The Need for Standardized Assessment of Muscle Quality in Skeletal Muscle Function Deficit and Other Aging-Related Muscle Dysfunctions: A Symposium Report

A growing body of scientific literature suggests that not only changes in skeletal muscle mass, but also other factors underpinning muscle quality, play a role in the decline in skeletal muscle function and impaired mobility associated with aging. A symposium on muscle quality and the need for standardized assessment was held on April 28, 2016 at the International Conference on Frailty and Sarcopenia Research in Philadelphia, Pennsylvania. The purpose of this symposium was to provide a venue for basic science and clinical researchers and expert clinicians to discuss muscle quality in the context of skeletal muscle function deficit and other aging-related muscle dysfunctions. The present article provides an expanded introduction concerning the emerging definitions of muscle quality and a potential framework for scientific inquiry within the field. Changes in muscle tissue composition, based on excessive levels of inter- and intra-muscular adipose tissue and intramyocellular lipids, have been found to adversely impact metabolism and peak force generation. However, methods to easily and rapidly assess muscle tissue composition in multiple clinical settings and with minimal patient burden are needed. Diagnostic ultrasound and other assessment methods continue to be developed for characterizing muscle pathology, and enhanced sonography using sensors to provide user feedback and improve reliability is currently the subject of ongoing investigation and development. In addition, measures of relative muscle force such as specific force or grip strength adjusted for body size have been proposed as methods to assess changes in muscle quality. Furthermore, performance-based assessments of muscle power via timed tests of function and body size estimates, are associated with lower extremity muscle strength may be responsive to age-related changes in muscle quality. Future aims include reaching consensus on the definition and standardized assessments of muscle quality, and providing recommendations to address critical clinical and technology research gaps within the field

Mediators of Monocyte Migration in Response to Recovery Modalities following Resistance Exercise

Mediators of monocyte migration, complement receptor-3 (CR3), and chemokine ligand-4 (CCL4) were measured in response to recovery modalities following resistance exercise. Thirty resistance-trained men (23.1 +/- 2.9 y; 175.2 +/- 7.1 cm; 82.1 +/- 8.4 kg) were given neuromuscular electric stimulation (NMES), cold water immersion (CWI), or control (CON) treatments immediately following resistance exercise. Blood samples were obtained preexercise (PRE), immediately (IP), 30 minutes (30 P), 24 hours (24 H), and 48 hours (48 H) after exercise for measurement of circulating CCL4 and CR3 expression on CD14+ monocytes, by assay and flow cytometry. Circulating CCL4 showed no consistent changes. Inferential analysis indicated that CR3 expression was likely greater in CON at 30 P than NMES (90.0%) or CWI (86.8%). NMES was likely lower than CON at 24H (92.9%) and very likely lower at 48H (98.7%). Expression of CR3 following CWI was very likely greater than CON (96.5%) at 24H. The proportion of CR3+ monocytes was likely greater following CWI than NMES (85.8%) or CON (85.2%) at 24 H. The change in proportion of CR3+ monocytes was likely (86.4%) greater following NMES than CON from IP to 30 P. The increased expression of CR3 and increased proportion of CR3+ monocytes following CWI at 24 H indicate a potentially improved ability for monocyte adhesion to the endothelium, possibly improving phagocytosis of damaged tissues

High-intensity interval training and beta-hydroxy-beta-methylbutyric free acid improves aerobic power and metabolic thresholds

Background: Previous research combining Calcium beta-hydroxy-beta-methylbutyrate (CaHMB) and running high-intensity interval training (HIIT) have shown positive effects on aerobic performance measures. The purpose of this study was to examine the effect of beta-hydroxy-beta-methylbutyric free acid (HMBFA) and cycle ergometry HIIT on maximal oxygen consumption (VO(2)peak), ventilatory threshold (VT), respiratory compensation point (RCP) and time to exhaustion (T-max) in college-aged men and women. Methods: Thirty-four healthy men and women (Age: 22.7 +/- 3.1 yrs; VO(2)peak: 39.3 +/- 5.0 ml center dot kg(-1)center dot min(-1)) volunteered to participate in this double-blind, placebo-controlled design study. All participants completed a series of tests prior to and following treatment. A peak oxygen consumption test was performed on a cycle ergometer to assess VO(2)peak, Tmax, VT, and RCP. Twenty-six participants were randomly assigned into either a placebo (PLA-HIIT) or 3 g per day of HMBFA (BetaTor (TM) ) (HMBFA-HIIT) group. Eight participants served as controls (CTL). Participants in the HIIT groups completed 12 HIIT (80-120% maximal workload) exercise sessions consisting of 5-6 bouts of a 2: 1 minute cycling work to rest ratio protocol over a four-week period. Body composition was measured with dual energy x-ray absorptiometry (DEXA). Outcomes were assessed by ANCOVA with posttest means adjusted for pretest differences. Results: The HMBFA-HIIT intervention showed significant (p \u3c 0.05) gains in VO(2)peak, and VT, versus the CTL and PLA-HIIT group. Both PLA-HIIT and HMBFA-HIIT treatment groups demonstrated significant (p \u3c 0.05) improvement over CTL for Tmax, and RCP with no significant difference between the treatment groups. There were no significant differences observed for any measures of body composition. An independent-samples t-test confirmed that there were no significant differences between the training volumes for the PLA-HIIT and HMBFA-HIIT groups. Conclusions: Our findings support the use of HIIT in combination with HMBFA to improve aerobic fitness in college age men and women. These data suggest that the addition of HMBFA supplementation may result in greater changes in VO(2)peak and VT than HIIT alone

