NAD supplements and their potential benefits are widely being discussed around the world. Some say NAD supplements enhance longevity but what is NAD and are NAD supplements beneficial?

NAD or NAD+ is an acronym of Nicotinamide Adenine Dinucleotide, and is the second most abundant molecule in the body after water. In the quest for compounds that slow down ageing, scientists are looking for enzymes and compounds that change as we age. One of the most important of these compounds is NAD+.

Scientists discovered NAD+ in 1906 and since then our understanding of this compound has expanded. It is found in the cells of virtually every organism where it displays two main functions. The first is to produce energy from nutrients and the second is its role as an enzyme for metabolic processes, cell function, DNA repair and numerous other processes. 

Why is NAD+ important?

Think of NAD+ as an enabler of multiple processes within our bodies. When levels decrease, our body does not function well and it is less effective at repairing itself, we have lower energy levels and our metabolic rate drops. Without sufficient NAD+, the body does not carry out its functions properly which can lead to health concerns in time. Basically NAD+ helps other biologically active molecules carry out their jobs.¹

Levels of NAD+ decline with age and this has been linked to numerous age-related disorders and diseases. Scientists have hypothesised that if we can restore our NAD+ levels, then our cells become healthier, our organs become healthier, performing optimally, and we become healthier.

What does NAD+ do for the body?

NAD+ enhances the functions of eight cellular anti-ageing mechanisms and it is this property that may help to prevent accelerated ageing. NAD+ may help to reduce risks associated with:

Immune system - The body’s immune system relies on a variety of hormones, compounds, white blood cells, nutrients, and glands that all have to perform to maintain a healthy immune response. Our immune system also relies on sirtuins which are proteins that help repair the body every minute of the day. Sirtuins consume NAD+ for energy giving them the ability to repair. Without NAD+, repair processes grind to a halt, DNA repair is decreased and the body is less able to fight diseases and infections.

Healthy heart: NAD+ helps healthy heart function – the elasticity of our arteries need to be in good condition is order to prevent heart disease. However, our arteries stiffen with age. By maintaining cellular energy, NAD+ may prolong the elasticity of the blood vessels and so avoid cardiovascular risks. An investigation by the University of Washington showed that inflammation in patients’ hearts was linked to poor energy production in the cells of the heart muscle tissue.²

NAD+ improves brain function: Some of the most devastating age-related diseases are those of the brain whereby the affected people are robbed of their memories. Whilst these are the end stages of brain diseases, many people suffer from an inability to learn or focus and NAD+ has been shown to improve brain function in rodents that have been affected by these brain diseases, reducing plaque in the brain which hinders brain function.³

NAD+ slows down ageing in eight ways: There is growing evidence that supplementing with a vitamin-like precursor of NAD+ called nicotinamide riboside can promote longevity. In one study, there was an average of 5% increase in the lifespan of old mice.⁴ This equates to gaining nearly four additional years based on an average human expectancy. 

NAD+ plays an important role in eight anti-ageing mechanisms which are:

1. NAD+ may prevent telomere shortening and may help to maintain or extend telomere length. Telomere shortening is a marker for cellular ageing and a marker for shorter lifespan.⁵
2. NAD+ promotes DNA repair. DNA damage can contribute to ageing and lifespan shortening diseases. Replenishing NAD+ levels to all cells can restore DNA repair and prevent cell death.⁶
3. NAD+ promotes energy enhancing enzymes. Every process in the body requires energy and as we age, we often lose cellular energy. Improving energy in cells means they can perform their role and protects them from early death.⁷
4. NAD+ ensure that our immune cells function as best as they can. As we age, some immune cells become overactive leading to autoimmune diseases, whilst others slow down leading to infections. This process, called immunosenescence, is influenced by mitochondrial function and energy balance in every cell and both these functions depend upon adequate levels of NAD+.⁸
5. NAD+ promotes chromosome stability. Studies indicate that when enzymes that require NAD+ are inactive, chromosomes malfunction, and cells are liable to mutate.⁹
6. NAD+ activates sirtuins which are proteins that govern the all the fundamental functions of cell energy, cell replication and cell death. NAD+ is required for the function of sirtuins.¹⁰
7. NAD+ is a neurotransmitter and so it relays signals between nerve cells and so regulates mood, appetite, and stress. 
8. There are numerous other benefits associated with adequate levels of NAD+ which governs metabolism, obesity, and other concerns.

Do NAD supplements raise NAD+ levels?

The problem is clear. NAD+ levels decline with age and so we need more of it as we age to give our cells the energy to repair and function effectively. NAD supplements do not increase NAD+ levels in the body by any notable amounts as NAD is very unstable and readily deactivated. 

So which NAD supplements raise NAD+ levels?

