Whey Protein Supplementation with or without Vitamin D on Sarcopenia-Related Measures: A Systematic Review and Meta-Analysis.

The effects of supplementation with whey protein alone or with vitamin D on sarcopenia-related outcomes in older adults are unclear. We aimed to assess the effect of whey protein supplementation alone or with vitamin D on lean mass (LM), strength, and function in older adults with or without sarcopenia or frailty. We searched PubMed, Web of Science, and SCOPUS databases. Randomized controlled trials (RCT) that investigated the effect of whey protein supplementation with or without vitamin D on sarcopenia outcomes in healthy and sarcopenic or frail older adults were included. Standardized mean differences (SMDs) were calculated for LM, muscle strength, and physical function data. The analysis showed that whey protein supplementation had no effect on LM and muscle strength; nevertheless, a significant improvement was found in physical function (SMD = 0.561; 95% confidence interval [CIs]: 0.256, 0.865, n = 33), particularly gait speed (GS). On the contrary, whey protein supplementation significantly improved LM (SMD = 0.982; 95% CI: 0.228, 1.736; n = 11), appendicular lean mass and physical function (SMD = 1.211; 95% CI: 0.588, 1.834; n = 16), and GS in sarcopenic/frail older adults. By contrast, co-supplementation with vitamin D enhanced LM gains (SMD =0.993; 95% CI: 0.112, 1.874; n = 11), muscle strength (SMD =2.005; 95% CI: 0.975, 3.035; n = 11), and physical function (SMD = 3.038; 95% CI: 2.196, 3.879; n = 18) significantly. Muscle strength and physical function improvements after whey protein supplementation plus vitamin D were observed without resistance exercise (RE) and short study duration subgroups. Moreover, the combination of whey protein and vitamin D with RE did not enhance the effect of RE. Whey protein supplementation improved LM and function in sarcopenic/frail older adults but had no positive effect in healthy older persons. By contrast, our meta-analysis showed that co-supplementation with whey protein and vitamin D is effective, particularly in healthy older adults, which is likely owing, we propose, to the correction of vitamin D insufficiency or deficiency. The trial was registered at https://inplasy.com as INPLASY202240167.

Increased protein intake derived from leucine-enriched protein enhances the integrated myofibrillar protein synthetic response to short-term resistance training in untrained men and women: a 4-day randomized controlled trial.

Leucine is a critical amino acid stimulating myofibrillar protein synthesis (MyoPS). The consumption of higher leucine-containing drinks stimulates MyoPS, but we know less about higher leucine solid foods. Here, we examined the effect of short-term resistance exercise training (STRT) combined with supplementation of a protein and leucine-enriched bar, compared with STRT alone, on integrated (%/day) rates of MyoPS and anabolic protein signaling. In a nonblinded, randomized crossover trial, eight young adults performed four sessions of STRT without or while consuming the study bar (STRT+Leu, 16 g of protein containing ∼3 g of leucine) for two 4-day phases, separated by 2 days nonexercise (Rest) washout. In combination with serial muscle biopsies, deuterated water permitted the measurement of MyoPS and protein signaling phosphorylation. MyoPS during STRT (1.43 ± 0.06%/day) and STRT+Leu (1.53 ± 0.06%/day) were greater than Rest (1.31 ± 0.05%/day), and MyoPS during STRT+Leu (1.53 ± 0.06%/day) was greater than STRT alone (1.43 ± 0.06%/day). STRT+Leu increased the ratio of phosphorylated to total mechanistic target of rapamycin and 4EBP1 compared to Rest. Engaging in STRT increased integrated MyoPS and protein signaling in young adults and was enhanced with increased protein intake derived from a leucine-enriched protein bar. This study was registered at clinicaltrials.gov as NCT03796897.

Heart rate reactivity to acute mental stress is associated with adiposity, carotid distensibility, sleep efficiency, and autonomic modulation in young men.

