Apigenin is a flavonoid that can boost testosterone naturally.
In this article, I’m going to show you the ideal dose for the best results. I’m also going to show you how apigenin can increase testosterone and what other benefits it has.
How apigenin increases testosterone
Apigenin has been shown to have the potential for increasing testosterone.
The available studies are in vitro, meaning, it hasn’t been done in animals or humans. It’s been done in cell cultures. It’s very difficult to extrapolate and say that apigenin can increase testosterone in humans. But regardless, in vitro evidence can show us that a compound has the potential to do something and it can also show us the mechanisms how.
I’m going to share with you 8 ways how apigenin can increase testosterone.
#1 Apigenin upregulates StAR
StAR (steroidogenic acute regulatory protein) is one of the rate-limited steps in testosterone production.
It transports free cholesterol from the outer to the inner mitochondrial membrane to initiate the steroidogenic process. Once cholesterol is inside the mitochondria, it’s converted to pregnenolone by CYP11A1 (aka cholesterol side-chain cleavage enzyme).
StAR becomes downregulated with age and two major inhibitors of StAR are COX-2 and DAX-1.
COX-2
COX-2 is the enzyme that converts polyunsaturated fat (arachidonic acid) into inflammatory prostaglandins. NSAIDs and many natural herbs inhibit COX-2 and reduce inflammation.
COX2 increases during Leydig cell aging, and this leads to the inhibition of StAR gene expression.
Feeding aged rats a selective COX2 inhibitor increased StAR protein and blood testosterone concentration (R, R).
DAX-1
Going 1 step further. COX creates prostaglandin H2 (PDH2), which is then converted to thromboxane A2 (TXA2) by TXA2 synthase. TXA2 acts on the TXA2 receptor. This is called the cyclooxygenase-2-thromboxane A synthase-thromboxane A2-receptor pathway.
TXA2, when it binds to its receptor increases the protein DAX-1 and DAX-1 correlates with Leydig cell insensitivity.
Thus blocking COX and TXA2 production lowers DAX-1 protein expression and increases Leydig cell sensitivity and StAR expression.
Apigenin on StAR
Since apigenin inhibits COX and TXA2 production and lower DAX-1 protein expression, it dramatically enhances StAR expression (R).
In summary, apigenin can prevent the decline and desensitization of StAR induced by COX and DAX-1.
In this graph, you can see how StAR is increased in a dose-dependent manner by apigenin.
As StAR goes up, more cholesterol is transported into the mitochondria. Cholesterol is then converted to pregnenolone, progesterone and testosterone.
As you can see in this graph, apigenin increased progesterone and testosterone production in a dose-dependent manner.
Combining cAMP (also a promotor of StAR) with apigenin synergistically increased progesterone and testosterone production. LH, thyroid hormone T3, caffeine and forskolin increase cAMP (R).
It’s likely that taking apigenin with caffeine and/or forskolin should boost testosterone even more.
#2 Apigenin inhibits aromatase
Aromatase is the enzyme that converts testosterone to estradiol. Too much estradiol can contribute to erectile dysfunction, fat gain in the lower body, gyno, hyperemotionality, etc.
Estradiol also inhibits LH release in the pituitary and aromatase inhibitors are great for boosting testosterone.
Apigenin has been shown to inhibit aromatase (R).
COX-2 is a potent stimulator of aromatase and apigenin is a potent inhibitor of COX-2 (R).
#3 Apigenin lowers cortisol
Excess cortisol inhibits Leydig cell function and lower testosterone production.
Apigenin is a great adaptogen and has calming, relaxing and anti-anhedonic effects (R).
German chamomile and apigenin have been shown to inhibit the production of ACTH and cortisol and buffer stress (R, R, R). Apigenin can reduce your reactivity to stress and help you feel more even-keeled.
According to this study, apigenin greatly helped to lower cortisol when under stress. As you can see in the graph below, LA (low dose apigenin (25mg/kg)) and HA (high dose apigenin (50mg/kg)) lowered nitrite and cortisol (R).
Low dose would be 2.03mg/kg (202mg for a 100kg person) and high dose would be 4.05mg/kg (405mg for a 100kg person).
#4 Apigenin increases dopamine and noradrenaline
Dopamine stimulates testosterone production by lowering prolactin and prolactin inhibits GnRH and LH release and testosterone production (R).
Noradrenaline promotes the release of LH stimulated by GnRH (R).
Apigenin has been shown to increase dopamine in the brain, reduce noradrenaline uptake (increasing noradrenaline levels) and inhibit MAO activity (inhibiting dopamine and noradrenaline breakdown) (R, R).
#5 Apigenin is pro-GABA
GABA is most well-known for reducing anxiety and depression and improving sleep quality.
Although GABA is classically an inhibitory neurotransmitter in the central nervous system, most mature GnRH neurons are stimulated by GABA. Thus GABA has an excitatory action on the hypothalamic-pituitary-gonadal (HPG) axis.
Apigenin has been shown to boost the rate-limited enzyme in GABA synthesis and is also a partial agonist of the GABA receptor (R, R, R).
#6 Apigenin lowers inflammation
Inflammation damages the Leydig cells and reduces testosterone production. A lot of inflammatory compounds, such as endotoxin (lipopolysaccharides), come from the gut and induce hypogonadism.
