薬理と治療

Objectives　To evaluate the effects of Geranium dielsianum extract administration on orchiectomized mouse male accessory sex glands, in order to determine the presence or absence of androgenic effect on male. Methods　ddY male mouse with sham operation group and orchiectomized mouse group （ORX group）were prepared. After 14 days of oral administration（ORX＋GD group）of Geranium dielsiaum, the prostate gland size was horizontally and vertically measured along with the weight of seminal vesicle and prostate gland. Results　The size of the prostate gland in ORX group and ORX＋GD group was significantly smaller than the sham operation group due to orchiectomy, however between ORX group and ORX＋GD group no significant difference was observed. Seminal vesicle（including prostate gland）wet weight in ORX group and ORX＋GD group showed significantly diminution compared with the sham ope group, however between ORX and ORX＋GD group there was not a significant difference. Conclusion　GD extract did not affect accessory gonad including seminal vesicle and prostate of male orchiectomized mouse, therefore GD does not have androgenic effect.

Objective　To evaluate the effect of ingestion of vanilla ice cream containing fructooligosaccharides（FOS）on postprandial blood glucose（PBG）levels.　Methods Fourteen healthy males（38.4±10.4 years old）were enrolled to participate in this randomized controlled, single dose, open cross-over study. Study subjects consumed ice cream with（test food）or without（control food）FOS. Fasting blood glucose（FBG）and PBG levels were measured at several time points after food consumption and changes in blood glucose parameters were compared between the test and control groups. Results　Data for 12 subjects that completed the study were analyzed. The test food group had significantly lower PBG levels compared to the control food group 15, 30, 45, and 60 minutes after consuming the ice cream（P＜0.05）. Furthermore, the iAUC, tAUC, Cmax and ΔCmax values were significantly decreased for the test food group relative to the control food group. Conclusions Vanilla ice cream containing FOS showed mild suppressive effects on PBG levels compared to ice cream lacking FOS. （UMIN ID：UMIN000037350）

Objectives　The purpose of this study was to evaluate the safety of six folds intake of the specified kiwifruit extract continuously for twelve weeks in healthy adult humans. Methods　We conducted a randomized double-blind placebo-controlled parallel-group study with healthy adult Japanese subjects allocated to either a specified kiwifruit extract group（47.4 ±7.9 years old, n＝12）or a placebo group （45.5±8.2 years old, n＝12）. The participants took 1800 mg/day of a specified kiwifruit extract or a placebo capsule for twelve weeks. Safety was evaluated using hematologic test, blood biochemical test, urine analysis, physical examination. Results　Statistically significant differences observed in some test parameters were considered clinically insignificant. There were no adverse events associated with six folds intake of a specified kiwifruit extract for twelve weeks. Conclusions　Our results suggest that there was no safety problem daily intake of the specified kiwifruit extract continuously. UMIN-CTR ID: UMIN000032657

Objective　The present study aimed to verify that the ingestion of specific kiwifruit extracts would reduce the postprandial blood triglyceride level of the healthy subjects. Methods　A randomized, double blind, placebo controlled, crossover study was conducted in 60 subjects. Serum triglyceride levels were measured before ingestion and 2, 3, 4 and 6 h after intake of high-fat meal that included 44.8 g of fat. We evaluated the serum triglyceride area under the curve. Results　Postprandial serum triglyceride areas under the curve were smaller on the specific kiwifruit extracts food, and serum triglyceride levels were suppressed 2, 3 and 4 h. Conclusion　These findings indicate that certain polyphenols in kiwifruit extracts suppress elevated serum triglycerides after a high-fat meal in healthy subjects. UMIN-CTR ID: UMIN000027893

Objectives　This study aimed to examine the effects of Mirai Protein®（Milei 80）on muscle strength, body composition, and subjective evaluation items in healthy adults. Methods　A single-arm study was conducted in 77 healthy adult women. Subjects were supplied with 20 g/day Milei 80 for 12 weeks. Muscle strength and body composition were measured at 0, 4, 8, and 12 weeks of treatment, and subjective evaluation items（fatigue, sleep conditions, skin condition, physical function, and menopausal symptoms）were evaluated using a questionnaire at 0 and 12 weeks of treatment. Results　Muscle strength significantly increased at 4, 8, and 12 weeks of treatment compared with that at 0 weeks of treatment. All subjective evaluation items significantly improved at 12 weeks of treatment. However, no significant changes in body composition were observed. Conclusion　These findings suggested that Milei 80 supplement may be effective for improving muscle strength and subjective evaluation items under study, including fatigue, sleep conditions, skin condition, physical function, and menopausal symptoms.