High-intensity interval training and beta-hydroxy-beta-methylbutyric free acid improves aerobic power and metabolic thresholds

Background: Previous research combining Calcium beta-hydroxy-beta-methylbutyrate (CaHMB) and running high-intensity interval training (HIIT) have shown positive effects on aerobic performance measures. The purpose of this study was to examine the effect of beta-hydroxy-beta-methylbutyric free acid (HMBFA) and cycle ergometry HIIT on maximal oxygen consumption (VO(2)peak), ventilatory threshold (VT), respiratory compensation point (RCP) and time to exhaustion (T-max) in college-aged men and women. Methods: Thirty-four healthy men and women (Age: 22.7 +/- 3.1 yrs; VO(2)peak: 39.3 +/- 5.0 ml center dot kg(-1)center dot min(-1)) volunteered to participate in this double-blind, placebo-controlled design study. All participants completed a series of tests prior to and following treatment. A peak oxygen consumption test was performed on a cycle ergometer to assess VO(2)peak, Tmax, VT, and RCP. Twenty-six participants were randomly assigned into either a placebo (PLA-HIIT) or 3 g per day of HMBFA (BetaTor (TM) ) (HMBFA-HIIT) group. Eight participants served as controls (CTL). Participants in the HIIT groups completed 12 HIIT (80-120% maximal workload) exercise sessions consisting of 5-6 bouts of a 2: 1 minute cycling work to rest ratio protocol over a four-week period. Body composition was measured with dual energy x-ray absorptiometry (DEXA). Outcomes were assessed by ANCOVA with posttest means adjusted for pretest differences. Results: The HMBFA-HIIT intervention showed significant (p \u3c 0.05) gains in VO(2)peak, and VT, versus the CTL and PLA-HIIT group. Both PLA-HIIT and HMBFA-HIIT treatment groups demonstrated significant (p \u3c 0.05) improvement over CTL for Tmax, and RCP with no significant difference between the treatment groups. There were no significant differences observed for any measures of body composition. An independent-samples t-test confirmed that there were no significant differences between the training volumes for the PLA-HIIT and HMBFA-HIIT groups. Conclusions: Our findings support the use of HIIT in combination with HMBFA to improve aerobic fitness in college age men and women. These data suggest that the addition of HMBFA supplementation may result in greater changes in VO(2)peak and VT than HIIT alone

Bioactive growth hormone in older men and women: Its relationship to immune markers and healthspan

Objective: The consequences of age-related decline in the somatotropic axis of humans are complex and remain largely unresolved. We tested the hypothesis that hGH measurements of plasma by bioassay vs immunoassay from samples obtained from free-living, elderly individuals would reveal a dichotomy in GH activities that are correlated with the functional status of the donors, i.e. their healthspan. Design: Forty-one men and women of advanced age (men: N=16, age, 80.5±6.5years; height, 173.1±6.9cm; body mass, 81.8±13.0kg) and (women: N=25, age, 80.7±7.2years; height, 157.7±6.0cm; body mass, 68.8±17kg), were recruited for a cross-sectional study. Participants filled out PROMIS (Patient-Reported Outcomes Measurement Information System, U. S. Department of Health and Human Services) scales, undertook physical performance tests and had fasted blood samples obtained at rest for measurement of hormonal and immunology biomarkers. Results: When measured by the well-established rat tibial line GH bioassay, one half of the plasma samples (n=20) contained bioassayable GH (bGH), but the other half (n=21) failed to mount increases in tibial plate width above saline injected controls. This difference did not correlate with the age, sex or physical functionality of the plasma donor. It also did not correlate with hGH concentrations measured by immunoassay. In those cases in which bGH was detected, various hierarchical regression models predicted that GHRH, c-peptide, VEGF, NPY, IL-4 and T-regulatory lymphocytes were associated with the difference and predicted bGH. Conclusion: Results from this study suggest that the actions of bGH at the cellular level may be modified by other factors and that this may explain the lack of correlations observed in this study