Acute mental stress (AMS) increases heart rate (HR) and blood pressure. Since obesity can impair the cardiovascular reactivity to AMS, a better understanding of the mechanisms involved in this response is needed. We aimed to evaluate the cardiovascular reactivity to AMS in young men with normal or excess body fat. We also assessed the association between cardiovascular reactivity to AMS and cardiovascular risk factors, including autonomic modulation, carotid artery distensibility, physical activity levels, and sleep efficiency. Sixty-six young men (26.1 ± 4.1 years old) underwent anthropometric and body fat assessment (dual-energy X-ray absorptiometry) and had right-carotid artery ultrasonography. Accelerometers assessed physical activity levels and sleep efficiency. AMS was induced through the Stroop color-word test while blood pressure, HR, and cardiac interval were measured. Analyses were performed in Normal and Excess fat groups divided by fat mass index (FMI). Continuous data was used for multiple linear regression analyses. An interaction between FMI and time for HR reactivity was observed. Cardiac interval variability analysis showed that only participants with normal fat displayed parasympathetic withdrawal during AMS (P < 0.05). Multiple linear regression analysis supported the role of adiposity and autonomic modulation in the HR reactivity to AMS and showed involvement of carotid distensibility and sleep efficiency (P < 0.05). Carotid distensibility was the only predictor for blood pressure reactivity (P < 0.05). Physical activity was not associated with AMS's cardiovascular reactivity. We conclude that increased adiposity is associated with reduced HR reactivity to AMS, which is possibly linked to an impaired parasympathetic withdrawal. Carotid distension and sleep efficiency seem to contribute to this response.

An umbrella review of systematic reviews of ß-hydroxy-ß-methyl butyrate supplementation in ageing and clinical practice.

The compound ß-hydroxy-ß-methyl butyrate (HMB) is proposed to increase or mitigate the loss of skeletal muscle and improve muscle function. We undertook a review of systematic reviews of HMB supplementation to promote gains or mitigate muscle loss in ageing and clinical populations. Following PRISMA guidelines, we searched for systematic reviews reporting the effect of HMB in our target populations. Dual-energy X-ray absorptiometry (DXA) measured lean soft-tissue mass (LSTM) was accepted as a proxy for muscle. We identified 15 systematic reviews that met our inclusion criteria, which were independently evaluated. The methodological quality of the reviews was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and standardized effectiveness statements were generated. Five of 15 studies found some evidence that HMB augmented LSTM; the remaining 10 studies reported some evidence favouring no difference (6/10 studies) or insufficient evidence to determine an effect (4/10 studies). Of the 12 studies that evaluated strength, 4/12 found some evidence, 5/12 found some evidence of no effect with one article finding some evidence in favour of patients in peri-hospitalized and no evidence for those that are community-dwelling, 4/12 had insufficient evidence to determine an effect, and 1/12 had insufficient evidence. No]study reported a positive effect of HMB on physical function; however, 2/10 studies found some evidence favouring no effect, and 7/10 studies reported insufficient evidence to determine an effect. The effectiveness of HMB supplementation in augmenting LSTM was heterogeneous, with most reviews finding no effect or inconclusive evidence to determine an effect. Most reviews concluded that HMB supplementation did not affect strength outcome measures or studies were inconclusive. The current evidence is insufficient to assess the impact of HMB supplementation on functional outcome measures. Our analysis shows minor, inconsistent support for HMB as part of an oral nutritional supplement or as a stand-alone supplement (or combined with other amino acids) to increase or promote retention of LSTM, improve strength, and no evidence that it improves physical function in older persons or clinical populations.

Dietary acid load is positively associated with insulin resistance: a population-based study.

