Science of NAD
How are your NAD levels today?
There is no doubt that NAD levels are implicated in muscle function, but here the results of human studies have been unclear, even though we have seen that muscle cells with that nicotinamide riboside pathway knocked out regenerate after damage more slowly than normal muscle cells.
Here are the studies:
Feb 6, 2023
Muscle - Diabetes - Obesity
Loss of NAMPT and SIRT2 but not SIRT1 Attenuate GLO1 Expression and Activity: Potential Mechanism for Obesity-Mediated GLO1 Attenuation in Human Muscle
Glyoxolase 1 (GLO1) [a rate-limiting enzyme for detoxification of methylglyoxal, which has been implicated in Type 2 diabetes (T2D) and other age-related disorders] is decreased in muscle from individuals with obesity prior to the development of T2D. In vitro modeling of this molecular milieu via GLO1 KD in human immortalized myotubes suggest that muscle lacking GLO1 is characterized by inflammation, stress, fibrosis, and muscle dysfunction. Mechanistic experiments in human myotubes and implicate SIRT2, NAMPT, and NAD+ as potential regulators of GLO1 protein and activity and suggest that NR or other NAD precursors may be able to augment GLO1....The findings presented here demonstrating that nicotinamide riboside NR can promote GLO1 transcripts, and activity, as well as NRF2 are perhaps the most exciting data which warrant further exploration of NR as a potential therapy for the prevention and treatment of metabolic dysfunction.
Feb 6, 2023
Muscle - Muscular Dystrophy
The vitamin B3 analogue nicotinamide riboside has only very minor effects on reducing muscle damage in mdx mice
Stan, Tiberiu Loredan
Our data showed a trend for increase in NAD+-levels in blood; only in the D2-mdx NR-treated mice the NAD+-levels were slightly increased. These markers were elevated in mdx models compared to controls, but not affected by the NR treatment. Histological analysis of muscle tissues indicated a mild treatment effect in D2-mdx mice. Based on our results, testing NR treatment in clinical trials in DMD patients is not warranted.
Oct 19, 2022
Muscle - Stem Cells
Frontiers in Cell Development Biology
Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration
During regeneration, muscle stem cells (MuSCs) from [mice with both NRK1 and NRK2 knocked out] hyper-proliferate but fail to differentiate. Double NRK Knockout also alters the recovery of NAD+ during muscle regeneration as well as mitochondrial adaptations and ECM remodeling required for tissue repair. These metabolic perturbations result in a transient delay of muscle regeneration which normalizes during myofiber maturation at late stages of regeneration via over-compensation of anabolic IGF1-Akt signaling.
Oct 10, 2022
Muscle - Aging - Stem Cells
A randomized placebo-controlled trial of nicotinamide riboside and pterostilbene supplementation in experimental muscle injury in elderly individuals
...The objective of this study was to investigate if supplementation with nicotinamide riboside and pterostilbene (NRPT) promotes skeletal muscle regeneration after muscle injury in elderly individuals by improved recruitment of MuSCs...Daily supplementation with 1,000 mg NR and 200 mg PT is safe but does not improve recruitment of the MuSC pool or other measures of muscle recovery in response to injury or subsequent regeneration in elderly individuals.
May 28, 2022
Reproduction - Muscle - Postpartum
Nicotinamide Riboside Supplementation to Suckling Male Mice Improves Lipid and Energy Metabolism in Skeletal Muscle and Liver in Adulthood
...Here, we studied the long-term programming effects of mild NR supplementation during the suckling period on lipid and oxidative metabolism in skeletal muscle and liver tissues using an animal model. ...These pre-clinical findings suggest that mild NR supplementation in early postnatal life beneficially impacts lipid and energy metabolism in skeletal muscle and liver in adulthood, serving as a potential preventive strategy against obesity-related disorders characterized by ectopic lipid accumulation.
May 1, 2022
Muscle - NMN - Aging
Chronic nicotinamide mononucleotide supplementation elevates blood nicotinamide adenine dinucleotide levels and alters muscle function in healthy older men
NMN oral supplementation at 250 mg/day in healthy older men for 12 weeks was safe and well-tolerated and significantly increased the levels of NAD + and NAD +-related metabolites in whole blood. Furthermore, NMN administration partly improved muscle performance, evaluated using gait speed and grip strength, in healthy older men...NMN did not affect the skeletal muscle mass of participants in our study...Thus, the chronic oral administration of NMN could be a therapeutic strategy for aging-related disorders in humans, such as sarcopenia.
