Tyrosine Is a Booster of Leucine-Induced Muscle Anabolic Response.

Leucine (Leu), an essential amino acid, is known to stimulate protein synthesis in the skeletal muscle via mTOR complex 1 (mTORC1) activation. However, the intrinsic contribution of other amino acids to Leu-mediated activation of mTORC1 signaling remains unexplored. This study aimed to identify amino acids that can promote mTORC1 activity in combination with Leu and to assess the effectiveness of these combinations in vitro and in vivo. We found that tyrosine (Tyr) enhanced Leu-induced phosphorylation of S6 kinase (S6K), an indicator of mTORC1 activity, although it exerted no such effect individually. This booster effect was observed in C2C12 cells, isolated murine muscle, and the skeletal muscles of mice orally administered the amino acids. To explore the molecular mechanisms underlying this Tyr-mediated booster effect, the expression of the intracellular Leu sensors, Sestrin1 and 2, was suppressed, and the cells were treated with Leu and Tyr. This suppression enabled Tyr alone to induce S6K phosphorylation and enhanced the booster effect, suggesting that Tyr possibly contributes to mTORC1 activation when Sestrin-GAP activity toward Rags 2 (GATOR2) is dissociated through Sestrin knockdown or the binding of Sestrins to Leu. Collectively, these results indicate that Tyr is a key regulator of Leu-mediated protein synthesis.

DOK7 Gene Therapy Enhances Neuromuscular Junction Innervation and Motor Function in Aged Mice.

Muscle denervation at the neuromuscular junction (NMJ), the essential synapse between motor neuron and skeletal muscle, is associated with age-related motor impairment. Therefore, improving muscle innervation at aged NMJs may be an effective therapeutic strategy for treating the impairment. We previously demonstrated that the muscle protein Dok-7 plays an essential role in NMJ formation, and, indeed, its forced expression in muscle enlarges NMJs. Moreover, therapeutic administration of an adeno-associated virus vector encoding human Dok-7 (DOK7 gene therapy) suppressed muscle denervation and enhanced motor activity in a mouse model of amyotrophic lateral sclerosis (ALS). Here, we show that DOK7 gene therapy significantly enhances motor function and muscle strength together with NMJ innervation in aged mice. Furthermore, the treated mice showed greatly increased compound muscle action potential (CMAP) amplitudes compared with the controls, suggesting enhanced neuromuscular transmission. Thus, therapies aimed at enhancing NMJ innervation have potential for treating age-related motor impairment.

Involvement of ammonia metabolism in the improvement of endurance performance by tea catechins in mice.

Blood ammonia increases during exercise, and it has been suggested that this increase is both a central and peripheral fatigue factor. Although green tea catechins (GTCs) are known to improve exercise endurance by enhancing lipid metabolism in skeletal muscle, little is known about the relationship between ammonia metabolism and the endurance-improving effect of GTCs. Here, we examined how ammonia affects endurance capacity and how GTCs affect ammonia metabolism in vivo in mice and how GTCs affect mouse skeletal muscle and liver in vitro. In mice, blood ammonia concentration was significantly negatively correlated with exercise endurance capacity, and hyperammonaemia was found to decrease whole-body fat expenditure and fatty acid oxidation-related gene expression in skeletal muscle. Repeated ingestion of GTCs combined with regular exercise training improved endurance capacity and the expression of urea cycle-related genes in liver. In C2C12 myotubes, hyperammonaemia suppressed mitochondrial respiration; however, pre-incubation with GTCs rescued this suppression. Together, our results demonstrate that hyperammonaemia decreases both mitochondrial respiration in myotubes and whole-body aerobic metabolism. Thus, GTC-mediated increases in ammonia metabolism in liver and resistance to ammonia-induced suppression of mitochondrial respiration in skeletal muscle may underlie the endurance-improving effect of GTCs.

Coffee polyphenols prevent cognitive dysfunction and suppress amyloid ß plaques in APP/PS2 transgenic mouse.

Epidemiological studies have found that habitual coffee consumption may reduce the risk of Alzheimer's disease. Coffee contains numerous phenolic compounds (coffee polyphenols) such as chlorogenic acids. However, evidence demonstrating the contribution of chlorogenic acids to the prevention of cognitive dysfunction induced by Alzheimer's disease is limited. The present study investigated the effect of chlorogenic acids on the prevention of cognitive dysfunction in APP/PS2 transgenic mouse model of Alzheimer's disease. Five-week-old APP/PS2 mice were administered a diet supplemented with coffee polyphenols daily for 5 months. The memory and cognitive function of mice was determined using the novel object recognition test, Morris water maze test, and the step-through passive avoidance test. Immunohistochemical analysis revealed that chronic treatment with coffee polyphenols prevented cognitive dysfunction and significantly reduced the amount of amyloid ß (Aß) plaques in the hippocampus. Furthermore, we determined that 5-caffeoylquinic acid, one of the primary coffee polyphenols, did not inhibit Aß fibrillation; however, degraded Aß fibrils. In conclusion, our results demonstrate that coffee polyphenols prevent cognitive deficits and reduce Aß plaque deposition via disaggregation of Aß in the APP/PS2 mouse.

