NAD+ Precursor: Regulator of Glucose Metabolism and CRP
Introduction
Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme in cells, a central cofactor of redox reaction and a central regulator of various metabolisms in the human body. It is involved in a variety of biological processes and a class of substances necessary for energy production, fatty acid and cholesterol synthesis, oxidation reaction, adenosine triphosphate (ATP) generation, gluconeogenesis and keto generation. Many clinical studies show that NAD+ supplementation has great beneficial effects on humans. On this basis, a recent investigation further unravels that supplementation of NAD+ precursors to boost NAD+ level might have a significant effect on glucose metabolism and C-reactive protein (CRP).
The association of NAD+ level and CRP level
CRP is an acute-phase response protein induced by IL-6 in hepatocytes, with distinct normal value in different population. When the body is subjected to inflammatory stimuli such as microbial invasion or tissue damage, CRP level will rise dramatically. Hence, CRP is deemed as an indicator of inflammation. The upregulation of CRP during inflammation is often accompanied by a downregulation of NAD+ level, due to the fact that the heightened inflammatory response can increase the demand for NAD+-consuming enzymes (e.g. CD38).| Population | Normal range of CRP for reference | Median |
| Adults and children | 0.068~8.2 mg/L | 0.58 mg/L |
| Newborn; umbilical cord blood | ≤0.6 mg/L | / |
| Infants aged four days to one month | ≤1.6 mg/L | / |
| Mother during delivery | ≤47 mg/L | / |
The involvement of NAD+ in regulating glucose metabolism
NAD+ plays an essential role in regulating glucose metabolism, especially in glycolysis, tricarboxylic acid (TCA) cycle and oxidative phosphorylation. NAD+ can be reduced to NADH, which in turn promotes energy production (i.e. ATP synthesis). This increased energy production helps to support various physiological functions of the body, including muscle activity and organ functioning. Furthermore, NAD+ metabolites exhibit pivotal roles in the signaling conduction, post-translational modifications, epigenetic changes and the modulation of RNA stability.The role of supplementing NAD+ precursors in glucose metabolism and liver enzymes
Following 12 weeks of NAD+ precursor supplementation, there is a significant increase in glucose (WMD: 2.17 mg/dL, 95% CI: 0.68, 3.66, P=0.004) and HbA1c (WMD: 0.11, 95% CI: 0.06, 0.16, P<0.001) as well as a marked decrease in CRP (WMD: -0.93 mg/l, 95% CI -1.47 to -0.40, P<0.001). However, no systemic changes are viewed in aspartate transaminase (AST), alanine transaminase (ALT), or alkaline phosphatase (ALP) levels in research subjects supplemented with NAD+ precursors.
Conclusion
NAD+ precursor supplementation might have an increase effect on glucose metabolism as well as a decrease in CRP, which may be especially useful for those suffering from metabolic problems (i.e. the elderly) or chronic inflammation.Reference
[1] Dall M, Hassing AS, Treebak JT. NAD+ and NAFLD - caution, causality and careful optimism. J Physiol. 2022;600(5):1135-1154. doi:10.1113/JP280908
[2] Sohouli MH, Tavakoli S, Reis MG, Hekmatdoost A, Guimarães NS. Changes in glucose metabolism, C-reactive protein, and liver enzymes following intake of NAD + precursor supplementation: a systematic review and meta-regression analysis. Nutr Metab (Lond). 2024;21(1):35. Published 2024 Jun 24. doi:10.1186/s12986-024-00812-0
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