Development of a cognitive function marker based on D-amino acid proportions using new chiral tandem LC-MS/MS systems.

The incidence of dementia, a clinical symptom characterized by severe cognitive decline, is increasing worldwide. Predictive biomarkers are therefore required for early identification and management. D-amino acids in the brain contribute to cognitive function and are suggested as useful biomarkers for diagnosing dementia risk. To clarify their relationship with human cognitive decline, we developed an identification method of chiral metabolomics for detecting slight differences in chiral amino acid amounts. Chiral tandem liquid chromatography-tandem mass spectrometry systems were applied for sensitive and selective amino acid species along with chiral species determination based on anion and zwitterion exchange mechanisms. In a comprehensive health cohort (cross-sectional study), we measured blood chiral amino acid levels from 305 women (65-80 years old) classified into Control, Mild-cognitive-Impairment (MCI), and Dementia groups using the Mini-Mental State Examination. MCI exhibited higher D-Pro (D-Pro/(D-Pro + L-Pro)) proportion vs the Control group, suggesting this proportion as a useful biomarker for MCI. Biomarker accuracy was improved in combination with D-Ser proportion. Receiver operating characteristics analysis of the Control vs. MCI proportion obtained area under the curve (0.80) with 70% sensitivity and 84% specificity at the optimal cutoff value (0.30). Thus, dementia monitoring can be improved by including trace D-amino acids measurements.

Light rhythmic exercise with dietary milk fat globule membrane improves physical fitness in an elderly Japanese population: a double-blind randomized placebo-controlled trial.

This study aimed to investigate the efficacy of home-based, light gymnastic exercise plus dietary milk fat globule membrane (MFGM) intake on physical fitness of an elderly Japanese sample in a pilot, double-blind, randomized, placebo-controlled trial. Seventy-one subjects (male, n = 13; female, n = 58) were randomly assigned into two groups: placebo (n = 35 [male, n = 6; female, n = 29]) and MFGM group (n = 36 [male, n = 7; female, n = 29]). The intervention was eight weeks. Subjects ingested either MFGM (1 g/day) or placebo tablets daily and engaged in an exercise program daily. Physical function tests were performed at baseline and after four and eight weeks. Foot tapping and open-close stepping scores significantly increased from baseline to eight weeks in the MFGM group. Study results suggest daily MFGM ingestion might further enhance the effects of light-intensity exercise in healthy elderly people.

Reduction in hydroxyhydroquinone from coffee increases postprandial fat utilization in healthy humans: a randomized double-blind, cross-over trial.

The present study aimed to clarify the effect of reduction in hydroxyhydroquinone (HHQ) from roasted coffee on energy utilization in humans. Indirect calorimetry showed that one-week ingestion of HHQ-reduced coffee led to significantly higher postprandial fat utilization than that of HHQ-containing coffee. This finding indicates that reduction in HHQ from coffee increases postprandial fat utilization.

Daily consumption of tea catechins improves aerobic capacity in healthy male adults: a randomized double-blind, placebo-controlled, crossover trial.

Our previous studies demonstrated that dietary supplementation with tea catechins combined with exercise improved endurance capacity in mice. This study aimed to demonstrate the effect of daily tea catechin consumption on aerobic capacity in humans. Sixteen Japanese non-athlete male subjects (aged 25-47 years) took 500 mL of a test beverage with or without tea catechins (570 mg) daily for 8 weeks and attended a training program twice a week. Aerobic capacity was evaluated by indirect calorimetry and near-infrared spectroscopy during graded cycle exercise. Catechin beverage consumption was associated with a significantly higher ventilation threshold during exercise and a higher recovery rate of oxygenated hemoglobin and myoglobin levels after graded cycle exercise when compared to subjects receiving the placebo beverage. These results indicate that daily consumption of tea catechins increases aerobic capacity when combined with semiweekly light exercise, which may be due to increased skeletal muscle aerobic capacity.

