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Ursolic acid has no additional effect on muscle strength and mass in active men undergoing a high-protein diet and resistance training: a double-blind, placebo-controlled trial
Abstract
Background
Ursolic acid (UA) is thought to have an anabolic effect on muscle mass in humans. This study sought to compare the effects of UA and a placebo on muscle strength and mass in young men undergoing resistance training (RT) and consuming a high-protein diet.
Methods
A clinical, double-blind, placebo-controlled trial was conducted for 8 weeks. The Control+RT group (CON n = 12) received 400 mg/d of placebo, and the UA+RT group (UA n = 10) received 400 mg/d of UA. Both groups ingested ∼1.6 g/kg of protein and performed the same RT program. Pre- and post-intervention, both groups were evaluated for anthropometric measures, body composition, food intake and muscle strength.
Results
Food intake remained unchanged throughout the study. Both groups showed significant increases in body weight (CON Δ: 2.12 ± 0.47 kg, p = 0.001 vs. UA Δ: 2.24 ± 0.67 kg, p = 0.009), body mass index (BMI) (CON Δ: 0.69 ± 0.15 kg/m², p = 0.001 vs. UA Δ: 0.75 ± 0.23, p = 0.011) and thigh circumference (CON Δ: 1.50 ± 0.36, p = 0.002 vs. UA Δ: 2.46 ± 0.50 cm, p = 0.003 vs. UA 1.84 ± 0.82 cm, p = 0.001), with differences between them. There was no difference in the arm, waist and hip circumferences. Both groups showed increases in muscle mass (CON Δ: 1.12 ± 0.26, p = 0.001 vs. UA Δ: 1.08 ± 0.28 kg, p = 0.004), but there was no significant difference between them. Additionally, there were significant increases in the one repetition maximum test in the bench press and in the 10-repetition maximum test in the knee extension (CON Δ: 5.00 ± 2.09, p = 0.036 vs. UA Δ: 7.8 ± 1.87, p = 0.340 and CON Δ: 3.58 ± 1.15, p = 0.010 vs. UA Δ: 1.20 ± 0.72, p = 0.133), respectively, with no difference between them.
Conclusions
Ursolic acid had no synergic effect on muscle strength and mass in response to RT in physically active men consuming a high-protein diet.
Brazilian Clinical Trials Registry (ReBEC)
RBR-76tbqs.
... In murine splenic lymphocytes stimulated with lipopolysaccharides (LPS) and treated with UA, was found lower secretion of IL-2, IL-4, IL-6 and TNF-α cytokines. However, no human studies have investigated the cytokine profile during the RT and UA consumption, including our previous study using the same individuals where we did not find gain in muscle mass with UA supplementation in physically active men consuming a high-protein diet and RT [14]. ...
... The inclusion criteria were healthy young men aged 18-35 years, body mass index (BMI) between 18.5 and 29 kg/m 2 , with an average protein intake of 1.6 g/kg without supplementation and who had been physically active in the last 6 months for at least 150 min per week. Were excluded participants who reported the use of any type of supplements; smokers; and those who had chronic diseases, as previously described [14]. During the study, participants were instructed to perform training three times a week in the afternoon and to suspend other physical activities they had performed before the study. ...
... As reported in our previous publication [14] with the same sample group, the software G*Power®, version 3.1.9.2, was used to calculate the ANOVA a priori test for repeated measures with two-group and time interactions (5% alpha error and 0.85 power), resulting in a minimum total sample of 16 participants. That way, assuming 20% of loss, this study was conducted with 27 subjects. ...
Ursolic acid (UA) is a natural compound that shows anti-inflammatory actions. However, no human studies have investigated the cytokine profile during the RT and UA consumption. The purpose of this study was to verify if UA is able to potentiate the anti-inflammatory activity after RT, reflecting in the reduction of blood inflammatory markers in healthy men. Twenty-seven participants were allocated to two groups: control (CON) (n = 13) and UA (n = 14). For 8 weeks, each group performed RT and consumed capsules containing a placebo (400 mg/day) or UA (400 mg/day). Serum cytokine concentrations were evaluated before and after the training period. There was no difference in the serum cytokine concentrations of TNF-α, IL-10 and IL-6 (p > 0.05). In conclusion, UA supplementation for 8 weeks was not able to change the blood TNF-α, IL-10, and IL-6 concentrations in healthy men undergoing RT. However, further studies are warranted to investigate other inflammatory markers.
... What is more, Lobo et al. assessed the impact of UA on muscle strength and body mass gain in active men (18-35 years-old) on a high-protein diet for 8 weeks. They stated that an isolated UA dosage of 400 mg/d did not provide any beneficial effects compared to the placebo group [96]. Interestingly, Church et al. demonstrated on nine physically active men that consuming 3 g of UA before resistance exercise does not affect the Akt/mTORC1 signaling pathway or serum IGF-1 and insulin hormones concentrations. ...
... This characteristic may also explain inconsistent results in the abovementioned studies. Based on the above research, it is worth mentioning that oral administration of UA in humans was welltolerated, and adverse effects did not occur or were not statistically significant [94][95][96][97]. ...
Ursolic acid (UA) is a natural pentacyclic triterpenoid found in a number of plants such as apples, thyme, oregano, hawthorn and others. Several in vitro and in vivo studies have presented its anti-inflammatory and anti-apoptotic properties. The inhibition of NF-κB-mediated inflammatory pathways and the increased scavenging of reactive oxygen species (ROS) in numerous ways seem to be the most beneficial effects of UA. In mice and rats, administration of UA appears to slow down the development of cardiovascular diseases (CVDs), especially atherosclerosis and cardiac fibrosis. Upregulation of endothelial-type nitric oxide synthase (eNOS) and cystathionine-λ-lyase (CSE) by UA may suggest its vasorelaxant property. Inhibition of metalloproteinases activity by UA may contribute to better outcomes in aneurysms management. UA influence on lipid and glucose metabolism remains inconsistent, and additional studies are essential to verify its efficacy. Furthermore, UA derivatives appear to have a beneficial impact on the cardiovascular system. This review aims to summarize recent findings on beneficial effects of UA that may make it a promising candidate for clinical trials for the management of CVDs.
... It is popular as a weight loss and muscle building supplement, albeit, without any proper scientific data that could support these uses; on the contrary, a study has just shown that ursolic acid (1) does not offer any additional effects on muscle strength and mass in active men. 19 In a recent study, Zhang et al. 20 have shown that ursolic acid could be useful in immunomodulatory therapies for multiple sclerosis, while it was found to improve intestinal damage and bacterial dysbiosis in liver fibrosis mice. 21 Although in the present study it has been shown that the cytotoxicity of ursolic acid (1) against various cancer cells could be mediated through the damage of plasma membrane, there are several other mechanisms implicated to its anticancer potential. ...
Arbutus pavarii Pamp. (Fam. Ericaceae), an endemic Libyan medicinal plant, is commonly known as "Shmeri", "Shmar" or "Libyan Strawberry", and almost exclusively found in the Al-Jabel Al-Akhdar mountainous region in Libya. This plant is a forage species for honeybees and thus, is important for honey production. A. pavarii has long been used in Libyan traditional medicine to treat both gastritis and kidney diseases. Previous limited phytochemical studies on this plant furnished the presence of simple phenolics like arbutin and gallic acid, and polyphenolics including flavonoids and tannins, for example, apigenin, epicatechin, hesperidin, kaempferol, naringin, quercetin and rutin, as well as some triterpenes and sterols. This paper describes, for the very first time, a cytotoxicity assay-guided isolation of the major active compound from the methanol extract of the leaves of A. pavarii, and its identification as ursolic acid (1) by comprehensive spectroscopic analyses.
... However, it significantly increased righthand grip strength in female individuals (p=0.047) as compared to the control group (Cho et al., 2016), while in another study ursolic acid did not support insulin resistance training in physically active men on a high protein diet. Also, it didn't show any effect on IGF-1, protein kinase levels, and mTORC1 pathway (Lobo et al., 2021). On contrary, decreased body mass index and increased insulin sensitivity have been observed in patients with metabolic syndrome compared to calcined magnesia supplemented individuals (Ramírez-Rodríguez et al., 2017). ...