Effects of beta-Hydroxy-beta-methylbutyrate Free Acid Ingestion and Resistance Exercise on the Acute Endocrine Response

Objective. To examine the endocrine response to a bout of heavy resistance exercise following acute beta-hydroxy-beta-methylbutyrate free acid (HMB-FA) ingestion. Design. Twenty resistance trained men were randomized and consumed either 1 g of HMB-FA (BetaTor) or placebo (PL) 30 min prior to performing an acute heavy resistance exercise protocol. Blood was obtained before (PRE), immediately after (IP), and 30 min after exercise (30P). Circulating concentrations of testosterone, growth hormone (GH), insulin-like growth factor (IGF-1), and insulin were assayed. Data were analyzed with a repeated measures ANOVA and area under the curve (AUC) was analyzed by the trapezoidal rule. Results. The resistance exercise protocol resulted in significant elevations from PRE in testosterone (P \u3c 0.01), GH (P \u3c 0.01), and insulin (P = 0.05) at IP, with GH (P \u3c 0.01) and insulin (P \u3c 0.01) remaining elevated at 30P. A significant interaction was noted between groups in the plasma GH response at IP, which was significantly higher following HMB-FA compared to PL (P \u3c 0.01). AUC analysis revealed an elevated GH and IGF-1 response in the HMB-FA group compared to PL. Conclusion. HMB-FA prior to resistance exercise augments the GH response to high volume resistance exercise compared to PL. These findings provide further support for the potential anabolic benefits associated with HMB supplementation

Tracking changes in the upper boundary of the heavy-intensity exercise domain: end-test power versus respiratory compensation point

The aim of this study was to compare how respiratory compensation point (RCP) and end-test power (EP) change in response to the same four-week high intensity interval training (HIIT). The power output associated with RCP and EP before and after HIIT were recorded in 24 recreationally-active participants (14 men and 10 women). RCP was determined from an incremental exercise test and EP was derived from a three-minute maximal effort test on a cycle ergometer. A significant time (pretest/posttest) × measurement (EP/RCP) interaction was found (F(1, 23)=5.119, p<.05). Results from a paired-sample t-test indicated that both EP (t(23)= -5.221, p<.05) and RCP (t(23)=-3.049, p<.05) increased significantly from pretest to posttest. Furthermore, a small effect size (d=.36, 90%CI=[.13, .58]) was calculated for the pre/posttest changes in the examined thresholds indicating greater potential improvements in EP compared to RCP. The pre/posttest change in EP (mean=21 W, 90%CI=[14, 28 W]) exceeded its standard error of estimate (14 W), while RCP did not. Correlation analysis revealed that EP correlated with RCP at both pretest (r=.813, p<.05) and posttest (r=.873, p<.05), however, delta values between the two measures were not significantly related. Both EP and RCP can be used to assess the change of aerobic capacity after HIIT, but may be reflective of different physiological adaptations. Further, EP may be preferred over RCP when assessing the effects of HIIT

The effect of a dietary supplement (N-oleyl-phosphatidyl-ethanolamine and epigallocatechin gallate) on dietary compliance and body fat loss in adults who are overweight: A double-blind, randomized control trial