Effects of Nutritional Supplementation with Milk Fat Globule Membrane on Physical and Muscle Function in Healthy Adults Aged 60 and Over with Semiweekly Light Exercise: A Randomized Double-Blind, Placebo-Controlled Pilot Trial.

This study aimed to demonstrate the beneficial effects of nutritional supplementation with dietary milk fat globule membrane (MFGM) on physical performance and skeletal muscle function in healthy adults aged 60 and over with semiweekly light exercise. The study was designed as a randomized double-blind controlled trial. Twenty-two Japanese participants (10 men, 12 women) aged 60-73 y were assigned to one of two groups (11 [5 men, 6 women] in each). One group received MFGM tablets (1 g MFGM/d), and the other received placebo tablets daily for 10 wk. Both groups participated in a twice-weekly light exercise program. Physical function tests and surface electromyography (EMG) were conducted at the baseline and after 5 and 10 wk. Chair stand time significantly shortened in both groups after 10 wk compared with that at the baseline. The average time shortened more considerably in the MFGM group than in the placebo group, although the change was not statistically significant. Both knee extension strength and the cross-sectional area of the quadriceps muscles significantly increased from baseline in the MFGM group but not in the placebo group. Surface EMG showed that muscle fiber conduction velocity increased significantly after 10 wk from the baseline only in the MFGM group. The increase from the baseline was significantly greater in the MFGM group than in the placebo group. Daily supplementation with MFGM increased motor unit action potential conduction and improved muscle strength and physical performance in healthy Japanese adults aged 60 y and over paired with semiweekly light exercise.

Dietary milk fat globule membrane supplementation combined with regular exercise improves skeletal muscle strength in healthy adults: a randomized double-blind, placebo-controlled, crossover trial.

BACKGROUND: Our previous studies demonstrated that dietary supplementation with milk fat globule membrane (MFGM) combined with habitual exercise improved muscle strength by stimulating neuromuscular development in mice. This study aimed to demonstrate the beneficial effects of dietary MFGM supplementation plus regular exercise on muscle strength and neuromuscular function in healthy humans. METHODS: The study was designed as a randomized, double-blind, placebo-controlled, crossover trial. Fourteen Japanese adults aged 31-48 years took daily MFGM (1 g) or placebo tablets during the 4-week study period and attended a training program twice a week. Physical function tests and surface electromyography (EMG) were conducted at baseline and at the end of the study period. RESULTS: The MFGM group had significantly greater leg extension strength than the placebo group after the 4-week study period. Surface EMG showed that the MFGM group had a significantly higher root mean square amplitude than the placebo group, which indicated that the MFGM group had higher motor unit activity. CONCLUSIONS: Dietary MFGM supplementation combined with regular exercise improves skeletal muscle strength, which may be due to increased motor unit recruitment in healthy Japanese middle-aged adults.

Daily consumption of milk fat globule membrane plus habitual exercise improves physical performance in healthy middle-aged adults.

Our recent studies demonstrated that habitual exercise plus dietary supplementation with milk fat globule membrane (MFGM) improved endurance capacity and muscle function by stimulating neuromuscular development in mice. The aim of this study was to investigate the efficacy of dietary MFGM supplementation plus habitual exercise on the physical performance of middle-aged Japanese adults in a pilot randomized, double-blind, placebo-controlled trial. Forty-four subjects (men, n = 22; women, n = 22) were randomly assigned into two groups: one received placebo tablets (placebo group, n = 22 [men, n = 11; women, n = 11]), while the other received MFGM tablets (MFGM group, n = 22 [men, n = 11; women, n = 11]). The subjects ingested either MFGM (1 g/day) or placebo (1 g/day of whole milk powder) tablets every day for the 10-week study period and engaged in an exercise training program twice per week. A physical function test was performed at baseline and at 5 and 10 weeks. A significant group-by-time interaction was found for the side step test, muscle cross-sectional area (CSA), and muscle fiber conduction velocity (MFCV). In the placebo group, there were no significant intragroup differences. In the MFGM group, side step score and muscle CSA were significantly greater at 10 weeks compared to the baseline, and MFCV was significantly higher than that in the placebo group at 10 weeks. The changes in percentage of the side step score, muscle CSA, and MFCV in the MFGM group were significantly higher than in the placebo group at 10 weeks. These results suggest that daily MFGM ingestion combined with regular exercise might enhance physical performance such as agility in middle-aged adults.