BACKGROUND & AIMS: Diabetes mellitus (DM) and cardiovascular disease (CVD) are among the biggest causes of death and health expenses worldwide. A higher dietary acid load (DAL) is associated with chronic low-grade metabolic acidosis, and may increase the risk of insulin resistance (IR), DM, hypertension, and CVD mortality. However, the association between DAL and IR still lacks population-based studies to confirm laboratory findings. METHODS: This is a population-based observational study including a sample of 545 individuals aged 25-64 years from Florianópolis (Southern Brazil) who participated in the EpiFloripa cohort study. All diet variables were obtained through two 24-h Food Recalls adjusted to obtain an estimate of habitual food consumption. DAL was measured by Potential Renal Acid Load (PRAL) and Net Endogenous Acid production (NEAP). Fasting blood samples were obtained from all participants. The primary outcome was IR, which was estimated by HOMA-IR. Secondary outcomes included HOMA-ß, glycosylated hemoglobin, and fasting blood glucose and insulin. Multiple linear regression models adjusted for sociodemographics, lifestyle, and clinical variables were used for analysis, with exposure and outcome variables standardized as Z-scores to allow comparability of the results. RESULT: The mean PRAL and NEAP in the sample were 16.9 ± 4.8 and 66.1 ± 7.1 mEq/day, respectively. The average HOMA-IR score was 2.4 ± 1.6. In adjusted analyses, PRAL was positively associated with HOMA-IR, fasting insulin, and fasting blood glucose (p-value <0.05 in all cases), but not with HOMA-ß or glycated hemoglobin. NEAP also showed a direct-trend relationship with HOMA-IR and fasting insulin, but not with fasting blood glucose or the other outcomes. The strongest association was between PRAL and HOMA-IR (ß, 0.20; 95% CI, 0.06-0.35). CONCLUSIONS: A higher DAL was consistently associated with higher IR and insulin levels but not with other glycaemic parameters. Apparently, ß-pancreatic cells function is not affected by DAL in this population. This is the first study that describes the DAL in a population-based sample of adults in Latin America and in a middle-income country population. Further longitudinal and interventional studies are required to establish a better causal effect between DAL and IR.

An Evidence-Based Narrative Review of Mechanisms of Resistance Exercise-Induced Human Skeletal Muscle Hypertrophy.

Skeletal muscle plays a critical role in physical function and metabolic health. Muscle is a highly adaptable tissue that responds to resistance exercise (RE; loading) by hypertrophying, or during muscle disuse, RE mitigates muscle loss. Resistance exercise training (RET)-induced skeletal muscle hypertrophy is a product of external (e.g., RE programming, diet, some supplements) and internal variables (e.g., mechanotransduction, ribosomes, gene expression, satellite cells activity). RE is undeniably the most potent nonpharmacological external variable to stimulate the activation/suppression of internal variables linked to muscular hypertrophy or countering disuse-induced muscle loss. Here, we posit that despite considerable research on the impact of external variables on RET and hypertrophy, internal variables (i.e., inherent skeletal muscle biology) are dominant in regulating the extent of hypertrophy in response to external stimuli. Thus, identifying the key internal skeletal muscle-derived variables that mediate the translation of external RE variables will be pivotal to determining the most effective strategies for skeletal muscle hypertrophy in healthy persons. Such work will aid in enhancing function in clinical populations, slowing functional decline, and promoting physical mobility. We provide up-to-date, evidence-based perspectives of the mechanisms regulating RET-induced skeletal muscle hypertrophy.

A higher energy-adjusted Dietary Inflammatory Index is positively associated with total and visceral body fat in young male adults.

BACKGROUND: The energy-adjusted Dietary Inflammatory Index (E-DII™) has been associated with a high body mass index and markers of chronic diseases. Also, pro-inflammatory diets with a high E-DII have been positively associated with metabolic disturbances such as glucose intolerance and type II diabetes mellitus. However, it is unclear whether E-DII scores are positively associated with body fat percentage and visceral fat per se. This cross-sectional study aimed to evaluate whether the E-DII is associated with body fat content and metabolic health indicators in lean and obese young men. METHODS: The present study was conducted on 59 participants, without comorbidities, not using tobacco, medication and nutritional supplements. Dietary data were obtained by 3-day food records to calculate E-DII scores based on 28 food parameters. Body composition was assessed by dual X-ray absorptiometry (DXA). Blood samples were taken to measure fasting glucose, insulin, triacylglycerols, total cholesterol, and low- and high-density lipoprotein cholesterol. An oral glucose tolerance test also was performed. Associations were determined by mixed-effects linear regression. RESULTS: E-DII scores ranged from -3.48 to +3.10. Energy intake was similar across E-DII tertiles. After adjusting for covariates, the highest E-DII tertile was associated with increased body fat, visceral adipose tissue and waist circumference. There was no association between E-DII scores and glycaemic parameters. CONCLUSIONS: In young participants, a dietary pattern with a higher E-DII (i.e., pro-inflammatory) score was associated with high body fat and markers of central adiposity assessed by DXA, regardless of body mass.

