Benefits
Hot flash reduction
In a 12-week placebo-controlled trial in 67 menopausal women, a hop extract giving 100 or 250 μg of 8-PN a day lowered hot flush scores more than placebo at 6 weeks. The overall symptom score (Kupperman index) beat placebo at 6 weeks for the 100 μg dose only, and not at 12 weeks, as placebo also improved. The higher dose did not work better.
Menopause symptom scores
In a 16-week crossover pilot, 36 menopausal women took the hop extract (100 μg 8-PN) and placebo for 8 weeks each. Both groups improved in the first 8 weeks, slightly more on placebo, and the overall estimate showed no significant difference. Lower Kupperman and visual analogue scores appeared only at week 16, in women who switched from placebo to the extract.
Total body bone density in postmenopausal women
In a one-year trial in 100 postmenopausal women with low bone density, all taking calcium and vitamin D3, adding the hop extract did not change spine bone density, the main outcome, versus placebo. Total body bone density rose 1.8% from baseline, about 1.0% more than placebo, which was not statistically significant. The trial was run by the extract maker.
Mechanism of action
Estrogen receptor alpha binding by 8-PN
8-PN binds mainly to estrogen receptor alpha, with about 100 times the affinity of the soy isoflavone genistein, and is described as a natural selective estrogen receptor modulator, acting like estrogen in some tissues and blocking it in others. In laboratory studies it also made estrogen-sensitive breast cancer cells grow.
Skin temperature in an animal model of hot flushes
In ovariectomized rats, 8-PN injected under the skin reversed the rise in tail skin temperature within 2 days, as estradiol did. Blocking estrogen receptors outside the brain stopped the effect, so the authors suggest the action is at least partly outside the brain. This is animal evidence, not a human result.
Isoxanthohumol conversion to 8-PN in the gut
The extract also contains isoxanthohumol, which gut bacteria in the lower colon can convert into 8-PN (up to 80% in studies summarized in a review). The amount of 8-PN a person ends up with may therefore vary with their gut bacteria.
Bone cells in laboratory studies
In cell studies summarized in a review, 8-PN helped bone-forming cells mature and held back bone-resorbing cells, more weakly than estradiol but more strongly than genistein. A one-year human trial did not confirm a bone density benefit.
Clinical trials
Randomized, double-blind, placebo-controlled trial of a hop extract standardized to 100 or 250 μg 8-PN per day for 12 weeks, scored with a modified Kupperman index and a patient questionnaire (Heyerick et al. 2006, Maturitas).
67 menopausal women.
All groups, including placebo, improved. The 100 μg dose beat placebo on the Kupperman index at 6 weeks (P=0.023) but not at 12 weeks (P=0.086). Hot flush scores fell more than placebo in both active groups at 6 weeks (P<0.01). The 250 μg dose was less active than 100 μg.
Randomized, double-blind, placebo-controlled crossover pilot: 8 weeks of hop extract (100 μg 8-PN per day) and 8 weeks of placebo in random order, scored with the Kupperman Index, Menopause Rating Scale and a visual analogue scale (Erkkola et al. 2010, Phytomedicine).
36 menopausal women, 16 weeks.
After 8 weeks both groups improved on all measures, with slightly larger drops on placebo. The overall treatment estimates were not significant. At 16 weeks, time-specific estimates favored the extract for the Kupperman Index (P=0.02) and visual analogue scale (P=0.03), with a borderline result for the Menopause Rating Scale (P=0.06).
Randomized, double-blind, placebo-controlled trial (NCT04004013) of Lifenol (100 μg 8-PN per day) or placebo, both added to calcium and vitamin D3, for 48 weeks (Lecomte et al. 2023, Nutrients).
100 postmenopausal women with osteopenia (low bone density).
Spine (L2 to L4) bone density, the primary outcome, did not differ significantly from placebo. Total body bone density rose 1.8% from baseline, 1.0% more than placebo (p=0.08), and more women on the extract gained at least 1% (odds ratio 2.41, p<0.05). Hip and femoral neck results did not differ. Gut bacterial diversity and short-chain fatty acids did not differ. Four authors were Givaudan employees.