Functional medicine, a biology-based approach that focuses on identifying and addressing the root cause of diseases, is a popular topic. And so is healthy aging. It’s no wonder, especially when we consider our desire to understand the root cause of diseases and sustain health throughout life’s many stages.

In previous decades, growing old equaled a diminished quality of life, where many pathologies associated with aging were unavoidable. We now understand that limiting stress, maintaining energy levels, striving to achieve a balanced immune system and performing DNA repair are just a few ways that may support a healthy aging process.

NAD: Central to Metabolism & Aging

Functional medicine practitioners recognize how nicotinamide adenine dinucleotide (NAD), a coenzyme required to metabolize carbohydrates, fats and amino acids to energy, influences healthy aging. NAD is found in all living cells and is comprised of two dynamic, energy exchanging forms: NAD+, the oxidized form, and NADH (H for hydrogen), the reduction form. NAD+ is a critical metabolic intermediate that serves as a universal electron acceptor in hundreds of oxidation/reduction reactions reduced to NADH.

NAD+ is used as a co-substrate by several different types of enzymes, such as sirtuins (SIRTs), adenosine diphosphate (ADP), ribose transferases (ARTs) and the cyclic ADP-ribose (cADPR) synthases. Through these activities, NAD+ metabolism and its intermediate metabolites regulate a broad spectrum of cellular functions, such as energy metabolism, DNA repair, regulation of epigenetics and inflammation (see image below).¹ Maintaining a healthy ratio of coenzymes NAD+/NADH affects many aspects of cellular health, including the dynamics between metabolism and immune cell functions.

However, NAD+ levels and NAD+/NADH ratios decline with age. These lower levels are associated with many of the symptoms that were previously considered an unavoidable part of aging. Many now recognize the relationship between NAD+ and insulin sensitivity, stress management, circadian rhythm and neurodegeneration.²

Impact of NAD Levels & Deficiencies

• Energy & Mitochondrial Function
  Production of adenosine triphosphate (ATP), the energy currency of the body related to mitochondria metabolic processes, is impacted by NAD+ levels and the ratio of NAD+/NADH. NAD deficiency is associated with lower energy levels and mitochondrial dysfunction or damage.³
• Sirtuins & DNA Repair
  Sirtuins, a group of proteins involved in the metabolism and aging of cells, serve as cellular responses to oxidative and genotoxic stress. Appropriate levels of NAD+ and NAD+/NADH ratios are necessary for sirtuins and sirtuin activity. Maintaining adequate levels of NAD+ can positively impact DNA regeneration and repair through NAD+’s capacity as a substrate for the sirtuins as well as the poly (adenine diphosphate-ribose) polymerases (PARPs).^4-7
• Cognitive Support
  Restoring NAD+ levels proved beneficial in animal models, with study results indicating NAD+ may play a role in the prevention of neurodegeneration and protection against free radicals. Multiple NAD+-dependent processes are involved in neuroplasticity — where neurons in the brain develop new learning and memory pathways — when previous synaptic junctions were damaged or lost.6,7 The effects of NAD+ availability may also help improve sleep and subsequently mental clarity.⁸
• Insulin Sensitivity
  NAD+ and NAD+-dependent sirtuins also modulate insulin sensitivity and glucose homeostasis. An overexpression of SIRT1 reportedly improved glucose intolerance and dyslipidemia. SIRT1 was shown to regulate glucose and lipid metabolism, as well as increase NAD+ contents and SIRT1 activity in adipose tissue to help prevent diet-induced insulin resistance.⁹
• Immune Balance and Inflammation
  NAD+ is an intermediate for many immune responses and its availability can have impacts on resolution of inflammatory conditions. While more research is needed, most studies show that increased NAD+ levels have anti-inflammatory effects. Inflammageing, an age-related increase in pro-inflammatory markers for chronic inflammation, decreased in many cases by increasing the availability of NAD+ through NAD+ precursors.¹⁰ Recent studies also show NAD+ contributes to anti-tumor T-cell responses.¹¹

Recognition of maintaining healthy NAD levels is growing. Many practitioners now recommend this important coenzyme as an oral supplement or administered intravenously during office visits.

