Enhancing NMN with Synergistic Supplements

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In the pursuit of healthy ageing and longevity, researchers have explored the potential of NAD+ boosting compounds, particularly nicotinamide mononucleotide (NMN). Recent insights from the study "Potential Synergistic Supplementation of NAD+ Promoting Compounds as a Strategy for Increasing Healthspan," authored by Arastu Sharma, Sophie Chabloz, Rebecca A. Lapides, Elisabeth Roider, and Collin Y. Ewald, explain how combining NMN with other geroprotective compounds could significantly enhance its effects.

Geroprotectors consist of multiple families of compounds that exert beneficial effects at various levels, allowing mitochondria to function longer. This research underscores the powerful synergy between NMN and supplements like stilbenes (resveratrol and pterostilbene), CoQ10, betaine (TMG), and flavonoids (quercetin and fisetin), which collectively offer a robust approach to improving healthspan and combating age-related decline.

Below, we explore the findings from this study and highlight how combining NMN with these supplements can boost NAD+ levels, clear senescent cells, and support healthy ageing.

The NAD+ Longevity Pathway

NAD+ is a coenzyme vital for cellular metabolism and signaling. Its levels naturally decline with age, contributing to mitochondrial dysfunction, increased oxidative stress, and impaired DNA repair. NMN is a precursor that boosts NAD+ levels, but its efficacy can be enhanced by compounds that modulate related pathways. The compounds discussed here provide unique mechanisms to amplify NAD+ activity while addressing other hallmarks of ageing.

1. Stilbenes: Resveratrol and Pterostilbene

Stilbenes are polyphenolic compounds with potent antioxidant and anti-inflammatory properties.

Resveratrol: Known for activating sirtuins, particularly SIRT1, Resveratrol enhances mitochondrial biogenesis and protects against oxidative stress. It also complements NMN by further activating NAD+-dependent enzymes, improving energy metabolism, and reducing cellular senescence.
Pterostilbene: Structurally similar to resveratrol but with superior bioavailability, pterostilbene offers additional anti-inflammatory and neuroprotective benefits. It promotes NAD+ metabolism by influencing sirtuin activity and protecting against age-related diseases like neurodegeneration and metabolic disorders.

The synergy of NMN, Resveratrol, and Pterostilbene: Together, these stilbenes enhance the cellular energy efficiency of NAD+ precursors and provide powerful protective effects across multiple ageing pathways.

For those looking to harness the full potential of NAD+ boosting compounds, Charava offers a product that already combines NMN, Resveratrol, and Pterostilbene, three key ingredients shown to work synergistically to enhance healthspan and support longevity.

2. Coenzyme Q10 (CoQ10)

CoQ10 is an essential cofactor in mitochondrial energy production and a potent antioxidant.

By mitigating mitochondrial dysfunction, CoQ10 reduces oxidative stress and prevents cellular damage associated with ageing.
CoQ10 also supports cardiovascular health, protects neurological function, and combats fatigue, making it a valuable addition to NAD+ boosting strategies.

The synergy of NMN and CoQ10: CoQ10 complements NMN by enhancing the electron transport chain's efficiency, increasing cellular ATP production, and reducing the oxidative burden on mitochondria.

3. Betaine (TMG)

Betaine, or trimethylglycine, plays a critical role in methylation - a biochemical process essential for DNA repair, gene regulation, and cellular health.

Methylation Support: Betaine supplies methyl groups to sustain DNA methylation, which may become depleted during NAD+ precursor supplementation due to increased NAD+ cycling.
Inflammation Reduction: Betaine suppresses inflammatory markers like TNF-α and NF-κB while optimising lipid and glucose metabolism.

The synergy of NMN and TMG: Supplementing Betaine alongside NMN ensures the preservation of a healthy methyl donor pool, supporting both methylation and NAD+ biosynthesis.

4. Flavonoids: Quercetin and Fisetin

Flavonoids are plant-derived compounds with significant anti-inflammatory, antioxidant, and senolytic properties.

Quercetin: Acts as a senolytic, clearing damaged cells to improve tissue health. It inhibits CD38, an enzyme that degrades NAD+, preserving NAD+ levels and enhancing sirtuin activity. It also promotes mitochondrial function by altering the NAD+/NADH ratio.
Fisetin: One of the most potent senolytics, it clears senescent cells and promotes tissue homeostasis. Fisetin activates SIRT1 and improves NAD+ availability through CD38 inhibition. Currently under clinical investigation for its potential to improve inflammation and mobility in elderly populations.

The synergy of NMN and Quercetin or Fisetin: Both flavonoids work synergistically with NMN by protecting and enhancing the NAD+ longevity pathway, addressing cellular senescence, and reducing inflammation.

Why Synergy Matters: A Multi-Faceted Approach to Longevity

Combining NMN with these geroprotectors provides a comprehensive strategy to tackle aging. Each compound contributes unique benefits while amplifying the effectiveness of NAD+ precursors.

Enhanced NAD+ Levels: Compounds like quercetin inhibit NAD+-depleting enzymes, preserving NAD+ stores for vital cellular functions.
Improved Mitochondrial Function: CoQ10 and stilbenes optimise mitochondrial energy production, reducing oxidative damage and supporting cellular repair mechanisms.
Senescent Cell Clearance: Fisetin and quercetin target and eliminate damaged cells, improving tissue health and resilience.
Systemic Anti-Inflammation: Betaine, flavonoids, and stilbenes reduce chronic inflammation, a key driver of age-related diseases.

This integrative approach addresses multiple ageing pathways, making it more effective than relying solely on NAD+ precursors.

Conclusion: A Comprehensive Strategy for Healthy Aging

The combination of NMN with geroprotectors like stilbenes, CoQ10, betaine, and flavonoids represents an exciting frontier in longevity science. These compounds work together to enhance NAD+ metabolism, reduce cellular damage, and promote longevity. While further research is ongoing to optimise dosages and formulations, the evidence suggests that synergistic supplementation is a promising strategy for healthy ageing.

By targeting the fundamental processes of ageing, this comprehensive approach offers a scientifically backed pathway to extend healthspan and improve quality of life.

Charava Products Mentioned

Full Study

Sharma, A.; Chabloz, S.; Lapides, R.A.; Roider, E.; Ewald, C.Y. Potential Synergistic Supplementation of NAD+ Promoting Compounds as a Strategy for Increasing Healthspan. Nutrients 2023, 15, 445. https://doi.org/10.3390/nu15020445