardiomyopathic phenotypes...NR also attenuated neuronal apoptosis and microglial activation...
Jun 27, 2022
Neurons - Neuropathy - Cancer - Chemotherapy
Nicotinamide riboside alleviates cisplatin-induced peripheral neuropathy via SIRT2 activation
We show that NR, an NAD+ precursor and pharmacologic activator of SIRT2, effectively prevents and alleviates CIPN in mice. We present in vitro and in vivo genetic evidence to illustrate the specific dependence on SIRT2 of NR-mediated CIPN mitigation. Importantly, we demonstrate that NAD+ mediates SIRT2-dependent neuroprotection without inhibiting cisplatin cytotoxic activity against cancer cells. NAD+ may, in fact, further sensitize certain cancer cell types to cisplatin.
Apr 28, 2022
Diabetes - Neuropathy - Neurons
International Journal of Molecular Sciences
NAD+ Precursors Repair Mitochondrial Function in Diabetes and Prevent Experimental Diabetic Neuropathy
Diabetic peripheral neuropathy (DPN) is a common neurological complication of diabetes. Currently, there is no therapy that permanently prevents or reverses neuropathy. ...Correction of NAD+ depletion [with dietary NR] in dorsal root ganglion neurons may be sufficient to prevent diabetic peripheral neuropathy, but does not significantly affect glucose tolerance, insulin levels, or insulin resistance.
Jan 3, 2022
Neurons - Neuropathy - Eye - Chemotherapy
Nicotinamide Riboside Alleviates Corneal and Somatic Hypersensitivity Induced by Paclitaxel in Male Rats
Paclitaxel-treated rats developed corneal hypersensitivity to tactile stimuli, enhanced sensitivity to capsaicin but not hyperosmolar saline, and increased basal tear production. Corneal nerve density visualized with anti–β-tubulin or calcitonin gene-related peptide (CGRP) was unaffected. Paclitaxel induced tactile and cool hypersensitivity of the hindpaw and a loss of nonpeptidergic hindpaw IENFs visualized with anti-protein gene product (PGP) 9.5 and CGRP. NR reversed tactile hypersensitivity of the cornea without suppressing tear production or chemosensitivity; it did not alter corneal afferent density. NR also reversed tactile and cool hypersensitivity of the hindpaw without reversing the loss of hindpaw IENFs.
Sep 1, 2021
Brain - Neurons
Mechanisms of Aging and Development
Risks and rewards of targeting NAD+ homeostasis in the brain
Strategies to correct declining nicotinamide adenine dinucleotide (NAD+) levels in neurological disease and biological ageing are promising therapeutic candidates. These strategies include supplementing with NAD+ precursors, small molecule activation of NAD+ biosynthetic enzymes, and treatment with small molecule inhibitors of NAD+ consuming enzymes such as CD38, SARM1 or members of the PARP family. While these strategies have shown efficacy in animal models of neurological disease, each of these has the mechanistic potential for adverse events that could preclude their preclinical use. Here, we discuss the implications of these strategies for treating neurological diseases, including potential off-target effects that may be unique to the brain.
Jun 17, 2021
Neurons - Brain - Parkinson's - Niacin
Frontiers in Aging Neuroscience
Niacin Enhancement for Parkinson’s Disease: An Effectiveness Trial
We previously reported that individuals with Parkinson’s disease (PD) present with lower vitamin B3 levels compared to controls. It may be related to carbidopa interaction, defective tryptophan metabolism, and stresses of night sleep disorder...These results suggest that niacin enhancement has the potential to maintain or improve quality of life in PD and slow disease progression.
Jun 1, 2021
Diabetes - Neurons - Kidney - NMN
Journal of the American Society of Nephrology
Could NAD+ Precursor Supplements Induce a Legacy of Protection against Diabetic Nephropathy?
Hyndman, Kelly A.
Diabetic nephropathy (DN) is a complex disease with microvascular complications, profound changes in metabolism, inflammation, and redox status, leading to structural and functional changes that can culminate in End Stage Kidney Disease (ESKD)...500NMN mice had lower mortality and significantly improved urinary albumin-creatinine ratios even at 20 weeks post-treatment compared with the db/db mice. ...Therapeutic protocols leading to legacy effects by epigenetic reprogramming of the salvage pathway to sustain or even increase kidney NAD+ show promise for slowing the development of DN.
Mar 2, 2021
Neurons - Neurodegeneration - NMN
SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration
Figley, Matthew D.
