Xanthohumol is a naturally occurring prenylated flavonoid. This plant compound has a unique chemical structure and is being actively studied by researchers due to its distinct properties and interactions with biological systems.
Natural Sources of Xanthohumol
Xanthohumol is primarily found in the hops plant, Humulus lupulus. It is concentrated within the tiny, yellowish lupulin glands of female hop flowers. These glands are responsible for producing many of hops’ characteristic properties, including its aroma and bitter taste.
The concentration of xanthohumol in hop cones ranges from 0.1% to 1.5% of their dry weight, depending on the hop variety. While hops are widely used in beer brewing, the amount of xanthohumol in finished beer is generally low. The brewing process’s heat transforms xanthohumol into other compounds, reducing its original concentration. Beer typically contains about 0.1 mg/L of xanthohumol, though total prenylated flavonoids can vary up to 4 mg/L in some beers.
Biological Activity and Potential Health Effects
Xanthohumol exhibits diverse biological activities, studied in laboratory and animal models. It functions as a broad-spectrum antioxidant, scavenging reactive oxygen species like hydroxyl and peroxyl radicals. It also inhibits the production of superoxide anion radicals and nitric oxide, which are implicated in cellular damage. Its antioxidant capacity is comparable to green tea catechins and surpasses vitamins C and E.
Xanthohumol also demonstrates anti-inflammatory effects by inhibiting inflammatory mediators such as nitric oxide, interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α). It achieves this by activating the NRF2-ARE signaling pathway, which upregulates heme oxygenase-1 (HO-1), and by inhibiting the NF-κB signaling pathway.
Research explores xanthohumol’s potential chemopreventive effects. It modulates enzymes involved in detoxification and carcinogen metabolism. In mouse mammary gland organ cultures, nanomolar concentrations prevented carcinogen-induced preneoplastic lesions, suggesting a role in inhibiting early cancer development.
Xanthohumol influences cellular processes related to cancer progression. It can inhibit DNA synthesis, induce cell cycle arrest in the S phase, promote programmed cell death (apoptosis), and encourage cell differentiation in various cancer cell lines. Studies also indicate its anti-angiogenic activity, inhibiting new blood vessel formation needed for tumor growth, partly by targeting NF-κB and Akt pathways.
For metabolic health, preclinical studies suggest xanthohumol may benefit conditions associated with metabolic syndrome. In animal models, it has prevented body weight gain, improved dyslipidemia, hyperglycemia, and insulin resistance. It has also shown promise in ameliorating fatty liver conditions and reducing the pro-inflammatory state linked to obesity and insulin resistance.
Absorption and Conversion in the Body
Once ingested, xanthohumol’s bioavailability, the amount that enters the bloodstream largely unchanged, is relatively low. A significant portion passes through the upper digestive tract and reaches the large intestine, where it undergoes substantial transformation by gut bacteria.
Xanthohumol spontaneously isomerizes into isoxanthohumol (IXN) in the stomach’s acidic environment. Specific gut bacteria, such as Eubacterium limosum, convert isoxanthohumol into 8-prenylnaringenin (8-PN) through O-demethylation. This conversion is noteworthy because 8-PN is one of the most potent phytoestrogens identified to date.
The activity and potential health effects attributed to xanthohumol consumption may be due to these microbial metabolites, especially 8-PN. Other metabolites include 6-prenylnaringenin, α,β-dihydroxanthohumol, and O-desmethyl-α,β-dihydroxanthohumol. An individual’s gut microbiota composition can influence the types and amounts of these metabolites, leading to variations in how xanthohumol affects different people.
Supplementation and Safety Considerations
Xanthohumol is available in dietary supplements, though no standard dosage is established. Supplement amounts are typically based on limited preclinical research. For example, some animal studies on metabolic effects used doses equivalent to 350 milligrams per day for a 70-kilogram person, much higher than amounts in dietary sources like beer.
Short-term studies show hops extracts containing xanthohumol can be used safely at doses up to 300 milligrams daily for three months. Hops bitter acids have been used safely at 35 milligrams daily for the same duration. Clinical trials for 8-prenylnaringenin (8-PN), a xanthohumol metabolite, have used doses as high as 500 or 750 milligrams.
Safety concerns for xanthohumol arise from its conversion to 8-PN, a potent phytoestrogen. Since 8-PN mimics estrogen, hormonal influences are possible with supplementation. Individuals with hormone-sensitive conditions, such as certain types of breast cancer or endometriosis, should use xanthohumol supplements with caution.
Preclinical research suggests 8-PN might enhance mammary gland tissue growth, requiring more conclusive studies. Some individuals may experience side effects like dizziness or sleepiness from hops-derived products. Due to insufficient reliable safety data, especially regarding hormonal impacts and long-term use, xanthohumol supplementation is generally advised against during pregnancy and breastfeeding.