Nutritional Value of Yogurt as a Protein Source: Digestibility/Absorbability and Effects on Skeletal Muscle.

Yogurt is a traditional fermented food that is accepted worldwide for its high palatability and various health values. The milk protein contained in yogurt exhibits different physical and biological properties from those of non-fermented milk protein due to the fermentation and manufacturing processes. These differences are suggested to affect the time it takes to digest and absorb milk protein, which in turn will influence the blood levels of amino acids and/or hormones, such as insulin, and thereby, the rate of skeletal muscle protein synthesis via the activation of intracellular signaling, such as the mTORC1 pathway. In addition, based on the relationship between gut microbiota and skeletal muscle conditions, yogurt, including lactic acid bacteria and its metabolites, has been evaluated for its role as a protein source. However, the substantial value of yogurt as a protein source and the additional health benefits on skeletal muscle are not fully understood. The purpose of this review is to summarize the research to date on the digestion and absorption characteristics of yogurt protein, its effect on skeletal muscle, and the contribution of lactic acid bacterial fermentation to these effects.

Synergistic Effect of Increased Total Protein Intake and Strength Training on Muscle Strength: A Dose-Response Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Protein supplementation augments muscle strength gain during resistance training. Although some studies focus on the dose-response relationship of total protein intake to muscle mass or strength, the detailed dose-response relationship between total protein intake and muscle strength increase is yet to be clarified, especially in the absence of resistance training. OBJECTIVE: We aimed to assess the detailed dose-response relationship between protein supplementation and muscle strength, with and without resistance training. DESIGN: Systematic review with meta-analysis. DATA SOURCES: PubMed and Ichushi-Web (last accessed on March 23, 2022). ELIGIBILITY CRITERIA: Randomized controlled trials investigating the effects of protein intake on muscle strength. SYNTHESIS METHODS: A random-effects model and a spline model. RESULTS: A total of 82 articles were obtained for meta-analyses, and data from 69 articles were used to create spline curves. Muscle strength increase was significantly augmented only with resistance training (MD 2.01%, 95% CI 1.09-2.93) and was not augmented if resistance training was absent (MD 0.13%, 95% CI - 1.53 to 1.79). In the dose-response analysis using a spline model, muscle strength increase with resistance training showed a dose-dependent positive association with total protein intake, which is 0.72% (95% CI 0.40-1.04%) increase in muscle strength per 0.1 g/kg body weight [BW]/d increase in total protein intake up to 1.5 g/kg BW/d, but no further gains were observed thereafter. CONCLUSION: Concurrent use of resistance training is essential for protein supplementation to improve muscle strength. This study indicates that 1.5 g/kg BW/d may be the most appropriate amount of total protein intake for maintaining and augmenting muscle strength along with resistance training.

Effects of low-dose milk protein supplementation following low-to-moderate intensity exercise training on muscle mass in healthy older adults: a randomized placebo-controlled trial.

PURPOSE: The purpose of this study was to examine whether long-term ingestion of low-dose milk protein supplementation causes a greater increase in muscle mass and strength of older adults during low-to-moderate intensity exercise training intervention than isocaloric carbohydrate. METHODS: In a randomized, double-blind, and placebo-controlled design, 122 healthy older adults (60-84 year) received either an acidified milk protein drink containing 10 g of milk protein (MILK; n = 61) or an isocaloric placebo drink (PLA; n = 61) daily throughout 6 months of body weight and medicine ball exercise training. Measurements before and after the intervention included body composition, physical performance and blood biochemistry. RESULTS: Lean body mass significantly increased in the MILK group (+ 0.54 kg, p < 0.001), but did not change in the PLA group (- 0.10 kg, p = 0.534). The increases in the MILK group were significantly greater than in the PLA group (p = 0.004). Fat mass (- 0.77 kg) and plasma uric acid levels (- 0.3 mg/dL) significantly decreased only in the MILK group (p < 0.001), with a significant group difference (p = 0.002 and p < 0.001, respectively). Most of the physical performance tests significantly improved in both groups, but no group differences were found. CONCLUSION: We conclude that low-dose milk protein supplementation (10 g of protein/day) combined with low-to-moderate intensity exercise training is associated with increased muscle mass, but not improved physical performance compared to carbohydrate combined with exercise in healthy older adults. This study was registered in the UMIN Clinical Trials Registry (UMIN000032189).