Leg swelling is a characteristic discomfort resulting from insufficient blood flow. Long pepper extract（LPE）is known to improve blood flow and might therefore be a useful treatment for leg swelling. However, clinical data regarding the effects of LPE on leg swelling are lacking. This study evaluated the effectiveness of LPE intake in reducing leg swelling in healthy Japanese women during prolonged sitting. The subjects were 36 healthy women with leg swelling. We conducted a randomized, double-blind, placebo-controlled crossover trial involving healthy women with leg swelling. The subjects were instructed to remain sitting and limit their leg movements for 6 hours after intake of LPE or placebo, to induce leg swelling. The primary outcome was the ratio of extracellular water（ECW）in the leg to total body water（TBW）, an indicator of leg swelling. No significant carry-over effect or period effect was observed for the ratio of ECW in the leg to TBW. However, LPE intake resulted in statistically significant improvements in the leg ECW ratio after 6 hours. Moreover, LPE intake tended to suppress increases in leg circumference. These results suggest that LPE intake might help inhibit leg swelling in healthy women who remain sitting for a prolonged period of time. （Clinical Trial Registration: UMIN000026718）

Objective　This study examined the effect of lemon-derived monoglucosyl hesperidin（LGH）on reducing serum uric acid（SUA）in healthy Japanese adults with high SUA levels. Methods　We conducted a randomized, placebo-controlled, double-blind, parallel-group study from December 18, 2018 to October 25, 2019 in 166 healthy Japanese adults aged 20-75 years with high SUA levels（6.1-7.9 mg/dL）. The subjects were randomly assigned to LGH or placebo group（n＝83╱group）using a computerized random number generator. Subjects in each group took either 4 LGH tablets or placebo tablets once daily for 12 weeks. The primary outcome was SUA level; secondary outcomes included urinary uric acid level, urinary creatinine level, urinary uric acid╱creatinine ratio, and subjective symptoms. Results　The final per-protocol set（PPS）efficacy analysis included 78 subjects（68 men and 10 women, 49.1±12.7 years）in the LGH group and 77 subjects（69 men and 8 women, 51.3 ±11.1 years）in the placebo group. In the PPS analysis, a significant decrease in SUA level was confirmed in the LGH group at 12 weeks after study initiation. No adverse events were observed. Conclusions　Our results demonstrate that continuous LGH intake for 12 weeks is effective in lowering the serum uric acid levels in Japanese adults with high SUA levels（6.1-7.9 mg╱dL）. Trial registration　UMIN-CTR: UMIN000035298 Foundation　SAPPORO HOLDINGS LTD.

Objectives　This study aimed to investigate the effects of an eight-week consumption of saw palmetto fruit extract（SP）on urination issues. Methods　A total of 44 Japanese men aged ≥40 years who woke ≥ twice at night to urinate participated in a randomized, double-blind, placebo-controlled study between December 2018 and April 2019. All subjects were randomly allocated into an SP group（n＝22）or a placebo group（P group, n＝22）using a computerized random-number generator. Each group took their assigned singular capsule（320 mg of SP or placebo）every day for eight weeks. Subjective symptoms and impacts on daily life were assessed using IPSS total score as a primary outcome and other subjective symptoms［Overactive Bladder Symptom Score（OABSS）and a questionnaire survey］. The ultrasonography of the post-void residual volume of urine and a safety evaluation were also performed. Results　All the subjects completed the trial and were analyzed. The simple main effect of the group was marginally significant in the measured values and changes in IPSS（P＜0.10）. At eight weeks in post hoc analysis, the IPSS of the SP group showed a significant decrease compared with that of the P group（P＜0.05）, suggesting reduced subjective symptoms related to urination issues. No safety concerns were noted. Conclusions　Consumption of one SP capsule for eight weeks relieved subjective symptoms related to urination, suggesting the improvement of urination issues in healthy Japanese men. Trial registration　UMIN-CTR: UMIN000035036 Funding　BGG Japan Co., Ltd.