Continuous Supplementation of Milk Fat Globule Membrane with Habitual Exercise from a Young Age Improves Motor Coordination and Skeletal Muscle Function in Aged Mice.

Since the decline of physical performance gradually progresses with aging, continuous exercise with nutritional supplementation from a young age is a feasible and effective way to maintain a comfortable life until late old age. We examined the effects of continuous milk fat globule membrane (MFGM) supplementation combined with voluntary running exercise (VR) for prevention of aging-associated declines in physical performance in naturally aging mice. The MFGM with VR group showed a significantly attenuated age-related decline in motor coordination and suppression of the loss of muscle mass and strength. Compared with the control group, the MFGM with VR group showed significantly higher mRNA and protein expression for docking protein 7, which maintains neuromuscular junction (NMJ) integrity, in the quadriceps muscles. These results suggest that dietary MFGM and VR attenuate natural aging-related decline in motor coordination and muscle function by regulating NMJ integrity.

The study of metabolic improvement by nutritional intervention controlling endogenous GIP (Mini Egg study): a randomized, cross-over study.

BACKGROUND: Given the major role of glucose-dependent insulinotropic polypeptide (GIP) in the regulation of adiposity, this study examined the effects induced by a diet based on the Japanese tradition (SMART WASHOKU) on the visceral fat area (VFA) and GIP secretions. METHODS: Overweight/obese men (n = 21; mean age, 41.0 ± 9.0 years; mean BMI, 25.2 ± 2.0 kg/m2) without diabetes were placed on either a SMART WASHOKU or control meal for 2 weeks, in a randomized, cross-over setup with a four-week washout period. RESULTS: For the meal tolerance test, blood samples were collected at 0, 30, 60, 120, 180, and 240 min post-meal, followed by measuring blood glucose, insulin, GIP, and glucagon-like peptide-1 (GLP-1) levels. Relative to a control meal, SMART WASHOKU meal yielded significantly lower plasma postprandial GIP concentrations (AUC: 700.0 ± 208.0 vs. 1117.0 ± 351.4 pmol/L・4 h, P < 0.05); however, between meals, there was no significant difference in the levels of GLP-1, peptide YY, and ghrelin. Compared to the control meal, SMART WASHOKU intervention significantly reduced VFA and the levels of LDL-cholesterol, triglyceride, and HbA1c after the chronic meal intervention. CONCLUSIONS: In conclusion, a SMART WASHOKU meal may decrease VFA and improve metabolic parameters in overweight/obese men, possibly via suppressing GIP secretion.

Identification of the Catechin Uptake Transporter Responsible for Intestinal Absorption of Epigallocatechin Gallate in Mice.

Many studies have shown that epigallocatechin gallate (EGCg) contribute to the health benefits of green tea, although its bioavailability is usually low. However, the mechanism underlying its intestinal absorption remains unclear. In human subjects, it has been reported that the bioavailability of EGCg increases after repeated oral catechin intake. We hypothesized that a certain uptake transporter was involved in this increase, and investigated a novel EGCg transporter. We first confirmed the increase in EGCg bioavailability in mice fed the catechin diet for two weeks. Then, in situ intestinal catechin infusion exhibited that the absorption of EGCg in the ileum was selectively increased in mice fed the catechin diet. A comprehensive analysis of plasma membrane proteins revealed 10 candidates for EGCg transporter, which were selectively increased in the ileum. EGCg uptake by a Xenopus laevis oocyte expressed with respective transporter revealed that oocytes microinjected with DTDST cRNA exhibited significantly higher EGCg uptake. Furthermore, uptake of EGCg by CHO-K1 cells stably expressing DTDST was significantly higher than that by mock cells, which was nullified by treating with a DTDST inhibitor. In conclusion, this study identified DTDST as a novel intestinal EGCg transporter that is upregulated after repeated oral catechin intake.

Metabolic Signature of a Functional High-Catechin Tea after Acute and Sustained Consumption in Healthy Volunteers through 1H NMR Based Metabolomics Analysis of Urine.

