
Science of NAD
How are your NAD levels today?



The liver is said to unhelpfully break down nicotinamide riboside into NAM, but the liver is itself a great consumer of NAD, and studies show that NAD replenishment can impact both alcoholic and non-alcohol fatty liver disease.
Here are the studies:
Feb 10, 2023
Liver - NAFLD
Cells
Hepatic Nampt Deficiency Aggravates Dyslipidemia and Fatty Liver in High Fat Diet Fed Mice
Wang, Dao-Xin
SUMMARY
Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis....Taken together, our results show that hepatic Nampt deficiency aggravates dyslipidemia and liver damage in HFD fed mice. Hepatocyte Nampt can be a protective target against dyslipidemia and fatty liver.
Feb 1, 2023
Liver - Fibrosis - Chronic Liver Disease - NMN
Preprint
NAMPT Inhibition and Increased NAD-Bioavailability Atenuate Liver Damage in CCI4-Induced Mice Liver Fibrosis
Suarez-Cuenca, J.
Jan 22, 2023
Liver - NAFLD - CD38
International Journal of Medical Sciences
Mechanism of CD38 via NAD+ in the Development of Non-alcoholic Fatty Liver Disease
Dong, Min
SUMMARY
NAFLD is the most common form of liver disease, but there are no licensed medications available for its treatment. The progression of NAFLD is closely related to chronic inflammation, insulin resistance, and lipid accumulation. NAD+ is currently considered as a potential therapeutic target for NAFLD. As the critical NAD+ degrading enzyme in mammals, inhibiting of CD38 can significantly increase NAD+ levels and prevent NAFLD progression. These ideas have been confirmed in animal studies, but clinical trials still need to be verified.
Dec 28, 2022
Liver - NAFLD
Biomedical and Biophysical Research Communications
Metabolomic analysis shows dysregulation in amino acid and NAD+ metabolism in palmitate treated hepatocytes and plasma of non-alcoholic fatty liver disease spectrum
Aggarwal, Savera
Dec 8, 2022
Liver - Bioavailability
Nature Communications
The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction
Hu, Guanlan
SUMMARY
We demonstrate supplementing with nicotinamide (NAM) and related components of this pathway improve mitochondrial and overall hepatic metabolic dysfunction. We find that the effects of modulating the TRP-NAD+ pathway are mediated through SIRT1...NAM treatment can either reduce mitochondria degradation or increase its biogenesis in our model of severe malnutrition...NAM was shown to increase SIRT1 levels. The effect was not specific to NAM, as Nicotinamide Riboside (NR) and Tryptophan (TRP) demonstrated a similar effect...In our study, NAM treatment did not significantly restore NAD+ levels whereas NR did...
Nov 8, 2022
Liver - Gut Microbiome - NAFLD - Intestinal Barrier Dysfunction
International Journal of Molecular Sciences
Microbiota Dysbiosis and Gut Barrier Dysfunction Associated with Non-Alcoholic Fatty Liver Disease Are Modulated by a Specific Metabolic Cofactors’ Combination
Quesada-Vazquez, Sergio
Sep 9, 2022
Liver - NAFLD
Hepatology
NRPT reduces markers of hepatic inflammation in non-alcoholic fatty liver disease: a double-blind, placebo-controlled clinical trial
Dellinger, Ryan
SUMMARY
The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing globally on a path to becoming the most frequent cause of chronic liver disease. Novel strategies for the prevention and treatment of NAFLD are urgently needed. A 6-month prospective, randomized, double-blind, placebo-controlled clinical trial was conducted to assess the efficacy of daily NRPT (commercially known as Basis; a combination of nicotinamide riboside and pterostilbene) supplementation in 111 adults with NAFLD...This study demonstrates that NRPT at the recommended dose is safe and may hold promise in lowering markers of hepatic inflammation in patients with NAFLD.
May 25, 2022
Obesity - Liver - Inflammation
Journal of Nutritional Biochemistry
Nicotinamide riboside supplementation exerts an anti-obesity effect and prevents inflammation and fibrosis in white adipose tissue of female diet-induced obesity mice
Kim, Mi-Bo
SUMMARY
...We previously reported that NR supplementation prevented the development of liver fibrosis in male mice. However, whether NR exerts a similar effect in females is unknown. Therefore, we determined whether NR supplementation can prevent obesity-induced inflammation and fibrosis in the liver and white adipose tissue (WAT) by providing NAD+ in obese female mice...Our results indicated that NR supplementation exerted an anti-obesity effect and prevented the development of inflammation and fibrosis in the white adipose tissue of old, but not young, female mice with diet-induced obesity.
Oct 25, 2021
Liver - NAFLD
Molecular Systems Biology
Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients
Zeybel, Mujdat
SUMMARY
Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMAs) [l-carnitine tartrate to facilitate mitochondrial fatty acid uptake from cytosol, the NAD+ precursor nicotinamide riboside to induce hepatic mitochondrial β-oxidation and facilitate fatty acid transfer through the mitochondrial membrane, and the potent glutathione precursors L-serine and N-acetyl-l-cysteine to reduce oxidative stress] promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria, and eventually removes excess fat from the liver...In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients.
Mar 19, 2021
Liver
JCI Insight
SIRT3 is required for liver regeneration but not for the beneficial effect of nicotinamide riboside
Mukherjee, Sarmistha
SUMMARY
Together, our data establish an essential role for the mitochondrial sirtuin SIRT3 in liver regeneration and provide mechanistic insight into the beneficial effects of NR. Loss of SIRT3 results in mitochondrial dysfunction, lipid accumulation, and loss of hepatocyte replication in the regenerating liver. Although increasing NAD concentration is sufficient to accelerate mitochondrial metabolism in hepatocytes or the regenerating liver, the effect is independent of both SIRT3 and its nuclear counterpart SIRT1...We identify SIRT3 as a critical new player in liver regeneration and show that NAD supplementation influences metabolism independently of both SIRT1 and SIRT3.