Apr 28, 2022
Muscle - Gut Microbiota - Stem Cells - Mitochondria - Obesity
Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation and gut microbiota composition in a twin study
We aimed to determine whether long-term nicotinamide riboside (NR) supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twins from 22 BMI-discordant monozygotic pairs were supplemented with an escalating dose of NR (250-1000 mg/day) for 5 months (clinicaltrials.gov entry NCT03951285). NR improved blood and tissue NAD+ metabolism, muscle mitochondrial number, myoblast differentiation and gut microbiota composition independent of BMI. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD+ metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.
Feb 2, 2022
Intravenous nicotinamide riboside elevates mouse skeletal muscle NAD + without impacting respiratory capacity or insulin sensitivity
In clinical trials, oral supplementation with nicotinamide riboside (NR) fails to increase muscle mitochondrial respiratory capacity and insulin sensitivity but also does not increase muscle NAD+ levels. This study tests the feasibility of chronically elevating skeletal muscle NAD+ in mice and investigates the putative effects on mitochondrial respiratory capacity, insulin sensitivity, and gene expression...We conclude that the chronic elevation of skeletal muscle NAD+ by the intravenous injection of NR is possible but does not affect muscle respiratory capacity or insulin sensitivity in either sedentary or physically active mice. Our data have implications for NAD+ precursor supplementation regimens.
Dec 16, 2021
Obesity - Muscle
Nicotinamide riboside supplementation confers marginal metabolic benefits in obese mice without remodeling the muscle acetyl-proteome
Williams, Ashley S.
...This investigation examined the impact of nicotinamide riboside supplementation on whole body energy homeostasis, skeletal muscle mitochondrial function, and corresponding shifts in the acetyl-lysine proteome, in the context of diet-induced obesity using C57BL/6NJ mice. The study also included a genetically modified mouse model that imposes greater demand on sirtuin flux and associated NAD+ consumption, specifically within muscle tissues. In general, whole body glucose control was marginally improved by nicotinamide riboside supplementation when administered at the midpoint of a chronic high-fat diet, but not when given as a preventative therapy upon initiation of the diet. Contrary to anticipated outcomes, the study produced little evidence that NRS increases tissue NAD+ levels, augments mitochondrial function, and/or mitigates diet-induced hyperacetylation of the skeletal muscle proteome.
Sep 13, 2021
Obesity - Muscle
Frontiers in Nutrition
Nicotinamide Riboside Neutralizes Hypothalamic Inflammation and Increases Weight Loss without Altering Muscle Mass in Obese Rats under Calorie Restriction: A Preliminary Investigation
Macedo de Castro, Josimar
Obesity treatments, such as calorie restriction (CR), eventually lead to muscle wasting and higher rates of neuroinflammation, whereas hypothalamic inflammatory conditions impair body weight (BW) control. Nicotinamide riboside (NR) has been proposed against obesity but with little evidence on skeletal muscle tissue (SMT) and neuroinflammation...NR supplementation, in all groups, enhanced weight loss and increased relative weight of the skeletal muscle tissue. Furthermore, in animals under calorie restriction, NR reversed increases TNF-α levels in the hypothalamus...NR emerges as a potential adjuvant for preventing muscle mass loss in the weight loss processes.
Jul 30, 2021
Diabetes - Muscle - Insulin Sensitivity
Comment on “Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
Yoshino et al. have reported that nicotinamide mononucleotide (NMN) increases muscle insulin sensitivity in prediabetic women. However, the 13 women who received NMN had hepatic lipid content of 6.3 ± 1.2%, whereas the 12 in the placebo group had 14.8 ± 2.0% (P = 0.003). Given that a target of NMN is liver fat clearance, this was not an effectively randomized trial
Jun 30, 2021
Muscle - NAM / NA
Journal of Nutrition
NAD+-Precursor Supplementation With L-Tryptophan, Nicotinic Acid, and Nicotinamide Does Not Affect Mitochondrial Function or Skeletal Muscle Function in Physically Compromised Older Adults
Boosting NAD+ via supplementation with niacin equivalents has been proposed as a potential modality capable of promoting healthy aging and negating age-dependent declines of skeletal muscle mass and function. We investigated the efficacy of NAD+-precursor supplementation (tryptophan, nicotinic acid, and nicotinamide) on skeletal muscle mitochondrial function in physically compromised older adults...skeletal muscle methyl-nicotinamide levels were significantly higher under NAD+-precursor supplementation, suggesting an increased NAD+ metabolism...Our findings are consistent with previous findings on NAD+ efficacy in humans, and we show in community-dwelling, older adults with impaired physical function that NAD+-precursor supplementation through L-tryptophan, nicotinic acid, and nicotinamide does not improve mitochondrial or skeletal muscle function.
