Nicotinamide adenine dinucleotide (NAD+) is essential for life. This coenzyme participates in hundreds of biological processes, including metabolism, energy production, and DNA repair. Over the years, scientific studies have demonstrated that boosting NAD+ levels can enhance healthspan, improve stress resistance, and potentially extend lifespan.
Two key players have emerged as popular NAD+ precursors: Nicotinamide Mononucleotide (NMN) andNicotinamide Mononucleotide Hydride (NMNH). While NMN has been studied extensively, NMNH is a newer, potentially more powerful alternative.
In this blog, we will explore the differences between NMN and NMNH, their roles in NAD+ biosynthesis, and why NMNH could be the future of NAD+ supplementation.
A Brief History of NMN and NAD+
NAD+ has been at the centre of longevity research for decades. Its importance in cellular function was first highlighted by early studies that demonstrated how increasing NAD+ levels could improve stress resistance and extend lifespan in simple organisms like yeast and fruit flies (Drosophila). In mice, NAD+ enhancement has been shown to delay the onset of age-related diseases and improve overall health.
Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are two well-researched precursors that can boost NAD+ levels. These molecules are converted into NAD+ inside the body, helping to replenish cellular reserves. Supplementation with NMN has shown numerous health benefits, such as improved muscle function, enhanced energy levels, and protection against age-related decline.
However, the quest to optimise NAD+ supplementation has led researchers to explore NMN's reduced form — NMNH.
What is NMN?
NMN is a direct precursor to NAD+. It is naturally found in small amounts in foods like broccoli, avocado, and edamame. Once ingested, NMN enters cells and is quickly converted into NAD+ by the enzyme NMNAT (nicotinamide mononucleotide adenylyltransferase).
NMN and its Role in NAD+ Production
Increasing NAD+ levels via NMN supplementation has been shown to:
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Improve energy metabolism
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Enhance DNA repair
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Support cardiovascular health
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Protect against age-related deterioration.
Despite its promising benefits, NMN’s bioavailability (how efficiently it is absorbed and utilised by the body) has been debated. Additionally, regulatory challenges in the USA have created uncertainty around NMN’s future availability as a supplement.
NMN in the USA: Regulatory Uncertainty
In the United States, the Food and Drug Administration (FDA) has recently raised concerns over the classification of NMN as a dietary supplement. The regulatory status remains unclear, as ongoing deliberations have not yielded a final decision. This uncertainty has led consumers and researchers to explore alternative NAD+ precursors that can deliver similar, if not superior, benefits.
Enter NMNH.
Introducing NMNH: The Reduced Form of NMN
Nicotinamide Mononucleotide Hydride (NMNH) is the reduced form of NMN. Unlike NMN, which supports NAD+ synthesis in its oxidised form, NMNH directly contributes to NADH production — the reduced counterpart of NAD+.
Why NMNH is a Game-Changer
Recent studies have shown that NMNH is a more potent NAD+ booster compared to NMN. Here are the reasons that make the NMNH unique:
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Higher Bioavailability: NMNH is up to five times more bioavailable than NMN, meaning the body can absorb and utilise it more efficiently.
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Enhanced NAD+ and NADH Levels: NMNH increases both NAD+ and NADH levels in cells. This dual effect can improve energy production, as NADH is critical for ATP generation via the electron transport chain.
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Metabolic Impact: NMNH has been shown to suppress glycolysis and the TCA cycle, affecting how cells generate energy. This suppression can have downstream effects on ageing and disease prevention.
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Cell Growth Regulation: Unlike NR or NMN, NMNH has been found to inhibit cell growth by causing cell cycle arrest. This could be beneficial in contexts where uncontrolled cell proliferation is a concern.
How is NMNH Made?
Researchers have developed a robust and scalable method to produce NMNH via chemical reduction. The process involves reducing NMN using thiourea dioxide (TDO), a stable and effective reducing agent. This method yields high-purity NMNH, making it suitable for both research and potential therapeutic applications.
Key Findings from NMNH Research
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Increased NADH Levels: NMNH significantly boosts cellular NADH levels, unlike other NAD+ precursors.
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Stable Under Alkaline Conditions: NMNH remains stable at alkaline pH and at low temperatures, though it is less stable at neutral pH than NMN.
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Safety in Long-Term Use: Studies have demonstrated that long-term administration of NMNH is safe in mouse models.
NMN vs. NMNH: Which One is Better?
| Feature | NMN | NMNH |
|---|---|---|
| Form | Oxidised | Reduced |
| Bioavailability | Moderate | High (5x more bioavailable) |
| Boosts | NAD+ | NAD+ and NADH |
| Metabolic Effects | Supports energy metabolism | Suppresses glycolysis and TCA cycle |
| Cell Growth | No effect on growth | Inhibits cell growth |
| Regulatory Status (USA) | Uncertain | Emerging alternative |
Conclusion: The Future of NAD+ Supplementation
As research advances, NMNH is emerging as a powerful alternative to NMN. With its higher bioavailability and dual impact on NAD+ and NADH levels, NMNH could offer superior benefits for those looking to support longevity, energy, and overall health.
Given NMN's regulatory challenges in the USA, NMNH provides a promising pathway for continued NAD+ enhancement. As we learn more about NMNH's unique properties and effects on cellular metabolism, it may become the preferred choice for those seeking to optimise their health and longevity.
The future of NAD+ supplementation is here.
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