Science of NAD
How are your NAD levels today?
Research involving rodents shows impressive results for NAD replenishment on models of diabetes and glucose/ insulin tolerance, but the results of human studies have not been nearly so clear...
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.
Nov 28, 2022
Diabetes - Aging
International Journal of Molecular Sciences
Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study
Nov 17, 2022
Brain - Alzheimer's - Neuroinflammation - Metabolism - Diabetes
Sirt3 deficiency induced down regulation of insulin degrading enzyme in comorbid Alzheimer’s disease with metabolic syndrome
Mitochondrial dysfunction, insulin resistance, metabolic dysregulation and neuroinflammation that contribute to cognitive decline in Alzheimer's Disease...The findings of this study suggest that SIRT3 is a potential therapeutic target for the treatment of AD. Sirtuins, including SIRT3, require NAD+ as a cosubstrate. Administration of NR, a precursor of NAD+, leads to increase in the cellular level of NAD+. In this study, we demonstrate that NR increases the levels of IDE as well as neprilysin and decreases the levels of BACE1 in vivo. Interestingly, NR also increases the levels of SIRT3, probably by autoregulation. NR has been reported to reverse insulin resistance and glucose intolerance in a mouse model for type 2 diabetes. NR has been shown to be effective in reducing neuroinflammation and improve cognition in Alzheimer’s mouse models. Therefore, NR-based treatment can be considered for the treatment of AD with comorbidities.
Nov 14, 2022
Obesity - Diabetes - Inflammation
Food & Function
Nicotinamide riboside ameliorates high-fructose-induced lipid metabolism disorder in mice via improving FGF21 resistance in the liver and white adipose tissue
Oct 17, 2022
Kidney - Inflammation - Diabetes
NAD metabolism modulates inflammation and mitochondria function in diabetic kidney disease
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.
Mar 18, 2022
Diabetes - Obesity
Nutrition & Metabolism
Effects of NAD+ precursor supplementation on glucose and lipid metabolism in humans: a meta-analysis
We found that the supplement of NAD+ precursors seems to have little effect on healthy people, but it has a significant beneficial effect on patients with cardiovascular disease and dyslipidemia. Due to the limitation of the number and quality of included studies, the above conclusions need to be verified by more high-quality studies.
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 11, 2021
NMN - Diabetes
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
In rodents, obesity and aging impair nicotinamide adenine dinucleotide (NAD+) biosynthesis, which contributes to metabolic dysfunction(1–8). Nicotinamide mononucleotide (NMN) availability is a rate-limiting factor in mammalian NAD+ biosynthesis. We conducted a 10-week, randomized, placebo-controlled, double-blind trial to evaluate the effect of NMN supplementation on metabolic function in postmenopausal women with prediabetes who were overweight or obese. Insulin-stimulated glucose disposal, assessed by using the hyperinsulinemic-euglycemic clamp, and skeletal muscle insulin signaling (phosphorylation of AKT and mTOR) increased after NMN supplementation, but did not change after placebo treatment. NMN supplementation up-regulated the expression of platelet-derived growth factor receptor β and other genes related to muscle remodeling. These results demonstrate NMN increases muscle insulin sensitivity, insulin signaling and remodeling in women with prediabetes who are overweight or obese.
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.
Jan 1, 2021
Vision - Cornea - Diabetes
Hyperglycemia-reduced NAD+ biosynthesis impairs corneal epithelial wound healing in diabetic mice
Hyperglycemia attenuated NAD+ content and NAMPT expression in the corneal epithelium of both type 1 DM mice and type 2 DM patients. Local knockdown of NAMPT by siRNA or FK866 consistently recapitulated the delayed corneal epithelial wound healing in normal mice. Moreover, NAD+ replenishment recovered the impaired proliferation and migration capacity by either FK866 or high glucose treatment in cultured corneal epithelial cells. Furthermore, in DM mice, NAD+ and its precursors nicotinamide mononucleotide and nicotinamide riboside also facilitated corneal epithelial and nerve regeneration, accompanied with the recovered expression of SIRT1 and phosphorylated EGFR, AKT, and ERK1/2 in epithelium and corneal sensitivity.
