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Chlorogenic acid (CGA), a polyphenolic compound found in various plants, has been reported to improve cognitive function. However, it remains unclear how long it takes for CGAs to exert their effects. Here, we evaluated the short-term effects of CGAs on cognitive function. We assessed the effects of 2-week CGA intake on cognitive function. The study was carried out as a randomized, double-blind, placebo-controlled, crossover trial. Twenty-six healthy Japanese participants (50-65 years of age) were randomly assigned to either the active beverage (CGAs: 270 mg) or the placebo beverage group daily for 2 weeks. After a 2-week washout period, the participants consumed the other beverages. We assessed cognitive function at baseline and following the first treatment period using the Japanese version of CNS Vital Signs. CGAs significantly improved the scores for psychomotor speed, motor speed, and right and left finger tapping compared to placebo. In addition, processing speed scores improved significantly from baseline only after CGA intake. In conclusion, CGAs were confirmed to improve cognitive function over a short period of two weeks.

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A reduction in estrogen levels in the perimenopausal and postmenopausal periods causes various symptoms in women, such as hot flushes, sweats, depression, anxiety, and insomnia. Chlorogenic acids (CGAs), which are phenolic compounds widely present in plants such as coffee beans, have various physiological functions. However, the effects of CGAs on menopausal symptoms are unknown. To examine the effects of CGAs on menopausal symptoms, especially hot flushes, a randomized, placebo-controlled, double-blind, parallel-group trial was conducted in healthy women. Eighty-two subjects were randomized and assigned to receive CGAs (270 mg) tablets or the placebo for 4 weeks. After 4 weeks of intake, the number of hot flushes, the severity of hot flushes during sleep, and the severity of daytime sweats decreased significantly in the CGA group compared to the placebo group. The modified Kupperman index for menopausal symptoms decreased significantly after 2 weeks in the CGA group compared to the placebo group. Adverse effects caused by CGAs were not observed. The results show that continuous intake of CGAs resulted in improvements in menopausal symptoms, especially hot flushes, in healthy women.

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BACKGROUND: Mild cognitive impairment (MCI) is a global-scale issue, due in large part to the rapidly growing elderly population. The main polyphenol contained in coffee beans, chlorogenic acid (CGA), improves attention in healthy individuals. The utility of CGAs for treating MCI, however, has not been evaluated. OBJECTIVE: To determine the effects of continuous CGA intake on cognitive function, especially attention, in patients diagnosed with MCI. METHODS: The study was a randomized controlled crossover trial including 34 patients with MCI. Participants were randomly divided into two groups: Those who first ingested a placebo beverage and those who first ingested an active beverage containing CGAs (553.6 mg/bottle) twice daily for 12 weeks. After a 4-week washout period, the subjects ingested the other beverage (i.e., placebo or active beverage) in the same manner. Endpoint measures included scores on the Japanese version of the Mini-Mental State Examination (MMSE), the Japanese version of the Alzheimer's Disease Assessment Scale-cognitive component (ADAS-cog) testing overall cognitive function, and the Japanese version of the Trail Making Test (TMT-A, TMT-B) testing attention, along with the results of blood tests to evaluate safety. RESULTS: In the TMT-B test, participants had a significantly reduced number of errors while ingesting the CGA beverage as compared with the placebo beverage (p < 0.05), although there was no difference in test completion time. Scores in the MMSE, ADAS-cog, and TMT-A did not differ significantly between conditions. CONCLUSION: Continuous intake of CGAs appears to improve attention and executive function among cognitive functions in MCI.

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Care of the musculoskeletal system, including the muscles, joints, and bones, is important for a healthy life expectancy in today's aging society. The aim of this randomized, double-blind, placebo-controlled study was to investigate the effect of consumption of milk-fat globule membrane (MFGM) and glucosamine on joint function and physical performance. Participants were healthy Japanese men and women, aged 60-74 y, with a history of mild knee or low back pain at rest. They were randomized to receive tablets containing MFGM 1.0 g+glucosamine 1.5 g or placebo tablets for 8 wk. We assessed passive range of motion, active range of motion (self-reported VAS score), JKOM and JLEQ, and physical performance. Data were available for analysis for 25 participants in the active treatment group and 28 in the placebo group. The active group showed significant improvements in passive range of motion at the knee and active range of motion at both the knee and low back. The active group also showed significant improvements in some physical performance, including obstacle walking speed and speed of ascending stairs. The findings of this study suggest that consumption of a combination of MFGM and glucosamine may improve joint function and physical performance.

