8-Prenylnaringenin: a natural anabolic for women

Humulus lupulus -Hop – scientific name Humulus lupulus – contains the oestrogenic flavonoid 8-prenylnaringenin, a substance with an unexpectedly strong anticatabolic effect. The animal study, published by researchers at the University of Tokushima in Japan in PloS One, suggests that 8-prenylnaringenin is a natural anabolic that works for women.

The active substances in Humulus lupulus are already available on the market. They are found in supplements intended to increase women’s breast size. The products may actually be effective, as 8-prenylnaringenin is capable of interacting with both the estradiol receptor alpha and the estradiol receptor beta, Dutch researchers discovered in 2004. [J Steroid Biochem Mol Biol. 2004 Jul;91(3):99-109.] Most plant-based phytoestrogens only interact with the estradiol receptor beta. Substances that activate the estradiol receptor beta strengthen bones and protect blood vessels. Substances that activate the estradiol receptor alpha stimulate breast growth.

Humulus lupulus contains small amounts of 8-prenylnaringenin, but it also contains a much more important bioactive substance: xanthohumol. But fermentation, as happens when beer is brewed, and also through conversion in the liver, changes xanthohumol into 8-prenylnaringenin. The figure below shows from left to right the structural formulae for xanthohumol, the intermediate product isoxanthohumol, 8-prenylnaringenin and on the far right naringenin. The latter substance is found in citrus fruits.

The prenyl group enhances the effect of all sorts of phenols in the body. You can also synthesise 8-prenylnaringenin by attaching the prenyl group to naringenin in a lab.

Oestrogens protect muscle tissue, so the Japanese were curious as to whether 8-prenylnaringenin does the same. They are open about their intentions: they want to develop super-foods or supplements for people whose muscles are withering, such as the elderly or bedridden.

The Japanese experimented with rats, in which the nerves leading to the muscles in one paw had been deactivated [denervation]. The figure on the left below shows how the mass of the gastrocnemius [GM] started to shrink after four days [black bars]. The white bars represent the gastrocnemius muscles that continued to function as they were supposed to.

On the right below you can see the effect of supplementation with an extract of Humulus lupulus on the decrease in muscle mass as a result of inactivity. The researchers started to give the animals feed containing 5 percent Humulus lupulus extract two weeks before the intervention. Four days after the intervention the rats in the control group had lost eight percent of the mass of their inactive gastrocnemius. In the Humulus lupulus group the figure was only three percent.




The figures above show exactly how 8-prenylnaringenin works. They are based on experiments in which the Japanese used synthetic 8-prenylnaringenin. On the right above you can see that 8-prenylnaringenin strongly inhibits the activity of the muscle withering protein atrogin-1. On the left above you can see how 8-prenylnaringenin slightly boosts the activity of the anabolic key molecule Akt. Black bars: phosphorylated Akt; white bars: total Akt.


Naringenin had hardly any effect in the Japanese experiments, and the figure above tells why. The researchers could not trace naringenin in the rats’ gastrocnemius. The muscle cells don’t absorb naringenin. So that’s why the prenyl group is important, the Japanese concluded.

The Japanese used high concentrations. The human equivalent would be 0.4 mg 8-prenylnaringenin per kg bodyweight per day. So if you weigh 70 kg you’d need 30 mg. To get that amount you’d have to eat 1.5 kg of hops. Fortunately supplements are available. Because of their oestrogenic effects, they are probably not suitable for men.

The researchers were paid by the Japanese government.

Prevention of disuse muscle atrophy by dietary ingestion of 8-prenylnaringenin in denervated mice.

Mukai R, Horikawa H, Fujikura Y, Kawamura T, Nemoto H, Nikawa T, Terao J.

Department of Food Science, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.


Flavonoids have attracted considerable attention in relation to their effects upon health. 8-Prenylnaringenin (8-PN) is found in the common hop (Humulus lupulus) and assumed to be responsible for the health impact of beer consumption. We wanted to clarify the effects of prenylation on the physiological functions of dietary flavonoids by comparing the effects of 8-PN with that of intact naringenin in the prevention of disuse muscle atrophy using a model of denervation in mice. Consumption of 8-PN (but not naringenin) prevented loss of weight in the gastrocnemius muscle further supported by the lack of induction of the protein content of a key ubiquitin ligase involved in muscle atrophy, atrogin-1, and by the activation of Akt phosphorylation. 8-PN content in the gastrocnemius muscle was tenfold higher than that of naringenin. These results suggested that, compared with naringenin, 8-PN was effectively concentrated into skeletal muscle to exert its preventive effects upon disuse muscle atrophy. It is likely that prenylation generates novel functions for 8-PN by enhancing its accumulation into muscle tissue through dietary intake.

PMID: 23028754 [PubMed – in process]
PMCID: PMC3446978

Source: http://www.ncbi.nlm.nih.gov/pubmed/23028754