The skeletal muscle (SkM) is the largest organ, which plays a vital role in controlling musculature, locomotion, body heat regulation, physical strength, and metabolism of the body. A sedentary lifestyle, aging, cachexia, denervation, immobilization, etc. Can lead to an imbalance between protein synthesis and degradation, which is further responsible for SkM atrophy (SmA). To date, the understanding of the mechanism of SkM mass loss is limited which also restricted the number of drugs to treat SmA. Thus, there is an urgent need to develop novel approaches to regulate muscle homeostasis. Presently, some natural products attained immense attraction to regulate SkM homeostasis. The natural products, i.e., polyphenols (resveratrol, curcumin), terpenoids (ursolic acid, tanshinone IIA, celastrol), flavonoids, alkaloids (tomatidine, magnoflorine), vitamin D, etc. exhibit strong potential against SmA. Some of these natural products have been reported to have equivalent potential to standard treatments to prevent body lean mass loss. Indeed, owing to the large complexity, diversity, and slow absorption rate of bioactive compounds made their usage quite challenging. Moreover, the use of natural products is controversial due to their partially known or elusive mechanism of action. Therefore, the present review summarizes various experimental and clinical evidence of some important bioactive compounds that shall help in the development of novel strategies to counteract SmA elicited by various causes.
... In a clinical trial, healthy volunteers and patients with solid tumors were treated with a single dose of UA entrapped in liposomes by the intravenous route; although low and mild doses were safe to volunteers, high doses of the formulation induce several side effects, including the elevation of hepatic enzymes [39]. On the other hand, it has been demonstrated that UA has been safely used as a daily dietary supplement, without toxic events [40][41][42]. It is worth remembering that UA is naturally synthesized by different fruits and vegetables present in the human diet [43]; therefore, UA toxicity may be related to the dosage, formulation, duration of treatment and route of administration. ...
Ursolic acid, a triterpene produced by plants, displayed leishmanicidal activity in vitro and in vivo; however, the low solubility of this triterpene limits its efficacy. To increase the activity of ursolic acid (UA), this triterpene was entrapped in nanostructured lipid carriers (UA-NLC), physical-chemical parameters were estimated, the toxicity was assayed in healthy golden hamsters, and the efficacy of UA-NLC was studied in experimental visceral leishmanisis. UA-NLC exhibited a spherical shape with a smooth surface with a size of 266 nm. UA-NLC displayed low polydispersity (PDI = 0.18) and good colloidal stability (−29.26 mV). Hamsters treated with UA-NLC did not present morphological changes in visceral organs, and the levels of AST, ALT, urea and creatinine were normal. Animals infected with Leishmania (Leishmania) infantum and treated with UA-NLC showed lower parasitism than the infected controls, animals treated with UA or Amphotericin B (AmB). The therapeutic activity of UA-NLC was associated with the increase in a protective immune response, and it was associated with a high degree of spleen and liver preservation, and the normalization of hepatic and renal functions. These data indicate that the use of lipid nanoparticles as UA carriers can be an interesting strategy for the treatment of leishmaniasis.
Sarcopenia is a geriatric condition characterized by a progressive loss of skeletal muscle mass and strength, with an increased risk of adverse health outcomes (e.g., falls, disability, institutionalization, reduced quality of life, mortality). Pharmacological remedies are currently unavailable for preventing the development of sarcopenia, halting its progression, or impeding its negative health outcomes. The most effective strategies to contrast sarcopenia rely on the adoption of healthier lifestyle behaviors, including adherence to high-quality diets and regular physical activity. In this review, the role of nutrition in the prevention and management of sarcopenia is summarized. Special attention is given to current "blockbuster" dietary regimes and agents used to counteract age-related muscle wasting, together with their putative mechanisms of action. Issues related to the design and implementation of effective nutritional strategies are discussed, with a focus on unanswered questions on the most appropriate timing of nutritional interventions to preserve muscle health and function into old age. A brief description is also provided on new technologies that can facilitate the development and implementation of personalized nutrition plans to contrast sarcopenia.
Natural bioactive compound, Ursolic acid (UA), plus different types of exercise may exert the action on glycemic control, leading to clinical benefits in the prevention and treatment of aging/diabetes-associated complications. So, this study examined the effects of eight weeks combination of 250 mg of UA per day per kilogram of body weight of rat as well as resistance/endurance training on miR-133a expression across serum, bone marrow, skeletal muscle, and Connexin 43 (Cx43)-Runt-related transcription factor 2 (Runx2) signaling axis in high-fat diet and low-dose streptozotocin-induced T2D (here, HFD/STZ-induced T2D). The study was conducted on 56 male Wistar rats (427 ± 44 g, 21 months old), having HFD/STZ-induced T2D randomly assigned into 7 groups of 8 including (1) sedentary non-diabetic old rats (C); (2) sedentary type 2 diabetes animal model (D); (3) sedentary type 2 diabetes animal model + UA (DU); (4) endurance-trained type 2 diabetes animal model (DE); (5) resistance-trained type 2 diabetes animal model (DR); (6) endurance-trained type 2 diabetes animal model + UA (DEU); and (7) resistance-trained type 2 diabetes animal model + UA (DRU). Resistance training included a model of eight weeks of ladder resistance training at 60-80% maximal voluntary carrying capacity (MVCC) for five days/week. Treadmill endurance exercise protocol included eight weeks of repetitive bouts of low-/high-intensity training with 30%-40% and 60%-75% maximal running speed for five days/week, respectively. UA Supplementary groups were treated with 500 mg of UA per kg of high-fat diet per day. The results revealed significant supplement and exercise interaction effects for the BM miR-133a (p = 0.001), the bone marrow Runx2 (p = 0.002), but not the serum miR-133a (p = 0.517), the skeletal muscle miR-133a (p = 0.097) and the Cx43 (p = 0.632). In conclusion, only eight weeks of resistance-type exercise could affect miR-133a profile in muscles and osteoblast differentiation biomarker RUNX2 in aged T2D model of rats. 250 mg of UA per kilogram of body weight rat per day was administered orally, less than the sufficient dose for biological and physiological impacts on osteoblast differentiation biomarkers in aged T2D model of rats following eight weeks.
Sarcopenia is a condition in which muscle mass, strength, and performance decrease with age. It is associated with chronic diseases such as diabetes, cardiovascular disease, and hypertension, and contributes to an increase in mortality. Because managing sarcopenia is critical for maintaining good health and quality of life for the elderly, the condition has sparked concern among many researchers. To counteract sarcopenia, intake of protein is an important factor, while a lack of either protein or vitamin D is a major cause of sarcopenia. In addition, essential amino acids, leucine, βhydroxy β-methylbutyrate (HMB), creatine, and citrulline are used as supplements for muscle health and are suggested as alternatives for controlling sarcopenia. There are many studies on such proteins and supplements, but it is necessary to actually organize the types, amounts, and methods by which proteins and supplements should be consumed to inhibit sarcopenia. In this study, the efficacy of proteins and supplements for controlling sarcopenia according to human clinical studies is summarized to provide suggestions about how the elderly may consume proteins, amino acids, and other supplements.
Sarcopenia is characterized by a gradual slowing of movement due to loss of muscle mass and quality, loss of power and strength, increased risk of injury from falls, and often frailty. In this article, we focus on recent advances in nutritional approaches to control sarcopenia. Because nutritional studies in humans are rather limited, this article includes many results from nutritional studies in mammals. The combination of supplements containing amino acids and resistance training is the gold standard for preventing sarcopenia. Protein (amino acid) supplements alone do not have a significant effect on muscle strength or muscle mass in sarcopenia. Tea catechins, soy isoflavones, and ursolic acid are interesting candidates to combat sarcopenia, but both more systematic basic research on this treatment and, of course, clinical studies in humans are needed. Mild caloric restriction (CR, 15–25%) may also be effective against age-related muscle atrophy in humans.
Background & Aims
Ursolic acid (UA) supplementation may have therapeutic effects on metabolic syndrome (MetS). Therefore, this study aimed to investigate the effects of UA supplementation associated with a combined exercise program on MetS components in postmenopausal women.