Nov 10, 2020
Brain - ALS - Neurons
Nicotinamide Riboside and Pterostilbene Cooperatively Delay Motor Neuron Failure in ALS SOD1(G93A) Mice
Oxidative stress-induced damage is a major mechanism in the pathophysiology of amyotrophic lateral sclerosis (ALS). A recent human clinical trial showed that the combination of nicotinamide riboside (NR) and pterostilbene (PT), molecules with potential to interfere in that mechanism, was efficacious in ALS patients. We examined the effect of these molecules in SOD1G93A transgenic mice, a well-stablished model of ALS. Assessment of neuromotor activity and coordination was correlated with histopathology, and measurement of proinflammatory cytokines in the cerebrospinal fluid. Cell death, Nrf2- and redox-dependent enzymes and metabolites, and sirtuin activities were studied in isolated motor neurons. NR and PT increased survival and ameliorated ALS-associated loss of neuromotor functions in SOD1G93A transgenic mice. NR and PT also decreased the microgliosis and astrogliosis associated with ALS progression. Increased levels of proinflammatory cytokines were observed in the cerebrospinal fluid of mice and humans with ALS. NR and PT ameliorated TNFα-induced oxidative stress and motor neuron death in vitro. Our results support the involvement of oxidative stress, specific Nrf2-dependent antioxidant defenses, and sirtuins in the pathophysiology of ALS. NR and PT interfere with the mechanisms leading to the release of proapoptotic molecular signals by mitochondria, and also promote mitophagy.
Oct 20, 2020
Neurons - Neurodegeneration
Deletion of CD38 and Supplementation of NAD+ Attenuate Axon Degeneration in a Mouse Facial Nerve Axotomy Model
We have shown that, following facial nerve axotomy, axon degeneration, demyelination, and infiltration of immune cells are suppressed in CD38 KO mice compared with that in WT mice. Furthermore, supplementation of NAD+ with NR slowed the axon degeneration and demyelination in WT mice....These results suggest that CD38 deletion and supplementation of NAD+ may protect transected axon cell-autonomously after facial nerve axotomy.
Oct 15, 2020
Brain - Neurons - Alzheimer's Disease
Frontiers in Aging Neuroscience
Axonal Degeneration in AD: The Contribution of Aβ and Tau
Oct 1, 2020
Neurons - Neuropathy - Cancer
Nicotinamide riboside relieves paclitaxel-induced peripheral neuropathy and enhances suppression of tumor growth in tumor-bearing rats
Nicotinamide riboside (NR) is a vitamin B3 precursor of NAD that blunts diabetic and chemotherapy-induced peripheral neuropathy in preclinical models. This study examined whether NR also blunts the loss of intraepidermal nerve fibers induced by paclitaxel, which is associated with peripheral neuropathy...Unexpectedly, concomitant administration of NR during paclitaxel treatment further decreased tumor growth; thereafter, tumor growth resumed at the same rate as vehicle-treated controls. Administration of NR also decreased the percentage of Ki67-positive tumor cells in these rats...These results further support the ability of NR to play a protective role after nerve injury. They also suggest that NR may not only alleviate peripheral neuropathy in patients receiving taxane chemotherapy, but also offer an added benefit by possibly enhancing its tumor-suppressing effects.
Jul 1, 2020
Neurons - Gulf War Illness
Targeting sirtuin activity with nicotinamide riboside reduces neuroinflammation in a GWI mouse model
...These findings suggest that targeting Nicotinamide Riboside mediated Sirt1 activation restores brain bioenergetics and reduces inflammation in GWI mice. Further evaluation of NR in GWI is warranted to determine its potential efficacy in treating GWI...we propose that strategies to increase NAD levels via NR intervention will likely be therapeutically beneficial in GWI.
Jun 22, 2020
Neurons - autism / anxiety
Nicotinamide riboside supplementation corrects deficits in oxytocin, sociability and anxiety of CD157 mutants in a mouse model of autism spectrum disorder
Oxytocin (OT) is a critical molecule for social recognition and memory that mediates social and emotional behaviours. In addition, OT acts as an anxiolytic factor and is released during stress...Here, we show that CD157 knockout mice have low levels of circulating OT in cerebrospinal fluid, which can be corrected by the oral administration of nicotinamide riboside, a recently discovered vitamin precursor of nicotinamide adenine dinucleotide (NAD)...Nicotinamide riboside corrects social deficits and fearful and anxiety-like behaviours in CD157 knockout males. These results suggest that elevating NAD levels with nicotinamide riboside may allow animals with cADPR- and OT-forming deficits to overcome these deficits and function more normally.