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The effects of exercise on sleep have been explored from various perspectives, but little is known about how the effects of acute exercise on sleep are produced through physiological functions. We used a protocol of multiple daytime sessions of moderate-intensity aerobic exercise and examined the subsequent effects on sleep structure, core body temperature (CBT), distal-proximal skin temperature gradient (DPG), and subjective parameters. Fourteen healthy men who did not exercise regularly were evaluated under the baseline (no exercise) and exercise conditions on a within-subject crossover basis. Under the exercise condition, each participant performed a 40-min aerobic workout at 40% of maximal oxygen intake, four times between morning and early evening. We observed a 33% increase in slow-wave sleep (SWS; P = 0.005), as well as increases in slow-wave activity (SWA; P = 0.026), the fast-sigma power/SWA ratio (P = 0.005), and subjective sleep depth and restorativeness the following morning. Moreover, both CBT and the DPG increased during sleep after exercise (P = 0.021 and P = 0.047, respectively). Regression analysis identified an increased nocturnal DPG during sleep after exercise as a factor in the increase in SWA. The fast-sigma/SWA ratio correlated with CBT. The performance of acute exercise promotes SWS with nocturnal elevation in the DPG. Both CBT and fast-sigma power may play a role in the specific physiological status of the body after exercise. NEW & NOTEWORTHY We used multiple daytime sessions of moderate-intensity aerobic exercise to examine the effects on the sleep structure, core body temperature (CBT), distal-proximal skin temperature gradient (DPG), and subjective parameters. Significant increases in slow-wave activity (SWA), CBT, DPG, fast-sigma power, and subjective parameters were observed during the night and the following morning. Nocturnal DPG is a factor in the increased SWA.

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Chlorogenic acids (CGAs) are found in abundance in coffee beans and have numerous health benefits. This study investigated the effect of CGAs extracted from coffee beans on fatigue and sleep in healthy participants. This crossover study involved 16 men (aged 30-54 years) who were daytime workers with weekends off work. The participants were randomized into two groups: One group was given a placebo beverage, and the other was given an active beverage containing 300 mg of CGAs. The test beverages were consumed for 13 days starting on a Sunday. The evaluation criteria were feelings of fatigue and sleep quality, sleep-related indices recorded by an activity meter, and biomarkers. Feelings of fatigue and sleep-related indices during the first (first half of week 1) and second (second half of week 2) halves of the consumption periods were compared. Within the first half of week 1, no differences in feelings of fatigue were observed between the groups. However, during the second half of week 2, fatigue upon awakening and sleep quality in the active group were significantly improved compared with those in the placebo group. Sleep efficiency and total nocturnal awakening time were significantly deteriorated in the second half of week 2 compared with the first half of week 1 in the placebo group. Furthermore, significant differences in these indices were observed between the two groups in the second half of week 2. These results suggest that the daily consumption of CGA-containing beverages may improve fatigue upon awakening and sleep quality.

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(1) Background: Chlorogenic acids (CGAs) have been attracting interest of late, owing to their health benefits. Here, we performed a randomized, double-blind, placebo-controlled trial to investigate whether CGAs improved cognitive function in humans. (2) Methods: Thirty-eight healthy participants were assigned to either the CGA group, which was given CGA-added beverage daily for 16 weeks, or the placebo group. Cognitive functions were assessed using the Japanese version of the CNS Vital Signs (Cognitrax). (3) Results: The CGA group showed significant increase in the Cognitrax domain scores for motor speed, psychomotor speed, and executive function compared with the placebo group, as well as an improvement in the shifting attention test scores. In blood analysis, the CGA group showed increased levels of apolipoprotein A1 and transthyretin, both of which are putative biomarkers for early-stage cognitive decline. (4) Conclusions: These results suggest that CGAs may improve some cognitive functions, which would help in the efficient performance of complex tasks.

