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Importance of NAD+
Importance of NAD+

Importance of NAD+

Most reading this have by now heard about NAD+, and the various supplements advertising the ability to raise NAD+ levels. NAD+ first popped onto my own radar in 2014, following David Sinclair’s paper, published late 2013 in Cell, which demonstrated that raising NAD+ levels in old mice restored mitochondrial function to that of young mice. It turns out Sinclair has been studying NAD+ in regards to aging for quite some time, first published a paper on the subject in 2002,  and later linking declining NAD+ with the aging process in 2010. 

In the last several years, research has exploded on compounds to raise NAD+ levels, with results in mice hinting that these compounds could be the fountain of youth. Raising NAD+ has shown to do just about everything for mice, and naturally, these results have had many humans thrilled, hopeful that similar results will be noted in our species. 




Importance of NAD+


As most of you who have read my blogs on hydrogen should remember, the redox status of our cells is critical for our health. NAD is critical for our cellular redox, with the oxidized and reduced forms (NAD+/NADH) being critical for cellular reduction and oxidation. NAD is also critical for our metabolism, with declining levels leading to metabolic disorders. Additionally, NAD+ is consumed by sirtuins, with sirtuin inhibition widely linked to aging and age-related diseases, potentially due to decreased metabolic function. With how critical NAD and ratios of NAD+/NADH are to our cellular health, it is no wonder why this area of research has exploded in recent years. 

Unfortunately, NAD levels decline as we age, particularly the ratio of NAD+/NADH, with NAD+ rapidly declining and NADH rising. Disrupted ratios not only lead to dys-homeostatic redox function, but to reduced function of sirtuins from a lack of NAD+ to consume, further disrupting our metabolic function and hastening the progression of aging and age-related diseases. Keeping our ratio’s intact, with NAD+ levels high, is absolutely critical in the goal of longevity and metabolic health. 




NAD+ Boosting Supplements


NAD+ boosting supplements have been miraculous for elderly mice, turning back the clock and leading to beneficial outcomes in numerous disease models. One study demonstrated that supplementation with an NAD+ precursor significantly increased the number of mitochondria and that both the precursor and exercise positively affected glucose tolerance, but through different mechanisms. A follow-up study found that both exercise and supplementation of an NAD+ precursor led to weight loss in obese mice, however, the NAD+ precursor was more prominent for the metabolism of liver fat than exercise. This is just the tip of the iceberg, as supplementation with NAD+ precursors has shown to turn back the reproductive clock in mice, improve cognitive function in elderly mice, and increase the number and quality of muscle stem cells, and muscle regeneration in mice leading to extended lifespan. This is in addition to NAD+ precursors demonstrating that supplementation can reverse fibrosis and cardiac hypertrophy and increase blood flow and endurance in elderly mice.

 

Why NAD+ Gold?



One paradox exists when assessing NAD+ precursor supplementation, namely, too much NAD+ can be detrimental and downregulate NQO1, which plays multiple roles in metabolism, cellular protection, and acts as a “redox switch”. This may have been seen in one of the human trials on an NAD+ precursor, where the lower dose worked better than a higher dose, despite the higher dosing being only 17.5% of the standard dose used in mice, after relative conversion. This is particularly interesting as results in humans, to date, are not what we have seen in mice, with dose-dependent results highly hypothesized. 

First off, in assessing nicotinamide riboside and nicotinamide mononucleotide (NR and NMN), I defer to the expert, David Sinclair, who has stated that he believes NMN is superior, citing data that NMN seems to work at a lower dose, and works when NR doesn’t, despite being listed as an inventor of an NR form one prominent company exclusively distributes. NAD+ Gold is the first liposomal delivery of NMN and in a study by the manufacturer using the Caco-2 assay, which is an intestinal permeability model, the data demonstrated that the liposomal form had 4x the bioavailability as the powder form. Some molecules can exert negative consequences through higher dosages, even when they are not biologically available (e.g. magnesium). NAD+ Gold allows a lower dose to be used to obtain the same biological capacity, potentially lowering the risk of negative consequences. Of course, this would need to be demonstrated through research, but for the time being, I am erring on the side of caution. 


Hydrogen and NAD+ boosters

An important question exists regarding what is more important: raising NAD+ through exogenous supplementation or protecting levels from depletion due to environmental assaults? Why not pursue both? As I have previously written about, molecular hydrogen has demonstrated the ability to preserve NAD+/NADH ratios against physiological assaults, with one published study showing it was capable of protecting these ratios and mitigating cellular senescence after cells were exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD is a persistent organic pollutant and carcinogen present in “Agent Orange” which was used in the chemical warfare program during the Vietnam War, as well in incidents, such as the Seveso Disaster. From the increasing evidence accruing for molecular hydrogen regarding metabolic health and improvements of the redox status in the cell, such as our recent clinical trial using the hydrogen tablets for metabolic syndrome which saw significant improvements in redox, it is not unreasonable to believe that hydrogen water may protect NAD+/NADH ratios against many other assaults, including obesity, daily life, and the normal aging process. This is actually one parameter we are investigating in a significant study that will hopefully begin in 2020, COVID-19 situation-dependent, as it was supposed to begin this March. 




AGEs and NAD+?

As I wrote about in Part 1 of my series on Advanced Glycation End-Product Crosslinking, In a cause-effect cyclical nature, AGEs can both be caused by and lead to excess oxidative stress, and require reactive oxygen species (ROS) to be formed and produced during formation. Chronically elevated AGEs have been shown to be potent suppressors of NAD+.





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Why Wouldn’t Everyone Take an NAD+ Booster?

One important consideration is that currently, I do not recommend supplementation of an NAD+ precursor for those younger than 40. In human evidence, only the elderly saw a benefit in exercise performance and redox status. In rodent models, it gets even trickier, with “young mice” seeing a drastic performance decrease after supplementation with an NAD+ precursor. Additionally, increased levels of NAD+, when baseline levels were not low, may potentially worsen rheumatoid arthritis through increased inflammation, with lowered levels potentially improving the outcomes.

Furthermore, significantly increased NAD+ levels when unnecessary has been linked to an increase in cellular senescence.



Starting an NAD+ booster to bolster effects of protective products, such as our Rejuvenation hydrogen tablets and AGEless Defense, could be a fantastic idea for those in their 40’s and on, in order to protect against assaults that could lower NAD+ levels while subtly raising said levels simultaneously. 


 


2 comments

  • Alex Tarnava

    Hi Santi, it is a coenzyme found in every cell in our body and declining ratios of NAD+/NADH have been heavily linked to the aging process in general


  • Santi Mercuri

    what is NAD??? sorry if the question is quite superficial


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