The Critical Role of NAD+ and Nitric Oxide Replenishment in Anti-Aging Medicine


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Dietary nitrate is an excellent way to rejuvenate mitochondrial health.23 However, this strategy is most effective when also ensuring that nicotinamide adenine dinucleotide (NAD+) levels are continuously being replenished. NAD+ is an essential resource for cellular energy production. The reduced form of NAD+ (NADH) is critical to the mitochondrial production of adenosine triphosphate (ATP), which serves as fuel for the cells of the body.24 Conversely, low levels of NAD+ may make mitochondria more vulnerable to damage.25

Between the ages of 40 and 50, we lose up to 50% of our NAD+ levels.26 This leads to adverse consequences to our health since low NAD+ levels contribute to diminished energy needed to maintain health as we age.24 Low NAD+ occurs in many neurodegenerative diseases, including Alzheimer’s, Parkinson’s, cardiovascular, and muscle atrophy.24 Furthermore, NAD+ depletion affects immunity.27,28

Age-Related Declines in NAD+ in Various Body Tissues29

Muscle30% – 85%
Liver40% – 90%
Adipose55% – 75%
Brain35% – 90%
Pancreas80% – 85%
Spleen35% – 40%
Heart30% – 70%
Kidney15% – 98%
Lung20% – 25%
Cerebrospinal fluid86%
Skin40% – 50%
Blood plasma15% – 92%
Testes100%


Sirtuins, which increase lifespan, require NAD+ to function properly. Sirtuins are important to increasing longevity and reducing stress responses.30 Enhancing sirtuin activity is linked to the delay of age-related diseases.30 Furthermore, increased sirtuin activity is thought to be the reason why lean diets and exercise lead to cardiometabolic benefits.30 For example, SIRT1 stops the decline in vascular endothelial function, metabolic syndrome, ischemia-reperfusion (IR) injury, obesity, and cardiomyopathy.30 However, during aging, NAD+ levels and sirtuin activity progressively decline, an effect made worse by obesity and sedentary lifestyles.30 Activation of sirtuins or increasing NAD+ levels leads to benefits such as improved insulin sensitivity in a number of age-related cardiovascular and metabolic disease models.30


NAD+ and Alzheimer’s

One of the best examples of the protective effect of NAD+ in aging is its role in cognitive function. Mitochondria in neurons synthesize ATP to produce the necessary energy needed for optimal activity. However, dysfunctional or damaged mitochondria build up in the neurons, affected in the brain during AD.31 NAD+ protects the neurons by rejuvenating mitochondrial health.32


How to Increase NAD+ Levels

Evidence indicates that interventions that replenish cellular NAD+ levels may suppress aspects of aging and inhibit some age-related diseases.24 Supplementation with nicotinamide riboside (NR) is an extremely effective way to raise NAD+ levels. NR administered as both a single dose and repeated use has been shown in human research to raise NAD+ levels.33

Research has investigated the use of NR in a number of age-related conditions. In a randomized, double-blind, controlled cross-over study of 30 middle-aged and older healthy male and female adults, 500 mg of NR were given twice per day orally for six weeks.33 NR supplementation tended to lower both systolic and diastolic blood pressure. The decline was more dramatic in subjects who had elevated blood pressure at baseline. Additionally, NR tended to decrease aortic stiffness and increase ATP levels. NAD+ levels increased by an average of 60% after NR supplementation. In another study of peripheral blood mononuclear cells from patients with heart failure, NR reduced inflammation and improved mitochondrial function.34

Preclinical studies in rodents also indicate NR may be of use in type 2 diabetes. In a mouse model of this condition, NR significantly reduced non-fasting and fasting blood glucose and was associated with reduced weight gain.35

Furthermore, NR treatment reduced memory loss in a mouse model of AD.36 In another study that included both mice with AD and aged mice, NR supplementation improved the short-term spatial memory of the aged animals and the contextual fear memory in the AD animals.37 In aged mice, NR also suppressed the activation of astrocytes while in AD mice it reduced the buildup of Amyloid beta.37


Conclusion

Although aging is inevitable, we can slow down the process by concentrating on two important aspects: healthy blood flow and mitochondrial rejuvenation. Maintaining circulation is critical to ensuring all cells of the body are perfused with the nutrients and oxygen they need to function their best. Likewise, our bodies must produce enough energy to fuel healthy cellular function. That’s why maintaining the health of the mitochondria is also important. Tending to these two factors with a nitrate-rich supplement containing beetroot and replenishing NAD+ levels with nicotinamide riboside can help patients feel healthier and more energetic as they age.


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