Dose-response relationship between protein intake and muscle mass increase: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Lean body mass is essential for health, yet consensus regarding the effectiveness of protein interventions in increasing lean body mass is lacking. OBJECTIVE: The aim of this systematic review was to evaluate the dose-response relationship of the effects of protein intake on lean body mass. DATA SOURCES: The PubMed and Ichushi-Web databases were searched electronically, and reference lists of the literature included here and in other meta-analyses were searched manually. STUDY SELECTION: Randomized controlled trials evaluating the effects of protein intake on lean body mass were included. DATA EXTRACTION: Two authors independently screened the abstracts; 5 reviewed the full texts. RESULTS: A total of 5402 study participants from 105 articles were included. In the multivariate spline model, the mean increase in lean body mass associated with an increase in protein intake of 0.1 g/kg of body weight per day was 0.39 kg (95%CI, 0.36-0.41) and 0.12 kg (95%CI, 0.11-0.14) below and above the total protein intake of 1.3 g/kg/d, respectively. CONCLUSIONS: These findings suggest that slightly increasing current protein intake for several months by 0.1 g/kg/d in a dose-dependent manner over a range of doses from 0.5 to 3.5 g/kg/d may increase or maintain lean body mass. SYSTEMATIC REVIEW REGISTRATION: UMIN registration number UMIN000039285.

Whey Protein Hydrolysate Increases Amino Acid Uptake, mTORC1 Signaling, and Protein Synthesis in Skeletal Muscle of Healthy Young Men in a Randomized Crossover Trial.

BACKGROUND: Muscle protein synthesis (MPS) can be stimulated by ingestion of protein sources, such as whey, casein, or soy. Protein supplementation can enhance muscle protein synthesis after exercise and may preserve skeletal muscle mass and function in aging adults. Therefore, identifying protein sources with higher anabolic potency is of high significance. OBJECTIVE: The aim of this study was to determine the anabolic potency and efficacy of a novel whey protein hydrolysate mixture (WPH) on mechanistic target of rapamycin complex 1 (mTORC1) signaling and skeletal MPS in healthy young subjects. METHODS: Ten young men (aged 28.7 ± 3.6 y, 25.2 ± 2.9 kg/m2 body mass index [BMI]) were recruited into a double-blind two-way crossover trial. Subjects were randomized to receive either 0.08 g/kg of body weight (BW) of WPH or an intact whey protein (WHEY) mixture during stable isotope infusion experiments. Fractional synthetic rate, leucine and phenylalanine kinetics, and markers of amino acid sensing were assessed as primary outcomes before and 1-3 h after protein ingestion using a repeated measures mixed model. RESULTS: Blood leucine concentration, delivery of leucine to muscle, transport of leucine from blood into muscle and intracellular muscle leucine concentration significantly increased to a similar extent 1 h after ingestion of both mixtures (P < 0.05). Phosphorylation of S6K1 (i.e. a marker of mTORC1 activation) increased equally by ∼20% 1-h postingestion (P < 0.05). Ingestion of WPH and WHEY increased mixed MPS similarly in both groups by ∼43% (P < 0.05); however, phenylalanine utilization for synthesis increased in both treatments 1-h postingestion but remained elevated 3-h postingestion only in the WPH group (P < 0.05). CONCLUSIONS: We conclude that a small dose of WPH effectively increases leucine transport into muscle, activating mTORC1 and stimulating MPS in young men. WPH anabolic potency and efficacy for promoting overall muscle protein anabolism is similar to WHEY, an intact protein source. This trial was registered at clinicaltrials.gov as NCT03313830.

Effects of whey protein hydrolysate ingestion on post-exercise muscle protein synthesis compared with intact whey protein in rats.