Methods
Twenty-six women (61 ± 7 years) were randomized into two groups: UA (n=13) and placebo (PLA, n=13). Both groups followed a combined exercise program for 8 weeks (twice a week; ∼60 min at moderate intensity) associated with either UA (450 mg/day) or placebo supplementation. Before and post-intervention, waist circumference (primary outcome), resting blood pressure, fasting blood analyses, body composition and physical function (secondary outcomes) were evaluated.
Results
Greater changes in the absolute (mean difference: 1.8 kgf, 95% CI 0.3, 3.2) and relative (0.03 kgf/kg, 95% CI 0.01, 0.05) handgrip strength was observed for the UA group compared with PLA. However, no significant effects between groups were observed for waist circumference and other secondary outcomes. Furthermore, remission of MetS (according to the NCEP ATP III criteria) occurred in 38.5% of the participants in both groups.
Conclusions
The UA supplementation did not promote additional MetS profile improvement after 8 weeks of free-living intervention. However, our data indicated that UA resulted in a higher response on handgrip strength than did placebo in postmenopausal women, but further long-term studies are needed.
Trial registration
Brazilian Registry of Clinical Trials (ensaiosclinicos.gov.br): number RBR-276rrt.
Background
The objective of the present study was to compare the effects of equal-volume resistance training (RT) performed with different training frequencies on muscle size and strength in trained young men.
Methods
Sixteen men with at least one year of RT experience were divided into two groups, G1 and G2, that trained each muscle group once and twice a week, respectively, for 10 weeks. Elbow flexor muscle thickness (MT) was measured using a B-Mode ultrasound and concentric peak torque of elbow extensors and flexors were assessed by an isokinetic dynamometer.
Results
ANOVA did not reveal group by time interactions for any variable, indicating no difference between groups for the changes in MT or PT of elbow flexors and extensors. Notwithstanding, MT of elbow flexors increased significantly (3.1%, P < 0.05) only in G1. PT of elbow flexors and extensors did not increase significantly for any group.
Discussion
The present study suggest that there were no differences in the results promoted by equal-volume resistance training performed once or twice a week on upper body muscle strength in trained men. Only the group performing one session per week significantly increased the MT of their elbow flexors. However, with either once or twice a week training, adaptations appear largely minimal in previously trained males.
ABSTRACT
Background & Aims: The Body Adiposity Index (BAI) is an anthropometric measure developed to estimate body composition in field settings. Although this novel measure has been validated against clinical measures of adiposity (%Fat), the relative accuracy of other anthropometric measures, such as Body Mass Index (BMI), and waist circumference (WC), have not been assessed in comparison to the BAI using a 4-compartment (4C) model. Purpose: The primary aim of this study was to examine the association between BMI, WC, BAI, and %Fat in young adults, and determine the relative accuracy of each anthropometric measure when predicting %Fat. Methods: BMI, WC, and BAI were assessed in a sample of young adults (n=188, 48.4% female, 21.8±4.8 years). %Fat assessed using the 4C model was derived from underwater weighing for body density, dual-energy X-ray absorptiometry for bone mineral content, and bioimpedance spectroscopy for total body water. Bivariate associations were assessed using Pearson’s r, with the relative accuracy of each measure assessed using multivariate linear regression and compared using Akaike’s information criterion, R2 and ∆R2 statistics. Results: BMI, WC, and BAI were associated with %Fat (r=0.192, 0.194, and 0.668, respectively, all p<.01). WC and BAI collectively explained 46.3% of the variation in %Fat, and removing BAI significantly reduced model fit (p<.001). When stratified by sex, BAI provided greater accuracy when predicting %Fat beyond WC in men (∆R2=2.6%, p=.022), but not women (∆R2=2.1%, p=.078). Conclusion: WC and BAI are more strongly associated with %Fat as measured by the 4C model than BMI in young adults.
Objective
We performed a systematic review, meta-analysis and meta-regression to determine if dietary protein supplementation augments resistance exercise training (RET)-induced gains in muscle mass and strength.
Data sources
A systematic search of Medline, Embase, CINAHL and SportDiscus.
Eligibility criteria
Only randomised controlled trials with RET ≥6 weeks in duration and dietary protein supplementation.
Design
Random-effects meta-analyses and meta-regressions with four a priori determined covariates. Two-phase break point analysis was used to determine the relationship between total protein intake and changes in fat-free mass (FFM).
Results
Data from 49 studies with 1863 participants showed that dietary protein supplementation significantly (all p<0.05) increased changes (means (95% CI)) in: strength—one-repetition-maximum (2.49 kg (0.64, 4.33)), FFM (0.30 kg (0.09, 0.52)) and muscle size—muscle fibre cross-sectional area (CSA; 310 µm² (51, 570)) and mid-femur CSA (7.2 mm² (0.20, 14.30)) during periods of prolonged RET. The impact of protein supplementation on gains in FFM was reduced with increasing age (−0.01 kg (−0.02,–0.00), p=0.002) and was more effective in resistance-trained individuals (0.75 kg (0.09, 1.40), p=0.03). Protein supplementation beyond total protein intakes of 1.62 g/kg/day resulted in no further RET-induced gains in FFM.
Summary/conclusion
Dietary protein supplementation significantly enhanced changes in muscle strength and size during prolonged RET in healthy adults. Increasing age reduces and training experience increases the efficacy of protein supplementation during RET. With protein supplementation, protein intakes at amounts greater than ~1.6 g/kg/day do not further contribute RET-induced gains in FFM.
This systematic review aimed at addressing the ursolic acid actions as an adjunctive treatment of the obesity-mediated metabolic abnormalities. To explore our aims, we used the literature search including clinical and animal studies using the Medline and Google Scholar (up to December 2015). Out of 63 screened studies, 17 presented eligibility criteria, such as the use of ursolic acid on adiposity, energy expenditure and skeletal muscle mass in mice and humans. In the literature, we found that several physiological and molecular mechanisms are implicated in the effects of ursolic acid on obesity, energy expenditure, hepatic steatosis, skeletal muscle mass loss and physical fitness, such as (1) increase of thermogenesis by modulation adipocyte transcription factors, activation of 5' adenosine monophosphate-activated protein kinase and overexpression of the uncoupling protein 1 thermogenic marker; (2) enhancement of skeletal muscle mass by activation in bloodstream growth hormone and insulin-like growth factor-1 concentrations secretion, as well as in the activation of mammalian target of rapamycin and inhibition of ring-finger protein-1; and (3) improvement of physical fitness by skeletal muscle proliferator-activated receptor gamma co-activator alpha and sirtuin 1 expression. Therefore, supplementation with ursolic acid may be an adjunctive therapy for prevention and treatment of obesity-mediated and muscle mass-mediated metabolic consequences.
Prior resistance training (RT) recommendations and position stands have discussed variables that can be manipulated when producing RT interventions. However, one variable that has received little discussion is set end points (i.e. the end point of a set of repetitions). Set end points in RT are often considered to be proximity to momentary failure and are thought to be a primary variable determining effort in RT. Further, there has been ambiguity in use and definition of terminology that has created issues in interpretation of research findings. The purpose of this paper is to: 1) provide an overview of the ambiguity in historical terminology around set end points; 2) propose a clearer set of definitions related to set end points; and 3) highlight the issues created by poor terminology and definitions. It is hoped this might permit greater clarity in reporting, interpretation, and application of RT interventions for researchers and practitioners.
Ursolic acid (UA) is the major active component of the loquat leaf extract (LLE) and several previous studies have indicated that UA may have the ability to prevent skeletal muscle atrophy. Therefore, we conducted a randomized, double-blind, and placebo-controlled study to investigate the effects of the LLE on muscle strength, muscle mass, muscle function, and metabolic markers in healthy adults; the safety of the compound was also evaluated. We examined the peak torque/body weight at 60°/s knee extension, handgrip strength, skeletal muscle mass, physical performance, and metabolic parameters at baseline, as well as after 4 and 12 weeks of intervention. Either 500 mg of LLE (50.94 mg of UA) or a placebo was administered to fifty-four healthy adults each day for 12 weeks; no differences in muscle strength, muscle mass, and physical performance were observed between the two groups. However, the right-handgrip strength of female subjects in the LLE group was found to be significantly better than that of subjects in the control group ( P=0.047 ). Further studies are required to determine the optimal dose and duration of LLE supplementation to confirm the first-stage study results for clinical application. ClinicalTrials.gov Identifier is NCT02401113 .