Mar 1, 2021
Poultry - Reproduction - Muscle
The effects of in ovo nicotinamide riboside dose on broiler myogenesis
The objective of this study was to determine the effects of in ovo injection of nicotinamide riboside (NR) on broiler embryonic myogenesis....Chicks injected with NR had greater Pectoralis major muscle weight and length...Injecting developing embryos at day 10 of incubation increased hatched chick Pectoralis major muscle morphometrics, which were partly because of the NR catalyzed increase in muscle fiber density.
Jan 19, 2021
Muscle - Aging
NAD+ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle
Aging is characterized by loss of proteostasis and mitochondrial homeostasis. Here, we provide bioinformatic evidence of dysregulation of mitochondrial and proteostasis pathways in muscle aging and diseases...Treatment of either aged N2 worms, a nematode model of amyloid-beta muscle proteotoxicity, human aged myotubes, or old mice with the NAD+ boosters nicotinamide riboside (NR) and olaparib (AZD) increases mitochondrial function and muscle homeostasis while attenuating amyloid accumulation. Hence, our data reveal that age-related amyloidosis is a contributing factor to mitochondrial dysfunction and that both are features of the aging muscle that can be ameliorated by NAD+ metabolism-enhancing approaches, warranting further clinical studies.
Oct 7, 2020
Need for NAD+: Focus on Striated Muscle Laminopathies
Laminopathies are a heterogeneous group of rare diseases caused by genetic mutations in the LMNA gene, encoding A-type lamins. A-type lamins are nuclear envelope proteins which associate with B-type lamins to form the nuclear lamina, a meshwork underlying the inner nuclear envelope of differentiated cells...Here, we have summarized these findings and reviewed the current knowledge about NAD+ alteration in striated muscle laminopathies, providing potential therapeutic approaches...NAMPT is important for muscle function. A recent study showed that deleting NAMPT in mice leads to a decreased NAD+ muscle content and a significant alteration in muscle mass and endurance...
Aug 1, 2020
Muscle - Obesity
American Journal of Clinical Nutrition
Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans
NR supplementation of 1000 mg/d for 6 wk in healthy overweight or obese men and women increased skeletal muscle NAD+ metabolites, affected skeletal muscle acetylcarnitine metabolism, and induced minor changes in body composition and sleeping metabolic rate. However, no other metabolic health effects were observed.
Jul 16, 2020
Poultry - Reproduction - Muscle
Translational Animal Science
In ovo feeding of nicotinamide riboside affects broiler pectoralis major muscle development
The objective of this study was to examine the effect of nicotinamide riboside (NR) on pectoralis major muscle (PM) development and growth...There were no treatment × location or main effects for all body morphometric measurements (P > 0.07), except chest width of chicks from eggs injected in the yolk were wider (P = 0.01) than chicks from eggs injected in the albumen... Injecting NR into the yolk sac of the developing embryo at day 10 of incubation increased pectoralis major development which was due to an increase in muscle density.
May 7, 2020
Muscle - Mitochondrial Myopathy
Niacin Cures Systematic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy
Our main question was whether NAD+ levels are depleted in mitochondrial dysfunction, as mitochondria are regulating NAD+ concentrations, and if so, whether NAD+ deficiency can be restored in the tissues of the patients...Here, we show that mitochondrial myopathy patients have depressed systemic NAD+ metabolism that can be functionally addressed with a high dose of niacin....
Apr 8, 2020
Muscle - Muscular Dystrophy
Nutraceutical and pharmaceutical cocktails did not preserve diaphragm muscle function or reduce muscle damage in D2-mdx mice
Duchenne muscular dystrophy is characterized by the absence of dystrophin protein and causes muscle weakness and muscle injury, culminating in respiratory failure and cardiomyopathy. Quercetin transiently improved respiratory function but failed to maintain long-term therapeutic benefits in mdx mice. In this study, we combined quercetin with nicotinamide riboside (NR), lisinopril and prednisolone to assess the efficacy of quercetin-based cocktails. We hypothesized that quercetin, NR and lisinopril independently would improve respiratory function and decrease diaphragmatic injury and when combined would have additive effects...Contrary to expectations, these functional and histological parameters of disease were not offset by any intervention. These data suggest that quercetin, NR and lisinopril, independently and in combination, did not prevent diaphragmatic injury or preserve respiratory function.