BACKGROUND: It is well known that ingestion of protein sources can stimulate muscle protein synthesis (MPS). The intake of whey protein is highly effective especially for accelerating MPS. Whey protein hydrolysate (WPH) can raise postprandial plasma concentration of amino acids, which impact stimulation of MPS more rapidly and highly than intact whey protein. However, it is unclear which is more effective for stimulating MPS, WPH or intact whey protein. The aim of the present study was to compare the effects of the WPH and whey protein on MPS in rats after exercise. METHODS: Rats were first subjected to a 2 h. swimming protocol. After this, in experiment 1, we evaluated time-dependent changes in the fractional synthetic rate (FSR) of the triceps muscle in Male Sprague-Dawley rats after ingestion of intact whey protein (30, 60, 90 or 120 min after ingestion). Then in experiment 2, at the time point that the results of Experiment 1 revealed postprandial FSR was highest (60 min after ingestion), we measured the FSR after ingestion of the WPH or whey protein at two different doses (0.5 or 2.0 g protein/kg body weight), or with deionized water (control), again after exercise. Plasma components and mammalian target of rapamycin (mTOR) signaling were also measured. RESULTS: In experiment 1, postprandial FSR was highest 60 min after whey protein was administered. In experiment 2, the FSR 60 min after ingestion of the WPH was higher than that of whey protein (significant treatment main effect). Moreover, at a lower dose, only the WPH ingestion caused greater MPS and phosphorylated 4E-binding protein 1 (4E-BP1) levels compared with the control group. CONCLUSION: These results indicate that ingestion of the WPH was associated with greater post-exercise MPS compared with intact whey protein, especially at lower doses.

Effects of Whey Protein Hydrolysate Ingestion on Postprandial Aminoacidemia Compared with a Free Amino Acid Mixture in Young Men.

To stimulate muscle protein synthesis, it is important to increase the plasma levels of essential amino acids (EAA), especially leucine, by ingesting proteins. Protein hydrolysate ingestion can induce postprandial hyperaminoacidemia; however, it is unclear whether protein hydrolysate is associated with higher levels of aminoacidemia compared with a free amino acid mixture when both are ingested orally. We assessed the effects of whey protein hydrolysate (WPH) ingestion on postprandial aminoacidemia, especially plasma leucine levels, compared to ingestion of a free amino acid mixture. This study was an open-label, randomized, 4 × 4 Latin square design. After 12⁻15 h of fasting, 11 healthy young men ingested the WPH (3.3, 5.0, or 7.5 g of protein) or the EAA mixture (2.5 g). Blood samples were collected before ingestion and at time points from 10 to 120 min after ingestion, and amino acids, insulin, glucose and insulin-like growth factor-1 (IGF-1) concentrations in plasma were measured. Even though the EAA mixture and 5.0 g of the WPH contained similar amounts of EAA and leucine, the WPH was associated with significantly higher plasma EAA and leucine levels. These results suggest that the WPH can induce a higher level of aminoacidemia compared with a free amino acid mixture when both are ingested orally.

Randomized trial of amino acid mixture combined with physical activity promotion for abdominal fat reduction in overweight adults.

PURPOSE: The purpose of this study was to test the efficacy of arginine, alanine, and phenylalanine mixture (A-mix) ingestion at 1,500 mg/day in combination with the promotion of physical activity for abdominal fat reduction in overweight adults. METHODS: A placebo-controlled, double-blind, parallel-group, randomized trial for 12 weeks combined with a 4-week follow-up period was conducted at a single center in Minato-ku, Tokyo, Japan, between December 2016 and May 2017. Data were analyzed between June and August 2017. The study participants were 200 overweight adults within the age range of 20-64 years. The participants were randomly assigned to the A-mix group (n=100) or a placebo group (n=100) and were administered 500 mL of test beverage containing 1,500 or 0 mg of A-mix, respectively, for 12 weeks. All participants maintained a physically active lifestyle between week 0 and week 12 through monthly sessions of physical activity. The primary outcomes were the 12-week changes in the abdominal total, subcutaneous, and visceral fat areas, as assessed by computed tomography. RESULTS: Of the 200 enrolled participants, 199 (99%) accomplished the 12-week intervention and 4-week follow-up period. The per-protocol-based analysis for 194 participants demonstrated that the abdominal total fat area decreased significantly in the A-mix group compared with that in the placebo group (difference, 10.0 cm2; 95% confidence interval [CI]: 0.4-19.6 cm2; P=0.041). Comparable outcomes were obtained for the abdominal subcutaneous fat area (difference, 7.4 cm2; 95% CI: 0.1-14.7 cm2; P=0.047). No study-related unfavorable events occurred. CONCLUSION: A-mix supplementation in combination with physical activity promotion facilitated abdominal fat reduction in overweight adults.

Post-Exercise Muscle Protein Synthesis in Rats after Ingestion of Acidified Bovine Milk Compared with Skim Milk.