Feb 25, 2021
Liver - NAFLD
Theranostics
NAD+-boosting therapy alleviates nonalcoholic fatty liver disease via stimulating a novel exerkine Fndc5/irisin
Li, Dong-Jie
SUMMARY
...In HFD-induced NAFLD mice model, NR displayed remarkable therapeutic effects on body weight gain, hepatic steatosis, steatohepatitis, insulin resistance, mitochondrial dysfunction, apoptosis and fibrosis...The findings from this research for the first time demonstrate that NAD+-boosting therapy reverses NAFLD by regulating SIRT2-deppendent Fndc5 deacetylation and deubiquitination, which results in a stimulation of Fndc5/irisin, a novel exerkine. These results suggest that Fndc5/irisin may be a potential nexus between physical exercise and NAD+-boosting therapy in metabolic pathophysiology.
Dec 21, 2020
Gut Microbiota - Liver
Food Science and Nutrition
Effect of nicotinamide riboside on lipid metabolism and gut microflora-bile acid axis in alcohol-exposed mice
Yu, Xioa
SUMMARY
...This study aimed to explore the effects of nicotinamide riboside (NR) on lipid metabolism and gut microflora-bile acid axis in alcohol-exposed mice. NR significantly improved liver histopathological damage and abnormal liver function... Therefore, NR supplementation has the potential to prevent Alcoholic Liver Disease (ALD), and its mechanism may be related to regulating lipid metabolism disorders and the gut microflora-bile acid axis.
May 31, 2020
Liver
Hepatology Communications
The NAD+ Metabolome is Functionally Depressed in Patients Undergoing Liver Transplantation for Alcohol-related Liver Disease
Parker, Richard
SUMMARY
These data constitute the first report of the NAD+ metabolome in human liver biopsies. Using samples from explanted and resected liver tissue, we show that the concentration of NAD+ and precursor molecules are significantly lower in ArLD compared to other liver diseases and NL tissue. The concentration of NAD+ is inversely correlated with disease activity...Liver samples from people with Alcohol-related Liver Disease show depressed NAD+ and precursor levels as well as depressed myeloperoxidase activity.
May 31, 2020
Liver - ALD
Heptology Communications
Nicotinamide Adenine Dinucleotide Metabolome Is Functionally Depressed in Patients Undergoing Liver Transplantation for Alcohol-Related Liver Disease
Parker, Richard
May 15, 2020
Metabolism - Obesity - Liver
American Journal of Clinical Nutrition
Fat Mobilization Without Weight Loss is a Potentially Rapid Response to Nicotinamide Riboside in Obese People: It’s Time to Test with Exercise
Fluharty, Noah T.
Sep 20, 2019
Liver - Bioavailability
Nature Communications
Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage
Sambeat, Audrey
SUMMARY
This work provides evidence that (1) endogenous NR metabolism is required to sustain hepatic NAD+ levels in situations of metabolic damage and lipotoxicity and, (2) the inability to use NR as a NAD+ precursor leads to mitochondrial dysfunction and amplifies the detrimental effects of HFD...There is no compensation through NAM to generate NMN and maintain hepatic NAD+ in this situation...The administration of NAM to NRK1 LKO mice neither increased NMN and NAD+ levels nor recovered their metabolic defects. Instead, the supplemented NAM seemed to be largely diverted towards clearance methylation/oxidation paths...
Sep 1, 2019
Liver - Fibrosis
Biochimica et Biophysica ⎼ Molecular Basis of Disease
Nicotinamide riboside, an NAD+ precursor, attenuates the development of liver fibrosis in a diet-induced mouse model of liver fibrosis
Pham, Tho
SUMMARY
Liver fibrosis is part of the non-alcoholic fatty liver disease (NAFLD) spectrum, which currently has no approved pharmacological treatment...Nicotinamide riboside (NR) supplementation significantly reduced body weight of mice only 7 weeks after mice were on the supplementation, but did not attenuate serum alanine aminotransferase levels, liver steatosis, or liver inflammation. However, NR markedly reduced collagen accumulation in the liver...The data suggest that NR may be developed as a potential preventative for human liver fibrosis.
Aug 28, 2019
Liver - Aging - NAFLD
PeerJ, Life and Environment
Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice
Han, Xue
SUMMARY
...Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of aging-induced NAFLD...NR repletion significantly reduced fat pat mass in aged mice, while not altered the body weight, food intake, and liver weight. NR repletion significantly rescued the NAD reduction in aged mice. The total cholesterol and triglyceride levels could be lowered by NR repletion in aged mice...Notably, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis could be markedly corrected by NR repletion. In addition, Kupffer cells accumulated and inflammatory infiltration could also be remarkably reversed by NR repletion in aged mice. Aging was associated with NAFLD-like phenotypes in mice, which could be reversed by oral NR repletion. Therefore, oral NR uptake might be a promising strategy to halt the progression of NAFLD.
May 15, 2019
Liver. - Fibrosis
Life Sciences
Nicotinamide riboside protects against liver fibrosis induced by CCl4 via regulating the acetylation of Smads signaling pathway
Jiang, Rui
Feb 13, 2019
Liver
Nutrition Research and Practice
Nicotinamide riboside regulates inflammation and mitochondrial markers in AML12 hepatocytes
Lee, Hee Jae