Resistance exercises can be considered to be multi-joint (MJ) or single-joint (SJ) in nature. Many strength coaches, trainers, and trainees believe that adding SJ exercises to a resistance training (RT) program may be required to optimize muscular size and strength. However, given that lack of time is a frequently cited barrier to exercise adoption, the time commitment resulting from these recommendations may not be convenient for many people. Therefore, it is important to find strategies that reduce the time commitment without negatively affecting results. The aim of this review was to analyze and discuss the present body of literature considering the acute responses to and long-term adaptations resulting from SJ and MJ exercise selection. Studies were deemed eligible for inclusion if they were experimental studies comparing the effects of MJ, SJ, or MJ ? SJ on dependent variables; studies were excluded if they were reviews or abstracts only, if they involved clinical populations or persons with articular or musculoskeletal problems, or if the RT intervention was confounded by other factors. Taking these factors into account, a total of 23 studies were included. For the upper and lower limbs, analysis of surface electromyographic (sEMG) activation suggests that there are no differences between SJ and MJ exercises when comparing the prime movers. However, evidence is contrasting when considering the trunk extensor musculature. Only one study directly compared the effects of MJ and SJ on muscle recovery and the results suggest that SJ exercises resulted in increased muscle fatigue and soreness. Long-term studies comparing increases in muscle size and strength in the upper limbs reported no difference between SJ and MJ exercises and no additional effects when SJ exercises were included in an MJ exercise program. For the lumbar extensors, the studies reviewed tend to support the view that this muscle group may benefit from SJ exercise. People performing RT may not need to include SJ exercises in their program to obtain equivalent results in terms of muscle activation and long-term adaptations such as hypertrophy and strength. SJ exercises may only be necessary to strengthen lumbar extensors and to correct muscular imbalances.
Ursolic acid is a lipophilic pentacyclic triterpenoid found in many fruits and herbs and is used in several herbal folk medicines for diabetes. In this study, we evaluated the effects of apple pomace extract (APE; ursolic acid content, 183 mg/g) on skeletal muscle atrophy. To examine APE therapeutic potential in muscle atrophy, we investigated APE effects on the expression of biomarkers associated with muscle atrophy and hypertrophy. We found that APE inhibited atrophy, while inducing hypertrophy in C2C12 myotubes by decreasing the expression of atrophy-related genes and increasing the expression of hypertrophy-associated genes. The in vivo experiments using mice fed a diet with or without APE showed that APE intake increased skeletal muscle mass, as well as grip strength and exercise capacity. In addition, APE significantly improved endurance in the mice, as evidenced by increased exhaustive running time and muscle weight, and reduced the expression of the genes involved in the development of muscle atrophy. APE also decreased the concentration of serum lactate and lactate dehydrogenase, inorganic phosphate, and creatinine, the indicators of accumulated fatigue and exercise-induced stress. These results suggest that APE may be useful as an ergogenic functional food or dietary supplement.
A main characteristic of aging is the debilitating, progressive and generalized impairment of biological functions, resulting in an increased vulnerability to disease and death. Skeletal muscle comprises approximately 40% of the human body; thus, it is the most abundant tissue. At the age of 30 onwards, 0.5‑1% of human muscle mass is lost each year, with a marked acceleration in the rate of decline after the age of 65. Thus, novel strategies that effectively attenuate skeletal muscle loss and enhance muscle function are required to improve the quality of life of older subjects. The aim of the present study was to determine whether loquat (Eriobotrya japonica) leaf extract (LE) can prevent the loss of skeletal muscle function in aged rats. Young (5-month-old) and aged (18‑19-month-old) rats were fed LE (50 mg/kg/day) for 35 days and the changes in muscle mass and strength were evaluated. The age‑associated loss of grip strength was attenuated, and muscle mass and muscle creatine kinase (CK) activity were enhanced following the administration of LE. Histochemical analysis also revealed that LE abrogated the age‑associated decrease in cross‑sectional area (CSA) and decreased the amount of connective tissue in the muscle of aged rats. To investigate the mode of action of LE, C2C12 murine myoblasts were used to evaluate the myogenic potential of LE. The expression levels of myogenic proteins (MyoD and myogenin) and functional myosin heavy chain (MyHC) were measured by western blot analysis. LE enhanced MyoD, myogenin and MyHC expression. The changes in the expression of myogenic genes corresponded with an increase in the activity of CK, a myogenic differentiation marker. Finally, LE activated the Akt/mammalian target of rapamycin (mTOR) signaling pathway, which is involved in muscle protein synthesis during myogenesis. These findings suggest that LE attenuates sarcopenia by promoting myogenic differentiation and subsequently promoting muscle protein synthesis.
In the Orient, loquat (Eriobotrya japonica) extract (LE) is widely used in teas, food and folk medicines. The leaves of the loquat tree have been used for generations to treat chronic bronchitis, coughs, phlegm production, high fever and gastroenteric disorders. One of the major active components of loquat leaves is ursolic acid, which was recently investigated in the context of preventing muscle atrophy. The present study investigated the therapeutic potential of LE on dexamethasone‑induced muscle atrophy in rats. Daily intraperitoneal injections of dexamethasone caused muscle atrophy and evidence of muscle atrophy prevention by LE was demonstrated using various assays. In particular, dexamethasone‑induced grip strength loss was alleviated by LE and the increase in serum creatine kinase activity, a surrogate marker of muscle damage, caused by dexamethasone injection was reduced by LE. Western blot analysis and immunoprecipitation demonstrated that dexamethasone markedly increased the protein expression levels of muscle ring finger 1 (MuRF1), which causes the ubiquitination and degradation of myosin heavy chain (MyHC), and decreased the protein expression levels of MyHC as well as increased the ubiquitinated MyHC to MyHC ratio. However, LE reduced the dexamethasone‑induced protein expression levels of MuRF1 and ubiquitinated MyHC. Additional experiments revealed that LE supplementation inhibited the nuclear translocation of FoxO1 induced by dexamethasone. These findings suggested that LE prevented dexamethasone‑induced muscle atrophy by regulating the FoxO1 transcription factor and subsequently the expression of MuRF1.
Ursolic acid (UA), a type of pentacyclic triterpenoid carboxylic acid purified from natural plants, can promote skeletal muscle development. We measured the effect of resistance training (RT) with/without UA on skeletal muscle development and related factors in men. Sixteen healthy male participants (age, 29.37±5.14 years; body mass index=27.13±2.16 kg/m(2)) were randomly assigned to RT (n=7) or RT with UA (RT+UA, n=9) groups. Both groups completed 8 weeks of intervention consisting of 5 sets of 26 exercises, with 10~15 repetitions at 60~80% of 1 repetition maximum and a 60~90-s rest interval between sets, performed 6 times/week. UA or placebo was orally ingested as 1 capsule 3 times/day for 8 weeks. The following factors were measured pre-and post-intervention: body composition, insulin, insulin-like growth factor-1 (IGF-1), irisin, and skeletal muscle strength. Body fat percentage was significantly decreased (p<0.001) in the RT+UA group, despite body weight, body mass index, lean body mass, glucose, and insulin levels remaining unchanged. IGF-1 and irisin were significantly increased compared with baseline levels in the RT+UA group (p<0.05). Maximal right and left extension (p<0.01), right flexion (p<0.05), and left flexion (p<0.001) were significantly increased compared with baseline levels in the RT+UA group. These findings suggest that UA-induced elevation of serum irisin may be useful as an agent for the enhancement of skeletal muscle strength during RT.