Nitrate consumption preserves HFD-induced skeletal muscle mitochondrial ADP sensitivity and lysine acetylation: A potential role for SIRT1.

Dietary nitrate supplementation, and the subsequent serial reduction to nitric oxide, has been shown to improve glucose homeostasis in several pre-clinical models of obesity and insulin resistance. While the mechanisms remain poorly defined, the beneficial effects of nitrate appear to be partially dependent on AMPK-mediated signaling events, a central regulator of metabolism and mitochondrial bioenergetics. Since AMPK can activate SIRT1, we aimed to determine if nitrate supplementation (4 mM sodium nitrate via drinking water) improved skeletal muscle mitochondrial bioenergetics and acetylation status in mice fed a high-fat diet (HFD: 60% fat). Consumption of HFD induced whole-body glucose intolerance, and within muscle attenuated insulin-induced Akt phosphorylation, mitochondrial ADP sensitivity (higher apparent Km), submaximal ADP-supported respiration, mitochondrial hydrogen peroxide (mtH2O2) production in the presence of ADP and increased cellular protein carbonylation alongside mitochondrial-specific acetylation. Consumption of nitrate partially preserved glucose tolerance and, within skeletal muscle, normalized insulin-induced Akt phosphorylation, mitochondrial ADP sensitivity, mtH2O2, protein carbonylation and global mitochondrial acetylation status. Nitrate also prevented the HFD-mediated reduction in SIRT1 protein, and interestingly, the positive effects of nitrate ingestion on glucose homeostasis and mitochondrial acetylation levels were abolished in SIRT1 inducible knock-out mice, suggesting SIRT1 is required for the beneficial effects of dietary nitrate. Altogether, dietary nitrate preserves mitochondrial ADP sensitivity and global lysine acetylation in HFD-fed mice, while in the absence of SIRT1, the effects of nitrate on glucose tolerance and mitochondrial acetylation were abrogated.

Disuse-induced skeletal muscle atrophy in disease and nondisease states in humans: mechanisms, prevention, and recovery strategies.

Decreased skeletal muscle contractile activity (disuse) or unloading leads to muscle mass loss, also known as muscle atrophy. The balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB) is the primary determinant of skeletal muscle mass. A reduced mechanical load on skeletal muscle is one of the main external factors leading to muscle atrophy. However, endocrine and inflammatory factors can act synergistically in catabolic states, amplifying the atrophy process and accelerating its progression. In addition, older individuals display aging-induced anabolic resistance, which can predispose this population to more pronounced effects when exposed to periods of reduced physical activity or mechanical unloading. Different cellular mechanisms contribute to the regulation of muscle protein balance during skeletal muscle atrophy. This review summarizes the effects of muscle disuse on muscle protein balance and the molecular mechanisms involved in muscle atrophy in the absence or presence of disease. Finally, a discussion of the current literature describing efficient strategies to prevent or improve the recovery from muscle atrophy is also presented.

Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults.

We performed a systematic review, meta-analysis, and meta-regression to determine if increasing daily protein ingestion contributes to gaining lean body mass (LBM), muscle strength, and physical/functional test performance in healthy subjects. A protocol for the present study was registered (PROSPERO, CRD42020159001), and a systematic search of Medline, Embase, CINAHL, and Web of Sciences databases was undertaken. Only randomized controlled trials (RCT) where participants increased their daily protein intake and were healthy and non-obese adults were included. Research questions focused on the main effects on the outcomes of interest and subgroup analysis, splitting the studies by participation in a resistance exercise (RE), age (<65 or ≥65 years old), and levels of daily protein ingestion. Three-level random-effects meta-analyses and meta-regressions were conducted on data from 74 RCT. Most of the selected studies tested the effects of additional protein ingestion during RE training. The evidence suggests that increasing daily protein ingestion may enhance gains in LBM in studies enrolling subjects in RE (SMD [standardized mean difference] = 0.22, 95% CI [95% confidence interval] 0.14:0.30, P < 0.01, 62 studies, moderate level of evidence). The effect on LBM was significant in subjects ≥65 years old ingesting 1.2-1.59 g of protein/kg/day and for younger subjects (<65 years old) ingesting ≥1.6 g of protein/kg/day submitted to RE. Lower-body strength gain was slightly higher by additional protein ingestion at ≥1.6 g of protein/kg/day during RE training (SMD = 0.40, 95% CI 0.09:0.35, P < 0.01, 19 studies, low level of evidence). Bench press strength is slightly increased by ingesting more protein in <65 years old subjects during RE training (SMD = 0.18, 95% CI 0.03:0.33, P = 0.01, 32 studies, low level of evidence). The effects of ingesting more protein are unclear when assessing handgrip strength and only marginal for performance in physical function tests. In conclusion, increasing daily protein ingestion results in small additional gains in LBM and lower body muscle strength gains in healthy adults enrolled in resistance exercise training. There is a slight effect on bench press strength and minimal effect performance in physical function tests. The effect on handgrip strength is unclear.