Stimulation of postprandial fat utilization in healthy humans by daily consumption of chlorogenic acids.

Long-term ingestion of coffee polyphenols (chlorogenic acids, CGAs) reduces body fat in humans and rodents. While CGA supplementation has been shown to increase fat utilization in rodents, evidence in humans is still limited. The present study clarifies the effect of daily CGA consumption on energy metabolism in humans. Eighteen healthy male subjects (36.1 ± 7.4 y of age) participated in a placebo-controlled, double-blind, crossover, intervention study with two different test beverages. The subjects consumed 185 mL of a test beverage with or without CGAs (329 mg) daily for 4 wk. The energy metabolism was evaluated by using indirect calorimetry before and after the test period during fasting and up to 180 min postprandially. Indirect calorimetry showed that a 4-wk ingestion of the CGA beverage led to a significantly higher postprandial energy expenditure than that of the control beverage. The subjects ingesting the CGA beverage exhibited higher postprandial fat utilization than those consuming the control beverage. The daily CGA consumption therefore increased postprandial fat utilization in healthy humans.

Tea catechins prevent contractile dysfunction in unloaded murine soleus muscle: a pilot study.

OBJECTIVE: Extended periods of muscle disuse, physical inactivity, immobilization, and bedrest result in a loss of muscle mass and a decrease in muscle force, which are accompanied by an increase in oxidative stress. We investigated the effects of the intake of green tea catechins on unloading-induced muscle dysfunction in tail-suspended mice. METHODS: Ten-week-old male BALB/c mice were fed a purified control diet or a diet containing 0.5% tea catechins for 14 d. Thereafter, the mice were subjected to continuous tail suspension for 10 d. On the final day, muscle mass, contractile force production, antioxidant potential, and carbonylated protein levels were evaluated. RESULTS: Hind limb unloading caused a loss of soleus muscle weight and muscle force. Intake of tea catechins significantly inhibited the unloading-induced decrease in force in isolated soleus muscle by 19% compared with the control group, although tea catechins did not affect muscle weight. In addition, intake of tea catechins suppressed the decrease in antioxidant potential and the increase in carbonyl myofibrillar protein. CONCLUSION: Ingestion of tea catechins minimized contractile dysfunction in skeletal muscle and muscle atrophy in unloaded muscle. This effect might be partly due to the lower oxidative modification of myofibrillar protein through the antioxidant activity of tea catechins.

Dietary diacylglycerol induces the regression of atherosclerosis in rabbits.

Recent studies of the relation between serum triacylglycerol concentration and the risk for coronary artery disease suggest that inefficient clearance of postprandial triacylglycerols promotes atherogenesis. We recently demonstrated that dietary diacylglycerol (DAG), rich in the 1,3-species, suppresses the postprandial increase in serum triacylglycerol levels compared with dietary triacylglycerol (TAG). Here, we investigated the effects of dietary DAG on atherosclerosis in rabbits with cholesterol-induced atherosclerosis. New Zealand White rabbits (n = 20) were fed a diet containing 3% lard and 1.3% cholesterol for 50 d to induce atherosclerotic lesions. Thereafter, the rabbits were assigned to 2 groups and fed 90 g/d nonpurified diet and orally administered 5 g DAG or TAG for an additional 34 d. Reference rabbits (n = 5) were fed only the nonpurified diet throughout the 84-d study. The area of atherosclerotic lesions and aortic lipid concentrations were significantly lower in DAG-fed rabbits compared with TAG-fed rabbits. The VLDL receptor and macrophage antigen-1 mRNA expression levels were significantly lower in DAG-fed rabbits than in TAG-fed rabbits. In the liver of DAG-fed rabbits, the triacylglycerol concentration was lower and the carnitine palmitoyltransferase activity higher than in TAG-fed rabbits. Stimulation of hepatic lipid catabolism might be related to the reduced lipid accumulation in the liver and aorta by reducing the release of triacylglycerol into the circulation. Thus, long-term consumption of DAG, which reduces postprandial lipemia, might be useful for the regression of atherosclerosis by stimulating hepatic lipid catabolism and thereby modulating monocyte/macrophage migration and aortic lipid accumulation.

