BackgroundHops are the main components of beer that provide flavor and bitterness. Iso-α-acids, the bitter components of beer, have been reported to reduce body fat in humans, but the bitterness induced by effective doses of iso-α-acids precludes their acceptance as a nutrient. The matured hop bitter acids (MHBA) of oxidized hops appear to have a more pleasant bitterness compared to the sharper bitterness of iso-α-acids. While there has been little information concerning the identity of the MHBA compounds and their physiological effects, MHBA was recently found to be primarily composed of oxides derived from α-acids, and structurally similar to iso-α-acids. Here, we investigated the effects of matured hop extract (MHE) containing MHBA on reducing abdominal body fat in healthy subjects with a body mass index (BMI) of 25 to below 30 kg/m2, classified as “obese level 1” in Japan or as “overweight” by the WHO.Trial designA randomized, double-blind, placebo-controlled parallel group study.MethodsTwo hundred subjects (male and female aged 20 to below 65 years with a BMI of 25 or more and less than 30 kg/m2) were randomly assigned to two groups. During a 12-week ingestion period, the subjects in each group ingested daily 350 mL of test-beverage, either containing MHE (with 35 mg MHBA), i.e. the namely active beverage, or a placebo beverage without MHE. The primary endpoint was reduction of the abdominal fat area as determined by CT scanning after continual ingestion of MHE for 12 weeks.ResultsCompared to the placebo group, a significant reduction was observed in the visceral fat area after 8 and 12 w, and in the total fat area after 12 w in the active group. There was also a concomitant decrease in body fat ratio in the active group compared to the placebo group. No adverse events related to the test beverages or clinically relevant abnormal changes in the circulatory, blood and urine parameters were observed in either group.ConclusionsThe present study suggests that continual ingestion of MHE safely reduces body fat, particularly the abdominal visceral fat of healthy overweight subjects.Trial registrationUMIN-CTR UMIN000014185 Electronic supplementary materialThe online version of this article (doi:10.1186/s12937-016-0144-2) contains supplementary material, which is available to authorized users.

Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB) appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA). Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional foods or beverages to counteract the accumulation of body fat.

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It has been demonstrated that successive ingestion of matured hop extract (MHE), produced by extraction from heat-treated hops, results in body fat reduction in animals and humans; however, preclinical safety studies have not been reported. In this study, we conducted in vitro and in vivo safety studies for MHE. Genotoxicity was evaluated using the Ames test, in vitro chromosomal aberration test, and in vivo micronucleus test. To assess acute safety, a single, oral administration of MHE to rats was monitored. Subchronic safety was assessed by repeated feeding with MHE for 90 days. The in vitro chromosomal aberration test was positive at 3,330 μg/mL and 5,000 μg/mL without metabolic activation. However, MHE did not induce any reverse mutation with or without metabolic activation in the Ames test, and no abnormalities were observed at a dose of 2,000 mg/kg body weight in the rat micronucleus test. In the acute and subchronic safety studies, no deaths or toxicological signs were recorded during the observation period. In addition, no changes in body weights, feed/water consumption, clinical signs, ophthalmoscopy, urinalysis, hematology, blood biochemistry, organ weights, or histopathology were observed after repeated administration of MHE. Therefore, the no-observed-adverse-effect-level (NOAEL) of MHE was considered to be over 3,484 and 4,022 mg/kg body weight/day in males and females, respectively. These results indicate that there is no safety concern for MHE in the present preclinical safety study.

BackgroundWe recently reported that successive ingestion of matured hop extract (MHE), produced by oxidation of hops, results in a reduction of body fat in healthy overweight participants. A combined effect of MHE and physical activity on body fat has not been investigated. Thus, we re-analyzed data from the previous study to explore the relationship between the effect of MHE and walking as an index of physical activity.MethodsThis analysis uses existing data from a randomized, double-blind, placebo-controlled parallel group study in which MHE (active) or placebo was given for 12 w to 200 healthy overweight Japanese, from May to December 2014. Correlation between the change in abdominal fat areas at 12 w and the number of steps taken per day was tested by Spearman’s correlation coefficient test. The subjects were stratified using the average number of steps per day of Japanese into walking less and walking more subgroups (WL and WM, respectively) as follows: placebo (WL, n = 43; WM, n = 44) and active (WL, n = 49; WM, n = 42). Reductions in total, visceral, and subcutaneous fat area (TFA, VFA and SFA, respectively) were evaluated. The interaction effect between ingestion (active/placebo) and walking (WL/WM) was analyzed using two-way analysis of variance (ANOVA).ResultsThere was a significant negative correlation between the change in VFA and daily steps taken in the active group (r = − 0.208, P = 0.048). No significant correlation in TFA or SFA. Although the interaction effect in TFA was not significant, the main effect of ingestion was significant (P = 0.045). In contrast, the interaction effect in VFA was suggested to be synergistic (P = 0.055).ConclusionThe results suggested that MHE ingestion combined with light intensity exercise would induce a greater reduction in VFA which would be beneficial for obese or overweight individuals in reducing obesity and obesity-related diseases.Trial registrationUMIN-CTR UMIN000014185 registered 6 June 2014.Electronic supplementary materialThe online version of this article (10.1186/s12937-018-0405-3) contains supplementary material, which is available to authorized users.