8-PN Hop Extract: A Potential Remedy for Osteopenia in Postmenopausal Women
Osteoporosis is a skeletal disease characterized by a reduction in bone mass and a deterioration of bone architecture, leading to increased bone fragility and the risk of fractures.
Postmenopausal women are particularly at risk, with approximately 30-40% affected by osteoporosis in the United States and Europe. The decline in endogenous estrogen during and after menopause accelerates the bone remodeling process with an imbalance between bone formation and resorption. In this context, phytoestrogens represent an interesting non-pharmacological intervention to prevent bone loss.
Phytoestrogens are polyphenolic compounds of plant origin with a structural resemblance to human endogenous estrogens, which accounts for their estrogenic activity. The main dietary sources of phytoestrogens are soy and red clover (isoflavones), flaxseeds (lignans), and hops (prenylflavonoids). Phytoestrogens are already widely used to alleviate menopausal symptoms, such as hot flashes and night sweats.
Furthermore, soy and red clover isoflavones have received considerable attention in managing postmenopausal bone loss, with a moderately beneficial overall effect against bone loss when consumed for at least twelve months.
The literature on the effect of hops (Humulus lupulus) on bone metabolism is limited, although hops contain one of the most potent phytoestrogens known to date: 8-prenylnaringenin (8-PN).
As a novel phytoestrogen, 8-PN is unique in that its receptor specificity and potency surpass that of any other phytoestrogen studied so far. In vitro, 8-PN has been shown to enhance the differentiation and maturation of osteoblasts and inhibit osteoclast differentiation with a response intensity greater than that observed with soy isoflavones.
Several in vivo studies have demonstrated that oral supplementation with a standardized hop extract can prevent estrogen deficiency-induced bone loss in osteoporotic rodent models. Additionally, in ovariectomized rats, 12 weeks of 8-PN supplementation improved bone biomechanical properties to the same extent as estradiol, while the other two tested phytoestrogens, genistein and resveratrol, had no significant impact.
From a clinical perspective, a bioavailability study in menopausal women indicates that prenylflavonoids (8-PN, 6-prenylnaringenin, isoxanthohumol, and xanthohumol) from a standardized hop extract are absorbed slowly, undergo enterohepatic circulation, and have a long half-life exceeding 20 hours.
Moreover, 8-prenylnaringenin appears to be significantly more bioavailable in healthy men compared to its isomer 6-prenylnaringenin. In terms of health effects, three clinical studies have demonstrated the effectiveness of standardized hop extract in reducing menopausal symptoms at a daily 8-PN dose for a minimum of 6 weeks. However, to date, the potential impact of hop extract and 8-PN in osteoporosis prevention has not been assessed in humans.
While the presence of 8-PN in hops is low, other more abundant prenylated phenols such as xanthohumol (X) and isoxanthohumol (IX) can be metabolically converted into 8-PN. The conversion of IX to 8-PN can be enzymatically accomplished by hepatic CYP1A2 or the intestinal microbiome.
However, a wide interindividual variability has been observed regarding the ability of the human intestinal microbiome to perform this transformation, with only about one-third of individuals efficiently carrying out this conversion. Eubacterium limosum has been identified as an intestinal bacterium capable of facilitating the conversion (O-demethylation) of IX into 8-PN.
Finally, the impact of the intestinal microbiome on host health has been increasingly studied in recent decades. In particular, a growing body of evidence suggests that the intestinal microbiome plays a key role in bone metabolism and the pathogenesis of osteoporosis, although the mechanisms of action have not been clearly elucidated.
Given the role of the intestinal microbiome in maintaining bone health and its importance in 8-PN generation, it is of great interest to study the intestinal microbiome as a potential key factor in the mechanism of action of hop extract.
This clinical study aims to determine whether one year of consumption of a standardized hop extract containing 8-PN can moderate the reduction in bone mineral density in postmenopausal women with osteopenia and explore the potential mechanism of action through the modulation of the intestinal microbiome.
Estrogen deficiency increases the risk of osteoporosis and fractures. The purpose of this study was to investigate whether a standardized hop extract containing 8-prenylnaringenin (8-PN), a potent phytoestrogen, could improve the bone status of osteopenic women and explore the role of the intestinal microbiome in this effect.
In this randomized, double-blind, placebo-controlled study, 100 postmenopausal osteopenic women were supplemented with calcium and vitamin D3 (CaD) tablets and a hop extract (HE) standardized in 8-PN or a placebo for 48 weeks. Bone mineral density (BMD) and bone metabolism were assessed using DXA measurements and plasma bone biomarkers, respectively. Participant quality of life (SF-36), intestinal microbiome composition, and short-chain fatty acid (SCFA) levels were also analyzed.
In addition to CaD supplementation, 48 weeks of HE supplementation increased total body BMD, with a higher percentage of women experiencing an increase compared to the placebo. An increase in SF-36 physical functioning score was observed with HE compared to the placebo. Intestinal microbiome diversity and SCFA levels did not differ between the groups.
However, the HE group exhibited a higher abundance of the Turicibacter and Shigella genera, both of which have been previously identified as associated with total body BMD. These results suggest that a standardized hop extract with 8-PN may have a positive impact on the bone health of postmenopausal women with osteopenia.
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Source: Lecomte, M.; Tomassi, D.; Rizzoli, R.; Tenon, M.; Berton, T.; Harney, S.; Fança-Berthon, P. Effect of a Hop Extract Standardized in 8-Prenylnaringenin on Bone Health and Gut Microbiome in Postmenopausal Women with Osteopenia: A One-Year Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients 2023, 15, 2688. https://doi.org/10.3390/nu15122688
