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Healthy ageing

The Synergistic Effects of Resveratrol and NMN on Healthy Ageing 

Resveratrol and NMN each offer significant health benefits on their own, but when combined, they create synergistic effects for even greater benefits.

Recent studies have highlighted growing evidence suggesting a potential synergistic effect between nicotinamide mononucleotide (NMN) and resveratrol, particularly in the context of enhancing NAD+ levels and activating sirtuins, which play key roles in cellular metabolism and healthy ageing.  

What is Resveratrol? 

Resveratrol is a naturally occurring compound, classified as a polyphenol, found primarily in the skin of grapes, certain berries, peanuts, and red wine. It has garnered interest due to its potential health benefits, often linked to healthy ageing and disease prevention, especially concerning cardiovascular and metabolic health. Resveratrol has many health benefits including:  

Antioxidant Properties

Resveratrol acts as an antioxidant, which helps protect cells from damage caused by free radicals, unstable molecules that can cause oxidative stress, potentially leading to inflammation and chronic conditions. [1] 

Cardiovascular Health

Resveratrol is known for its potential to contribute to heart health by promoting the relaxation of blood vessels, reducing inflammation, and preventing the oxidation of LDL (bad cholesterol) which may contribute to the hardening of the arteries. Studies show that resveratrol activates a protein called SIRT1, which helps protect the cells lining blood vessels from oxidative stress and inflammation. This action can lower blood pressure, reduce the risk of blood clot formation, and improve circulation. [1] 

Healthy Ageing

The activation of SIRT1 may also contribute to DNA repair, improving mitochondrial function, and maintaining genome integrity, all of which can contribute to healthy ageing. [8] 

Anti-inflammatory Effects

Chronic inflammation is a key driver of many health conditions, including heart conditions. Resveratrol has anti-inflammatory properties that may help reduce inflammation and, in turn, the risk of these conditions. Resveratrol can inhibit the activity of certain enzymes and transcription factors involved in the inflammatory response, such as NF-kB, thus reducing the production of pro-inflammatory molecules. [7] 

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What is NMN? 

Nicotinamide mononucleotide (NMN) is a naturally occurring compound found in small amounts in various foods, such as broccoli, avocado, and cabbage. It is a derivative of niacin (vitamin B3) and is a precursor to NAD+ (nicotinamide adenine dinucleotide), a critical molecule involved in cellular energy production, DNA repair, and healthy ageing. NMN has gained attention for its potential anti-ageing and health-boosting properties, largely due to its role in promoting NAD+ levels, which tend to decline with age. NMN has many health benefits including: 

Promotion of Cellular Energy and Metabolism

NMN is a precursor to NAD+, a coenzyme essential for energy production in cells. NAD+ is involved in mitochondrial function, where the cells generate energy. By increasing NAD+ levels, NMN helps to maintain cellular energy, which is crucial for metabolism and overall health. [2] 

Healthy Ageing

Declining NAD+ levels can lead to mitochondrial dysfunction, cellular damage, and reduced energy metabolism. NMN helps to restore NAD+ levels, which can slow the ageing process by supporting DNA repair, reducing oxidative stress and improving overall cellular health. [2] 

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The Synergy Between Resveratrol and NMN 

Resveratrol and NMN each offer significant health benefits on their own, but when combined, they create synergistic effects for even greater benefits. Here’s how their combined action may amplify the effects on cellular health and healthy ageing: 

  • Enhanced Sirtuin Function: By increasing NAD+ levels, NMN ensures that there is enough NAD+ available for resveratrol-activated sirtuins (like SIRT1) to function optimally. When resveratrol activates SIRT1, it increases the demand for NAD+, and NMN supplementation can supply more NAD+ to meet this demand, ensuring maximal sirtuin activity, leading to the maintenance of mitochondrial health and regulation of gene expression linked to healthy ageing. [3] 

  • May Amplify DNA Repair: Sirtuins, particularly SIRT1, play a crucial role in DNA repair by stabilising the genome and repairing DNA breaks that accumulate over time. With NMN boosting NAD+ levels and resveratrol enhancing sirtuin activation, this combination can significantly enhance the body’s ability to repair DNA damage by facilitating repair pathways. This may help reduce the accumulation of genetic mutations and cellular dysfunction associated with ageing. [3] 

  • Improved Mitochondrial Function: Both NMN and resveratrol support mitochondrial health, but through different mechanisms.  NMN, being a stable precursor for NAD+, boosts mitochondrial function by increasing NAD+ which is necessary for efficient energy production in cells. Meanwhile, as resveratrol activates SIRT1, this promotes the creation of new mitochondria and enhances the function of existing ones. Together, they may improve overall energy metabolism, reduce mitochondrial damage, and enhance energy efficiency, all of which are vital for healthy ageing. [3] 

