Apigenin
Apigenin, a flavone found in parsley, celery and chamomile
Written by Aaron CuhaReviewed Sep 2026
Also known as: 4',5,7-trihydroxyflavone, Chamomile flavone
Sold as a CD38 inhibitor that defends the NAD pool, on the strength of one 2013 paper in cells and obese mice. No human study has ever measured whether apigenin changes CD38 activity or NAD in a person, and human plasma after a large dietary dose peaks in the nanomolar range.
Overview
Apigenin occupies a specific and growing niche in NAD marketing. The pitch is that instead of pushing more precursor in, you stop the leak: CD38 is the enzyme that consumes NAD and its activity rises with age, so inhibiting it should preserve NAD. That reasoning is sound and the underlying enzymology is real. The evidence that apigenin does it in a human is absent.
The CD38 story rests on solid work. A 2016 Cell Metabolism paper established that CD38 expression and activity increase with age, that CD38 is required for the age-related NAD decline and associated mitochondrial dysfunction through a SIRT3-dependent route, and that CD38 is the main enzyme degrading NMN in vivo. That last point is genuinely important: it means CD38 is degrading the precursor supplements as well as the NAD.
Apigenin enters the story through a 2013 Diabetes paper from the same laboratory, which characterised quercetin and apigenin as CD38 inhibitors. In cell culture, apigenin raised intracellular NAD and decreased global protein acetylation including acetylation of p53 and RelA-p65. Administered to obese mice, it raised NAD, decreased global protein acetylation and improved several aspects of glucose and lipid homeostasis.
The part that gets left out is what happened next. When the same laboratory wanted to test the CD38 hypothesis properly in ageing mice, they did not use apigenin. They used 78c, a purpose-built thiazoloquinazolinone inhibitor described in the paper as highly potent and specific, and that compound reversed age-related NAD decline and improved glucose tolerance, muscle function, exercise capacity and cardiac function. The strongest evidence for the CD38 strategy was generated with a drug that is not on sale.
And the human pharmacokinetics are unflattering. In 11 healthy adults given a single oral bolus of blanched parsley at 2 g per kilogram of body weight, delivering about 66 micromoles of apigenin, plasma apigenin peaked at 127 nanomoles per litre after about seven hours and was undetectable by 28 hours, with only 0.22 percent of the dose recovered in urine.
Mechanism of action
CD38 is a membrane-bound NAD glycohydrolase, one of the principal consumers of NAD in mammalian tissue, whose expression and activity rise with age and which is also the main enzyme degrading NMN in vivo. Inhibiting it raises intracellular NAD without supplying any precursor, which in turn increases sirtuin activity and reduces global protein acetylation. Apigenin inhibits CD38 in cell-free and cell-culture systems, which is the entire basis for its use here. It is also a flavone with a long list of other in vitro activities including antioxidant effects, GABA-A receptor binding, and reported senolytic-adjacent and anti-inflammatory actions, most of which are characterised at concentrations far above what an oral dose achieves in human plasma.
Human evidence
One pharmacokinetic study in 11 healthy adults measuring how much apigenin reaches the blood after a dietary dose. No human study has measured CD38 activity, NAD levels or any ageing outcome with apigenin.
- n=11 healthy adults, single oral bolus from parsley delivering about 66 micromoles of apigenin: peak plasma 127 nanomoles per litre at about 7 hours, undetectable by 28 hours, 0.22 percent of the dose recovered in urine.
- No human trial has measured blood or tissue NAD after apigenin.
- No human trial has measured CD38 activity after apigenin.
- No human trial has measured any clinical or functional ageing outcome with apigenin.
- The clinical-looking claims circulating for apigenin come from cell culture and obese mice, and the strongest CD38 mouse result used a different, non-commercial compound.
What this does not tell you: A single-dose bioavailability study in 11 people tells you how much of a compound gets into blood and nothing about what it does there. Apigenin is also consumed in ordinary food, notably parsley, celery and chamomile, so the relevant question for a supplement is whether a capsule achieves exposure that food does not, and that has not been studied either. Nanomolar plasma concentrations against a mechanism characterised in cell culture is the specific gap this page exists to point out.
Reading the research record
The CD38 hypothesis is one of the better ideas in NAD biology and should not be dismissed along with the supplement. Blocking the enzyme that consumes NAD is mechanistically cleaner than flooding the system with precursor, particularly given that CD38 is also the main enzyme destroying NMN in vivo, which means a person taking NMN and an inhibitor may be doing two things that interact. In ageing mice, a potent and specific inhibitor reversed the NAD decline and improved glucose tolerance, muscle function, exercise capacity and cardiac function. That is a strong preclinical result for the strategy.
It is not a result for apigenin. The compound used was 78c, purpose-built and not for sale. The 2013 apigenin paper predates it, used cell culture and obese mice, and reported improvements in glucose and lipid handling rather than an ageing outcome.
The pharmacokinetic gap is the practical problem. Human plasma apigenin after a large dietary bolus peaked at 127 nanomoles per litre and was gone within a day, with almost none of the dose recovered intact. Enzyme inhibition characterised in cell culture is typically demonstrated at concentrations well above that range, and nobody has published the comparison for apigenin and CD38 in a person. Until someone measures CD38 activity or NAD in humans taking apigenin, the claim that a capsule defends the NAD pool is an extrapolation across three species and three orders of magnitude of concentration.