Endotoxin has a direct inhibitory effect on StAR.
Apigenin reduces inflammation in the gut and inhibits endotoxin-induced inflammation (R).
The antioxidant and anti-inflammatory effects of apigenin also protect the testes against all sorts of toxins, such as heavy metals, plastics, pesticides, etc.
#7 Apigenin increases NAD
NAD is crucial for energy production as well as keeping oxidative stress under control.
A low NAD to NADH ratio can lead to oxidative stress and damage to the testicles.
The first step of steroidogenesis is the transport of cholesterol into the mitochondria. The mitochondria are where energy production happens. However, it’s also where the most oxidative stress is created if NAD is low. Free radicals can oxidize cholesterol, creating oxidized cholesterol (ox-LDL) and ox-LDL has been shown to inhibit steroidogenesis (R).
Aging is associated with a continuous decline of blood and tissue NAD levels, as well as a decline in testicular functions (R).
This study found that NAD levels decline with aging and this leads to reduced mitochondrial function, increased ROS production and low testosterone (R).
Supplementing these rats with niacinamide reduced ROS, increased ATP production and restored LH, FSH and testosterone levels.
As you can see in this graph, the increase in testosterone correlates with the increase in NAD.
The ideal niacinamide dose was 400mg, which would translate to 64.86mg/kg for a human (6486.49mg for a 100kg person). Yes close to 6g of niacinamide is a high dose. Another way you can boost NAD is by inhibiting NAD catabolism.
NAD is created from vitamin B3 and is broken down by PARP enzymes and CD38.
Apigenin can increase NAD by inhibiting CD38 and reducing oxidative stress (R, R). Combining apigenin with niacinamide will dramatically help to boost NAD levels.
#8 Apigenin improves sleep quality
Poor sleep, especially sleep apnea and insomnia, is strongly correlated with low testosterone and erectile dysfunction (R).
Apigenin is known for improving sleep and that will have a positive effect on testosterone.
The ideal dose of apigenin for testosterone
Different doses of Apigenin have been used in the clinical results, and even at high doses, no toxicity has been reported.
For maximizing testosterone you want to use roughly 500mg of apigenin (maybe even higher).
The researchers in this study showed that apigenin could increase testosterone when they bathed Leydig cells in 10μM of apigenin.
To find the ideal dose for humans, we have to see how effectively apigenin ingestion increases apigenin concentrations in the blood.
In this human study, ingestion of 2g parsley/kg body weight (yielding ∼17mg of apigenin) resulted in plasma concentrations of 28-337nmol/L at 6-10h after consumption, which then fell below detection at 28h (R).
1 μM = 1000 nmol/l, so 337nmol/ would be 0.34μM. If we extrapolate linearly, 170mg will reach a concentration of between 280-3370 nmol/L (0.28-3.37uM). We need to get to 10μM, which is what they used in the study.
500mg of apigenin will increase plasma apigenin to 0.84-10.11μM.
There is a large difference in plasma concentration in apigenin between individuals, so some people will need more than others.
Here is a review of someone who had good results with liposomal apigenin.
“I do a lot of sports: bouldering, bodybuilding, jump rope. I’ve only been taking it for 4 days now. I don’t feel any effect on performance. I take 200mg before sleeping and it seems to slightly improve my deep sleep by a few minutes but I still have too little perspective. To be seen over several weeks… (R)
Here is a little feedback: I have my total testosterone measured and I have never seen it so high: 44 nmol/l, the last two times I measured my testo a few years ago the values were 30 and 37 nmol/l.
My libido is very good but no more than before apigenin. My usual sport is bouldering and bodybuilding. I still added loads since August and I took 2kg of muscle without gaining fat (I’m very dry MG = between 5 and 6%).
I don’t know if it’s the apigenin that I’ve been taking for several weeks… but it’s possible that it is because it’s the only supplement I’ve changed in my routine. In terms of feeling I find that I have better energy than usual and more deep sleep.”
Other benefits of apigenin
Apigenin
- Has anti-prostate cancer benefits (R).
- Improves kidney function in diabetes (R).
- Improves insulin sensitivity and reduces vascular dysfunction (R).
- Improves sleep quality.
- Reduces anxiety (R).
- Helps build muscle by stimulating the mTOR pathway and up-regulating the expression of IGF 1 & 2 (R).
- Protects against the harms of a Western diet by improving the microbiome and intestinal barrier (prevent leaky gut) and preventing endotoxin absorption.
- Can be helpful for Alzheimer’s disease, and can even improve memory in mice with Alzheimer’s disease (R).
- Has a pain-killing effect (R).
- Is an NMDA antagonist, thus having similar anti-depressant effects as magnesium, theanine, zinc, ketamine, etc. (R)
Summary
Apigenin has many benefits such as improving sleep and mood, reducing anxiety, increasing testosterone and NAD and much more. It’s definitely a beneficial flavonoid.
If you suffer from poor sleep, low mood and testosterone as well as anxiety, give apigenin is shot.
A good way to do so is to drink Chamomile tea. I personally haven’t noticed much from Chamomile tea. If that’s the case with you as well, consider high-dose supplements.
Start with 200mg and work up from there as needed.
Recommended brand: Nootropics Depot
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