Background　Our preliminary open-label study suggested that intake of kale lowered blood pressure（BP）in subjects with potential metabolic syndrome. Objective　To verify the hypotensive effect of kale consumption in subjects with elevated BPs in a randomized, double-blind, placebo-controlled, parallel-group study. Methods/study design　Eligible volunteers（n＝92）, aged 20-64 years, were randomly assigned to an investigational food that contained 14 g of kale powder （group A; n＝46）or a placebo food（group P; n＝46）. Systolic and diastolic BPs （SBP and DBP, respectively）were assessed before and during the intake period of 12 weeks, and changes in BP levels（ΔBP）during the observation period were compared between groups. Results　Although 92 subjects completed the study, 4 subjects were excluded. Efficacy was analyzed in a total of 88 subjects（n＝44 in both groups）. Although there were no between-group differences in ΔBP, a stratified analysis revealed a significant intergroup difference in ΔSBP in the high-normal BP group（DBP 85-89 mm Hg or SBP 130-139 mm Hg）. At week 8 of the intake period, ΔSBP was－9.7±8.9 mm Hg in group A and －3.8±7.9 mm Hg in group P（P＝0.04）. A trend of ΔSBP decrease in group A was also found at week 12（－10.8±10.7 mm Hg compared to－4.6±9.2 mm Hg in group P; P＝0.07）. No serious adverse events were observed. Conclusion　Kale intake is suggested to reduce BP in high-normal BP individuals. UMIN study ID：UMIN000031450

Objectives　The aim of this study was to evaluate whether the intake of fermented milk with Lactobacillus acidophilus L-55（L-55）alleviated subjective symptoms of perennial allergic rhinitis. Methods　We performed a randomized, double-bind, placebo-controlled, parallel-group comparison study. Fifty Japanese subjects were randomly divided into two groups and ingested fermented milk with L-55（2.0×109 cells）or placebo once a day for 12 weeks. Allergic subjective symptoms were evaluated using the Japanese Rhino-conjunctivities Quality of Life Questionnaire once every two weeks at preingestion and during the ingestion period. Additionally, to assess the safety of this study beverage, a physical and blood examination were performed. Results　Itchy nose score and itchy eyes score of L-55 group were significantly lower compared with the placebo group at 8 weeks and 4 weeks after ingestion, respectively. Furthermore, the L-55 group had a significantly lower the quality of life（QOL）score about social life compared to the placebo group at 6 weeks after ingestion. There were no adverse effects due to the ingestion of the beverage. Conclusion　These results suggest that daily intake of L-55 can improve nasal and ocular symptoms in the subjects of perennial allergic rhinitis. （UMIN000035776）

Background/Objectives　Cognitive function, which refers to intellectual abilities such as memory, attention, language, and judgment, declines with age. As the aging population of the world increases, it is important to prevent cognitive decline in the elderly before they develop dementia. The objective of this study was to evaluate the effect of intake 200 mg of γ-aminobutyric acid（GABA）on cognitive function in healthy adult subjects aged over 40 years. Methods　This was a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Thirty healthy participants were each assigned to either the placebo group or the GABA group; those in the latter group were given capsules containing 200 mg GABA daily for 12 weeks. Cognitive functions were assessed using Cognitrax and the Repeatable Battery for the Assessment of Neuropsychological Status（RBANS）test. Quality of life（QOL）was assessed using the MOS 36-Item Short-Form Health Survey（SF-36）. Results　GABA improved or maintained cognitive function on the domain of Non-Verbal Reasoning, Working Memory, and Sustained Attention in Cognitrax and on the domain of Visuospatial/Constructional and Delayed Memory in RBANS. Regarding QOL, the GABA group showed significant improvement in SF-36 domain of Role-Physical, Vitality, and Mental Health. IGF-1 levels within the GABA group increased in comparison to the levels before intake. No adverse effects or clinically concerning changes were observed. Conclusions　These results indicate that GABA treatment appeared to safely enhance a wide range of cognitive functions in healthy adults. （UMIN000036725）

