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The powerhouse at the bottom of the anti-aging world——NMNH

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The powerhouse at the bottom of the anti-aging world——NMNH

2024-08-27 10:00:38


Since the discovery of NMN by the team of Harvard professor David Sinclair in 2013, NMN has continued to be popular in the anti-aging community and is known and used by more and more people. However, in 2021, the team of Professor Deng Haiteng of Tsinghua University published an article titled "Reduced Nicotinamide Mononucleotide (NMNH) Potently Enhances NAD+ and Suppresses Glycolysis, the TCA Cycle, and Cell Growth" in the "Journal of Proteome Research", indicating: As a new type of NAD+ supplement, NMNH has better anti-aging ability in vivo and in vitro than NMN.

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01.NMNH increases cellular NAD+ and NADH levels. Researchers compared the effects of NMN and NMNH on increasing cellular NAD+ levels. Treatment with NMNH (100 μM) increased cellular NAD+ levels by 5-fold in HepG2 cells, whereas 100 μM NMN only slightly increased NAD+ levels. In addition to HepG2 cells, the researchers also confirmed that NMNH enhanced NAD+ in ES-2 cells and 3T3-L1 cells, which are human ovary-derived cells and mouse embryonic fibroblast-derived cells, respectively. And the researchers also found that NMNH increased cellular NAD+ levels in 786-O cells in a time- and concentration-dependent manner. The researchers measured NADH using mass spectrometry and found that NADH levels in NMNH-treated HepG2 cells were 2.5 times higher than untreated and NMN-treated cells, and elevated NADH levels were also detected in NMNH-treated 786-O cells. We also found that 340 mg/kg NMNH treatment increased NADH levels in mouse livers by 3-fold, while 340 mg/kg NMN treatment increased NADH levels by 1.7-fold.
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Figure 1.2. NMNH increases NAD+ levels

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Figure 3.4. NMNH increases NMNH levels

02NMNH inhibits glycolysis and TCA cycle. The accumulation of NADH slows down glycolysis and TCA cycle. To examine the metabolic response of cells to NMNH treatment, the researchers performed metabolomic analysis of NMNH- and NMN-treated cells. It was found that NMNH treatment not only reduced the levels of glycolysis intermediates, but also reduced the levels of TCA cycle intermediates. These results indicate that the accumulation of NADH produced by NMNH inhibits cellular glycolysis and TCA cycle.
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Figure 5. Reduced glycolysis and TCA cycle intermediates

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Figure 6. Metabolomics analysis

03.NMNH inhibits cell growth Researchers explored the effect of NMNH on cell growth and found that NMNH treatment inhibited HepG2 cell growth at concentrations higher than 250 μM. The researchers analyzed the cell cycle in HepG2 cells treated with 1 mM NMNH or NMN for 12 hours and found that NMNH caused cell cycle arrest, while NMN had no effect on the cell cycle. In addition, the researchers also found that 500 μM NMNH completely blocked the growth of 786-O cells; 250 μM NMNH could effectively inhibit cell growth in HK-2 cells.
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Figure 7.8.NMNH inhibits cell growth in vitro

04.NMNH safety researchers conducted experiments on whether high doses of NMNH induce hepatotoxicity. Treatment of C57BL/6J male mice with 50, 100, 500, or 1000 mg/kg NMNH via intraperitoneal injection every other day for one week revealed no decrease in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Elevated, indicating that NMNH is not hepatotoxic at high doses. In addition, the researchers also found that NMNH treatment increased the NAD+ content in mouse livers in a dose-dependent manner. Treatment with 1000 mg/kg NMNH increased the NAD+ levels in mouse livers by more than 10 times.
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Figure 10.NMNH increases the level of NAD+ in the liver of mice

Studies have demonstrated that NMNH is a better NAD+-boosting supplement than NMN both in vitro and in vivo; additionally, NMNH increases reduced NAD (NADH) levels in cells and mouse livers. Metabolomic analysis showed that NMNH inhibits glycolysis and TCA cycle. In vitro experiments show that NMNH induces cell cycle arrest and inhibits cell growth. Taken together, this study demonstrates that NMNH is a potent NAD+ enhancer and inhibits glycolysis, TCA cycle, and cell growth.

The Chinese name of NMNH is "reduced β-nicotinamide mononucleotide", which is the reduced form of NMN and is an amorphous yellow powder. Molecular formula: C11H17N2O8P Molecular weight: 336.23g/molCAS No.: 108347-85-9 The latest research literature shows that NMNH increases NAD+ levels faster and at a higher concentration, on average 5 times that of NMN
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