Ursolic acid (UA), a pentacyclic triterpene acid found in apple peels (Malus domestica, Borkh, Rosaceae), has a large spectrum of pharmacological effects. However, the vegetal matrix usually produces highly viscous and poorly soluble extracts that hamper the isolation of this compound. To overcome this problem, the crude EtOH-AcOEt extract of commercial apple peels was exhaustively treated with diazomethane, after which methyl ursolate (MU) was purified by column chromatography and characterized spectrometrically. The anti-inflammatory effects of UA and MU (50 mg/kg) were analyzed by zymosan-induced paw edema, pleurisy and in an experimental arthritis model. After 4 h of treatment with UA and MU, paw edema was reduced by 46 and 44 %, respectively. Both UA and MU inhibited protein extravasation into the thoracic cavity; tibio-femoral edema by 40 and 48 %, respectively; and leukocyte influx into the synovial cavity after 6 h by 52 and 73 %, respectively. Additionally, both UA and MU decreased the levels of mediators related to synovial inflammation, such as KC/CXCL-1 levels by 95 and 90 %, TNF-α levels by 76 and 71 %, and IL-1β levels by 57 and 53 %, respectively. Both the compounds were equally effective when assayed in different inflammatory models, including experimental arthritis. Hence, MU may be considered to be a useful anti-inflammatory derivative to overcome the inherent poor solubility of UA for formulating pharmaceutical products.
Aim:
The purpose of the present study was to compare the effects of equal-volume resistance training (RT) performed once or twice a week on muscle mass and strength of the elbow flexors in untrained young men.
Methods:
Thirty men (23 ± 3 years) without previous resistance training experience were divided into two groups: Group 1 (G1) trained each muscle group only once a week and group 2 (G2) trained each muscle twice a week during 10 weeks. Baseline and 10 weeks post-test elbow flexors muscle thickness (MT) were measured using a B-Mode ultrasound. Peak torque (PT) was assessed by an isokinetic dynamometer before and after the training program.
Results:
Elbow flexors MT increased significantly (P<0.05) from 31.70 ± 3.31 to 33.43 ± 3.46 mm in G1, and from 32.78 ± 4.03 to 35.09 ± 3.55 mm in G2. Elbow flexors PT also increased (P<0.05) from 50.77 ± 9.26 to 54.15 ± 10.79 N.m in G1, and from 48.99 ± 11.52 to 55.29 ± 10.24 N.m in G2. The results of ANOVA did not reveal group by time interactions for any variable, indicating no difference between groups for the changes in MT or PT.
Conclusion:
The results from the present study suggest that untrained men experience similar gains in muscle mass and strength with equal volume RT performed one or two days per week.
A recent study identified ursolic acid (UA) as a potent stimulator of muscle protein anabolism via PI3K/Akt signaling, thereby suggesting that UA can increase Akt-independent mTORC1 activation induced by resistance exercise via Akt signaling. The purpose of the present study was to investigate the effect of UA on resistance exercise-induced mTORC1 activation. The right gastrocnemius muscle of male Sprague Dawley rats aged 11 weeks was isometrically exercised via percutaneous electrical stimulation (stimulating ten 3-scontractions per set for 5 sets), while the left gastrocnemius muscle served as the control. UA or placebo (PLA) (corn oil only) was injected intraperitoneally immediately after exercise. The rats were killed 1 or 6 h after the completion of exercise and the target tissues removed immediately. With placebo injection, the phosphorylation of p70S6K at Thr389 increased 1 h after resistance exercise but attenuated to the control levels 6 h after the exercise. On the contrary, the augmented phosphorylation of p70S6K was maintained even 6 h after exercise when UA was injected immediately after exercise. A similar trend of prolonged phosphorylation was observed in PRAS40 Thr246 while UA alone or resistance exercise alone did not alter its phosphorylation level at 6 h after intervention. These results indicate that UA is able to sustain resistance exercise-induced mTORC1 activity.
Widespread use of supplements is observed among world athletes in different fields. The aim of this study was to estimate the prevalence and determinants of using supplements among body builder athletes.
This cross-sectional study was conducted on 250 men and 250 women from 30 different bodybuilding clubs. Participants were asked to complete a self-administered standardized anonymous check-list.
Forty nine percent of the respondents declared supplement use. Men were more likely to take supplements than women (86.8% vs. 11.2%, p = 0.001). Reasons for using supplements were reported to be for health (45%), enhancing the immune system (40%) and improving athletic performance (25%). Most athletes (72%) had access to a nutritionist but underused this resource. Coaches (65%) had the greatest influence on supplementation practices followed by nutritionists (30%) and doctors (25%) after them.
The prevalence of supplement use among bodybuilders was high. Sex, health-related issues and sport experts were determinant factors of supplement use.
Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.
Our purpose was to assess muscular adaptations during 6 weeks of resistance training in 36 males randomly assigned to supplementation with whey protein (W; 1.2 g/kg/day), whey protein and creatine monohydrate (WC; 0.1 g/kg/day), or placebo (P; 1.2 g/kg/day maltodextrin). Measures included lean tissue mass by dual energy x-ray absorptiometry, bench press and squat strength (1-repetition maximum), and knee extension/flexion peak torque. Lean tissue mass increased to a greater extent with training in WC compared to the other groups, and in the W compared to the P group (p < .05). Bench press strength increased to a greater extent for WC compared to W and P (p < .05). Knee extension peak torque increased with training for WC and W (p < .05), but not for P. All other measures increased to a similar extent across groups. Continued training without supplementation for an additional 6 weeks resulted in maintenance of strength and lean tissue mass in all groups. Males that supplemented with whey protein while resistance training demonstrated greater improvement in knee extension peak torque and lean tissue mass than males engaged in training alone. Males that supplemented with a combination of whey protein and creatine had greater increases in lean tissue mass and bench press than those who supplemented with only whey protein or placebo. However, not all strength measures were improved with supplementation, since subjects who supplemented with creatine and/or whey protein had similar increases in squat strength and knee flexion peak torque compared to subjects who received placebo.
Flavonoids and phenolics are abundant in loquat flowers. Methanol had the highest extraction efficiency among five solvents, followed by ethanol. Considering the safety and residue, ethanol is better as extraction solvent. The average content of flavonoids and phenolics of loquat flower of five cultivars were 1.59 ± 0.24 and 7.86 ± 0.87 mg/g DW, respectively, when using ethanol as extraction solvent. The contents of both bioactive components in flowers at different developmental stages and in the various flower tissues clearly differed, with the highest flavonoids and phenolics content in flowers of stage 3 (flower fully open) and petal, respectively. The antioxidant capacity was measured using FRAP, DPPH, and ABTS methods. The values of ABTS method was highest, followed by DPPH, the lowest was FRAP, when using vitamin C equivalent antioxidant capacity (VCEAC) as unit. Correlation analysis showed that the ABTS method showed the highest correlation coefficients with flavonoids and phenolics, i.e., 0.886 and 0.973, respectively.
This study investigated the effect of heat stress (HS) on mammalian target of rapamycin (mTOR) signaling involved in translation initiation after resistance exercise in human skeletal muscle. Eight young male subjects performed four sets of six maximal repetitions of knee extension exercises, with or without HS, in a randomized crossover design. HS was applied to the belly of the vastus lateralis by using a microwave therapy unit prior to and during exercise. Muscle biopsies were taken from the vastus lateralis before, immediately after, and 1 h after exercise. HS significantly increased the phosphorylation of Akt/PKB, mTOR, and ribosomal protein S6 at 1 h after exercise (P < 0.05), and the 4E-BP1 phosphorylation level, which had initially decreased with exercise, had recovered by 1 h after exercise with HS. In addition, the phosphorylation of ribosomal S6 kinase 1 was significantly increased immediately after exercise with HS (P < 0.05). These results indicate that HS enhances mTOR signaling after resistance exercise in human skeletal muscle.
Pentacyclic triterpenes are secondary plant metabolites widespread in fruit peel, leaves and stem bark. In particular the lupane-, oleanane-, and ursane triterpenes display various pharmacological effects while being devoid of prominent toxicity. Therefore, these triterpenes are promising leading compounds for the development of new multi-targeting bioactive agents. Screening of 39 plant materials identified triterpene rich (> 0.1% dry matter) plant parts. Plant materials with high triterpene concentrations were then used to obtain dry extracts by accelerated solvent extraction resulting in a triterpene content of 50 - 90%. Depending on the plant material, betulin (birch bark), betulinic acid (plane bark), oleanolic acid (olive leaves, olive pomace, mistletoe sprouts, clove flowers), ursolic acid (apple pomace) or an equal mixture of the three triterpene acids (rosemary leaves) are the main components of these dry extracts. They are quantitatively characterised plant extracts supplying a high concentration of actives and therefore can be used for development of phytopharmaceutical formulations.