Bovine milk proteins have a low absorption rate due to gastric acid-induced coagulation. Acidified milk remains liquid under acidic conditions; therefore, the absorption rate of its protein may differ from that of untreated milk. To investigate how this would affect muscle protein synthesis (MPS), we compared MPS after ingestion of acidified versus skim milk in rats. Male Sprague-Dawley rats swam for 2 h and were immediately administered acidified or skim milk, then euthanized at 30, 60, 90, and 120 min afterwards. Triceps muscle samples were excised for assessing fractional synthetic rate (FSR), plasma components, intramuscular free amino acids and mTOR signaling. The FSR in the acidified milk group was significantly higher than in the skim milk group throughout the post-ingestive period. Plasma essential amino acids, leucine, and insulin levels were significantly increased in the acidified milk group at 30 min after administration compared to the skim milk group. In addition, acidified milk ingestion was associated with greater phosphorylation of protein kinase B (Akt) and ribosomal protein S6 kinase (S6K1), and sustained phosphorylation of 4E-binding protein 1 (4E-BP1). These results indicate that compared with untreated milk, acidified milk ingestion is associated with greater stimulation of post-exercise MPS.

The effects of phenylalanine on exercise-induced fat oxidation: a preliminary, double-blind, placebo-controlled, crossover trial.

BACKGROUND: When combined with exercise, dietary amino acid (AA) supplementation is an effective method for accelerating fat mobilization. However, the effects of single AAs combined with exercise on fat oxidation remains unclear. We hypothesized that consumption of a specific amino acid, L- phenylalanine, may result in the secretion of glucagon, and when combined with exercise may promote fat oxidation. METHODS: Six healthy, active male volunteers were randomized in a crossover study to ingest either phenylalanine (3 g/dose) or placebo. Thirty minutes after ingestion each subject performed workload trials on a cycle ergometer for 1 h at 50% of maximal oxygen consumption. RESULTS: Oral intake of phenylalanine caused a significant increase in the concentrations of plasma glycerol and glucagon during exercise. The respiratory exchange ratio was also decreased significantly following ingestion of phenylalanine. CONCLUSION: These results suggested that pre-exercise supplementation of phenylalanine may stimulate whole body fat oxidation. No serious or study-related adverse events were observed. TRIAL REGISTRATION: UMIN000027502 Registered 26 May 2017. Restrospectively registered.

Dose-ranging pilot randomized trial of amino acid mixture combined with physical activity promotion for reducing abdominal fat in overweight adults.

OBJECTIVE: The objective of this study was to determine the effective dose of an amino acid mixture comprising arginine, alanine, and phenylalanine combined with physical activity promotion in reducing abdominal fat among overweight adults. METHODS: A 12-week randomized, double-blind, placebo-controlled, dose-ranging, pilot trial was conducted in Mito, Japan, from January through April 2016, and the data were analyzed from May through November 2016. The study participants were 35 overweight adults, aged 20-64 years, with no regular exercise habit. Participants were randomly assigned to high-dose (3,000 mg/d, n=9), medium-dose (1,500 mg/d, n=9), low-dose (750 mg/d, n=8), or placebo (0 mg/d, n=9) groups, and the test beverage containing the amino acid mixture or placebo was administered for 12 weeks. All participants maintained a physically active lifestyle during the study period through monthly physical activity promotion sessions and smartphone-based self-monitoring with wearable trackers. Primary outcomes were changes in abdominal total, subcutaneous, and visceral fat areas, assessed by computed tomography. RESULTS: Of the 35 enrolled participants, 32 completed the 12-week follow-up visit. The intention-to-treat analysis revealed that the changes in abdominal total fat area were -14.6 cm2 (95% confidence interval [CI], -39.6 cm2 to 10.4 cm2), -25.3 cm2 (95% CI, -71.0 cm2 to 20.3 cm2), -23.2 cm2 (95% CI, -48.0 cm2 to 1.6 cm2), and -12.5 cm2 (95% CI, -29.1 cm2 to 4.0 cm2) in the high-dose, medium-dose, low-dose, and placebo groups, respectively. Similar results were obtained for visceral and subcutaneous fat areas. No study-related adverse events were reported. CONCLUSION: Compared with placebo, a medium or low dose of the amino acid mixture may facilitate abdominal fat reduction among overweight adults. A larger randomized trial with sufficient statistical power should be implemented to validate the effectiveness of this supplement.

Combination of aerobic exercise and an arginine, alanine, and phenylalanine mixture increases fat mobilization and ketone body synthesis.

