Nicotinamide riboside chloride: metabolism and pharmacodynamics

General Description

Nicotinamide riboside chloride is a form of vitamin B3 that has been shown to increase levels of NAD+ in the body. NAD+ is an important coenzyme involved in many cellular processes, including energy metabolism and DNA repair. Nicotinamide riboside supplementation has been found to increase NAD+ levels in a dose-dependent manner, which may have potential health benefits. However, recent research on mice has found little evidence to support the supposed metabolic advantages of nicotinamide riboside chloride. Nicotinamide riboside;chloride has also been shown to have neuroprotective effects and promote recovery after brain ischemia. Additionally, nicotinamide riboside;chloride and its derivatives have been shown to affect the composition and function of intestinal bacterial populations. Further research is needed to fully understand the potential benefits of nicotinamide riboside supplementation.

Figure .1 Nicotinamide riboside chloride

Metabolism

Nicotinamide riboside chloride is a form of vitamin B3 that has been shown to increase levels of NAD+ in the body. NAD+ is an important coenzyme involved in many cellular processes, including energy metabolism and DNA repair. Nicotinamide riboside chloride is metabolized into NMN (nicotinamide mononucleotide), which is then converted into NAD+. The increase in NAD+ levels from nicotinamide riboside supplementation has been shown to be dose-dependent, with higher doses resulting in greater increases in blood NAD+ levels. In addition, nicotinamide riboside supplementation has been found to increase the levels of NAM (nicotinamide), a byproduct of NAD+ metabolism, as well as its oxidation products Me2PY and Me4PY, which are considered to be biomarkers of increased NAD+ metabolism. These effects have been observed in both plasma and urinary samples and have also been shown to be dose-dependent. Overall, nicotinamide riboside;chloride supplementation appears to be an effective way to increase NAD+ levels in the body, which may have potential health benefits. ¹

Pharmacodynamics

Metabolic benefits

Nicotinamide riboside chloride can enhance NAD+ biosynthesis, mitochondrial function, and the activities of NAD-dependent sirtuin deacetylase enzymes. These potential benefits have been linked to cardiometabolic and musculoskeletal health. However, a recent investigation conducted on mice found little evidence that NRS increased tissue NAD+ levels, augmented mitochondrial function, and/or mitigated diet-induced hyperacetylation of the skeletal muscle proteome. ²

Promoting the recovery after brain ischemia

Nicotinamide riboside chloride is critical for supplying energy to the brain. It has been shown to be a neuroprotective factor following chronic brain injuries. However, it is unclear whether it can improve cognition after acute ischemia. In a study, mice with middle cerebral artery occlusion were treated with NR chloride (NRC) 20 minutes after reperfusion. The results showed that NRC treatment improved learning and memory function, reduced hippocampal infarct volume, neuronal loss and apoptosis. This was accompanied by an increase in Sirtin-1 and adenosine 5′ monophosphate-activated protein kinase activity, elevated NAD content and strengthened adenosine triphosphate production in the hippocampal tissues. Overall, acute NRC treatment increased energy supply, protected the hippocampus, reduced neuronal loss and apoptosis, and ultimately promoted the recovery of cognitive function after brain ischemia. ³

Alterations in intestinal bacterial populations

Nicotinamide riboside chloride and its derivatives have been shown to affect the composition and function of cecal microbial populations. In a study using Gallus gallus, intra-amniotic administration of nicotinamide riboside chloride and its derivatives resulted in altered intestinal bacterial populations, including an increase in Clostridium with Nicotinamide riboside;chloride treatment and an increase in Bifidobacterium, Lactobacillus, and E. coli with NRCl treatment. Additionally, NRTBCl exposure increased cecum weight. Duodenal gene expression analysis revealed that NRCl, NRTBCl, and NRTOCl treatments upregulated the expression of ZnT1, MUC2, and IL6, suggesting alterations in brush border membrane functionality. Further research is needed to fully understand the effects of nicotinamide riboside;chloride and its derivatives on inflammatory biomarkers and specific intestinal bacterial populations. ⁴

Reference

1. Conze D, Brenner C, Kruger CL. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Sci Rep, 2019, 9(1):9772.

2. Williams AS, Koves TR, Pettway YD, Draper JA, Slentz DH, Grimsrud PA, Ilkayeva OR, Muoio DM. Nicotinamide riboside supplementation confers marginal metabolic benefits in obese mice without remodeling the muscle acetyl-proteome. iScience, 2021, 25(1):103635.

3. Cheng YH, Zhao JH, Zong WF, Wei XJ, Xu Z, Yuan Y, Jiang YF, Luo X, Wang W, Qu WS. Acute Treatment with Nicotinamide Riboside Chloride Reduces Hippocampal Damage and Preserves the Cognitive Function of Mice with Ischemic Injury. Neurochem Res, 2022, 47(8):2244-2253.

4. Kolba N, Zarei A, Cheng J, Agarwal N, Dadmohammadi Y, Khazdooz L, Abbaspourrad A, Tako E. Alterations in Intestinal Brush Border Membrane Functionality and Bacterial Populations Following Intra-Amniotic Administration (Gallus gallus) of Nicotinamide Riboside and Its Derivatives. Nutrients, 2022, 14(15):3130.

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