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OBJECTIVE: To evaluate the effect of chlorogenic acids (CGAs) intake on cognitive function. METHODS: In this pilot study, the Cogstate and CNS Vital Signs test batteries were used to evaluate cognitive function in 8 healthy elderly men and women complaining of subjective memory loss after a 6-month intake of a test beverage containing 330 mg of CGAs just before bedtime. RESULTS: After a 6-month CGA intake period, significant improvement was observed in the One Back Test of the Cogstate, the Shifting Attention Test, and Finger Tapping Test as well as in the composite memory, verbal memory, complex attention, cognitive flexibility, executive function, and motor speed domains of the CNS Vital Signs test battery. CONCLUSION: A 6-month intake of CGAs may improve attentional, executive, and memory functions in the elderly with complaints of subjective memory loss.

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We conducted a randomised, double-blind, placebo-controlled trial to elucidate the effects of dietary milk fat globule membrane (MFGM) on the physical performance of community-dwelling Japanese adults. For this 24-week study, 115 middle-aged subjects (range 50-70 years old) were invited, of whom 113 (seventy-two women, forty-one men) completed the trial. Participants were then divided into either the placebo control or MFGM group. Measurements of physical performance (without undertaking any mandatory exercise) examining muscle strength, agility and balance were tested every 6 weeks until 24 weeks. Analyses were performed using the intention-to-treat method for all participants. Although the effects of MFGM on muscle strength and agility were not significant, we noted that the parameter for balance (such as the ability to stand on one leg with eyes closed for longer durations) increased in the MFGM group (mean 10·1 (95 % CI 8·25, 12·4) s) compared with the placebo (mean 7·53 (95 % CI 6·11, 9·30) s) (P = 0·046). Similarly, application of the mixed-effect model for repeated measures under unstructured covariance also revealed that the effect of MFGM was significant when compared with the placebo (10·2 (95 % CI 8·33, 12·4) v. 7·61 (95 % CI 6·17, 9·30) s) (P = 0·045). In conclusion, we demonstrated that MFGM had an effect on the physical performance of community-dwelling Japanese adults despite mandatory exercise. However, studies using larger cohorts of individuals from different demographic backgrounds are required to further elucidate the mechanisms underlying these effects and to extend the application of MFGM.

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Chlorogenic acids (CGA) are the most abundant polyphenols in coffee. Continuous consumption of CGA reduces body fat and body weight. Since energy metabolism and sleep are controlled by common regulatory factors, consumption of CGA might modulate sleep. Lack of sleep has been identified as a risk factor for obesity, hypertension and type 2 diabetes. The aim of this study was to determine the effects of ingesting CGA over 5 d on energy metabolism and sleep quality in humans. A total of nine healthy subjects (four male and five female) completed a placebo-controlled, double-blinded, cross-over intervention study. Subjects consumed a test beverage containing 0 or 600 mg of CGA for 5 d. On the fifth night, subjects stayed in a whole-room metabolic chamber to measure energy metabolism; sleep was evaluated using polysomnographic recording. It was found that CGA shortened sleep latency (9 (sem 2) v. 16 (sem 4) min, P<0·05) compared with the control, whereas no effect on sleep architecture, such as slow-wave sleep, rapid eye movement or waking after sleep onset, was observed. Indirect calorimetry revealed that consumption of CGA increased fat oxidation (510 (sem 84) kJ/8 h (122 (sem 20) kcal/8 h) v. 331 (sem 79) kJ/8 h (81 (sem 19) kcal/8 h), P<0·05) but did not affect energy expenditure during sleep. Consumption of CGA enhanced parasympathetic activity assessed from heart-rate variability during sleep (999 (sem 77) v. 919 (sem 54), P<0·05). A period of 5-d CGA consumption significantly increased fat oxidation during sleep, suggesting that beverages containing CGA may be beneficial to reduce body fat and prevent obesity. Consumption of CGA shortened sleep latency and did not adversely affect sleep quality.