Apigenin in food is a different question from apigenin in a capsule sold on an NAD claim, and nothing here argues against parsley or chamomile.
Three claim types get collapsed into one in almost all consumer writing about this pathway, and keeping them apart is most of the work. A biomarker claim is that a compound raises blood NAD. That is easy to demonstrate and for several of these compounds it is simply true. A surrogate claim is that it moves something sitting between a biomarker and a symptom, such as arterial stiffness or an acylcarnitine profile. A clinical claim is that a person walks further, remembers more, gets fewer cancers or lives longer. A compound can be firmly established at the first level and have nothing at all at the third, and that is the actual position of most of the NAD pathway. There is no published human trial of any NAD precursor with a hard clinical endpoint that reported a benefit, with one exception on this list, and that exception is nicotinamide in skin cancer, which works through DNA repair in sun-damaged skin rather than through anything to do with ageing.
The evidence, charted
Fig. 1 · evidence composition
1of 4 citations (25%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 4 distinct years, 2006 to 2018, counted from the citation list on this page. The newest citation on file is from 2018, more than five years ago; the published record may have gone quiet.
Fig. 3 · legal status at a glance
US
Not approved
UK
Not approved
AU
Not approved
CA
Not approved
Not approved in any of the four jurisdictions shown. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Animal2013
Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome
The paper the entire apigenin-for-NAD market is built on. Cell culture plus obese mice. The authors characterise quercetin and apigenin as CD38 inhibitors, show that pharmacological CD38 inhibition raises intracellular NAD, and that treating cell cultures with apigenin decreases global protein acetylation including acetylation of p53 and RelA-p65. Apigenin given to obese mice increased NAD, decreased global protein acetylation and improved several aspects of glucose and lipid homeostasis. No human data.
Diabetes - Animal2016
CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism
The mechanistic foundation, in mice. CD38 expression and activity increase with age, CD38 is required for the age-related NAD decline and mitochondrial dysfunction via a pathway mediated at least in part by SIRT3, and CD38 is the main enzyme degrading the NAD precursor NMN in vivo. That last finding matters for anyone taking NMN, because it identifies the enzyme that destroys it.
Cell Metabolism - Animal2018
A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD(+) Decline
The strongest evidence for the CD38 strategy, and it was not generated with apigenin. 78c, a highly potent and specific thiazoloquinazolinone CD38 inhibitor, reversed age-related NAD decline and improved glucose tolerance, muscle function, exercise capacity and cardiac function in mouse models of natural and accelerated ageing. The effects depended on tissue NAD levels and were reversed by inhibiting NAD synthesis. A declared conflict: an author holds a patent on the use of CD38 inhibitors for metabolic disease. 78c is not commercially available and has no human data.
Cell Metabolism - Human2006
Bioavailability of apigenin from apiin-rich parsley in humans
The only human number on this page, and it is a pharmacokinetic one. 11 healthy adults aged 23 to 41 consumed a single oral bolus of blanched parsley at 2 g per kilogram of body weight, corresponding to 65.8 plus or minus 15.5 micromoles of apigenin. Mean peak plasma apigenin was 127 plus or minus 81 nanomoles per litre at 7.2 hours, with wide variation between people, falling below the 2.3 nanomole detection limit by 28 hours. Urinary recovery was 0.22 percent of the ingested dose. The authors conclude that a small portion of dietary apigenin reaches the circulation.
Annals of Nutrition and Metabolism
Frequently asked questions
Does apigenin raise NAD in humans?
Nobody has measured it. There is no human study of apigenin with NAD, or with CD38 activity, as an endpoint. The NAD increases attributed to apigenin were measured in cell culture and in obese mice.
Is apigenin a CD38 inhibitor?
In cell-free and cell-culture systems, yes, and that was established in a 2013 paper alongside quercetin. Whether it inhibits CD38 at the concentrations an oral dose produces in human plasma, which peaked at 127 nanomoles per litre after a large parsley bolus, has not been tested.
Should I take apigenin with NMN or NR?
The theory is coherent: CD38 is the main enzyme degrading NMN in vivo, so inhibiting it should make a precursor last longer. No human study has tested that combination on any endpoint, including blood NAD. It is a hypothesis with a mechanism, not a protocol with evidence.
What about 78c?
78c is the potent, specific CD38 inhibitor that produced the strong results in ageing mice: reversed NAD decline, better glucose tolerance, muscle function, exercise capacity and cardiac function. It is not commercially available, has no human data, and is not apigenin. Marketing that quotes those mouse benefits next to an apigenin product is attributing one compound's results to another.
Is apigenin safe?
It is a normal constituent of parsley, celery and chamomile and is consumed in food without incident, which is reassurance about dietary exposure. Supplement doses are far higher than dietary ones and have no published human safety trial. Apigenin also binds GABA-A receptors in vitro and is the compound usually credited with chamomile's sedative reputation, so interaction with sedatives is a reasonable thing to raise with a clinician.