How can we live healthier for longer? Research has shown how healthy ageing and longevity is closely connected to NAD+ levels and its precursors NMN and NR, in supporting our overall cellular health. But if our body’s natural NAD starts to decline with age – is it possible to re-address the balance and extend our healthy years? Nutritionist Will Jordan delves into the research and explains how it’s all linked.
Understanding Longevity and Ageing
What does longevity mean? Longevity is described ‘living for a long time’. Coming from the Latin words ‘longus’ meaning long, and ‘aevum’, meaning age. The original context for the word was having a long quantity of life, but modern contexts refer more to the length of healthy life. [1] This is known as “peakspan”. Ageing is a natural part of life and is genetically coded into us. As we age, our cells begin to work less efficiently and this can lead to increased inflammation, and oxidative stress, which are often considered a feature of ageing.
Why mitochondria function is key to cellular health
The mitochondria is the powerhouse of the cell and also known for its critical role in aging and the development of age-related diseases. [2] Studies have recognised that healthy mitochondrial function, energy balance, and stress management are key pillars in optimal cellular function. [3] Therefore, protecting the mitochondria and cells as a whole is vital for cellular energy production. Furthermore, a high functioning and healthy mitochondria support muscle, brain, and immune functions, as well as aids mechanisms for repairing the body by producing the energy the body needs in order to heal. [4]
How do we make energy?
Every cell in your body requires energy to function. This energy comes primarily from cellular energy production, the process of producing Adenosine Triphosphate (ATP). Research is still in its early stages in this area and scientists are beginning to understand it fully in a human system and its influence on our health, however, the key parts are the Krebs Cycle, and the Electron Transport Chain (ETC), and how Nicotinamide Adenine Dinucleotide (NAD+) fits in.
NAD+ is a co-enzyme that is critical for enzymes that fuel energy production, carrying electrons from one reaction to another.
The Krebs cycle, in simple terms, is a series of chemical reactions that help breaks down and release energy stored in food, , which takes place in the mitochondria. The Krebs cycle produces very little ATP, and alternatively creates a lot of ‘energy carriers’ including NADH, made from NAD+, which is used in the ETC. The ETC, also in the mitochondria is where the majority of the ATP is produced by the cell. [5] NAD+ concentrations reduce during ageing and higher concentrations of NAD+ are strongly associated with prolonged lifespan and good health. [6]
The role of NAD to our long-term health
NAD+ is found in every living cell in the human body and is a co-enzyme critical to fuelling energy production, carrying electrons from one reaction to another. NAD+ powers DNA repair [7] and is involved in sirtuins, a family of NAD+ dependant signalling proteins, which manage inflammation control and mitochondrial maintenance and DNA repair mechanisms. [8] A decline in NAD+ is generally associated with age which causes mitochondrial dysfunction, accumulated DNA damage, chronic inflammation, and increased risk of metabolic disease. [9]
Nutrients that may help to support the body’s natural NAD production.
Nicotinamide is the non-flushing form of vitamin B3, and a precursor for NAD+. [10] Nicotinamide is converted into nicotinamide mononucleotide (NMN), which is then converted into NAD+. [11] Supplementing with nicotinamide can increase NAD+ levels effectively in healthy adults. [12]
Nicotinamide Riboside (NR) is a form of and one of the most studied NAD+ precursors. There are multiple studies that show supplementing adults with NR, ranging from single dose, or over several months have consistently demonstrated improved NAD+ concentrations when baseline levels are low. [13] Research has found that both nicotinamide (vitamin B3) and NR enters the cell relatively easily and is then converted into NMN, and eventually to NAD+ [14]. However, NMN is often converted into NR in the body before it can enter the cell.
Further studies have demonstrated additional benefits. Supplementing with NAD+ has been found to effectively increase NAD+ levels in the body and also support different aspects of health, including inflammation, cognitive functioning and cardiovascular health. [15]
How does NMN compare with NR?
If NMN and NR are both precursors to NAD+, are there any advantages to taking one over the other? NMN from supplements has to be converted into NR to enter the cell. So while in the cell NMN is closer to NAD+, from a supplement point of view it is actually further away. NMN as a supplement is not approved for sale in the UK, where NR has human research and is approved.
Co-enzyme Q10 (Co-Q10) is a powerful antioxidant, but it also has a significant role in cellular production, which we produce naturally in our bodies. All cells are sensitive to Co-Q10 deficiency, and this is linked with diseases related to ageing, such as neurodegenerative diseases. [16] Co-Q10 plays a vital role as a co-enzyme for the ETC and cellular energy production. Co-Q10 also acts as an antioxidant in this process, preventing damage to the surrounding cell during energy production [17]. Co-Q10 levels will naturally decline as we age. The body’s peak production is in early adult hood, usually around 20 years old, and then will begin to decline slowly as we age, as much as 50% by 60.
[18]
Fatigue is closely associated with low cellular energy availability and increases systemic inflammation. Co-Q10 has been reported to support this. [19] A systematic review and meta-analysis investigating fatigue included 13 trials that supplemented a pooled participant group of 1,126 individuals with 60-500mg of Co-Q10 per day. The results found that there was a positive relationship between treatment duration and fatigue reduction. Furthermore, lower Co-q10 levels in participants were associated with increased fatigue. [20]
Vitamin E is not directly involved with energy production, but it is key for supporting cell health and managing inflammation. [21] Vitamin E’s main function is protecting and stabilising cell membranes, including the mitochondrial membrane, by reducing inflammation and oxidative stress which in turn will support cellular energy production indirectly. [22] [23]
Conclusion
Supporting cellular health is fundamental to longevity. The more effective your cells are at producing energy, managing inflammation and oxidative stress, the longer your life expectancy, and likelihood of extending your healthy years. Longevity affects all aspects of health, from joint health, and bone health, to inflammation and cognitive health. Supporting cellular health alongside targeted supplements containing NR, and vitamin B3 that effectively raise the body’s natural NAD+ levels can also go a long way to improving longevity.
Author: Will Jordan, BSc (Hons) MSc, is a Nutrition Advisor at Viridian Nutrition. He holds a Master’s degree in Sports and Exercise Nutrition, BSc in Food and Nutrition.
References
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