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

Abstract

Estrogen deficiency increases the risk of osteoporosis and fracture. The aim of this study was to investigate whether a hop extract standardized in 8-prenylnaringenin (8-PN), a potent phytoestrogen, could improve bone status of osteopenic women and to explore the gut microbiome roles in this effect. In this double-blind, placebo-controlled, randomized trial, 100 postmenopausal, osteopenic women were supplemented with calcium and vitamin D3 (CaD) tablets and either a hop extract (HE) standardized in 8-PN (n = 50) or a placebo (n = 50) for 48 weeks. Bone mineral density (BMD) and bone metabolism were assessed by DXA measurements and plasma bone biomarkers, respectively. Participant's quality of life (SF-36), gut microbiome composition, and short-chain fatty acid (SCFA) levels were also investigated. In addition to the CaD supplements, 48 weeks of HE supplementation increased total body BMD (1.8 ± 0.4% vs. baseline, p < 0.0001; 1.0 ± 0.6% vs. placebo, p = 0.08), with a higher proportion of women experiencing an increase ≥1% compared to placebo (odds ratio: 2.41 ± 1.07, p < 0.05). An increase in the SF-36 physical functioning score was observed with HE versus placebo (p = 0.05). Gut microbiome α-diversity and SCFA levels did not differ between groups. However, a higher abundance of genera Turicibacter and Shigella was observed in the HE group; both genera have been previously identified as associated with total body BMD. These results suggest that an 8-PN standardized hop extract could beneficially impact bone health of postmenopausal women with osteopenia.

Keywords: 8-PN; bone; hop; menopause; microbiome; osteopenia; osteoporosis; phytoestrogen.

Figure 1

CONSORT flow diagram. FAS: full analysis set, SS: safety set.

Figure 2

Relative changes from baseline at week 48 of BMD at L2-L4 lumbar spine and total body (A); percentage of women with a total body BMD change from baseline at week 48 ≥ 1% (B); sub-group analysis with relative changes from baseline at week 48 of BMD at L2-L4 lumbar spine and total body in vitamin D sufficient vs. insufficient women at baseline (C). All data are represented as mean ± SEM. # Odds ratio for relative change from baseline (probability modeled for class ≥ 1%) (HE vs. Placebo) (95% CI): 2.41 (1.01; 5.74), p < 0.05. * p = 0.05 versus placebo.

Figure 3

Microbiome components differentiating between HE and placebo at week 48. For each specific level ((A). Family, (B). Genus and (C). Species), we displayed in the left panel the importance of each selected taxon to differentiate between the two groups, in the middle panel the effect size, by reporting the log-fold difference between the mean abundance of the taxon in each group, and finally in the rightmost panel the prevalence of the selected taxa on each compared group. Green = HE; Black = placebo.