The purpose of this study was to develop and cross-validate predictive equations for estimating skeletal muscle (SM) mass using bioelectrical impedance analysis (BIA). Whole body SM mass, determined by magnetic resonance imaging, was compared with BIA measurements in a multiethnic sample of 388 men and women, aged 18-86 yr, at two different laboratories. Within each laboratory, equations for predicting SM mass from BIA measurements were derived using the data of the Caucasian subjects. These equations were then applied to the Caucasian subjects from the other laboratory to cross-validate the BIA method. Because the equations cross-validated (i.e., were not different), the data from both laboratories were pooled to generate the final regression equation SM mass (kg) = [(Ht<SUP>2</SUP>/ R x 0.401) + (gender x 3.825) + (age x -0. 071)] + 5.102 where Ht is height in centimeters; R is BIA resistance in ohms; for gender, men = 1 and women = 0; and age is in years. The r(2) and SE of estimate of the regression equation were 0.86 and 2.7 kg (9%), respectively. The Caucasian-derived equation was applicable to Hispanics and African-Americans, but it underestimated SM mass in Asians. These results suggest that the BIA equation provides valid estimates of SM mass in healthy adults varying in age and adiposity.
Daily requirements for protein are set by the amount of amino acids that is irreversibly lost in a given day. Different agencies have set requirement levels for daily protein intakes for the general population; however, the question of whether strength-trained athletes require more protein than the general population is one that is difficult to answer. At a cellular level, an increased requirement for protein in strength-trained athletes might arise due to the extra protein required to support muscle protein accretion through elevated protein synthesis. Alternatively, an increased requirement for protein may come about in this group of athletes due to increased catabolic loss of amino acids associated with strength-training activities. A review of studies that have examined the protein requirements of strength-trained athletes, using nitrogen balance methodology, has shown a modest increase in requirements in this group. At the same time, several studies have shown that strength training, consistent with the anabolic stimulus for protein synthesis it provides, actually increases the efficiency of use of protein, which reduces dietary protein requirements. Various studies have shown that strength-trained athletes habitually consume protein intakes higher than required. A positive energy balance is required for anabolism, so a requirement for "extra" protein over and above normal values also appears not to be a critical issue for competitive athletes because most would have to be in positive energy balance to compete effectively. At present there is no evidence to suggest that supplements are required for optimal muscle growth or strength gain. Strength-trained athletes should consume protein consistent with general population guidelines, or 12% to 15% of energy from protein.
Resistance exercise is fundamentally anabolic and as such stimulates the process of skeletal muscle protein synthesis (MPS) in an absolute sense and relative to skeletal muscle protein breakdown (MPB). However, the net effect of resistance exercise is to shift net protein balance (NPB = MPS - MPB) to a more positive value; however, in the absence of feeding NPB remains negative. Feeding stimulates MPS to an extent where NPB becomes positive, for a transient time. When combined, resistance exercise and feeding synergistically interact to result in NPB being greater than with feeding alone. This feeding- and exercise-induced stimulation of NPB is what, albeit slowly, results in muscle hypertrophy. With this rudimentary knowledge we are now at the point where we can manipulate variables within the system to see what impact these interventions have on the processes of MPS, MPB, and NPB and ultimately and perhaps most importantly, muscle hypertrophy and strength. We used established models of skeletal muscle amino acid turnover to examine how protein source (milk versus soy) acutely affects the processes of MPS and MPB after resistance exercise. Our findings revealed that even when balanced quantities of total protein and energy are consumed that milk proteins are more effective in stimulating amino acid uptake and net protein deposition in skeletal muscle after resistance exercise than are hydrolyzed soy proteins. Importantly, the finding of increased amino acid uptake would be independent of the differences in amino acid composition of the two proteins. We propose that the improved net protein deposition with milk protein consumption is also not due to differences in amino acid composition, but is due to a different pattern of amino acid delivery associated with milk versus hydrolyzed soy proteins. If our acute findings are accurate then we hypothesized that chronically the greater net protein deposition associated with milk protein consumption post-resistance exercise would eventually lead to greater net protein accretion (i.e., muscle fiber hypertrophy), over a longer time period. In young men completing 12 weeks of resistance training (5d/wk) we observed a tendency (P = 0.11) for greater gains in whole body lean mass and whole as greater muscle fiber hypertrophy with consumption of milk. While strength gains were not different between the soy and milk-supplemented groups we would argue that the true significance of a greater increase in lean mass that we observed with milk consumption may be more important in groups of persons with lower initial lean mass and strength such as the elderly.
Mechanical stimuli have often been suggested to be the major determinant of resistance training adaptations; however, some studies suggested that metabolic changes also play an important role in the gains of muscle size and strength. Several resistance training methods (RTM) have been employed with the purpose of manipulating mechanical and metabolic stimuli; however, information about their physiological effects are scarce. The objective of this study was to compare the time under tension (TUT) and blood lactate responses among four different RTM reported in the literature. The four RTM were performed in a knee extension machine at 10 repetition maximum (RM) load by 12 recreationally trained young men. The RTM tested were: 10RM, super-slow (SL-subjects performed one 60-second repetition with 30 seconds for eccentric and 30 seconds for concentric phase), functional isometrics (FI-in each repetition, a five-second maximal isometric contraction was executed with the knees fully extended) and adapted vascular occlusion (VO-subjects performed a 20-second maximal isometric contraction with the knees fully extended and immediately proceeded to normal isoinertial lifts). According to the results, all RTM produced significant increases in blood lactate levels. However, blood lactate responses during FI (4.48+/-1.57 mM) and VO (4.23+/-1.66 mM) methods were higher than the SL method (3.41+/-1.14 mM). The TUT for SL (60 s), FI (56.33+/-6.46 s), and VO (53.08+/-4.76 s) methods were higher than TUT for 10RM (42.08+/-3.18 s). Additionally, TUT for the SL method was higher than TUT during the VO method. Therefore, the SL method may not be recommended if one wants to provide a high metabolic stimulus. The FI method appeared to be especially effective in promoting both type of stimuli.
To evaluate the effect of ursolic acid on metabolic syndrome, insulin sensitivity, and inflammation. A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients (30-60 years) with a diagnosis of metabolic syndrome without treatment. They were randomly assigned to two groups of 12 patients, each to receive orally 150 mg of ursolic acid or homologated placebo once a day for 12 weeks. Before and after the intervention, the components of metabolic syndrome, insulin sensitivity (Matsuda index), and inflammation profile (interleukin-6 and C-reactive protein) were evaluated. After ursolic acid administration, the remission of metabolic syndrome occurred in 50% of patients (P = .005) with significant differences in body weight (75.7 ± 11.5 vs. 71 ± 11 kg, P = .002), body mass index (BMI) (29.9 + 3.6 vs. 24.9 ± 1.2 kg/m(2), P = .049), waist circumference (93 ± 8.9 vs. 83 + 8.6 cm, P = .008), fasting glucose (6.0 ± 0.5 vs. 4.7 ± 0.4 mmol/L, P = .002), and insulin sensitivity (3.1 ± 1.1 vs. 4.2 ± 1.2, P = .003). Ursolic acid administration leads to transient remission of metabolic syndrome, reducing body weight, BMI, waist circumference and fasting glucose, as well as increasing insulin sensitivity.
Objective:
Ursolic acid administration following resistance exercise increases mammalian target of rapamycin complex 1 (mTORC1) activity and skeletal muscle IGF-1 concentration in murines in a manner similar to l-leucine yet remains unexamined in humans. This study examined serum and skeletal muscle insulin-like growth factor-1 (IGF-1) and Akt/mTORC1 signaling activity following ingestion of either ursolic acid or l-leucine immediately after resistance exercise.