Consumption of High-Leucine-Containing Protein Bar Following Breakfast Impacts Aminoacidemia and Subjective Appetite in Older Persons.

BACKGROUND: Limited data are available examining dietary interventions for optimizing protein and leucine intake to stimulate muscle protein synthesis (MPS) in older humans. OBJECTIVES: We aimed to investigate the aminoacidemia and appetite responses of older adults after consuming breakfast, a meal frequently consumed with high-carbohydrate and below-par amounts of protein and leucine for stimulating MPS. METHODS: Five men and 3 women (means ± SD; age: 74 ± 7 y, BMI: 25.7 ± 4.9 kg/m2, fat- and bone-free mass: 63 ± 7 kg) took part in this experiment in which they consumed breakfasts with low-protein (LP = 13 ± 2 g), high-protein (HP = 32 ± 5 g), and LP followed by a protein- and leucine-enriched bar formulation 2 h later (LP + Bar = 29 ± 2 g). The LP, HP, and LP + Bar breakfast conditions contained 519 ± 86 kcal, 535 ± 83 kcal, and 739 ± 86 kcal, respectively. Blood samples were drawn for 6 h and analyzed for amino acid, insulin, and glucose concentrations. Visual analog scales were assessed for hunger, fullness, and desire to eat. RESULTS: The net AUC for essential amino acid (EAA) exposure was similar between the LP + Bar and HP conditions but greater in the HP condition compared with the LP condition. Peak leucinemia was higher in the LP + Bar condition compared with the HP, and both were greater than the LP condition. Net leucine exposure was similar between HP and LP + Bar, and both were greater than LP. Hunger was similarly reduced in LP + Bar and HP, and LP + Bar resulted in a greater hunger reduction than LP. Both LP + Bar and HP resulted in greater net fullness scores than LP. CONCLUSIONS: Consuming our bar formulation increased blood leucine availability and net exposure to EAAs to a similar degree as consuming a high-protein meal. High-protein at breakfast results in a greater net exposure to EAAs and leucine, which could support MPS in older persons. This study was registered at clinicaltrials.gov as NCT03712761.

Insulin rapidly increases skeletal muscle mitochondrial ADP sensitivity in the absence of a high lipid environment.

Reductions in mitochondrial function have been proposed to cause insulin resistance, however the possibility that impairments in insulin signaling negatively affects mitochondrial bioenergetics has received little attention. Therefore, we tested the hypothesis that insulin could rapidly improve mitochondrial ADP sensitivity, a key process linked to oxidative phosphorylation and redox balance, and if this phenomenon would be lost following high-fat diet (HFD)-induced insulin resistance. Insulin acutely (60 min post I.P.) increased submaximal (100-1000 µM ADP) mitochondrial respiration ∼2-fold without altering maximal (>1000 µM ADP) respiration, suggesting insulin rapidly improves mitochondrial bioenergetics. The consumption of HFD impaired submaximal ADP-supported respiration ∼50%, however, despite the induction of insulin resistance, the ability of acute insulin to stimulate ADP sensitivity and increase submaximal respiration persisted. While these data suggest that insulin mitigates HFD-induced impairments in mitochondrial bioenergetics, the presence of a high intracellular lipid environment reflective of an HFD (i.e. presence of palmitoyl-CoA) completely prevented the beneficial effects of insulin. Altogether, these data show that while insulin rapidly stimulates mitochondrial bioenergetics through an improvement in ADP sensitivity, this phenomenon is possibly lost following HFD due to the presence of intracellular lipids.