Functional tea beverages have emerged as a novel approach to achieving health benefits associated with tea. The use of metabolomics may improve the evaluation of their consumption and their effects. The current study aimed at exploring the urinary signature of exposure to a functional high-catechin tea (HCT) using untargeted NMR-based metabolomics. Ten volunteers participated in a crossover intervention study. Individuals consumed an HCT or a control beverage over a period of 28 days. Multilevel partial least-squares discriminant analysis (ML-PLS-DA) was used for paired comparisons. A further crossover model was performed to assess the significant changes. The consumption of the HCT resulted in the excretion of theanine, epicatechin, pyrogallol sulfate, and higher levels of 3-methyl-2-oxovalerate and succinate, as well as unknown compounds. In conclusion, the present work established novel urinary signatures of a functional drink. Such signatures may be potential biomarkers and/or reflect certain benefits of functional tea beverages.

Rice bran triterpenoids improve postprandial hyperglycemia in healthy male adults: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Compared to white rice, brown rice induces a lower glycemic response in healthy and diabetic humans. This effect is partly attributed to the higher amounts of water- or oil-soluble bran components and dietary fiber in brown rice. We hypothesized that dietary supplementation with oil-soluble rice bran triterpenoids (RBTs; triterpene alcohol and sterol prepared from rice bran) might reduce the incidence of postprandial hyperglycemia in healthy humans. OBJECTIVE: We examined the acute effects of a single RBT-supplemented meal on the postprandial blood glucose responses of healthy male adults in a double-blind, randomized, placebo-controlled, crossover trial. DESIGN: Nineteen subjects consumed a test meal containing either placebo- or RBT-supplemented olive oil. Blood biomarkers were evaluated in a fasting state and up to 240 min postprandially. RESULTS: Compared to the placebo-supplemented meal, the RBT-supplemented meal significantly suppressed the increase in postprandial blood glucose level. A subclass analysis revealed that RBT-supplemented oil significantly reduced blood glucose increases in subjects with higher postprandial blood glucose elevations. Postprandial increases in blood insulin, glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptide-1 (GLP-1) levels did not differ between the groups. CONCLUSION: These results suggest that RBT consumption improves postprandial hyperglycemia in healthy humans, especially those with higher postprandial glucose increases.

Combined Supplementation of Pre-Exercise Carbohydrate, Alanine, and Proline and Continuous Intake of Green Tea Catechins Effectively Boost Endurance Performance in Mice.

Continuous intake of green tea catechins (GTC) increases fatty acid utilization as an energy source and improves endurance capacity. Conversely, the single pre-exercise intake of maltodextrin (MD) as a carbohydrate source and the gluconeogenic amino acids alanine (Ala) and proline (Pro) effectively maintain blood glucose levels and increase endurance performance. In this study, we investigated the synergistic combinational effect of these interventions on endurance performance in mice. Male BALB/c mice were fed a 0.5% GTC diet or Control diet for 8 weeks. Maximum running time was measured every 2 weeks. MD (2 g/kg body weight (B.W.)), MD (1 g/kg B.W.) + AlaPro (9:1, 1 g/kg B.W.), and vehicle were orally administrated 60 mins before measurements in each diet group. The GTC + MD + AlaPro group showed significantly higher endurance performance than the Control-Vehicle group at all measurements. Indirect calorimetry analysis during running exercise at 4 weeks in the Control and GTC groups supplemented with pre-exercise MD + AlaPro administration revealed significantly higher fat oxidation in the GTC groups compared to the Control group. The combined increase in fatty acid utilization through continuous GTC intake and pre-exercise MD + AlaPro carbohydrate energy supplementation synergistically improves endurance capacity.

Hydroxyhydroquinone impairs fat utilization in mice by reducing nitric oxide availability.

Habitual consumption of chlorogenic acid compounds (CGAs) from coffee increases fat catabolism and reduces body fat; however, the contribution of roasted coffee remains unclear. Hydroxyhydroquinone (HHQ) impairs the vasodilatory and antihypertensive effects of CGAs by reducing nitric oxide (NO) bioavailability. Since HHQ also reduces fat catabolism, we hypothesized that HHQ does so by decreasing NO availability. Therefore, we investigated the effect of HHQ on energy metabolism in KKAy mice. In HHQ-treated mice, fat oxidation was significantly low and dose-dependent, serum and urinary hydrogen peroxide were high, and plasma NO metabolites and S-nitrosylated liver proteins were low. In HHQ-treated mouse hepatocytes, the palmitate-induced increase in cellular oxygen consumption was negatively affected, and HHQ or L-NAME reduced cellular fatty acid utilization. In conclusion, HHQ can impair fat utilization by reducing NO availability in mice. Protein S-nitrosylation reduction in liver cells after HHQ consumption may be associated with impaired fatty acid oxidation.