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To reveal the effect of coffee bean polyphenols (CBPs) on blood vessels, this study aimed to investigate the effect of CBPs on acute postprandial endothelial dysfunction. Thirteen healthy non-diabetic men (mean age, 44.9 ± 1.4 years) consumed a test beverage (active: containing CBPs, placebo: no CBPs) before a 554-kcal test meal containing 14 g of protein, 30 g of fat and 58 g of carbohydrates. Then, a crossover analysis was performed to investigate the time-dependent changes in flow-mediated dilation (FMD) in the brachial artery. In the active group, the postprandial impairment of FMD was significantly improved, the two-hour postprandial nitric oxide metabolite levels were significantly increased and the six-hour postprandial urinary 8-epi-prostaglandin F2α levels were significantly reduced compared to the placebo group. The test meal increased the levels of blood glucose, insulin and triglycerides in both groups with no significant intergroup differences. These findings indicate that CBPs intake ameliorates postprandial endothelial dysfunction in healthy men.

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Consumption of milk fat globule membrane (MFGM) in combination with habitual exercise suppresses age-associated muscle loss. The effects of high dose MFGM, however, are not known. A double-blind, randomized controlled trial with parallel group design was conducted to evaluate the safety of consuming high dose MFGM tablets. The subjects were 32 healthy adult men and women. Subjects were given 5 times the recommended daily intake of the tablets containing 6.5 g of MFGM or whole milk powder for 4 weeks. Stomach discomfort and diarrhea were observed; however, these symptoms were transitory and slight and were not related to consumption of the test tablets. In addition, there were no clinically significant changes in anthropometric measurements or blood tests. Total degree of safety assessed by the physicians of all subjects was "safe." These findings suggest that consumption of the tablets containing 6.5 g MFGM for 4 weeks is safe for healthy adults.

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OBJECTIVE: The aim of this study was to assess the relationship between dietary factors and abdominal subcutaneous and visceral adipose tissue in overweight and obese men. METHODS: A pooled cross-sectional analysis was conducted to evaluate the associations between dietary factors (nutrition, dietary pattern and alcohol consumption) and subcutaneous fat area (SFA) and visceral fat area (VFA) in 301 Japanese men, aged 21-65 years. RESULTS: The standardized regression coefficients of major dietary items (total energy intake, energy intake from breakfast, lunch, supper, between-meal, protein, fat, carbohydrate and alcohol) were positive for VFA in multiple linear regression analyses with the use of age and dietary items as independent variables. The energy intake from between-meal snacks correlated with SFA (standardized regression coefficient ß = 0.174, p = 0.002). The coefficient of alcohol intake was positive for VFA and negative for SFA, and alcohol intake correlated with the VFA/total fat area (TFA) ratio (ß = 0.130, p = 0.009). Alcohol intake was positively correlated with the blood non-esterified fatty acid concentration. Alcohol consumption additively increased energy intake from supper. The risk of an increase to VFA ≥ 100 cm(2) was 2.02 times higher (95% CI: 1.15, 3.56) for subjects whose energy intake was ≥ 2200 kcal/d, and 2.07 times higher (95% CI: 1.26, 3.42) in those who consumed ≥ 3 g/d alcohol. The risk of an increase to a VFA/TFA ratio ≥ 0.4 was 1.81 times higher (95% CI: 1.01, 3.23) for subjects whose energy intake from supper was ≥ 1000 kcal/d. CONCLUSION: Our results indicate that habitual alcohol drinking and high-energy intake from supper are associated with disproportionate accumulation of visceral fat.

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Brewed coffee is a widely consumed beverage, and many studies have examined its effects on human health. We investigated the vascular effects of coffee polyphenols (CPPs), hypothesizing that a single ingestion of CPP during glucose loading would improve endothelial function. To test this hypothesis, we conducted a randomized acute clinical intervention study with crossover design and measured reactive hyperemia index (RHI) to assess the acute effects of a 75-g glucose load with CPP in healthy, nondiabetic adult men. Blood glucose and insulin levels were elevated after glucose loading with and without CPP, with no significant differences between treatments. The RHI did not significantly decrease after glucose loading without CPP. With CPP, however, RHI significantly (P < .05) increased over baseline after glucose loading. The difference between treatments was statistically significant (P < .05). No significant changes were observed in an oxidative stress marker after glucose loading with or without CPP. These findings suggest that a single ingestion of CPP improves peripheral endothelial function after glucose loading in healthy subjects.