In vitro ketone-supported mitochondrial respiration is minimal when other substrates are readily available in cardiac and skeletal muscle.

KEY POINTS: Ketone bodies are proposed to represent an alternative fuel source driving energy production, particularly during exercise. Biologically, the extent to which mitochondria utilize ketone bodies compared to other substrates remains unknown. We demonstrate in vitro that maximal mitochondrial respiration supported by ketone bodies is low when compared to carbohydrate-derived substrates in the left ventricle and red gastrocnemius muscle from rodents, and in human skeletal muscle. When considering intramuscular concentrations of ketone bodies and the presence of other carbohydrate and lipid substrates, biological rates of mitochondrial respiration supported by ketone bodies are predicted to be minimal. At the mitochondrial level, it is therefore unlikely that ketone bodies are an important source for energy production in cardiac and skeletal muscle, particularly when other substrates are readily available. ABSTRACT: Ketone bodies (KB) have recently gained popularity as an alternative fuel source to support mitochondrial oxidative phosphorylation and enhance exercise performance. However, given the low activity of ketolytic enzymes and potential inhibition from carbohydrate oxidation, it remains unknown if KBs can contribute to energy production. We therefore determined the ability of KBs (sodium dl-ß-hydroxybutyrate, ß-HB; lithium acetoacetate, AcAc) to stimulate in vitro mitochondrial respiration in the left ventricle (LV) and red gastrocnemius (RG) of rats, and in human vastus lateralis. Compared to pyruvate, the ability of KBs to maximally drive respiration was low in isolated mitochondria and permeabilized fibres (PmFb) from the LV (∼30-35% of pyruvate), RG (∼10-30%), and human vastus lateralis (∼2-10%). In PmFb, the concentration of KBs required to half-maximally drive respiration (LV: 889 µm ß-HB, 801 µm AcAc; RG: 782 µm ß-HB, 267 µm AcAc) were greater than KB content representative of the muscle microenvironment (∼100 µm). This would predict low rates (∼1-4% of pyruvate) of biological KB-supported respiration in the LV (8-14 pmol s-1 mg-1 ) and RG (3-6 pmol s-1 mg-1 ) at rest and following exercise. Moreover, KBs did not increase respiration in the presence of saturating pyruvate, submaximal pyruvate (100 µm) reduced the ability of physiological ß-HB to drive respiration, and addition of other intracellular substrates (succinate + palmitoylcarnitine) decreased maximal KB-supported respiration. As a result, product inhibition is likely to limit KB oxidation. Altogether, the ability of KBs to drive mitochondrial respiration is minimal and they are likely to be outcompeted by other substrates, compromising their use as an important energy source.

Behavioral, cardiovascular and endocrine alterations induced by chronic stress in rats fed a high-fat diet.

Chronic stress is a risk factor for cardiovascular diseases (CVD) and anxiety disorders (AD). Obesity also increases the risk of CVD and AD. The modern lifestyle commonly includes high-fat diet (HFD) intake and daily exposure to stressful events. However, it is not completely understood whether chronic stress exacerbates HFD-induced behavioral and physiological changes. Thus, this study aimed to evaluate the effects of the exposure to chronic variable stress (CVS) on behavioral, cardiovascular, and endocrine parameters in rats fed an HFD. Male Wistar rats were divided into four groups: control-standard chow diet (control-SD), control-HFD, CVS-SD, and CVS-HFD. The control-HFD and CVS-HFD groups were fed with HFD for six weeks. The CVS-HFD and CVS-SD groups were exposed to a CVS protocol in the last ten days of the six weeks. The behavioral analysis revealed that CVS decreased the open-arm exploration time during the elevated plus-maze test (p < 0.05). HFD promoted metabolic disorders and increased angiotensin II and leptin blood levels (p < 0.05). CVS or HFD increased blood pressure and the sympathetic nervous system (SNS) modulation of the heart and vessels and decreased baroreflex activity (p < 0.05). Combining CVS and HFD exacerbated the cardiac SNS response and increased basal heart rate (HR) (p < 0.05). CVS or HFD did not affect vascular function and aorta nitrate (p > 0.05). Taken together, these data indicate a synergism between HFD and CVS on the HR and cardiac SNS responses, suggesting an increased cardiovascular risk. Besides, neuroendocrine and anxiogenic disturbers may contribute to the cardiovascular changes induced by HFD and CVS, respectively.