Dietary steamed wheat bran increases postprandial fat oxidation in association with a reduced blood glucose-dependent insulinotropic polypeptide response in mice.

Obesity is a global epidemic associated with a higher risk of cardiovascular disease and metabolic disorders, such as type 2 diabetes. Previous studies demonstrated that chronic feeding of steamed wheat bran (WB) decreases obesity. To clarify the underlying mechanism and the responsible component for the anti-obesity effects of steamed WB, we investigated the effects of dietary steamed WB and arabinoxylan on postprandial energy metabolism and blood variables. Overnight-fasted male C57BL/6J mice were fed an isocaloric diet with or without steamed WB (30%). Energy metabolism was evaluated using an indirect calorimeter, and plasma glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) levels were measured for 120 min after feeding. We similarly investigated the effect of arabinoxylan, a major component of steamed WB. Mice fed the WB diet had higher postprandial fat oxidation and a lower blood GIP response compared with mice fed the control diet. Mice fed the arabinoxylan diet exhibited a dose-dependent postprandial blood GIP response; increasing the arabinoxylan content in the diet led to a lower postprandial blood GIP response. The arabinoxylan-fed mice also had higher fat oxidation and energy expenditure compared with the control mice. In conclusion, the findings of the present study revealed that dietary steamed WB increases fat oxidation in mice. Increased fat oxidation may have a significant role in the anti-obesity effects of steamed WB. The postprandial effects of steamed WB are due to arabinoxylan, a major component of WB. The reduction of the postprandial blood GIP response may be responsible for the increase in postprandial fat utilization after feeding on a diet containing steamed WB and arabinoxylan.

Safety assessment of green tea based beverages and dried green tea extracts as nutritional supplements.

The safety of green tea infusions and green tea extract (GTE)-based products is reviewed regarding catechins. Epigallocatechin 3-gallate (EGCG), the major catechin present in green tea, is suspected of being responsible for liver toxicity reported in humans consuming food supplements. Intake of EGCG with green tea infusions and GTE-based beverages is up to about 450mg EGCG/person/day in Europe and higher in Asia. Consumption of green tea is not associated with liver damage in humans, and green tea infusion and GTE-based beverages are considered safe in the range of historical uses. In animal studies, EGCG's potency for liver effects is highly dependent on conditions of administration. Use of NOAELs from bolus administration to derive a tolerable upper intake level applying the margin of safety concept results in acceptable EGCG-doses lower than those from one cup of green tea. NOAELs from toxicity studies applying EGCG with diet/split of the daily dose are a better point of departure for risk characterization. In clinical intervention studies, liver effects were not observed after intakes below 600mg EGCG/person/day. Thus, a tolerable upper intake level of 300mg EGCG/person/day is proposed for food supplements; this gives a twofold safety margin to clinical studies that did not report liver effects and a margin of safety of 100 to the NOAELs in animal studies with dietary administration of green tea catechins.

Effect of α-linolenic acid-rich diacylglycerol oil on protein kinase C activation in the rat digestive tract and lingual mucosa.

1,2-Diacylglycerol with short chain fatty acids is an endogenous activator of protein kinase C (PKC), which involved in multiple cellular processes implicated in cancer. The aim of the present study was to assess the effects of dietary α-linolenic acid-rich diacylglycerol (ALA-DAG) oil on PKC activation in the rat digestive tract and lingual mucosa in comparison with the effects of α-linolenic acid-rich triacylglycerol (ALA-TAG) oil, and common dietary oil. Membranous PKC activity in the lingual mucosa of male Wistar rats was significantly activated by treatment of the tongue with 1,2-tetradecarnoylphorbol-13-acetate (100 µM) twice in 1 day. In contrast, animals consuming a diet containing either ALA-DAG oil (7.5% or 30%), ALA-TAG oil (7.5% or 30%), or rapeseed oil (30%) for 4 weeks exhibited no significant differences in the cytosolic and membrane PKC activity in the lingual, esophageal, gastric, small intestinal, and colonic mucosa. Dose-related increases in PKC activity were not observed in the ALA-DAG oil-fed groups. Thus, the effects of dietary ALA-DAG oil on PKC activation in the digestive tract and lingual mucosa was similar to those of the ALA-TAG and rapeseed oils. These findings suggest that replacement of common dietary oil with ALA-DAG oil would not increase the risk of carcinogenesis.

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.

