Steven K. Baker

Resistance exercise load does not determine training-mediated hypertrophic gains in young men

We have reported that the acute postexercise increases in muscle protein synthesis rates, with differing nutritional support, are predictive of longer-term training-induced muscle hypertrophy. Here, we aimed to test whether the same was true with acute exercise-mediated changes in muscle protein synthesis. Eighteen men (21 ± 1 yr, 22.6 ± 2.1 kg/m(2); means ± SE) had their legs randomly assigned to two of three training conditions that differed in contraction intensity [% of maximal strength (1 repetition maximum)] or contraction volume (1 or 3 sets of repetitions): 30%-3, 80%-1, and 80%-3. Subjects trained each leg with their assigned regime for a period of 10 wk, 3 times/wk. We made pre- and posttraining measures of strength, muscle volume by magnetic resonance (MR) scans, as well as pre- and posttraining biopsies of the vastus lateralis, and a single postexercise (1 h) biopsy following the first bout of exercise, to measure signaling proteins. Training-induced increases in MR-measured muscle volume were significant (P < 0.01), with no difference between groups: 30%-3 = 6.8 ± 1.8%, 80%-1 = 3.2 ± 0.8%, and 80%-3= 7.2 ± 1.9%, P = 0.18. Isotonic maximal strength gains were not different between 80%-1 and 80%-3, but were greater than 30%-3 (P = 0.04), whereas training-induced isometric strength gains were significant but not different between conditions (P = 0.92). Biopsies taken 1 h following the initial resistance exercise bout showed increased phosphorylation (P < 0.05) of p70S6K only in the 80%-1 and 80%-3 conditions. There was no correlation between phosphorylation of any signaling protein and hypertrophy. In accordance with our previous acute measurements of muscle protein synthetic rates a lower load lifted to failure resulted in similar hypertrophy as a heavy load lifted to failure.

Low-load high volume resistance exercise stimulates muscle protein synthesis more than high-load low volume resistance exercise in young men.

Background We aimed to determine the effect of resistance exercise intensity (% 1 repetition maximum—1RM) and volume on muscle protein synthesis, anabolic signaling, and myogenic gene expression. Methodology/Principal Findings Fifteen men (21±1 years; BMI = 24.1±0.8 kg/m2) performed 4 sets of unilateral leg extension exercise at different exercise loads and/or volumes: 90% of repetition maximum (1RM) until volitional failure (90FAIL), 30% 1RM work-matched to 90%FAIL (30WM), or 30% 1RM performed until volitional failure (30FAIL). Infusion of [ring-13C6] phenylalanine with biopsies was used to measure rates of mixed (MIX), myofibrillar (MYO), and sarcoplasmic (SARC) protein synthesis at rest, and 4 h and 24 h after exercise. Exercise at 30WM induced a significant increase above rest in MIX (121%) and MYO (87%) protein synthesis at 4 h post-exercise and but at 24 h in the MIX only. The increase in the rate of protein synthesis in MIX and MYO at 4 h post-exercise with 90FAIL and 30FAIL was greater than 30WM, with no difference between these conditions; however, MYO remained elevated (199%) above rest at 24 h only in 30FAIL. There was a significant increase in AktSer473 at 24h in all conditions (P = 0.023) and mTORSer2448 phosphorylation at 4 h post-exercise (P = 0.025). Phosporylation of Erk1/2Tyr202/204, p70S6KThr389, and 4E-BP1Thr37/46 increased significantly (P<0.05) only in the 30FAIL condition at 4 h post-exercise, whereas, 4E-BP1Thr37/46 phosphorylation was greater 24 h after exercise than at rest in both 90FAIL (237%) and 30FAIL (312%) conditions. Pax7 mRNA expression increased at 24 h post-exercise (P = 0.02) regardless of condition. The mRNA expression of MyoD and myogenin were consistently elevated in the 30FAIL condition. Conclusions/Significance These results suggest that low-load high volume resistance exercise is more effective in inducing acute muscle anabolism than high-load low volume or work matched resistance exercise modes.

