Our dosing of Apigenin for Anxiolytic, Sedative, and Sleep applications

Apigenin basic specifications

Chemical name / classification: 4′, 5, 7-trihydroxyflavone / Flavonoid: flavone:

Molar mass: 270.0528 g/mol;

Visual characteristics: Yellow (with light green hue), crystalline solid;

Smell: ND

Taste: Not discernible, crystalline gritty silt texture

Introduction to Apigenin

With apigenin's rapid rise to fame via Andrew Huberman's promotion for sleep benefits, use and interest has dramatically increased. This is certainly for good reason as apigenin is indeed a fantastic standalone sleep supporting compound, which also crosses over well into antiaging via CD38 inhibition and NAD+ promotion for metabolism and increased sirtuin activation benefits.

HOWEVER - with regard to dose selection we do face one major hurdle.
Very limited human clinical trials have been performed on apigenin, and to my knowledge as of 2022 there are none performed for the purpose of investigating anti-stress or sleep benefits. This has led to a plethora of unsupported claims for various benefits at doses unlikely to be relevant to said benefit.

Due to the lack of human trials for the application of anxiolytic, sedative, and sleep actions - it seems appropriate to discuss personal anecdotal experience, and then move onto a breakdown of dosing from a single mouse study.

The goal in this to provide some surrounding context for use of apigenin regarding sleep and stress, but not to be used as the end-all-be-all of discussion on dosing. Until we have strong body of research in humans available I expect this to be an ever evolving conversation.

The popular 50mg dose

First looking at the overwhelmingly dominant consumer product dose of 50mg. This is time and number proven for safety, but regarding function there is little support. According to pharmacokinetic studies in animals this dose has very little measurable effect. This is likely due to the poor bioavailability of apigenin and extensive first pass metabolism to luteolin. 

Anecdotally for once-off dosing, the mood effect at 50mg is minor to none and effects on improving sleep quality fell within normal variation. Some consideration may be made for chronic dosing over extended weeks however there is no evidence to show that this would yield better returns, nor is it the manner in which supplemental apigenin is advertised to consumers. Key to note about this common 50mg dose point:

  • Likely began as an industry trend formed around a singular parsley study;
  • Is the advertised dose for a wide plethora of different benefits of apigenin (prostate health, muscle gains, sleep, anxiety, cognitive performance), with no accomodation to variation in dose that these actions may require.
  • Apigenin is a relatively expensive raw ingredient, and as such is subject to under-dosing incentives by companies following a single sale model.

Considering the range of doses that yield statistically significant results in animal and human cell studies, this popular dose falls short. Goal concentrations for therapeutic effects in clinical literature falls in the range of 1μmol/L and 20μmol/L, while the 50mg dose taken orally can be expected to yield approximately 0.3μmol/L.

Anecdotally effective dose size and timing 


Approximately +30min to threshold, +75min to peak, +120min to taper, +240min to afterglow point which then lasts for up to +6 hours post dosing. 


  • Doses in the range 200mg to 400mg non-sedative to very mild sedative, however are provides an easily observable relaxation and inhibition lowering as well as notable improvements in deep sleep and reduced wake-ups. 
  • By backward extrapolation, doses 100mg to 200mg may be justified for very mild anxiolytic function, however effects are so minor they are difficult to observe or discern from normal variation and placebo anecdotally. 
  • Doses above 400mg begin to cause observable sedative actions such as slowing of speech and decreased reaction speed, with 600mg and above increasing total sleep time and causing mild drowsiness on wake

Some feedback contrary to personal experience has been that even 300mg results in potent sedative action for sleep, including sleeping through loud noise (ie. baby crying) as well as lethargy and struggling to wake in the morning. This provides a prime example of how individual response can vary.

The mouse study calculation deriving dose size and timing

The following calculation is derived from the mouse study "Apigenin, a Component of Matricaria recutita Flowers, is a Central Benzodiazepine Receptors-Ligand with Anxiolytic Effects" with cross reference to other mouse and rat studies.


Across multiple animal studies the peak serum concentration has been demonstrated in a range between 30mins and 2.5hr. 


  • Minor anxiolytic evidence at 189mg (10mg/kg mouse converted to 70kg adult by vascular surface area ratio);
  • Sedative action beginning between the doses 189mg and 581mg (from equivalent to mouse dose 10mg/kg to 30mg/kg and natural mouse movement  decreased 26% at 30mg/kg);
  • Significant sedative action at 1937mg (100mg/kg mouse dose resulting in 48% reduction in movement).


Human estimated threshold dose for sedation from mouse study dose conversion is between 0.8mg/kg and 2.5mg/kg IV, at 

"Apigenin produced no changes in spontaneous ambulatory locomotor activity of mice injected with doses up to 10mg/kg. At 30mg/kg and 100mg/kg here was a 26% to 48 % reduction in the locomotor activity.”  doi.org/10.1055/s-2006-958058

To yield human dose based off vascular surface area, divide by ~12. Drug Dose Conversion. Hence 10mg/kg in mice (where no sedative action is found) translates to approximately 0.8mg/kg in humans, 30mg/kg translates to 2.5mg/kg.

Oral bioavailability to serum concentrations of apigenin is demonstrated in rats and humans to be approximately 30%. Hence a 0.8mg/kg to 2.5mg/kg IV is approximately 2.7mg/kg to 8.3mg/kg oral. 

“Apigenin taken orally is systemically absorbed and recirculated by enterohepatic and local intestinal pathways. Its bioavailability is in the region of 30%.” doi: 10.3389/fphar.2021.681477

In a 70kg adult this would then translate to 189mg to 581mg dose range as a starting point of inducing sedative actions.This is ~1.4μmol/L to 4.2μmol/L serum concentration. 

Final considerations and a personal approach to Apigenin use 

When looking at an ingredient like apigenin and for applications that are limited in human research, the original chemist approach of "test it yourself" is my ethos, so any use should first begin with an individual calibration stage. Especially with apigenin I personally have confidence in the freedom to do so, where it is widely regarded as a compound with excellent safety profile, similar in structure and metabolism as many other flavonoids we consume. However each individual should always asses their tolerance to risk when looking at under-researched compounds such as apigenin, and as always, I am not a medical authority.

 The advantage is that for anxiolytic and sedative responses, a self reflective person is able to easily track response, and at the very least assess performance on reaction speed tests or other metrics. Additionally for sleep measurement we now have a wide arrange of sleep tracking accessories that can provide indication on how total sleep time and sleep phases are altered. 

My opinion on best apigenin use is much like any other compound that has limited research. Start the dose at the lower end of demonstrated effect (or even microdose to check for allergies) and then slowly step the dose up until desired effect. Being a curious person, I tend to do a few trials at even doses past desired effect to better understand a compound, which for flavonoids like apigenin we have the luxury of room for experimentation due to its high safety profile. After numerous variation over the course of the last 7 months, doses in the range of 200mg to 400mg are my sweet spot for sleep and mood support. For sleep supporting benefits stacking with the likes of Magnesium L-threonate, L-theanine and Reishi are great too.

For those that are interested in more Apigenin reading, you can see an ongoing study of apigenin and other compounds at the Thomas Kirk Patreon (which features an abundance of open access discussion) and keep an eye out for future posts discussing application for NAD+ modulation via its CD38 inhibition properties, certainly another very interesting lever which apigenin gets involved in.

Any questions or further discussion are very welcomed. 

- Thomas Kirk

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