Raising NAD+ levels back to youthful levels to combat aging is an exciting new field of research.
Rather than boosting NAD+ levels, an alternative and/or complementary approach seeks to remedy the cause of WHY NAD+ levels drop as we age.
Recent studies have found the enzyme CD38 RISES at the same time NAD+ levels decline, and seems to destroy NAD+. They found that inhibiting CD38 results in much higher NAD+ levels.
Other studies have found Flavonoids like Quercetin and Apigenin are effective at inhibiting CD38, resulting in higher NAD+ levels.
WHAT IS QUERCETIN
It is found in many vegetable, tea, coffee and red wine.
Quercetin supplements are highly bioavable with a half-life of 11-28 hours which means that supplementation results in greatly increased blood plasma levels.
In human studies, quercetin has been found to be safe and well tolerated, with no adverse effects.
You can read more about Quercetin here
CD38 INCREASES, NAD+ DECLINES AS WE AGE
This June 2016 study shows that CD38 increases dramatically with age and plays a key role in destroying Nicotinamide MonoNucleotide (NMN), a NAD+ precursor.
The authors show that protein levels of CD38 increased in multiple tissues during aging.
They then compared the relationship of CD38 levels to NAD+ of normal mice vs CD38 Knockout mice (Mice bred without the gene to product CD38).
The NAD+ levels of normal mice aged 32 months are about 1/2 that of young mice, whereas the CD38 knockout mice showed no decrease in NAD+ levels at the same age.
This study did not suggest a cause for the rapid increase in CD38 activity but other studies have shown a link to CD38 increase with inflammation from disease and injury as we age.
The exponential rise suggests that CD38 may deplete NAD+ needed for other processes and directly relate to the aging process.
Finally, the authors addressed how CD38 may affect therapies designed to raise NAD+ levels. Currently, the favored approach in mouse and humans is to treat with NAD+ precursors, such as nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN).
Interestingly, CD38 not only degrades NAD+ in vivo, but also NMN. When CD38 knockout mice were given injections of NAD+, NMN, or NR (which is converted to NMN), circulating levels of NAD metabolites remained stable after 150 min, long after they began to fall in the wild-type animals.
Furthermore, when compared to the wild-type, CD38 knockout mice on a high-fat diet exhibited a much larger improvement in glucose tolerance when given NR.
NAD+ DECLINE LINKED TO AGING
Prior research shows that declining NAD+ levels is linked to many age related diseases and metabolic disorders such as diabetes, and a possible contributing factor to aging (4).
A landmark 2013 study by Dr David Sinclair demonstrated that increased levels of NAD+ have been shown to reverse age related degeneration in mice, giving older mice the muscle capacity, endurance and metabolism of much younger mice (5).
Other studies have shown that supplementing old mice with NAD+ precursors can greatly improve metabolic health such as increased insulin sensitivity, improved mitochondrial function, reduced stem cell senescence, and increased lifespan (6,7,8)
This suggests that many of the the normal age related conditions are at least partly driven by decreased mitochondrial functioning, and that increasing NAD+ levels can restore mitochondrial functioning and reverse many age related problems (9).
QUERCETIN INHIBITS CD38
While many of the health benefits of Quercetin are well documented, the mechanisms of action are not completely understood.
In this study published April 2013, obese mice that received Apigenen or Quercetin showed improved glucose homeostasis, glucose tolerance, and lipid metabolism.
The authors theorized the mechanism may be the anti-inflammatory properties inhibit CD38 which results in increased NAD+ levels in tissues.
First, they measured the effect of quercetin on endogenous cellular CD38 activity and found that quercetin promotes an increase in intracellular NAD+ in a dose-dependent manner (Fig. 4B).
They also compared NAD+ levels of normal mice with CD38 knockout mice after supplementation with Quercetin and found it promotes an increase in NAD+ in normal mice but does not further increase NAD+ levels in CD38 knockout mice (Fig. 4D), indicating that the effect of quercetin on NAD+ levels is CD38 dependent.
They were able to demonstrate that Quercetin inhibits CD38 and promotes an increase in NAD+ levels.
QUERCETIN INCREASES EFFECTIVENESS OF NICOTINAMIDE RIBOSIDE
Supplementation with NAD+ precursors such as Nicotinamide Riboside is generating a lot of excitement as recent research is proving it is effective at raising NAD+ levels in humans, which has tremendous therapeutic potential to treat metabolic and age-related disease.
Dr Sinclair is at the forefront of research on NAD+ levels and their effects on aging. In this video (18 minute mark), he demonstrates recent research supplementing with NAD+ precursors to return old mice to youthful states.
He recently published this article that reviews the studies on CD38, with the following findings:
- Results from these and other studies with CD38 demonstrate that combating the rise of CD38 is also a promising approach to protect NAD+ levels.
- These findings suggest that the efficacy of NAD+ precursors may be enhanced by co-supplementation with CD38 inhibitors
Thorne Research is WAY ahead of the competition here. Their RESVERACEL has:
- Nicotinamide Riboside – 300 mg
- Quercetin Phytosome – 250 mg
- Trans-Resveratrol – 150 mg
- Betaine Anhydrous (Trimethyglycine) – 50 mg