For the reasons mentioned above, precursors of NAD+ have emerged notably Nicotinamide Riboside (NR), NADH and Nicotinamide Mononucleotide, NMN supplements. I am not going to bore you with the science of the pathways of how your body makes NAD+ however both NR and NMN supplements need to be broken down into Nicotinamide and Ribose to manufacture NAD+. NMN is a very large molecule that cannot enter the cells and has to be converted into NR which is then broken down further into Nicotinamide and Ribose so NMN supplements are an inefficient way of increasing NAD+ levels. NADH is the reduced form of NAD+ and so whilst this increases energy, it does not play the wide and varied roles that NAD+ plays in the body. 

A new patented extract, RiaGev®, outperforms Nicotinamide Ribose (NR) and Nicotinamide Mononucleotide (NMN).^11,12,13 It is the next generation NAD+ supplement because:

• It targets all three biomarkers for healthy ageing in one single ingredient, NAD, ATP for energy and GSH for antioxidant support.
• RiaGev® increases NAD+ more efficiently and effectively than NR or NMN. With RiaGev, the body doesn’t have to go through the process of first breaking it down to make it bioavailable and risk losing its effectiveness during digestion.
• It is more bioavailable that NMN or NAD and is the only NAD booster which survives the digestive process intact.
• It is highly stable.
• RiaGev® also provides more sustained energy with decreased fatigue. 
• It improves glucose tolerance which is the body’s ability to deal with excess glucose in the bloodstream.
• It reduces stress hormones levels such as cortisol.
• It improves brain function, concentration and motivation. 

Fortunately, RiaGev® is now available in an NAD+ supplement aptly named NAD+ Generator. Everyone interested in energy, wellness and healthy ageing should look at RiaGev® and this is one of the best NAD supplements currently on the market. It uniquely combines Bioenergy Ribose with Vitamin B3 in the form of nicotinamide to enhance NAD+ levels markedly more so than NMN supplements or Nicotinamide Riboside (NR).

So are NAD supplements beneficial? NAD supplements containing NAD+ will not be effective in raising NAD+ levels. Neither will NMN supplements nor NR supplements be effective in raising NAD+ levels as significant as RiaGev® in NAD+ Generator. 

Choosing the correct NAD+ supplement may promote healthy ageing, a noticeably better quality of life, and overall wellness by enhancing levels of NAD+ as well as ATP for energy and GSH (glutathione) for oxidative stress. All these three actives go hand in hand. Preserving NAD+ levels by taking NAD supplements such as NAD+ Generator has been shown to preserve youthful function, slow down cellular ageing, protect our genetic material, enhance energy and so much more. 

References:

1. NAD+ metabolism & its role in cellular processes. Nat Rev Mol Cell Bio Feb22
2. Boosting NAD level supresses inflammatory activation of PBMCs in heart failure. Bo Zhou et al J.Clinical Invest. Nov 2020
3. Xiaonan Wang, Wuejun Hu, Yang Yang, Toshihiro Takata, Takashi Sakurai. Nicotinamide mononucleotide protects against ß-amyloid oligomer-induced cognitive impairment and neuronal death. Brain Res, 2016; DOI: 10.1016/j.brainres.2016.04.060.
4. Zhang H, Ryu D, Wu Y, et al. NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016;352(6292):1436-43.
5. Heidinger BJ, Blount JD, Boner W, et al. Telomere length in early life predicts lifespan. Proc Natl Acad Sci U S A. 2012;109(5):1743-8
6. Wang S, Xing Z, Vosler PS, et al. Cellular NAD replenishment confers marked neuroprotection against ischemic cell death: role of enhanced DNA repair. Stroke. 2008;39(9):2587-95.
7. Ziegler DV, Wiley CD, Velarde MC. Mitochondrial effectors of cellular senescence: beyond the free radical theory of aging. Aging Cell. 2015;14(1):1-7.
8. Rottenberg H, Wu S. Mitochondrial dysfunction in lymphocytes from old mice: enhanced activation of the permeability transition. Biochem Biophys Res Commun. 1997;240(1):68-74.
9. Fatoba ST, Okorokov AL. Human SIRT1 associates with mitotic chromatin and contributes to chromosomal condensation. Cell Cycle. 2011;10(14):2317-22.
10. Canto C, Auwerx J. Targeting sirtuin 1 to improve metabolism: all you need is NAD(+)? Pharmacol Rev. 2012;64(1):166-87.
11. Avery B (Department of Pharmaceutics and Drug Delivery, The University of Mississippi), 2017. Pharmacokinetic Analysis of Plasma Nicotinamide and 1-Methyl Nicotinamide Concentrations in Toxicokinetic Study of NIAGEN (Nicotinamide Riboside). Study Report No AV151003. Unpublished Study Report, 9 pp.
12. Liu L. et al. Quantitative analysis of NAD synthesis-breakdown fluxes. CellMetab.27, 1067–1080 (2018).
13. Xue, YQ, Increasing NAD level by D-ribose and its combinations. PCT/US2019/031889 patent pending.

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