Methods:
Nine resistance-trained men performed 3 lower-body resistance exercise sessions involving 4 sets of 8-10 repetitions at 75%-80% one repetition maximum (1-RM) on the angled leg press and knee extension exercises. Immediately following each session, participants orally ingested 3 g cellulose placebo (PLC), l-leucine (LEU), or ursolic acid (UA). Blood samples were obtained pre-exercise and at 0.5, 2, and 6 hours postexercise. Muscle biopsies were obtained pre-exercise and at 2 and 6 hours postexercise.
Results:
Plasma leucine increased in LEU at 2 hours postexercise compared to PLC (p = 0.04). Plasma ursolic acid increased in UA at 2 h and 6 hours postexercise compared to PLC and LEU (p < 0.003). No significant differences were observed for serum insulin (p = 0.98) and IGF-1 (p = 0.99) or skeletal muscle IGF-1 receptor (IGF-1R; p = 0.84), Akt (p = 0.55), mTOR (p = 0.09), and p70S6K (p = 0.98). Skeletal muscle IGF-1 was significantly increased in LEU at 2 hours postexercise (p = 0.03) and 6 hours postexercise (p = 0.04) compared to PLC and UA.
Conclusion:
Three grams of l-leucine and ursolic acid had no effect on Akt/mTORC1 signaling or serum insulin or IGF-1; however, l-leucine increased skeletal muscle IGF-1 concentration in resistance-trained men.
Body composition assessment is an integral feature of elite sport as optimization facilitates successful performance. This study aims to refine the use of B-mode ultrasound in the assessment of athlete body composition by determining suitable sites for measurement. 67 elite athletes recruited from the Human Performance Laboratory, University College Cork, Ireland, underwent dual measurement of body composition. Subcutaneous adipose tissue thickness at 7 anatomical sites were measured using ultrasound and compared to percentage body fat values determined using Dual-Energy X-ray Absorptiometry. Multiple linear regressions were performed and an equation to predict percentage body fat was derived. The present study found subcutaneous adipose tissue depths at the triceps, biceps, anterior thigh and supraspinale sites correlated significantly with percentage body fat by X-ray absorptiometry (all p<0.05). Summation of the depths at these locations correlated strongly with percentage body fat by Dual-Energy X-ray Absorptiometry (R²=0.879). The triceps, biceps, anterior thigh and supraspinale sites are suitable anatomical landmarks for the estimation of %BF using B-mode ultrasound. Use of B-mode ultrasound in the assessment of athlete body composition confers many benefits including lack of ionising radiation and its potential to be used as a portable field tool.
© Georg Thieme Verlag KG Stuttgart · New York.
A liquid chromatography-mass spectrometry method has been developed and validated for rapid simultaneous determination of the oleanolic and ursolic acid contents in rat plasma with betulinic acid as the internal standard (IS). The plasma samples were prepared by a liquid-liquid extraction procedure. Chromatographic separation was performed with a Chromasil-C18 column (250 mm × 4.6 mm, i.d. 5 μm) with methanol-water as mobile phase at 1 mL/min. The detection was accomplished under selected-ion-monitoring mode with a negative electrospray ionization interface. Linear calibration curves were obtained between the range of 0.86-421.2 and 0.94-462.0 ng/mL for oleanolic and ursolic acids, with lower limits of quantification at 0.43 and 0.47 ng/mL, respectively. The extraction recovery exceeded 70% in plasma. The intra- and interday precision values were <9.8% with the accuracy as -7.0 to 9.9% at three different QC levels in both cases. The pharmacokinetic behaviors of oral dosage of QingGanSanJie decoctions were then studied in rats following the developed approach. The t1/2 values of the oleanolic and ursolic acids after oral administration of the monarch medicine extract were significantly different (P < 0.05) from other prescription extracts containing different herb pieces with different compatibilities. Bimodal phenomena appeared in every concentration-time curve for the oleanolic and ursolic acids at 3-8 h after administration. The minister, assistant and guide medicines in the formula could prolong the metabolism of the oleanolic and ursolic acids in vivo, providing an experimental basis for the slow onset and long action of the Traditional Chinese Medicine compound.
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Abstract—Prescribed and supervised resistance training (RT) enhances muscular strength and endurance, functional capacity and independence, and quality of life while reducing disability in persons with and without cardiovascular
Quantity and timing of protein ingestion are major factors regulating myofibrillar protein synthesis (MPS). However, the effect of specific ingestion patterns on MPS throughout a 12 h period is unknown. We determined how different distribution of protein feeding during 12 h recovery after resistance exercise affects anabolic responses in skeletal muscle. 24 healthy trained males were assigned to three groups (n=8/group) and undertook a bout of resistance exercise followed by ingestion of 80 g of whey protein throughout 12 h recovery as either: 8x10 g every 1.5 h (PULSE); 4x20 g every 3 h (intermediate: INT); or 2x40 g every 6 h (BOLUS). Muscle biopsies were obtained at rest and after 1, 4, 6, 7 and 12 h post-exercise. Resting and post-exercise MPS (L-[ring-13C6] phenylalanine), and muscle mRNA abundance and cell signalling were assessed. All ingestion protocols increased MPS above rest throughout 1-12 h recovery (88-148%, P<0.02), but INT elicited greater MPS than PULSE and BOLUS (31-48%, P<0.02). In general signalling showed a BOLUS>INT>PULSE hierarchy in magnitude of phosphorylation. MuRF-1 and SLC38A2 mRNA were differentially expressed with BOLUS. In conclusion, 20 g of whey protein consumed every 3 h was superior to either PULSE or BOLUS feeding patterns for stimulating MPS throughout the day. This study provides novel information on the effect of modulating the distribution of protein intake on anabolic responses in skeletal muscle and has potential to maximise outcomes of resistance training for attaining peak muscle mass.
Objective:
The purpose of this study was to investigate the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of ursolic acid liposomes (UAL), as a new drug, in healthy adult volunteers and patients with advanced solid tumors.
Methods:
All subjects received a single-dose of UAL (11, 22, 37, 56, 74, 98, and 130 mg/m(2)) administered as a 4-h intravenous infusion. Toxicity was assessed and plasma samples were analyzed using validated ultra-performance liquid chromatograph/tandem mass spectroscopy method.
Results:
A total of 63 subjects including 4 patients and 35 healthy adult volunteers for toxicity study and 24 healthy adult volunteers for pharmacokinetic study were enrolled in this trial. The DLT was encountered at 74, 98, and 130 mg/m(2), and consisted of hepatotoxicity and diarrhea. Other adverse events included grade 1 nausea, grade 2 abdominal distention, grade 1 microscopic hematuria, grade 2 elevated serum sodium, grade 1 vascular stimulation, and grade 1 skin rash. The MTD was 98 mg/m(2). The single-dose pharmacokinetic parameters revealed a linear relationship between C(max), AUC(0→24 h), or AUC(0→∞) and escalated doses.
Conclusions:
The clinical data reported for the first time that UAL had manageable toxicities with MTD of 98 mg/m(2). The DLT were hepatotoxicity and diarrhea. Meanwhile, UAL had a linear pharmacokinetic profile. The registration number of this trial is ChiCTR-ONC-12002385.
Skeletal muscle atrophy is a common and debilitating condition that lacks a pharmacologic therapy. To develop a potential therapy, we identified 63 mRNAs that were regulated by fasting in both human and mouse muscle, and 29 mRNAs that were regulated by both fasting and spinal cord injury in human muscle. We used these two unbiased mRNA expression signatures of muscle atrophy to query the Connectivity Map, which singled out ursolic acid as a compound whose signature was opposite to those of atrophy-inducing stresses. A natural compound enriched in apples, ursolic acid reduced muscle atrophy and stimulated muscle hypertrophy in mice. It did so by enhancing skeletal muscle insulin/IGF-I signaling and inhibiting atrophy-associated skeletal muscle mRNA expression. Importantly, ursolic acid's effects on muscle were accompanied by reductions in adiposity, fasting blood glucose, and plasma cholesterol and triglycerides. These findings identify a potential therapy for muscle atrophy and perhaps other metabolic diseases.