Supplementation with the Leucine Metabolite ß-hydroxy-ß-methylbutyrate (HMB) does not Improve Resistance Exercise-Induced Changes in Body Composition or Strength in Young Subjects: A Systematic Review and Meta-Analysis.

ß-hydroxy-ß-methylbutyrate (HMB) is a leucine metabolite that is purported to increase fat-free mass (FFM) gain and performance in response to resistance exercise training (RET). The aim of this systematic review and meta-analysis was to determine the efficacy of HMB supplementation in augmenting FFM and strength gains during RET in young adults. Outcomes investigated were: total body mass (TBM), FFM, fat mass (FM), total single repetition maximum (1RM), bench press (BP) 1RM, and lower body (LwB) 1RM. Databases consulted were: Medical Literature Analysis and Retrieval System Online (Medline), Excerpta Medica database (Embase), The Cumulative Index to Nursing and Allied Health Literature (CINAHL), and SportDiscus. Fourteen studies fit the inclusion criteria; however, 11 were analyzed after data extraction and funnel plot analysis exclusion. A total of 302 participants (18-45 y) were included in body mass and composition analysis, and 248 were included in the strength analysis. A significant effect was found on TBM. However, there were no significant effects for FFM, FM, or strength outcomes. We conclude that HMB produces a small effect on TBM gain, but this effect does not translate into significantly greater increases in FFM, strength or decreases in FM during periods of RET. Our findings do not support the use of HMB aiming at improvement of body composition or strength with RET.

Nitrate attenuates high fat diet-induced glucose intolerance in association with reduced epididymal adipose tissue inflammation and mitochondrial reactive oxygen species emission.

KEY POINTS: Dietary nitrate is a prominent therapeutic strategy to mitigate some metabolic deleterious effects related to obesity. Mitochondrial dysfunction is causally linked to adipose tissue inflammation and insulin resistance. Whole-body glucose tolerance is prevented by nitrate independent of body weight and energy expenditure. Dietary nitrate reduces epididymal adipose tissue inflammation and mitochondrial reactive oxygen species emission while preserving insulin signalling. Metabolic beneficial effects of nitrate consumption are associated with improvements in mitochondrial redox balance in hypertrophic adipose tissue. ABSTRACT: Evidence has accumulated to indicate that dietary nitrate alters energy expenditure and the metabolic derangements associated with a high fat diet (HFD), but the mechanism(s) of action remain incompletely elucidated. Therefore, we aimed to determine if dietary nitrate (4 mm sodium nitrate via drinking water) could prevent HFD-mediated glucose intolerance in association with improved mitochondrial bioenergetics within both white (WAT) and brown (BAT) adipose tissue in mice. HFD feeding caused glucose intolerance (P < 0.05) and increased body weight. As a result of higher body weight, energy expenditure increased proportionally. HFD-fed mice displayed greater mitochondrial uncoupling and a twofold increase in uncoupling protein 1 content within BAT. Within epididymal white adipose tissue (eWAT), HFD increased cell size (i.e. hypertrophy), mitochondrial H2 O2 emission, oxidative stress, c-Jun N-terminal kinase phosphorylation and leucocyte infiltration, and induced insulin resistance. Remarkably, dietary nitrate consumption attenuated and/or mitigated all these responses, including rendering mitochondria more coupled within BAT, and normalizing mitochondrial H2 O2 emission and insulin-mediated Akt-Thr308 phosphorylation within eWAT. Intriguingly, the positive effects of dietary nitrate appear to be independent of eWAT mitochondrial respiratory capacity and content. Altogether, these data suggest that dietary nitrate attenuates the development of HFD-induced insulin resistance in association with attenuating WAT inflammation and redox balance, independent of changes in either WAT or BAT mitochondrial respiratory capacity/content.

The Influence of Omega-3 Fatty Acids on Skeletal Muscle Protein Turnover in Health, Disuse, and Disease.