During exercise, blood levels of several hormones increase acutely. We hypothesized that consumption of a specific combination of amino acids (arginine, alanine, and phenylalanine; A-mix) may be involved in secretion of glucagon, and when combined with exercise may promote fat catabolism. Ten healthy male volunteers were randomized in a crossover study to ingest either A-mix (3 g/dose) or placebo (3 g of dextrin/dose). Thirty minutes after ingesting, each condition subsequently performed workload trials on a cycle ergometer at 50% of maximal oxygen consumption for 1 h. After oral intake of A-mix, the concentrations of plasma ketone bodies and adrenalin during and post-exercise were significantly increased. The area under the curve for glycerol and glucagon was significantly increased in the post-exercise by A-mix administration. These results suggest that pre-exercise ingestion of A-mix causes a shift of energy source from carbohydrate to fat combustion by increasing secretion of adrenalin and glucagon.

Effects of Whey, Caseinate, or Milk Protein Ingestion on Muscle Protein Synthesis after Exercise.

Whey protein (WP) is characterized as a "fast" protein and caseinate (CA) as a "slow" protein according to their digestion and absorption rates. We hypothesized that co-ingestion of milk proteins (WP and CA) may be effective for prolonging the muscle protein synthesis response compared to either protein alone. We therefore compared the effect of ingesting milk protein (MP) to either WP or CA alone on muscle protein synthesis after exercise in rats. We also compared the effects of these milk-derived proteins to a control, soy protein (SP). Male Sprague-Dawley rats swam for two hours. Immediately after exercise, one of the following four solutions was administered: WP, CA, MP, or SP. Individual rats were euthanized at designated postprandial time points and triceps muscle samples collected for measurement of the protein fractional synthesis rate (FSR). FSR tended to increase in all groups post-ingestion, although the initial peaks of FSR occurred at different times (WP, peak time = 60 min, FSR = 7.76%/day; MP, peak time = 90 min, FSR = 8.34%/day; CA, peak time = 120 min, FSR = 7.85%/day). Milk-derived proteins caused significantly greater increases (p < 0.05) in FSR compared with SP at different times (WP, 60 min; MP, 90 and 120 min; CA, 120 min). Although statistical analysis could not be performed, the calculated the area under the curve (AUC) values for FSR following this trend were: MP, 534.61; CA, 498.22; WP, 473.46; and SP, 406.18. We conclude that ingestion of MP, CA or WP causes the initial peak time in muscle protein synthesis to occur at different times (WP, fast; MP, intermediate; CA, slow) and the dairy proteins have a superior effect on muscle protein synthesis after exercise compared with SP.

Dietary supplementation with fructooligosaccharides attenuates allergic peritonitis in mice.

Fructooligosaccharides (FOS) are a prebiotic supplement, which can enhance immunological responses in the host to activate mucosal immunity probably through regulation of gastrointestinal microflora. Nonetheless, the therapeutic potential of prebiotics on allergic pathologies has not been fully elucidated. Therefore, the purpose of this study was to evaluate the preventive and therapeutic effects of dietary supplementation with FOS on a murine model of allergic peritonitis induced by ovalbumin (OVA). Male C3H/HeN mice were intraperitoneally administrated with OVA (1 µg) bi-weekly (Day 0-42, total four times) and were fed a diet containing 0 or 2.5% FOS ad libitum (Day 7-43). At Day 43, mice were killed and several parameters were evaluated. As results, supplementation with FOS alleviated OVA-related peritoneal inflammation characterized by trafficking of polymorphonuclear leukocytes such as eosinophils and neutrophils in the peritoneal cavity. Also, FOS significantly suppressed the protein level of interleukin (IL)-5 and eotaxin in the peritoneal lavage fluid elicited by OVA. In addition, a FOS-supplemented diet significantly reduced the serum allergen specific-IgG(1) level, whereas it significantly increased total IgA levels in the cecal contents as compared with a control diet in the presence of OVA. These results suggest that dietary supplementation with FOS can prevent/ameliorate allergic peritoneal inflammation induced by OVA. The efficacy can at least partially be associated with the regulation of Ig class switching and inhibition of the local expression of IL-5 and eotaxin.

Dietary soya protein intake and exercise training have an additive effect on skeletal muscle fatty acid oxidation enzyme activities and mRNA levels in rats.