New Product from Wellness Works

Wellness Works is pleased to announce a new product: NAD+Vitality. Our nutritional supplement contains Bioenergy RiaGev®-WS™, a proprietary combination of Bioenergy Ribose® and nicotinamide ascorbate (vitamin B3). A triple-blind, randomized, placebo-controlled pilot study showed a nicotinamide and d-ribose combination of the new RiaGev increased NAD+ levels in the blood, reduced waking cortisol, showed improved glucose levels and enhanced circulating antioxidants. No reports of skin flushing, which occurs in many NAD+ precursor supplements, were reported. In addition, NAD+ Vitality resolves the need to break down the combination and conversion of NAD+, like many other precursor supplements on the market.11

These statements have not been evaluated by the Food and Drug Administration. Products referenced in this article are not intended to diagnose, treat, cure or prevent any disease.

References

1. Navarro, Maria N., Gomez de las Heras, MM., Mittelbrunn, M. (2021) Nicotinamide adenine dinucleotide metabolism in the immune response, autoimmunity and inflammageing. British J Pharma, 179, 9, 1839–1856. Open access publication. Accessed 09/2023 at https://doi.org/10.1111/bph.15477
2. Ruszkiewicz, J. A., Bürkle, A., Mangerich, A. (2022) Fueling genome maintenance: On the versatile roles of NAD+ in preserving DNA integrity. J Bio Chem, 298(6). Accessed 09/2023 at https://doi.org/10.1016/j.jbc.2022.102037
3. Diaz-Vegas, A., Sanchez-Aguilera, P., Krycer, J.R., et al. (2020) Is mitochondrial dysfunction a common root of noncommunicable chronic diseases? Endo Reviews, 41(3). Accessed 09/2023 at https://doi.org/10.1210/endrev/bnaa005
4. Grabowska, W., Sikora, E, Bielak-Zmijewska, A. (2017) Sirtuins, a promising target in slowing down the ageing process.” Biogeron, 18(4) 447–476, Accessed 09/2023 at https://doi.org/10.1007/s10522-017-9685-9
5. Amjad, S., Nisar, S., Bhat, A.A., et al. (2021) Role of NAD+ in regulating cellular and metabolic signaling pathways. Mol Met 49. Accessed 09/2023 at https://doi.org/10.1016/j.molmet.2021.101195
6. Imai, S., Guarente, L. (2014) NAD+ and sirtuins in aging and disease. Trends Cell Bio, 24(8) 464–471. Accessed 09/20233 at https://doi.org/10.1016/j.tcb.2014.04.002
7. Wilk, A., Hayata, F., Cunningham, R., et al. (2020) Extracellular NAD+ Enhances PARP-Dependent DNA Repair Capacity Independently of CD73 Activity. Nature News/Scientific Reports. Accessed 09/20233 at https://www.nature.com/articles/s41598-020-57506-9
8. Conlon, N. J. (2021) The role of nad+ in Regenerative Medicine. Plas & Recon Sur, 150. Accessed 09/20233 at https://doi.org/10.1097/prs.0000000000009673
9. Yamaguchi, S., Yoshino, J. (2017) Adipose tissue nad+ biology in obesity and insulin resistance: From mechanism to therapy.” BioEssays, 39(5), 1600227. . Accessed 09/20233 at https://doi.org/10.1002/bies.201600227
10. Navarro, M. N., Gomez de las Heras, M.M., Mittlebrunn, M. (2021) Nicotinamide adenine dinucleotide metabolism in the immune response, autoimmunity and inflammageing. British J Pharma 179(9) 1839–1856. Accessed 09/20233 at https://doi.org/10.1111/bph.15477
11. Xue, Y., Shamp, T., Nagana Gowda, et al. (2022). A Combination of Nicotinamide and D-Ribose (RiaGev) Is Safe and Effective to Increase NAD+ Metabolome in Healthy Middle-Aged Adults: A Randomized, Triple-Blind, Placebo-Controlled, Cross-Over Pilot Clinical Trial. Nutrients, 14(11), 2219. Accessed 09/20233 at https://doi.org/10.3390/nu14112219