Resistance exercise‐induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men

We aimed to determine whether exercise‐induced elevations in systemic concentration of testosterone, growth hormone (GH) and insulin‐like growth factor‐1 (IGF‐1) enhanced post‐exercise myofibrillar protein synthesis (MPS) and phosphorylation of signalling proteins important in regulating mRNA translation. Eight young men (20 ± 1.1 years, BMI = 26 ± 3.5 kg m−2) completed two exercise protocols designed to maintain basal hormone concentrations (low hormone, LH) or elicit increases in endogenous hormones (high hormone, HH). In the LH protocol, participants performed a bout of unilateral resistance exercise with the elbow flexors. The HH protocol consisted of the same elbow flexor exercise with the contralateral arm followed immediately by high‐volume leg resistance exercise. Participants consumed 25 g of protein after arm exercise to maximize MPS. Muscle biopsies and blood samples were taken as appropriate. There were no changes in serum testosterone, GH or IGF‐1 after the LH protocol, whereas there were marked elevations after HH (testosterone, P < 0.001; GH, P < 0.001; IGF‐1, P < 0.05). Exercise stimulated a rise in MPS in the biceps brachii (rest = 0.040 ± 0.007, LH = 0.071 ± 0.008, HH = 0.064 ± 0.014% h−1; P < 0.05) with no effect of elevated hormones (P= 0.72). Phosphorylation of the 70 kDa S6 protein kinase (p70S6K) also increased post‐exercise (P < 0.05) with no differences between conditions. We conclude that the transient increases in endogenous purportedly anabolic hormones do not enhance fed‐state anabolic signalling or MPS following resistance exercise. Local mechanisms are likely to be of predominant importance for the post‐exercise increase in MPS.

Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors

The aim of our study was to determine whether resistance exercise-induced elevations in endogenous hormones enhance muscle strength and hypertrophy with training. Twelve healthy young men (21.8 +/- 1.2 yr, body mass index = 23.1 +/- 0.6 kg/m(2)) trained their elbow flexors independently for 15 wk on separate days and under different hormonal milieu. In one training condition, participants performed isolated arm curl exercise designed to maintain basal hormone concentrations (low hormone, LH); in the other training condition, participants performed identical arm exercise to the LH condition followed immediately by a high volume of leg resistance exercise to elicit a large increase in endogenous hormones (high hormone, HH). There was no elevation in serum growth hormone (GH), insulin-like growth factor (IGF-1), or testosterone after the LH protocol but significant (P < 0.001) elevations in these hormones immediately and 15 and 30 min after the HH protocol. The hormone responses elicited by each respective exercise protocol late in the training period were similar to the response elicited early in the training period, indicating that a divergent postexercise hormone response was maintained over the training period. Muscle cross-sectional area (CSA) increased by 12% in LH and 10% in HH (P < 0.001) with no difference between conditions (condition x training interaction, P = 0.25). Similarly, type I (P < 0.01) and type II (P < 0.001) muscle fiber CSA increased with training with no effect of hormone elevation in the HH condition. Strength increased in both arms, but the increase was not different between the LH and HH conditions. We conclude that exposure of loaded muscle to acute exercise-induced elevations in endogenous anabolic hormones enhances neither muscle hypertrophy nor strength with resistance training in young men.

An assessment by the Statin Muscle Safety Task Force: 2014 update

The National Lipid Associations Muscle Safety Expert Panel was charged with the duty of examining the definitions for statin-associated muscle adverse events, development of a clinical index to assess myalgia, and the use of diagnostic neuromuscular studies to investigate muscle adverse events. We provide guidance as to when a patient should be considered for referral to neuromuscular specialists and indications for the performance of a skeletal muscle biopsy. Based on this review of evidence, we developed an algorithm for the evaluation and treatment of patients who may be intolerant to statins as the result of adverse muscle events. The panel was composed of clinical cardiologists, clinical lipidologists, an exercise physiologist, and a neuromuscular specialist.

Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men

•  Essential amino acids (EAAs) stimulate increased rates of myofibrillar protein synthesis (MPS). •  Leucine is a key regulator of MPS in rodents; however, its importance relative to the other EAAs is not clear. •  About 20 g of protein maximally stimulates MPS after resistance exercise in young men, but we do not know if smaller doses can be made better by adding certain amino acids. •  We report that a suboptimal dose of whey protein (6.25 g) supplemented with either leucine or a mixture of EAAs without leucine stimulates MPS similar to 25 g of whey protein under resting conditions; however, only 25 g of whey sustains exercise‐induced rates of MPS. •  Adding leucine or a mixture of EAAs without leucine to a suboptimal dose of whey is as effective as 25 g whey at stimulating fed rates of MPS; however, 25 g of whey is better suited to increase resistance exercise‐induced muscle anabolism.