A fast and sensitive liquid chromatography–mass spectrometry method was developed for the determination of ursolic acid (UA) in rat plasma and tissues. Glycyrrhetinic acid was used as the internal standard (IS). Chromatographic separation was performed on a 3.5 μm Zorbax SB-C18 column (30 mm × 2.1 mm) with a mobile phase consisting of methanol and aqueous 10 mM ammonium acetate using gradient elution. Quantification was performed by selected ion monitoring with (m/z)− 455 for UA and (m/z)− 469 for the IS. The method was validated in the concentration range of 2.5 − 1470 ng mL−1 for plasma samples and 20 − 11760 ng g−1 for tissue homogenates. The intra- and inter-day assay of precision in plasma and tissues ranged from 1.6% to 7.1% and 3.7% to 9.0%, respectively, and the intra- and inter-day assay accuracy was 84.2 − 106.9% and 82.1 − 108.1%, respectively. Recoveries in plasma and tissues ranged from 83.2% to 106.2%. The limits of detections were 0.5 ng mL−1 or 4.0 ng g−1. The recoveries for all samples were >90%, except for liver, which indicated that ursolic acid may metabolize in liver. The main pharmacokinetic parameters obtained were T
max = 0.42 ± 0.11 h, C
max = 1.10 ± 0.31 μg mL−1, AUC = 1.45 ± 0.21 μg h mL−1 and K
a = 5.64 ± 1.89 h−1. The concentrations of UA in rat lung, spleen, liver, heart, and cerebellum were studied for the first time. This method is validated and could be applicable to the investigation of the pharmacokinetics and tissue distribution of UA in rats.
Figure
The mean plasma concentration–time curve and tissue distributions of UA in rats after oral administration of UA
Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as "myokines." Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.
The rates of protein synthesis and degradation and of amino acid transport were determined in the leg muscle of untrained postabsorptive normal volunteers at rest and approximately 3 h after a resistance exercise routine. The methodology involved use of stable isotopic tracers of amino acids, arteriovenous catheterization of the femoral vessels, and biopsy of the vastus lateralis muscle. During postexercise recovery, the rate of intramuscular phenylalanine utilization for protein synthesis increased above the basal value by 108 +/- 18%, whereas the rate of release from proteolysis increased by 51 +/- 17%. Muscle protein balance improved (P < 0.05) after exercise but did not become positive (from -15 +/- 12 to -6 +/- 3 nmol phenylalanine.min-1.100 ml leg volume-1). After exercise, rates of inward transport of leucine, lysine, and alanine increased (P < 0.05) above the basal state from 132 +/- 16 to 208 +/- 29, from 122 +/- 8 to 260 +/- 8, and from 384 +/- 71 to 602 +/- 89 nmol.min-1.100 ml leg-1, respectively. Transport of phenylalanine did not change significantly. These results indicate that, during recovery after resistance exercise, muscle protein turnover is increased because of an acceleration of synthesis and degradation. A postexercise acceleration of amino acid transport may contribute to the relatively greater stimulation of protein synthesis.
Single-frequency bioelectrical impedance analyzers used to assess body composition are being replaced by multiple-frequency analyzers. At low frequencies, the current flows primarily through extracellular fluids; at high frequencies, it completely penetrates all body tissues. Measures of bioelectrical impedance at multiple frequencies can differentiate total and extracellular fluid compartments in the body. This has considerable value for assessing clinical and nutritional status. Impedance measures at a single frequency contain only a small window of the available impedance spectrum information, which may explain the difficulty in discriminating among individuals. The impedance spectrum and its analysis may provide a much clearer picture of individual differences in body water and body composition. With increasing clinical uses of bioelectrical impedance in individuals and sample populations, the use of multiple-frequency impedance may help to elucidate differences that are not discernible with single-frequency impedance.
To check whether ingestion of (-)-epicatechin (EC) affects the antioxidative defense in blood plasma, we studied the oxidizability of plasma from Wistar rats after intragastrical EC administration at 10 or 50 mg/rat. The plasma pool obtained from control or EC-administered rats was oxidized with copper sulfate or 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH). EC metabolites in plasma 1 h after EC administration contained glucuronide and glucuronide-sulfate conjugates in both the free and O-methylated form. After 6 h, the plasma concentration of total EC metabolites decreased and the remaining conjugates were mostly present as the O-methylated form. Compared to the control group, the plasma obtained from rats 1 and 6 h after EC administration was more resistant against copper sulfate-induced oxidation on the basis of cholesteryl ester hydroperoxide (CE-OOH) accumulation. Also, the consumption of alpha-tocopherol during oxidation was suppressed in the plasma obtained from EC-treated rats. The content of CE-OOH and consumption of alpha-tocopherol in the plasma from EC-administered animals was much lower than those expected from the amount of nonmetabolized EC present in the plasma. Similar results were obtained from AAPH-induced oxidation of rat plasma after EC administration, except for the fact that CE-OOH accumulation was less suppressed in the plasma 6 h following administration. The O-methylated form was found to be more stable than the free form when EC-administered rat plasma was auto-oxidized at 37 degrees. These results suggest that EC metabolites, particularly conjugates in the free form, possess an effective antioxidative activity in blood plasma.
Reliability refers to the reproducibility of values of a test, assay or other measurement in repeated trials on the same individuals. Better reliability implies better precision of single measurements and better tracking of changes in measurements in research or practical settings. The main measures of reliability are within-subject random variation, systematic change in the mean, and retest correlation. A simple, adaptable form of within-subject variation is the typical (standard) error of measurement: the standard deviation of an individual's repeated measurements. For many measurements in sports medicine and science, the typical error is best expressed as a coefficient of variation (percentage of the mean). A biased, more limited form of within-subject variation is the limits of agreement: the 95% likely range of change of an individual's measurements between 2 trials. Systematic changes in the mean of a measure between consecutive trials represent such effects as learning, motivation or fatigue; these changes need to be eliminated from estimates of within-subject variation. Retest correlation is difficult to interpret, mainly because its value is sensitive to the heterogeneity of the sample of participants. Uses of reliability include decision-making when monitoring individuals, comparison of tests or equipment, estimation of sample size in experiments and estimation of the magnitude of individual differences in the response to a treatment. Reasonable precision for estimates of reliability requires approximately 50 study participants and at least 3 trials. Studies aimed at assessing variation in reliability between tests or equipment require complex designs and analyses that researchers seldom perform correctly. A wider understanding of reliability and adoption of the typical error as the standard measure of reliability would improve the assessment of tests and equipment in our disciplines.
Oleanolic acid and ursolic acid are ubiquitous triterpenoids in plant kingdom, medicinal herbs, and are integral part of the human diet. During the last decade over 700 research articles have been published on their research, reflecting tremendous interest and progress in our understanding of these triterpenoids. This included the isolation and purification of these tritepernoids from various plants and herbs, the chemical modifications to make more effective and water soluble derivatives, the pharmacological research on their beneficial effects, the toxicity studies, and the clinical use of these triterpenoids in various diseases including anticancer chemotherapies. A briefly commentary is attempted here for their research perspectives.
Skeletal muscle is the most abundant tissue in the human body and its normal physiology plays a fundamental role in health and disease. During many disease states, a dramatic loss of skeletal muscle mass (atrophy) is observed. In contrast, physical exercise is capable of producing significant increases in muscle mass (hypertrophy). Maintenance of skeletal muscle mass is often viewed as the net result of the balance between two separate processes, namely protein synthesis and protein degradation. However, these two biochemical processes are not occurring independent of each other but they rather appear to be finely coordinated by a web of intricate signaling networks. Such signaling networks are in charge of executing environmental and cellular cues that will ultimate determine whether muscle proteins are synthesized or degraded. In this review, recent findings are discussed demonstrating that the AKT1/FOXOs/Atrogin-1(MAFbx)/MuRF1 signaling network plays an important role in the progression of skeletal muscle atrophy. These novel findings highlight an important mechanism that coordinates the activation of the protein synthesis machinery with the activation of a genetic program responsible for the degradation of muscle proteins during skeletal muscle atrophy.
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Composition of Foods Raw, Processed, Prepared USDA National Nutrient 631 Database for Standard Reference
Composition of Foods Raw, Processed, Prepared USDA National Nutrient
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