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Apigenin and CD38: What the Research Actually Shows About NAD+ Consumption

Published 2026-09-16 · Last reviewed 2026-09-16 · By Andy Palenzuela, Founder

Nearly every NAD+ formula is built as a supply problem: add precursor, expect more NAD+. Almost none of them ask where NAD+ goes. One of the largest answers is an enzyme called CD38, and apigenin — a flavonoid found in chamomile, parsley, and celery — is the compound most studied for inhibiting it. This article explains what CD38 does, what the apigenin research measured and in what kind of model, where the evidence stops, and why CELLUNAD+ includes 100 mg of it anyway. It is written by the founder of Age Revive, who spent 14+ years inside regulated nutrition supply chains before formulating a NAD+ foundation that addresses consumption as well as supply.

Key facts

  • CD38: is an enzyme that breaks down NAD+. It sits on the surface of many cells, especially immune cells, and is one of the body's main NAD+ consumers. Its activity has been reported to rise with age.
  • Apigenin: is a flavone found in chamomile, parsley, celery, and other plants.
  • Escande 2013: showed apigenin inhibited CD38 enzymatic activity in vitro and reported higher NAD+ levels in tissue when apigenin was given to mice. That is preclinical work — cells and animals.
  • No human trial: has established what an oral apigenin dose does to CD38 activity or NAD+ levels in people. Oral bioavailability at supplement doses is an open question.
  • Why it is in CELLUNAD+ anyway: a formula that supports NAD+ supply and ignores NAD+ consumption is addressing half the equation. Apigenin is the researched flavonoid for the other half, included at 100 mg — a formulation decision, not a proven outcome.
  • Not a sleep ingredient here: Apigenin appears in sleep stacks for a different, unrelated reason. CELLUNAD+ makes no sleep claim.

What CD38 is and why it matters for NAD+

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme in every living cell, central to cellular energy metabolism. It is not static. Several enzyme families consume it: sirtuins (cellular maintenance and gene regulation), PARPs (DNA repair processes), and a group of NAD+-degrading enzymes, of which CD38 is the most prominent.

CD38 is an ecto-enzyme — it sits largely on the outer surface of cells, particularly immune cells — and it cleaves NAD+ as part of its signaling role. It is unusually inefficient at it: CD38 consumes many NAD+ molecules to produce a small amount of its signaling product, which is why it is often described as one of the body's main NAD+ sinks.

CD38 activity has been reported to rise with age in preclinical research, and that observation sits underneath a simple argument: if NAD+ declines with age partly because consumption goes up, then supporting NAD+ metabolism means thinking about the drain as well as the supply.

What apigenin is

Apigenin is a flavone — a subclass of flavonoids — with the chemical name 4',5,7-trihydroxyflavone. It occurs naturally in chamomile (the reason chamomile tea is its best-known source), parsley, celery, and a number of other herbs and vegetables. Like most flavonoids, it is poorly soluble in water, which becomes relevant when discussing how much of an oral dose is absorbed.

Apigenin has been studied for a range of activities in laboratory settings. This article concerns one of them: its interaction with CD38.

What Escande 2013 measured

The study most cited for apigenin and CD38 is Escande et al., published in Diabetes in 2013. It is worth being exact about what it was.

In vitro: using purified recombinant human CD38, the authors tested apigenin and quercetin across a range of concentrations and found both inhibited CD38's NAD+-degrading activity. Apigenin was the more effective of the two in their assays.

In cells: treating cell cultures with apigenin was associated with higher intracellular NAD+ and reduced global protein acetylation — a downstream marker consistent with higher sirtuin activity.

In mice: apigenin administration was associated with higher NAD+ levels in liver tissue.

What it established: apigenin inhibits CD38 in the test tube and in cell culture, and giving it to mice was associated with higher tissue NAD+.

What it did not: anything in humans. No human dose was tested, no oral bioavailability was measured in people, and no human NAD+ outcome was reported.

The oral bioavailability question

This is where honest NAD+ brands and dishonest ones part ways.

The concentrations that inhibited CD38 in Escande 2013 were achieved in a dish and by dosing mice. Whether a 100 mg capsule of apigenin produces meaningful CD38 inhibition in a human being depends on how much is absorbed, how quickly it is metabolized, and what concentration reaches the relevant cells. Apigenin's low water solubility and extensive metabolism mean those numbers are not simply assumed from the preclinical work.

So a label that says apigenin "blocks CD38" or "protects your NAD+" is converting a cell-culture result into a human promise. Age Revive does not do that. The accurate statement is narrower: apigenin is a flavonoid researched for its role in CD38 management, and it is included to address the consumption side of NAD+ metabolism with the compound that has the strongest preclinical case.

Why CELLUNAD+ includes it at 100 mg

Two reasons, both about formulation logic rather than proof.

First, completeness. An NAD+ formula has three jobs: supply the precursor, cover the methylation demand that NAD+ turnover creates, and address consumption. Most NAD+ products do the first and skip the other two. CELLUNAD+ pairs 500 mg of nicotinamide riboside with TMG, methylfolate, methyl-B12, and P-5-P for methylation balance, 200 mg of R-lipoic acid for mitochondrial oxidative balance — and 100 mg of apigenin for CD38 pathway interest. Not one ingredient. A system.