Ingestion of omega-3 fatty acids is known to exert favorable health effects on a number of biological processes such as improved immune profile, enhanced cognition, and optimized neuromuscular function. Recently, data have emerged demonstrating a positive influence of omega-3 fatty acid intake on skeletal muscle. For instance, there are reports of clinically-relevant gains in muscle size and strength in healthy older persons with omega-3 fatty acid intake as well as evidence that omega-3 fatty acid ingestion alleviates the loss of muscle mass and prevents decrements in mitochondrial respiration during periods of muscle-disuse. Cancer cachexia that is characterized by a rapid involuntary loss of lean mass may also be attenuated by omega-3 fatty acid provision. The primary means by which omega-3 fatty acids positively impact skeletal muscle mass is via incorporation of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) into membrane phospholipids of the sarcolemma and intracellular organelles. Enrichment of EPA and DHA in these membrane phospholipids is linked to enhanced rates of muscle protein synthesis, decreased expression of factors that regulate muscle protein breakdown, and improved mitochondrial respiration kinetics. However, exactly how incorporation of EPA and DHA into phospholipid membranes alters these processes remains unknown. In this review, we discuss the interaction between omega-3 fatty acid ingestion and skeletal muscle protein turnover in response to nutrient provision in younger and older adults. Additionally, we examine the role of omega-3 fatty acid supplementation in protecting muscle loss during muscle-disuse and in cancer cachexia, and critically evaluate the molecular mechanisms that underpin the phenotypic changes observed in skeletal muscle with omega-3 fatty acid intake.

Equivalent Hypertrophy and Strength Gains in ß-Hydroxy-ß-Methylbutyrate- or Leucine-supplemented Men.

Ingestion of proteins with high leucine content during resistance training (RT) can augment hypertrophy. Some data suggest that a leucine metabolite, ß-hydroxy, ß-methylbutyrate (HMB), is substantially more anabolically efficacious than leucine. PURPOSE: We aimed to test whether supplementation with HMB versus leucine, added to whey protein, would result in differential muscle hypertrophy and strength gains in young men performing RT. METHODS: Twenty-six resistance-trained men (23 ± 2 yr) performed 12 wk of RT with three phases. Phase 1: 8 wk of periodized RT (three training sessions per week). Phase 2: 2 wk overreaching period (five sessions per week). Phase 3: 2 wk taper (three sessions per week). Participants were randomly assigned to twice daily ingestion of: whey protein (25 g) plus HMB (1.5 g) (whey+HMB; n = 13) or whey protein (25 g) plus leucine (1.5 g) (whey+leu; n = 13). Skeletal muscle biopsies were performed before and after RT. Measures of fat- and bone-free mass, vastus lateralis (VL) muscle thickness and muscle cross-sectional area (CSA) (both by ultrasound), muscle fiber CSA, and 1-repetition maximum (1-RM) strength tests were determined. RESULTS: We observed increases in fat- and bone-free mass, VL muscle thickness, muscle CSA and fiber type CSA and 1-RM strength with no differences between groups at any phase. We observed no differences between groups or time-group interactions in hormone concentrations at any phase of the RT program. CONCLUSIONS: ß-Hydroxy-ß-methylbutyrate added to whey did not result in greater increases in any measure of muscle mass, strength, or hormonal concentration compared to leucine added to whey. Our results show that HMB is no more effective in stimulating RT-induced hypertrophy and strength gains than leucine.

Does L-leucine supplementation cause any effect on glucose homeostasis in rodent models of glucose intolerance? A systematic review.

L-Leucine has been used to improve metabolic outcomes in glucose-intolerant rodent models. However, because studies have used different experimental models and conditions it is difficult to establish the best approach for new clinical trials evaluating the potential effects of L-leucine on glucose homeostasis. We performed a systematic review to report the effect of L-leucine supplementation on glucose homeostasis in rodents with glucose intolerance. The search engines MEDLINE and ScienceDirect were applied using MeSH terms. Thirty-four studies were included in this systematic review. Based on the current data, ingestion of 90-140 mg day-1 of isolated L-leucine in diet-induced obesity (DIO) models shows improvement in metabolic markers if offered during the development of the metabolic disorder in almost all the studies, but not after. Branched-chain amino acid supplementation was effective in streptozotocin-induced ß-cells death but not in DIO models. L-Leucine supplementation seems to have an optimal dose and timing for supplementation to improve glucose homeostasis in DIO.