Apigenin: An Alternative Way of Boosting NAD+
At the recent Ending Age-Related Diseases 2021 online conference, Dr. Eric Verdin of the Buck Institute gave a talk in which he described the mechanism behind the well-known drop in NAD+ with age, for which lots of anti-aging folks are spending significant $ taking NR or NMN, with very limited results in humans. Verdin attributed the NAD+ loss to a rise with age of an enzyme called CD38, which destroys the NAD+, removing it from the normal cycle. It turns out that the readily available flavonoid Apignin is an inhibitor of CD38.
Therefore, there is leak in the NAD+ bucket. Instead of loading up with NAD+ precursors like NR and NMN that don't really fix the leak, I suggest talking a daily dose of Apigenin. Swanson sells 90 x 50 mg Apigenin capsules for $8.76, (or you can just eat a lot of parsley.)
One step further they found last year
"Here, we show that pro-inflammatory M1-like macrophages accumulate in visceral white adipose tissue and liver. These M1-like macrophages express high levels of the NAD-consuming enzyme CD38 and have enhanced CD38-dependent NADase activity, thereby reducing tissue NAD levels.
We also find that senescent cells progressively accumulate in visceral white adipose tissue and liver during ageing and that inflammatory cytokines secreted by senescent cells induce the macrophages to proliferate and express CD38
So if you kill off the senescent cells in your fat and liver it should help lower cd38 and boost NAD too.
Apigenin is already pretty cheap but it can also be purchased in bulk from Liftmode. They are suggesting 250mg per serving, up to 3 times per day for its calming effect. They state: "In terms of general dosing, studies have shown Apigenin is most effective and safe in doses ranging from 200 mg to 1500 mg." They do note that possible toxicity has been show in mice at dosage of 100mg/kg. My plan is to take a daily 50mg/day capsule along with 50mg resveratrol and 5mg Bioperine.
Niacin as primary NAD booster?
When I read this I think it might be a relevant strategy to focus in on niacin and apigenin as primary supplements to boost NAD levels. The resaerch is done on human patients with mitochondrial myopathies. It does not mean that we automatically can translate the results to humans without this condition. But there might be something in this approach. I remember that Nuchidos main product (time) to boost NAD levels use B3 and Apigenin:
- Mitochondrial myopathy patients have NAD+ deficiency in muscle and blood
- Niacin is an efficient NAD+ booster in humans
- Niacin improves muscle strength and fatty liver in mitochondrial myopathy
- boosts muscle mitochondrial biogenesis and respiratory chain activity in humans
NAD+ is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD+ depletion occurs in patients with degenerative disorders and whether NAD+ repletion improves their symptoms has remained open. Here, we report systemic NAD+ deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD+-booster niacin, a vitamin B3 form (to 750–1,000 mg/day; clinicaltrials.gov NCT03973203) for patients and their matched controls for 10 or 4 months, respectively. Blood NAD+ increased in all subjects, up to 8-fold, and muscle NAD+ of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%. Our evidence indicates that blood analysis is useful in identifying NAD+ deficiency and points niacin to be an efficient NAD+ booster for treating mitochondrial myopathy.
Context and Significance
NAD+ is a molecule with important roles in regulating metabolism in our tissues. Its roles in the context of longevity, aging, and disease are under intense investigation, so far mainly in model organisms. However, the relevance of NAD+ levels for human disease progression has remained elusive. Here, researchers at the University of Helsinki report that mitochondrial muscle disease leads to low NAD+ levels in both blood and muscle. Importantly, they show that treatment with niacin, a vitamin B3 form and an NAD+ precursor, improves NAD+ levels, disease signs, and muscle metabolism in patients, also improving muscle strength and performance. These results indicate that NAD+ depletion occurs in human diseases, and its repletion is a potential therapy for mitochondrial myopathies."
My question from the beginning was: how do we know that increased NAD+ in the blood will cause increased NAD+ levels in the target cells in the healthy ageing human body. Now I know that we act on the results from mice.
The paper I posted a Link to was a human study (Brenner was one of the contributers) they found that increased levels of NAD+ in the blood of Patients with severly low NAD+ in their muscles had a normalizing effect on the levels of NAD+ in the patients muscles.
But in the healthy controls with normal levels of NAD+ in their muscles already from the beginning, even a dramatically increased level of NAD+ in the blood did nothing to increase the NAD+ levels in the muscle cells.
This result made me curious about how effective an intervention with increased NAD+ in blood actually is? And I asked myself uf we have human studies that show total body rejuvination after boosting NAD+ in the blood?
So will increased NAD+ in the blood of healthy persons with normal NAD+ Levels be a rejuvenating intervention? Now I know ( from Brenner) that, based on results from mice, we assume it does.