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NMNH & NRH: Powerful But Complex
Both NMNH and NRH are reduced forms of the more widely known counterparts. This structural difference means they enter the NAD+ pathway in a form closer to NADH, potentially skipping several enzymatic steps that slow the process. (2) As a result, they're absorbed and converted much more quickly and raise NAD+ several times higher than equal amounts of NMN or NR, but in biology higher levels don't always translate to better or safer. (3)
The NADH Surge: A Double-Edged Sword
A key issue is that unlike NMN or NR, which steadily increase NAD⁺, NMNH and NRH first cause a flood of NADH before it balances into NAD⁺. This overload disrupts the cell's energy systems, slowing down normal energy pathways and sometimes putting the cell under stress. (4)
In healthy cells with strong mitochondria, the excess NADH may be quickly processed to make ATP, which could explain the short-term "energy boost" some users report. However, in aging or stressed cells, NADH can accumulate, worsening oxidative stress (an imbalance in harmful free radicals), rather than reducing it. (5)
In other words: the shortcut that makes these compounds so powerful may also make them risky, especially for those with compromised cell health or weaker metabolic function.
What Studies Show
Studies show NMNH strongly raises NAD⁺ but also suppresses glycolysis and the TCA cycle, key pathways for cellular energy production. (4) Some mouse studies show this rise in NADH levels imbalances the NAD⁺/NADH ratio, while in cell cultures NMNH has even halted growth and cell division. (4) This can be useful in cancer research, but potentially harmful in healthy tissues.
In immune cells, NRH promotes inflammation, activating pathways linked to "inflammaging." (1) These results suggest that while reduced precursors can deliver rapid NAD⁺ gains, they may also disrupt cellular balance in ways that negatively affect tissue and metabolic health.
Human Data: Promising but Incomplete
The first small clinical trial of NMNH supplementation in healthy adults reported no immediate safety issues, and a large increase in NAD⁺ and reported energy levels. However, the study was brief and limited to healthy participants. It also did not measure factors like inflammation, cellular balance, or long-term safety. The study is not yet peer-reviewed, and the full dataset has not been made publicly available. (5)
Why Renue By Science Is Waiting
Although NMNH is FDA-legal and available online, we believe longevity science deserves rigorous validation rather than trend-following. Our approach is to wait until both safety and benefit are clearly demonstrated. Currently, NMNH raises unanswered questions about cellular stress, metabolism, inflammation, and long-term safety, and for us a cautious approach is essential.
Conclusion
NMNH and NRH are important advances in NAD⁺ biology, delivering unprecedented boosts in NAD⁺. But their mechanism of flooding cells with NADH before conversion introduces risks of energy imbalance and unpredictable cellular responses. In healthy, resilient cells this may not matter, but in aging or stressed cells it could do more harm than good. (5)
At Renue By Science, we are optimistic about the future of NAD⁺ research and continue to watch these compounds closely. For now, however, they remain best viewed as research tools, not safe or validated supplements.
They show real promise, but too many questions remain. Until science provides clear proof of safety and benefit, we will wait.