Background/Objectives　As the aging population of the world is increasing, it is important to prevent cognitive decline in the elderly before they develop dementia. Previously, in a preliminary study using animal model, we found that GABA might improve cognitive function. Thus, we aimed to evaluate the effect of 100 mg of γ-aminobutyric acid（GABA）intake on cognitive function in healthy adult subjects aged ≥40 years for practical applications. Methods　This was a randomized, double -blind, placebo-controlled, parallel-group clinical trial. Thirty healthy participants each were assigned to either the placebo group or the GABA group; those in the latter group were given capsules containing 100 mg GABA daily for 12 weeks. Cognitive functions were assessed using Cognitrax and the Repeatable Battery for the Assessment of Neuropsychological Status（RBANS）test. Quality of life（QOL）was assessed using the MOS 36-Item Short Form Health Survey（SF-36）. Results　GABA improved or maintained cognitive function on the domain of Visuospatial/ Constructional and Delayed Memory in RBANS. Regarding QOL, the GABA group showed significant improvements in SF-36 domain of Physical Functioning. No adverse effects or clinically concerning changes were observed. Conclusions　These results indicate that GABA treatment appeared to safely enhance memory and spatial cognitive function in healthy adults. （UMIN000036726）

Objective　This study was aimed to evaluate the effect of oral intake of chicken leg peptides （CLP）on knee pain. Methods　This was a 12-week, randomized, double-blind, placebo-controlled clinical trial. The subjects were 26 healthy Japanese adults with mild knee pain but no osteoarthritis. The subjects were randomly divided into two groups: the CLP intake group（47.7 mg/day of CLP） and the placebo group. Knee pain, functional impairment of the knee, and the associated limitation on daily activities were evaluated using the Japanese Knee Osteoarthritis Measure （JKOM）. The safety of long-term CLP intake was assessed by urine and blood tests. Results　Compared to the placebo group, the CLP group showed significant improvement in JKOM Question-7（Do you have pain in your knees when bending to the floor or standing up?） and Question-20（Were things that you usually do［some kind of lesson, meeting friends, etc.］ difficult because of knee pain during the last one month?）. Furthermore, oral intake of 47.7 mg of CLP daily for 12 weeks showed no significant adverse effects in urine and blood tests. Conclusions　Oral intake of CLP for 12 weeks could relieve mild knee pain and improve subjectsʼ quality of life. The safety of long-term intake of CLP was also confirmed.

Saffron, a spice, is the dried stigma of a perennial of the family Iridaceae, originating from South-western Asia. In addition to being used as a spice, is known for its sedative and analgesic effects and is used in herbal medicine in China and other countries. Due to these effects, it is known to induce relaxation and improve sleep. The pharmacologically active components are thought to be crocin and safranal. To investigate the effects of saffron extract on sleep, we conducted a placebo-controlled parallel-group trial with 52 individuals who consumed a dietary supplement containing saffron extract. The main evaluation items were the Oguri-Shirakawa-Azumi sleep inventory MA version（OSA-MA）and sleep analysis by electroencephalography （EEG）. Finally, a total of 45 individuals were analyzed. As for the OSA-MA, the group which consumed the saffron supplement showed significant improvement compared to the control group regarding sleepiness upon rising, initiation and maintenance of sleep, and frequent dreaming. Analysis of EEG recordings during sleep showed that the group that consumed the saffron supplement experienced significantly shorter sleep onset latency and significantlyreduced nocturnal awakening. Furthermore, the time spent in non-REM sleep increased. Thus, saffron extract, containing crocin and safranal, encourages sleep onset, increases deep sleep, reduces nocturnal awakening, and improves sleep rhythm. The study was registered with the University Hospital Medical Information Network（UMIN）Clinical Trial Registry before implementation（UMIN000035882）.