Aug 27, 2019
Diabetes - Brain
International Journal of Molecular Science
Supplementation with Nicotinamide Riboside Reduces Brain Inflammation and Improves Cognitive Function in Diabetic Mice
Lee, Hee Jae
The purpose of this study is to investigate whether nicotinamide riboside (NR) can improve inflammation and cognitive function in diabetic mice. ICR male mice were fed for 14 weeks with either high-fat chow diet (HF, 60% kcal fat) or standard chow diet (CON, 10% kcal fat). HF, streptozotocin, and nicotinamide were used to induce hyperglycemia. NR or vehicle was delivered via stomach gavage for six weeks. Oral glucose tolerance test, Y-maze test, and nest construction test were conducted before and after the NR treatment period. NR treatment induced down-regulation of NLRP3, ASC, and caspase-1. NR reduced IL-1 expression significantly by 50% in whole brains of hyperglycemic mice. Other inflammatory markers including TNF-α and IL-6 were also attenuated by NR. Brain expression of amyloid-β precursor protein and presenilin 1 were reduced by NR. In addition, NR induced significant reduction of amyloid-β in whole brains of diabetic mice. NR treatment restored hyperglycemia-induced increases in brain karyopyknosis to the levels of controls. Nest construction test showed that NR improved hippocampus functions. Spatial recognition memory and locomotor activity were also improved by NR supplementation. These findings suggest that NR may be useful for treating cognitive impairment by inhibiting amyloidogenesis and neuroinflammation.
Aug 1, 2018
Diabetes - Obesity
American Journal of Clinical Nutrition
A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: Safety, insulin-sensitivity, and lipid-mobilizing effects
...The aim of this study was to test the safety of dietary NR supplementation over a 12-wk period and potential to improve insulin sensitivity and other metabolic parameters in obese, insulin-resistant men...Insulin sensitivity, endogenous glucose production, and glucose disposal and oxidation were not improved by NR supplementation. Similarly, NR supplementation had no effect on resting energy expenditure, lipolysis, oxidation of lipids, or body composition. No serious adverse events due to NR supplementation were observed and safety blood tests were normal. 12 wk of NR supplementation in doses of 2000 mg/d appears safe, but does not improve insulin sensitivity and whole-body glucose metabolism in obese, insulin-resistant men.
Dec 6, 2017
Diabetes - Gut Microbiome
Targeted Microbiome Intervention by Microencapsulated Delayed-Release Niacin Beneficially Affects Insulin Sensitivity in Humans
In humans in vivo, gut-targeted delayed-release NA but not NAM produced a significant increase in the abundance of Bacteroidetes. In the absence of systemic side effects, these favorable microbiome changes induced by microencapsulated delayed-release NA were associated with an improvement of biomarkers for systemic insulin sensitivity and metabolic inflammation. Targeted microbiome intervention by delayed-release NA might represent a future therapeutic option for prediabetes and type 2 diabetes.
May 27, 2016
Diabetes - Neurons - Liver
Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice
Male C57BL/6J mice raised on high fat diet (HFD) become prediabetic and develop insulin resistance and sensory neuropathy. The same mice given low doses of streptozotocin are a model of type 2 diabetes (T2D), developing hyperglycemia, severe insulin resistance and diabetic peripheral neuropathy involving sensory and motor neurons. Because of suggestions that increased NAD+ metabolism might address glycemic control and be neuroprotective, we treated prediabetic and T2D mice with nicotinamide riboside (NR) added to HFD. NR improved glucose tolerance, reduced weight gain, liver damage and the development of hepatic steatosis in prediabetic mice while protecting against sensory neuropathy. In T2D mice, NR greatly reduced non-fasting and fasting blood glucose, weight gain and hepatic steatosis while protecting against diabetic neuropathy. The neuroprotective effect of NR could not be explained by glycemic control alone. Corneal confocal microscopy was the most sensitive measure of neurodegeneration. This assay allowed detection of the protective effect of NR on small nerve structures in living mice. Quantitative metabolomics established that hepatic NADP+ and NADPH levels were significantly degraded in prediabetes and T2D but were largely protected when mice were supplemented with NR. The data justify testing of NR in human models of obesity, T2D and associated neuropathies.
Dec 1, 2012
Reproduction - Pregnancy - Diabetes
Current Medicinal Chemistry
Nicotinamide Supplementation Protects Gestational Diabetic Rats by Reducing Oxidative Stress and Enhancing Immune Responses
The control group had elevated glucose and reduced insulin while nicotinamide (100 & 200 mg/kg) supplementation reversed these changes...These findings provide evidence for utilizing nicotinamide as supplement or adjunct to support existing therapeutic agents for gestational diabetes and in pregnant individuals with weakened immune systems.
Mar 20, 2004
European Nicotinamide Diabetes Intervention Trial (ENDIT): A randomised controlled trial of intervention before the onset of type 1 diabetes.