Second, dose adequacy. Some formulas that include apigenin do so at 5–25 mg, which puts the word on the label at a fraction of the amount anyone would seriously argue for. 100 mg is a research-informed decision: high enough to be a real inclusion, disclosed on the label, and paired with 5 mg of BioPerine to support absorption. It is not a clinically validated CD38 dose, because no such dose exists.

Every dose is printed on the label. If the apigenin question matters to you, the number is there to check.

The sleep-stack confusion

Apigenin shows up in a lot of "sleep" supplements, usually credited to chamomile's traditional use. That is a separate line of interest with its own research questions, and it has nothing to do with why apigenin is in an NAD+ formula. CELLUNAD+ makes no sleep claim, is non-stimulant by design, and is taken as a daily foundation, not a bedtime product. If you see apigenin marketed as a sleep aid and a CD38 inhibitor in the same breath, someone has stacked two unrelated stories to sell one capsule.

What the research does not show

  • No human trial has shown that oral apigenin inhibits CD38 or raises NAD+ in people. The evidence is in vitro, cell culture, and mouse.
  • Apigenin does not "protect your NAD+." That is a therapeutic framing of a preclinical result.
  • CELLUNAD+ has not been tested in any study. Escande 2013 tested apigenin alone; the NR trials tested NR alone. The formula's combination is a design decision.
  • 100 mg is not a validated dose. It is a research-informed amount in a disclosed formula, chosen to be a real inclusion rather than a label decoration.
  • CD38's age-related rise is a preclinical observation, not a diagnosis of anything in you.

How to read apigenin on a label

  1. Is it there at all? Most NAD+ formulas do not include it. That is not a flaw in itself — it is a formula that addresses supply only.
  2. What is the dose? 5–25 mg is a label decision. 100 mg is a formula decision.
  3. Is anything supporting absorption? Apigenin is poorly water-soluble. Look for a stated absorption support ingredient, or accept that the brand has not thought about it.
  4. What claim is attached? "Researched for CD38 management" is honest. "Blocks CD38" is not.
  5. Is it sold as a sleep ingredient in the same formula? If so, ask which job it is supposed to be doing.

The full seven-check test for any NAD+ product is in How to Choose an NAD+ Supplement. The reasoning behind the methylation co-factors that sit alongside apigenin is in Should You Take TMG With NR?.

Frequently asked questions

Does apigenin increase NAD+? In laboratory research, apigenin inhibited CD38 — an enzyme that breaks down NAD+ — in vitro, and apigenin given to mice was associated with higher tissue NAD+ (Escande 2013). No human trial has established that oral apigenin raises NAD+ in people. Age Revive describes apigenin as a flavonoid researched for CD38 management, not as an NAD+ booster.

What is CD38? CD38 is an enzyme, found largely on the surface of cells, that breaks down NAD+. It is one of the body's main NAD+ consumers, and its activity has been reported to rise with age in preclinical research.

How much apigenin is in CELLUNAD+? 100 mg per daily serving (2 capsules), alongside 500 mg NR, four methylation co-factors, 200 mg R-lipoic acid, and 5 mg BioPerine. The apigenin is included to address the NAD+ consumption side of the formula; it is not a validated CD38 dose, because none exists in humans.

Is apigenin in CELLUNAD+ for sleep? No. Apigenin appears in sleep products for a separate reason tied to chamomile's traditional use. CELLUNAD+ includes it for CD38 pathway interest, makes no sleep claim, and is a non-stimulant daily foundation, not a bedtime product.

Sources

  1. Escande C, Nin V, Price NL, et al. Flavonoid apigenin is an inhibitor of the NAD+ase CD38 Diabetes. 2013;62(4):1084-1093. doi:10.2337/db12-1139. PMID 23172919.
  2. Trammell SAJ, Schmidt MS, Weidemann BJ, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature Communications. 2016;7:12948. doi:10.1038/ncomms12948. PMID 27721479.

Related reading

  • How to Choose an NAD+ Supplement: The Seven-Check Label Test — Most premium NAD+ brands now print every dose on the label, but transparency alone does not separate a good formula from a lazy one.
  • Should You Take TMG With NR? Methylation and NAD+ Precursors, Explained — Where NR and methylation intersect, what is established biochemistry versus hypothesis, and why TMG alone is only part of the co-factor picture.
  • What Is Nicotinamide Riboside? NR, NAD+, and What Human Trials Measured — NR is a form of vitamin B3 the body converts to NAD+. Learn how it works, what human trials measured, the doses used, and how to read an NR label.

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About the author

Andy Palenzuela is the founder of Age Revive and has 14+ years of experience in regulated nutrition supply chains, including manufacturing oversight, ingredient sourcing, and quality assurance for consumer health products. Age Revive formulas are developed based on published peer-reviewed research and manufactured at cGMP-certified facilities. LinkedIn

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. The information in this article is for educational purposes only and is not intended as medical advice. Consult your healthcare provider before starting any supplement regimen.