Type-3 ryanodine receptor involved in Ca2+-induced Ca2+ release and transmitter exocytosis at frog motor nerve terminals.

Ca(2+)-induced Ca2+ release (CICR) occurs in frog motor nerve terminals after ryanodine receptors (RyRs) are primed for activation by conditioning large Ca2+ entry. We studied which type of RyR exists, whether CICR occurs without conditioning Ca2+ entry and how RyRs are primed. Immunohistochemistry revealed the existence of RyR3 in motor nerve terminals and axons and both RyR1 and RyR3 in muscle fibers. A blocker of RyR, 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) slightly decreased rises in intracellular Ca2+ ([Ca2+]i) induced by a short tetanus (50 Hz, 1-2s), but not after treatment with ryanodine. Repetitive tetani (50 Hz for 15s every 20s) produced repetitive rises in [Ca2+]i, whose amplitude overall waxed and waned. TMB-8 blocked the waxing and waning components. Ryanodine suppressed a slow increase in end-plate potentials (EPPs) induced by stimuli (33.3 Hz, 15s) in a low Ca2+, high Mg2+ solution. KN-62, a blocker of Ca(2+)/calmoduline-activated protein kinase II (CaMKII), slightly reduced short tetanus-induced rises in [Ca2+]i, but markedly the slow waxing and waning rises produced by repetitive tetani in both normal and low Ca2+, high Mg2+ solutions. Likewise, KN-62, but not KN-04, an inactive analog, suppressed slow increases in EPP amplitude and miniature EPP frequency during long tetanus. Thus, CICR normally occurs weakly via RyR3 activation by single impulse-induced Ca2+ entry in frog motor nerve terminals and greatly after the priming of RyR via CaMKII activation by conditioning Ca2+ entry, thus, facilitating transmitter exocytosis and its plasticity.

Ingestion of a tea rich in catechins leads to a reduction in body fat and malondialdehyde-modified LDL in men.

BACKGROUND: Catechins, the major component of green tea extract, have various physiologic effects. There are few studies, however, on the effects of catechins on body fat reduction in humans. It has been reported that the body mass index (BMI) correlates with the amount of malondialdehyde and thiobarbituric acid-reactive substances in the blood. OBJECTIVE: We investigated the effect of catechins on body fat reduction and the relation between oxidized LDL and body fat variables. DESIGN: After a 2-wk diet run-in period, healthy Japanese men were divided into 2 groups with similar BMI and waist circumference distributions. A 12-wk double-blind study was performed in which the subjects ingested 1 bottle oolong tea/d containing 690 mg catechins (green tea extract group; n = 17) or 1 bottle oolong tea/d containing 22 mg catechins (control group; n = 18). RESULTS: Body weight, BMI, waist circumference, body fat mass, and subcutaneous fat area were significantly lower in the green tea extract group than in the control group. Changes in the concentrations of malondialdehyde-modified LDL were positively associated with changes in body fat mass and total fat area in the green tea extract group. CONCLUSION: Daily consumption of tea containing 690 mg catechins for 12 wk reduced body fat, which suggests that the ingestion of catechins might be useful in the prevention and improvement of lifestyle-related diseases, mainly obesity.