  • Synergistic Impact on Energy Metabolism: NAD+ is a key molecule in metabolic pathways, particularly those that convert food into energy. Resveratrol may increase insulin sensitivity and glucose metabolism by activating SIRT1, which regulates how cells respond to energy demand. At the same time, NMN supports these processes by ensuring that cells have sufficient NAD+ to fuel the metabolic reactions. When combined, NMN and resveratrol may enhance energy balance, insulin sensitivity, and overall metabolic health, which are crucial for preventing age-related metabolic conditions. [3]  

  • Reduced Inflammation and Oxidative Stress: Sirtuins (activated by resveratrol) help suppress inflammatory pathways, such as NF-κB, which are often elevated by various environmental factors and age. By increasing NAD+, NMN enhances sirtuin activity, thus allowing resveratrol to help further suppress inflammation and protect cells from oxidative damage.  [7] 

  • Healthy Ageing Benefits: The combination of NMN and resveratrol is believed to have a cumulative effect on the healthy ageing pathways due to its promotion of DNA stability and repair, reduction of cellular damage, enhancement of energy metabolism and mitochondrial efficiency, improvement of physical energy and endurance, reduction of inflammation and oxidative stress, protection against age-related conditions, and improvement of insulin sensitivity and glucose metabolism, all of which support healthy ageing. [3] 

Evidence from Studies and Clinical Trials

Biologist and academic David Sinclair has previously mentioned in interviews and presentations that combining NAD+ precursors like NMN with resveratrol can enhance sirtuin activation and improve mitochondrial function. He has suggested that resveratrol alone activates sirtuins but may not be as effective when NAD+ levels are low due to ageing. He has stated how NMN, by increasing NAD+ levels, helps resveratrol fully activate sirtuins, which can provide synergistic benefits. [4] 

Several studies on mice have shown that combining NAD+ precursors with sirtuin activators like resveratrol leads to greater improvements in metabolic health and mitochondrial function compared to either compound alone. For example, a study from 

2018 demonstrated that NMN supplementation improved muscle function and endurance in mice, effects that could potentially be amplified by resveratrol’s activation of sirtuins. Resveratrol studies on their own have shown benefits for metabolism and mitochondrial function, however, the most significant results are shown when it is combined with NAD+ precursors in animal models. [5] 

The synergy between NMN and resveratrol lies in their interconnected roles in cellular health: NMN provides the NAD+ needed for optimal sirtuin function, while resveratrol activates these vital proteins. Together, they amplify healthy ageing benefits by enhancing cellular metabolism, reducing oxidative stress, and supporting DNA repair and mitochondrial function, creating a powerful foundation for sustained cellular health and vitality. 

1. Wein, H. Resveratrol: Benefits, Side Effects and Dosage. Healthline. 2023. Available from: https://www.healthline.com/nutrition/resveratrol#TOC_TITLE_HDR_3

2. Shade C. The Science Behind NMN–A Stable, Reliable NAD+Activator and Anti-Aging Molecule. Integrative Medicine: A Clinician’s Journal [Internet]. 2020 Feb;19(1):12. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7238909/

3. Sharma A, Chabloz S, Lapides RA, Roider E, Ewald CY. Potential Synergistic Supplementation of NAD+ Promoting Compounds as a Strategy for Increasing Healthspan. Nutrients [Internet]. 2023 Jan 1;15(2):445. Available from: https://www.mdpi.com/2072-6643/15/2/445

4. Sinclair D. Rhonda Patrick interview with David Sinclair, Ph.D. FoundMyFitness. 2019. Available from: https://www.foundmyfitness.com/episodes/david-sinclair

5. Kane AE, Sinclair DA. Sirtuins and NAD+ in the Development and Treatment of Metabolic and Cardiovascular Diseases. Circ Res. 2018 Sep 14; 123(7): 868–885. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206880/

6. Aman Y, Qiu Y, Tao J, Fang EF. Therapeutic potential of boosting NAD+ in aging and age-related diseases. Translational Medicine of Aging [Internet]. 2018 Jan 1;2:30–7. Available from: https://www.sciencedirect.com/science/article/pii/S2468501118300063

7. Pan Z, Dong H, Huang N, Fang J. Oxidative stress and inflammation regulation of sirtuins: New insights into common oral diseases. Frontiers in Physiology. 2022 Aug 19;13.

8. Grabowska W, Sikora E, Bielak-Zmijewska A. Sirtuins, a promising target in slowing down the ageing process. Biogerontology [Internet]. 2017 Mar 3;18(4):447–76. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514220/

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