Background: A dietary supplement containing a blend of 170 mg of N-oleyl-phosphatidylethanolamine (NOPE) and 100 mg of epigallocatechin-3-gallate (EGCG) has been shown to improve compliance to low caloric diets. Considering the cost of dietary ingredients, many manufacturers attempt to determine the lowest efficacious dose. Thus, the purpose of this study was to evaluate the efficacy of 8-weeks of supplementation with a daily intake of 120 mg of NOPE and 105 mg of EGCG in conjunction with a low caloric diet and regular, moderate exercise on dietary compliance in healthy, overweight adults. An additional purpose was to examine the effect of this supplement/diet/exercise paradigm on changes in body composition, sensation of appetite, mood and severity of binge eating. Methods: Fifty healthy, overweight (BMI \u3e 25 m.kg(2)) men (15) and women (35) (SUP; n = 25; 32.7 +/- 13.75 y; BMI = 33.4 +/- 6.2; PLA; n = 25, 34.3 +/- 12.7 years; BMI = 33.2 +/- 6.8) were recruited for a double-blind, placebo controlled study. Each volunteer was randomly assigned to either the supplement (SUP; n = 25) or placebo group (PLA; n = 25). Based upon a self-reported 3-day dietary recall all volunteers were recommended a 500 kcal or 30% (maximum of 1000 kcal) reduction in caloric intake. Volunteers were also encouraged to exercise 30 minutes per day, three times per week. Results: Subjects in SUP were significantly more compliant (x(2) = 3.86, p = 0.049) in maintaining a low caloric diet at week 4, but this was not able to be maintained through the 8-week study. In addition, a significant difference in mood, feelings of fatigue and confusion were noted between the groups at week 4, but again not maintained by week 8 where only feelings of tension were improved. No differences between groups (p \u3e 0.05) were observed for body mass, body composition, feelings of hunger, and binge eating after eight weeks. Conclusion: Supplementing with a combination of 120 mg of NOPE and 105 mg of EGCG does appear to enhance compliance to a low caloric diet and improve mood for 4-weeks, but loses its effectiveness by week 8

Efficacy of phosphatidic acid ingestion on lean body mass, muscle thickness and strength gains in resistance-trained men

Background: Phosphatidic acid (PA) has been reported to activate the mammalian target of rapamycin (mTOR) signaling pathway and is thought to enhance the anabolic effects of resistance training. The purpose of this pilot study was to examine if oral phosphatidic acid administration can enhance strength, muscle thickness and lean tissue accruement during an 8-week resistance training program. Methods: Sixteen resistance-trained men were randomly assigned to a group that either consumed 750 mg of PA (n = 7, 23.1 +/- 4.4 y; 176.7 +/- 6.7 cm; 86.5 +/- 21.2 kg) or a placebo (PL, n = 9, 22.5 +/- 2.0 y; 179.8 +/- 5.4 cm; 89.4 +/- 13.6 kg) group. During each testing session subjects were assessed for strength (one repetition maximum [1-RM] bench press and squat) and body composition. Muscle thickness and pennation angle were also measured in the vastus lateralis of the subject\u27s dominant leg. Results: Subjects ingesting PA demonstrated a 12.7% increase in squat strength and a 2.6% increase in LBM, while subjects consuming PL showed a 9.3% improvement in squat strength and a 0.1% change in LBM. Although parametric analysis was unable to demonstrate significant differences, magnitude based inferences indicated that the Delta change in 1-RM squat showed a likely benefit from PA on increasing lower body strength and a very likely benefit for increasing lean body mass (LBM). Conclusions: Results of this study suggest that a combination of a daily 750 mg PA ingestion, combined with a 4-day per week resistance training program for 8-weeks appears to have a likely benefit on strength improvement, and a very likely benefit on lean tissue accruement in young, resistance trained individuals

An Evidence-Based Comparison of Operational Criteria for the Presence of Sarcopenia

Background. Several consensus groups have previously published operational criteria for sarcopenia, incorporating lean mass with strength and/or physical performance. The purpose of this manuscript is to describe the prevalence, agreement, and discrepancies between the Foundation for the National Institutes of Health (FNIH) criteria with other operational definitions for sarcopenia. Methods. The FNIH Sarcopenia Project used data from nine studies including: Age, Gene and Environment Susceptibility-Reykjavik Study; Boston Puerto Rican Health Study; a series of six clinical trials from the University of Connecticut; Framingham Heart Study; Health, Aging, and Body Composition Study; Invecchiare in Chianti; Osteoporotic Fractures in Men Study; Rancho Bernardo Study; and Study of Osteoporotic Fractures. Participants included in these analyses were aged 65 and older and had measures of body mass index, appendicular lean mass, grip strength, and gait speed. Results. The prevalence of sarcopenia and agreement proportions was higher in women than men. The lowest prevalence was observed with the FNIH criteria (1.3% men and 2.3% women) compared with the International Working Group and the European Working Group for Sarcopenia in Older Persons (5.1% and 5.3% in men and 11.8% and 13.3% in women, respectively). The positive percent agreements between the FNIH criteria and other criteria were low, ranging from 7% to 32% in men and 5% to 19% in women. However, the negative percent agreement were high (all >95%). Conclusions. The FNIH criteria result in a more conservative operational definition of sarcopenia, and the prevalence was lower compared with other proposed criteria. Agreement for diagnosing sarcopenia was low, but agreement for ruling out sarcopenia was very high. Consensus on the operational criteria for the diagnosis of sarcopenia is much needed to characterize populations for study and to identify adults for treatment