Increased plasma levels of glucose-dependent insulinotropic polypeptide are associated with decreased postprandial energy expenditure after modern Japanese meals.

PURPOSE: The nutritional changes that have accompanied the modernization of Japanese dietary patterns have led to significant increases in the number of people who are overweight or obese. This study aimed to clarify the effects of these nutritional changes on postprandial energy expenditure and the release of metabolism-regulating hormones. METHODS: The total daily energy content (20 % breakfast, 40 % lunch, and 40 % dinner) and macronutrient composition (carbohydrate/fat/protein) was 8807.3 kJ and 364.3:30.1:66.4 (g) for the traditional test diet and 9217.6 kJ and 331.7:66.1:76.9 (g) for the modern test diet. In experiment 1, nine healthy Japanese men participated in a crossover study during which they ingested a test diet comprising three meals; postprandial blood parameters were measured after each meal. In experiment 2, another ten men participated in a crossover study during which they ingested 2 meals, after which metabolic responses and blood variables were evaluated. RESULTS: The modern diet induced greater blood levels of glucose-dependent insulinotropic polypeptide (GIP) and ghrelin than did the traditional diet. The expected increase in postprandial energy expenditure (∆REE) tended to be dampened after the modern compared with the traditional diet. GIP was inversely correlated with ∆REE after lunch, and ghrelin was positively associated with ∆REE. CONCLUSION: Both GIP and ghrelin are robust indicators of postprandial energy expenditure. The nutritional changes accompanying the modernization of Japanese dietary patterns may increase the levels of the anabolic intestinal hormone GIP, which is associated with ∆REE, in the Japanese population. The contribution of an increased ghrelin concentration to the decreased ∆REE after the modern diet warrants further investigation.

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.

The Effects of a Hypocaloric Diet on Diet-Induced Thermogenesis and Blood Hormone Response in Healthy Male Adults: A Pilot Study.

Calorie restriction is a common strategy for weight loss and management. Consumption of food and nutrients stimulates diet-induced thermogenesis (DIT), as well as pancreatic and gastrointestinal hormone secretion that may regulate energy metabolism. Yet, little is known about the impact of hypocaloric diets on energy metabolism-related parameters. In this study, we assessed the effects of hypocaloric diets on hormonal variance in relation to DIT in healthy adults. Ten healthy male adults were enrolled in a randomized crossover study comprising three meal trials. Each subject was given a meal of 200 (extremely hypocaloric), 400 (moderately hypocaloric), or 800 kcal (normocaloric). Postprandial blood variables and energy expenditure were measured for 4 h (after the 200- and 400-kcal meals) or 6 h (after the 800-kcal meal). DIT and postprandial changes in blood pancreatic peptide and ghrelin were significantly smaller after the extremely or moderately hypocaloric diet than after the normocaloric diet but were similar between the hypocaloric diets. Postprandial blood insulin, amylin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide type-1 (GLP-1) increased in a calorie-dependent manner. Thermogenic efficiency (DIT per energy intake) was negatively correlated with the maximum blood level (Cmax) (p=0.01) and incremental area under the curve (p=0.01) of the blood GIP response. Calorie restriction thus leads to hormonal responses and lower DIT in healthy adults. Extreme calorie restriction, however, led to greater thermogenic efficiency compared with moderate calorie restriction. The postprandial GIP response may be a good predictor of postprandial thermogenic efficiency.

Triterpene alcohols and sterols from rice bran reduce postprandial hyperglycemia in rodents and humans.

SCOPE: Hyperglycemia is a major public health problem worldwide and there is increasing demand for prevention of postprandial hyperglycemia in diabetic, prediabetic, and healthy humans. METHODS AND RESULTS: We investigated whether rice bran and triterpene alcohol and sterol preparation (TASP) lowered hyperglycemia in mice and humans. Brown rice and white rice supplemented with TASP lowered the postprandial hyperglycemia in humans. TASP and its components (cycloartenol [CA], 24-methylene cycloartanol, ß-sitosterol, and campesterol) decreased postprandial hyperglycemia in C57BL/6J mice. Glucose transport into everted rat intestinal sacs and human HuTu80 cells transfected with sodium-glucose cotransporter-1 (SGLT1) was significantly reduced by the addition of CA. Intracellular localization analysis suggested that SGLT1 translocation to the apical plasma membrane was inhibited when the cells were treated with CA. CONCLUSIONS: We demonstrated for the first time that TASP from rice bran lowered postprandial hyperglycemia in mice and humans. The smaller increase in blood glucose following TASP consumption may be due to the CA-induced decrease in glucose absorption from the intestine, which may be related to decreased membrane translocation of SGLT1.

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.