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OBJECTIVE: Several epidemiological investigations have reported that green tea reduces cardiovascular and cerebral vascular risks. Green tea catechins may improve peripheral endothelial dysfunction in smokers. The purpose of this study was to elucidate the beneficial effect of green tea catechins on the repair of endothelial dysfunction in smokers. METHODS: Thirty healthy male smokers divided into three groups ingested a green tea beverage containing 0 mg (control group), 80 mg (middle dose group) or 580 mg (high dose group) of green tea catechins (GTC) daily for two weeks, and endothelial-dependent vasodilatation was investigated by measuring forearm blood flow (FBF) response to reactive hyperemia (RH) by venous occlusion strain-gauge plethysmography. RESULTS: An acute effect was that the FBF response to RH significantly increased 2 hr after GTC intake in the high dose group. However, no increase was observed in the other groups. The chronic administration of GTC for one or two weeks ameliorated the FBF responses to RH in the high dose group. On the other hand, no significant increase was observed in the FBF responses to RH in the other groups. Moreover, the plasma concentration of 8-OHdG, IL-6, TNF-alpha, and soluble Fas decreased significantly for two weeks in the high dose group, however, the level of IL-1 beta remained unchanged over this period. CONCLUSION: Green tea consumption over short and long periods appears to ameliorate endothelial dysfunction by scavenging free radicals with anti-inflammatory and anti-apoptotic properties in healthy male smokers.

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BACKGROUND: Because green tea reduces cardiovascular and cerebrovascular risk, the purpose of this study aimed to elucidate the effect of green tea catechins (GTC) on endothelial dysfunction in smokers. METHODS AND RESULTS: The 30 healthy male smokers were divided into 3 groups and given green tea beverages containing 0 mg (control group), 80 mg (medium-dose group) or 580 mg (high-dose group) of GTC daily for 2 weeks. Endothelial-dependent and- independent vasodilatation was investigated by measuring the forearm blood flow (FBF) responses to acetylcholine and sodium nitroprusside using venous occlusion strain-gauge plethysmography. The FBF response to acetylcholine significantly increased at 2 h and 1 and 2 weeks after GTC intake in the high-dose group, but no increase was observed in the other groups. FBF responses to sodium nitroprusside did not alter in any group at any time point. A significant increase in plasma nitric oxide and a decrease in asymmetrical dimethylarginine, malondealdehyde and 4-hydroxynonenal, C-reactive protein, monocyte chemotactic protein-1, and soluble CD40 ligand levels were detected after chronic consumption of high-dose GTC. CONCLUSIONS: GTC have antiatherosclerotic effects on dysfunctional vessels in smokers through increasing the level of nitric oxide and reducing oxidative stress.

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Recent studies suggest that chlorogenic acids, which are the main components of the polyphenol class in coffee, decrease blood pressure, and that hydroxyhydroquinone (HHQ), which is generated by roasting coffee beans, inhibits the antihypertensive effect of chlorogenic acids in brewed coffee. Here, we examined the vasoreactivity and antihypertensive effects of HHQ-reduced coffee in mild hypertension. The study design was a double blind, randomized, placebo-controlled intervention study, with a 4-week run-in period, followed by an 8-week test beverage ingestion period. The subjects were Japanese men and women with mild hypertension and vascular failure, who were not taking any antihypertensive drugs. During the test beverage ingestion period, the subjects ingested either active or placebo HHQ-reduced coffee (chlorogenic acids per 184 ml of coffee: active, 300 mg; and placebo, 0 mg) daily. Subjects were randomly divided into two groups: active group (n=9) and placebo group (n=12). In the active beverage group, endothelium-dependent, flow-mediated vasodilation impairment was significantly ameliorated and systolic blood pressure was significantly decreased from the baseline, but not in the placebo group. There were no test beverage consumption-related changes in other parameters that may influence blood pressure, such as pulse, cardiac output, body weight or 24-h urine volume. Ingestion of the active beverage significantly decreased urinary isoprostane levels, suggesting a reduced oxidative stress. These findings indicate that HHQ-reduced coffee decreased blood pressure in subjects with mild hypertension. The decreased blood pressure was associated with improved vascular endothelial function.

