A flavonoid compound found in bee pollen and propolis. Can boost testosterone when injected into testicles; otherwise isn't absorbed at all. Unless better absorption arises, chrysin remains a pretty interesting colon cancer preventative agent that does not boost testosterone.
Sources and Structure
Chrysin is a bioflavonoid compound that is touted to enhance testosterone levels and male virility.
Sources of Chrysin include:
- Passiflora caerulea and Incarnata
Chrysin has failed to inhibit any of the major phosphodiesterase enzymes (PDE1-PDE5) at concentrations below 100µM.
Like most bioflavonoids, chrysin suffers from poor bioavailability in isolated form which limits their practical usage. This poor bioavailability measured at less than 1% seems to be due to both extensive metabolism (sulphation and glucuronidation accounting for about 99% of orally ingested chrysin) and subpar intestinal transportation, as although chrysin is transported across the intestines an oral dose of 400mg results in less than 1% free chrysin (unconjugated) in the urine but only 1-7% of the total chrysin dose even when conjugates are included; most is left unabsorbed.
Chrysin can be absorbed, but it is poorly absorbed. Beyond that, chrysin is also very readily conjugated by the liver and other organs containing the P450 system into its metabolites (chrysin glucuronide and chrysin sulphate) which may not be bioactive. Less than 1% of chrysin is absorbed
One study found Chrysin to induce UGT1A1 expression in intestinal cells (Caco-2), which increases glucuronidation rates. When tested in vivo, the side-effects of a pro-drug associated with insufficient glucuronidation were reduced, contributing some validity to the results seen in vitro.
To add insult to injury, chrysin upregulates the enzyme that mediates its own conjugation
The Cmax values from an oral dose of 400mg Chrysin was 3-16ng/mL while the AUC was 5-193 ng/mL/h. The Cmax was reached (Tmax) about 1 hour after ingestion, fell rapidly at 6 hours, and returned to baseline 48 hours after ingestion. The half-life for the first 12 hours was 4.6 hours.
Chrysin (free form) can be detected in the plasma in the 3-16ng/mL range
After oral ingestion of 400mg Chrysin, plasma levels of Chrysin sulphate appear to be 30-fold higher than plasma levels of bioactive Chrysin. Glucuronide conjugates appear to be present in plasma at undetectable levels, and together conjugates consist of 99% of total oral chrysin. In rats, glucuronide conjugates are 10-fold higher but this is likely due to species differences.
The majority of serum chrysin is conjugated, with the predominant conjugate being chrysin sulphate
When tested in vivo and vitro, there does not appear to be any evidence of oxidative metabolism of Chrysin. Oxidative metabolism is known as Phase I of drug metabolism, and structurally modifies drugs for better conjugation in Phase II, but chrysin seems to directly and readily get conjugated by Phase II.
There is no apparent Phase I oxidative metabolism of chrysin
Chrysin is fairly potent in inhibiting aromatase in vitro with a Ki of 2.6+/-0.1µM and an IC50 of 4.2μM, comparable efficacy to apigenin and hesperidin as hydroxylated flavonoids seem to be among the flavonoid structures with most efficacy in inhibiting this enzyme (more than methoxylated).
This aromatase inhibiting property likely does not apply to humans following oral ingestion of chrysin due to its poor absorption, as the 4.2μM IC50 value (also reported to be 1.1µg/mL) is about 69 times greater than the 16ng/mL concentration reported from ingestion of 400mg chrysin.
In vitro, chrysin appears to be quite a potent aromatase inhibitor similar to other lightly hydroxylated flavonoids. This likely does not apply to standard chrysin supplementation due to very poor absorption
Interactions with Hormones
Chrysin appears to be able to inhibit a protein known as DAX-1, which is a negative regulator of the StAR protein (rate limit in testosterone synthesis) resulting in an upregulation of StAR and testosterone synthesis (also can be seen as a 'sensitization' of the testes to stimulated testosterone production); the suppression of COX2 from chrysin may also play a role, as COX2 is known to be a negative regulator of StAR. This effect was only seen at concentrations of 5µM or higher, which is over 70-fold higher than the detectable serum concentrations from 400mg oral chrysin ingestion.
Similar to D-Aspartic Acid, Chrysin's molecular target appears to be the StAR protein. However, rather than directly stimulating this protein's actions chrysin reduces the influence of negative regulators and causes an indirect increase in StAR activity
In rats, an increase in testosterone of approximately 30% has been noted with oral intake of 50mg/kg bodyweight for 60 days, which is a human estimated dose of 8mg/kg bodyweight.
There are a variety of studies investigating testosterone production of which include chrysin, but are too highly confounded with other active agents (such as Dehydroepiandrosterone) to attribute benefits to the chrysin being used at 300-625mg. One study with of propolis and eucalyptus honey (1,280mg and 20g, respectively) conferring 69.12mg flavonoids and 20mg chrysin failed to significantly influence testosterone levels in otherwise healthy men.
Although there was once rat study showing that supplementation of chrysin could increase testosterone, this does not appear to occur in humans based on the limited testing available
Interactions with Cancer Metabolism
Chrysin appears to be an modifier of P-glycoprotein efflux pumps and reduce their activity; this can act synergistically with compounds that are subject to P-gp efflux, such as the anti-cancer drug epirubicin. It shows potential at alleviating multi-drug resistance and exhibits anti-proliferative properties in isolation and in conjunction with other compounds.
Safety and Toxicology