Exercise training and regular physical activity increase oxidation of fat. Enhanced oxidation of fat is important for preventing lifestyle diseases such as hypertension and obesity. The aim of the present study in rats was to determine whether intake of dietary soya protein and exercise training have an additive effect on the activity and mRNA expression of enzymes involved in skeletal muscle fatty acid oxidation. Male Sprague-Dawley rats (n 32) were assigned randomly into four groups (eight rats per group) and then divided further into sedentary or exercise-trained groups fed either casein or soya protein diets. Rats in the exercise groups were trained for 2 weeks by swimming for 120 min/d, 6 d/week. Exercise training decreased hepatic triacylglycerol levels and retroperitoneal adipose tissue weight and increased skeletal muscle carnitine palmitoyltransferase 1 (CPT1) activity and mRNA expression of CPT1, beta-hydroxyacyl-CoA dehydrogenase (HAD), acyl-CoA oxidase, PPARgamma coactivator 1alpha (PGC1alpha) and PPARalpha. Soya protein significantly decreased hepatic triacylglycerol levels and epididymal adipose tissue weight and increased skeletal muscle CPT1 activity and CPT1, HAD, acyl-CoA oxidase, medium-chain acyl-CoA dehydrogenase, PGC1alpha and PPARalpha mRNA levels. Furthermore, skeletal muscle HAD activity was the highest in exercise-trained rats fed soya protein. We conclude that exercise training and soya protein intake have an important additive role on induction of PPAR pathways, leading to increased activity and mRNA expression of enzymes involved in fatty acid oxidation in skeletal muscle and reduced accumulation of body fat.

Dietary whey protein downregulates fatty acid synthesis in the liver, but upregulates it in skeletal muscle of exercise-trained rats.

OBJECTIVE: This study compared the effects of casein and whey protein as the source of dietary protein on the activity of lipogenic enzymes and mRNA levels in the liver and skeletal muscle of exercise-trained rats. METHODS: Twenty-eight male Sprague-Dawley rats were randomly assigned to one of four groups (n = 7/group). Rats were assigned to sedentary or exercise-trained groups and were fed the casein or whey protein diet. Rats in the exercise groups were trained for 2 wk using a swimming exercise for 120 min/d and 6 d/wk. RESULTS: A significant decrease in the activity of the hepatic lipogenic enzymes, glucose-6-phosphate dehydrogenase, malic enzyme, adenosine triphosphate citrate lyase, acetyl-coenzyme A carboxylase, and fatty acid synthase (FASN) was observed in rats fed whey protein compared with animals fed casein. Compared with the casein diet, the whey protein diet also lowered mRNA expression of these enzymes, except for FASN. In contrast to the findings in liver, whey protein, as compared with casein, increased skeletal muscle FASN activity and mRNA. Further, exercise training resulted in increased skeletal muscle glucose-6-phosphate dehydrogenase and FASN activity and adenosine triphosphate citrate lyase, acetyl-coenzyme A carboxylase-1, and FASN mRNA expression. CONCLUSIONS: Exercise training or whey protein may play an important role in suppressing hepatic fatty acid synthesis, thereby decreasing accumulation of body fat and stimulating the skeletal muscle to increase energy substrate as fat during prolonged exercise.

Dietary whey protein increases liver and skeletal muscle glycogen levels in exercise-trained rats.

We investigated the effect of different types of dietary protein on glycogen content in liver and skeletal muscle of exercise-trained rats. Twenty-four male Sprague-Dawley rats (approximately 100 g; n 6 per group) were divided into sedentary or exercise-trained groups with each group being fed either casein or whey protein as the source of dietary protein. Rats in the exercised groups were trained during 2 weeks using swimming exercise for 120 min/d, 6 d/week. Exercise training resulted in an increase in the skeletal muscle glycogen content. Furthermore, the whey protein group significantly increased the skeletal muscle glycogen content compared with the casein group. The increase in glycogen content in liver was significantly greater in rats fed the whey protein diet compared with those fed the casein diet. We also found that the whey protein diet increased the activity of liver glucokinase, whereas it decreased the activities of 6-phosphofructokinase and pyruvate kinase compared with the casein diet. However, hepatic total glycogen synthase activity and mRNA expression were similar with the two diets. In the skeletal muscle, whey protein decreased only 6-phosphofructokinase activity compared with casein. Total glycogen synthase activity in the skeletal muscle in the whey protein group was significantly higher than that in the casein group. The present study is the first to demonstrate that a diet based on whey protein may increase glycogen content in liver and skeletal muscle of exercise-trained rats. We also observed that whey protein regulated glycogen metabolism in these two tissues by different mechanisms.

Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans.

Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, suppresses allergic immunoglobulin responses and inflammation caused by polymorphonuclear leukocytes (PMNL) in mice. However, few placebo-controlled clinical trials have examined the efficacy and safety of polyphenolic phytochemicals for treatment of allergic inflammatory diseases in humans. The present study determined whether oral supplementation with rosmarinic acid is an effective intervention for patients with seasonal allergic rhinoconjunctivitis (SAR). In this 21-day, randomized, double-blind, age-matched, placebo-controlled parallel group study, patients with mild SAR were treated daily with extract of Perilla frutescens enriched for rosmarinic acid (200 mg [n=10] or 50 mg [n=9]) or placebo (n=10). Patients recorded symptoms daily in a diary. Profiles of infiltrating cells and concentrations of eotaxin, IL-1beta, IL-8, and histamine were measured in nasal lavage fluid. Serum IgE concentrations and routine blood tests were also examined. As compared with placebo supplementation, supplementation with extract of Perilla frutescens enriched for rosmarinic acid resulted in a significant increase in responder rates for itchy nose, watery eyes, itchy eyes, and total symptoms (P<0.05). Active treatment significantly decreased the numbers of neutrophils and eosinophils in nasal lavage fluid (P<0.05 vs. placebo). Patients reported no adverse events, and no significant abnormalities were detected in routine blood tests. In conclusion, extract of Perilla frutescens enriched for rosmarinic acid can be an effective intervention for mild SAR at least partly through inhibition of PMNL infiltration into the nostrils. Use of this alternative treatment for SAR might reduce treatment costs for allergic diseases.

Anti-inflammatory and anti-allergic effect of rosmarinic acid (RA); inhibition of seasonal allergic rhinoconjunctivitis (SAR) and its mechanism.

The present study was undertaken to determine whether oral supplementation with rosmarinic acid (RA) is an effective intervention for patients with SAR. In addition, the anti-inflammatory mechanism of RA also estimated in the ear edema models. CLINICAL TRIAL: Patients were treated daily with RA (200 mg or 50 mg) or placebo for 21 days. Patients recorded symptoms daily and profiles of infiltrating cells and concentration of cytokines were measured in nasal lavage fluid. Compared to placebo, supplementation with RA resulted in a significant decrease in responder rates for each symptom. RA also significantly decreased the numbers of neutrophils and eosinophils in nasal lavage fluid. ANIMAL STUDY: Topical application RA showed anti-inflammatory activity 5-hours after 12-tetradecanoylphorbol 13-acetate (TPA) treatment with marked inhibition of neutrophil infiltration. Up regulation of ICAM-1, VCAM-1 cyclooxygenase-2 (COX-2), KC and MIP-2 by TPA were markedly reduced by pre-treatment with extract of perilla (PE) or RA. Reactive oxygen radical production detected as thiobarbituric acid reactive substance (TBARS), lipid peroxide (LPO) and 8-hydroxy-2'deoxyguanosine (8OH-dG), by double treatment of TPA was reduced by pretreatment with PE or RA. RA is an effective intervention for SAR that is mediated by inhibition of PMNL infiltration. This effect of RA is due to two independent mechanisms: inhibition of the inflammatory response and scavenging of ROS.

Rosmarinic acid inhibits lung injury induced by diesel exhaust particles.

Epidemiological and experimental studies have suggested that diesel exhaust particles (DEP) may be involved in recent increases in lung diseases. DEP has been shown to generate reactive oxygen species. Intratracheal instillation of DEP induces lung inflammation and edema in mice. Rosmarinic acid is a naturally occurring polyphenol with antioxidative and anti-inflammatory activities. We investigated the effects of rosmarinic acid on lung injury induced by intratracheal administration of DEP (500 microg/body) in mice. Oral supplementation with administration of rosmarinic acid (2 mg/body for 3 d) inhibited DEP-induced lung injury, which was characterized by neutrophil sequestration and interstitial edema. DEP enhanced the lung expression of keratinocyte chemoattractant (KC), interleukin-1beta, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1alpha, which was inhibited by treatment with rosmarinic acid. DEP enhanced expression of iNOS mRNA and formation of nitrotyrosine and 8-OHdG in the lung, which was also inhibited by rosmarinic acid. These results suggest that rosmarinic acid inhibits DEP-induced lung injury by the reduction of proinflammatory molecule expression. Antioxidative activities of rosmarinic acid may also contribute to its protective effects.