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A method using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was developed for the simultaneous analysis of nine chlorogenic acids (CGAs), three isomers each of caffeoylquinic acids (CQAs), feruloylquinic acids (FQAs) and dicaffeoylquinic acids (dCQAs), and their two metabolites, caffeic acid (CA) and ferulic acid (FA), in human plasma. In simultaneous multiple reaction monitoring (MRM) measurements using ESI-MS/MS with a negative ion mode, a deprotonated molecular ion derived from each of the 11 molecules was used as a precursor ion while three diagnostic product ions characteristic for each were selected for the qualitative analysis. To obtain maximal intensities for all diagnostic product ions, the collision energy was optimized for each one. LC separation was achieved under conditions of a reversed-phase Inertsil ODS-2 column combined with a gradient elution system using 50mM acetic acid with 3% acetonitrile aqueous solution and 50 mM acetic acid with 100% acetonitrile. In the quantitative analysis, one of the three diagnostic product ions for each of the 11 molecules was selected. Application of simultaneous LC-ESI-MS/MS MRM measurements to analyze the 11 standards spiked into blank human plasma indicated that all diagnostic product ions were detected without any interference, and that the sensitivity, linearity and recovery of this method were acceptable. When using this method to analyze those 11 molecules in the plasma after oral ingestion of 250 ml of a drink containing a green coffee bean extract (300 mg CGAs), all 11 molecules were identified and CQAs, FQAs and FA were quantified. CQAs, FQAs and dCQAs in human plasma were detected for the first time. This method should be useful to understand the biological and pharmacological effects of CGAs, such as improvement of human hypertension.

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Our previous study revealed the antihypertensive effects of green coffee bean extract (GCE) ingestion in spontaneously hypertensive rats. We suggested that this antihypertensive action was due to the fact that GCE contains chlorogenic acid (CQA) as a major phenolic compound, and CQA in turn contains ferulic acid as a metabolic component that acts on nitric oxide (NO) derived from the vascular endothelium. In this study, the effects of GCE on blood vessels were evaluated in healthy males. The subjects were 20 healthy males with reduced vasodilation responses measured by strain gauge plethysmograms (SPG) to ischemic reactive hyperemia. Of the 20 subjects, 10 (mean age, 37.2 years) ingested a test drink containing GCE (CQA: 140 mg/day), and the other 10 (mean age, 34.8 years) ingested a placebo drink for 4 months. During the ingestion period, SPG, pulse wave velocity (PWV), and serum biochemical parameters were measured, and acceleration plethysmograms (APG) were taken. The reactive hyperemia ratio (RHR) in the test drink group began to increase after ingestion for 1 month and was significantly higher (p <0.05) than that in the placebo group after ingestion for 3 months and 4 months. In addition, after ingestion for 4 months, the test drink group showed a significant decrease (p <0.01) in the plasma total homocysteine level compared with the pre-ingestion level. However, there were no significant differences in PWV or APG between the test drink group and the placebo drink group. The improvement in RHR after ingestion of a drink containing GCE suggested an improvement in vasoreactivity by this component.

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It has been reported that cedarwood oil has sedative effects when inhaled. In this study, we evaluated sedative effects of inhaled cedrol, which is a major component of cedarwood oil. Accumulative spontaneous motor activity was significantly decreased in the cedrol-exposed Wistar rats. Similar results were confirmed in caffeine-treated Wistar rats, spontaneously hypertensive rats (SHR), and ddY mice. In addition, exposure to cedrol prolonged pentobarbital-induced sleeping time in Wistar rats. To investigate whether cedrol, which has a very faint aroma, affects the olfactory system, the nasal cavities of Wistar rats were treated with zinc sulfate to reduce olfactory function. Two days later, the pentobarbital-induced sleep time was measured as described above. Compared to intact rats, the sleep prolongation effect was decreased in a lavender-roman chamomile mixed oil exposure positive control group, indicating that olfactory function was impaired. In contrast, prolongation of the sleeping time did not change in the cedrol exposure group. The above findings indicate that cedrol inhalation had marked sedative effects regardless of the animal species or the functional state of the autonomic nerves, suggesting that the mechanism of action is via a pathway other than the olfactory system.

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