Enhanced Amino Acid Sensitivity of Myofibrillar Protein Synthesis Persists for up to 24 h after Resistance Exercise in Young Men

We aimed to determine whether an exercise-mediated enhancement of muscle protein synthesis to feeding persisted 24 h after resistance exercise. We also determined the impact of different exercise intensities (90% or 30% maximal strength) or contraction volume (work-matched or to failure) on the response at 24 h of recovery. Fifteen men (21 ± 1 y, BMI = 24.1 ± 0.8 kg · m(-2)) received a primed, constant infusion of l-[ring-(13)C(6)]phenylalanine to measure muscle protein synthesis after protein feeding at rest (FED; 15 g whey protein) and 24 h after resistance exercise (EX-FED). Participants performed unilateral leg exercises: 1) 4 sets at 90% of maximal strength to failure (90FAIL); 2) 30% work-matched to 90FAIL (30WM); or 3) 30% to failure (30FAIL). Regardless of condition, rates of mixed muscle protein and sarcoplasmic protein synthesis were similarly stimulated at FED and EX-FED. In contrast, protein ingestion stimulated rates of myofibrillar protein synthesis above fasting rates by 0.016 ± 0.002%/h and the response was enhanced 24 h after resistance exercise, but only in the 90FAIL and 30FAIL conditions, by 0.038 ± 0.012 and 0.041 ± 0.010, respectively. Phosphorylation of protein kinase B on Ser473 was greater than FED at EX-FED only in 90FAIL, whereas phosphorylation of mammalian target of rapamycin on Ser2448 was significantly increased at EX-FED above FED only in the 30FAIL condition. Our results suggest that resistance exercise performed until failure confers a sensitizing effect on human skeletal muscle for at least 24 h that is specific to the myofibrillar protein fraction.

Resistance exercise volume affects myofibrillar protein synthesis and anabolic signalling molecule phosphorylation in young men

We aimed to determine if any mechanistic differences exist between a single set (1SET) and multiple sets (i.e. 3 sets; 3SET) of resistance exercise by utilizing a primed constant infusion of [ring‐13C6]phenylalanine to determine myofibrillar protein synthesis (MPS) and Western blot analysis to examine anabolic signalling molecule phosphorylation following an acute bout of resistance exercise. Eight resistance‐trained men (24 ± 5 years, BMI = 25 ± 4 kg m−2) were randomly assigned to perform unilateral leg extension exercise at 70% concentric one repetition maximum (1RM) until volitional fatigue for 1SET or 3SET. Biopsies from the vastus lateralis were taken in the fasted state (Fast) and fed state (Fed; 20 g of whey protein isolate) at rest, 5 h Fed, 24 h Fast and 29 h Fed post‐exercise. Fed‐state MPS was transiently elevated above rest at 5 h for 1SET (2.3‐fold) and returned to resting levels by 29 h post‐exercise. However, the exercise induced increase in MPS following 3SET was superior in amplitude and duration as compared to 1SET at both 5 h (3.1‐fold above rest) and 29 h post‐exercise (2.3‐fold above rest). Phosphorylation of 70 kDa S6 protein kinase (p70S6K) demonstrated a coordinated increase with MPS at 5 h and 29 h post‐exercise such that the extent of p70S6K phosphorylation was related to the MPS response (r= 0.338, P= 0.033). Phosphorylation of 90 kDa ribosomal S6 protein kinase (p90RSK) and ribosomal protein S6 (rps6) was similar for 1SET and 3SET at 24 h Fast and 29 h Fed, respectively. However, 3SET induced a greater activation of eukaryotic translation initiation factor 2Bɛ (eIF2Bɛ) and rpS6 at 5 h Fed. These data suggest that 3SET of resistance exercise is more anabolic than 1SET and may lead to greater increases in myofibrillar protein accretion over time.

Muscle time under tension during resistance exercise stimulates differential muscle protein sub-fractional synthetic responses in men

Non‐technical summary  A single bout of resistance exercise stimulates the synthesis of new muscle proteins. Chronic performance of resistance exercise (i.e. weight training) is what makes your muscles grow bigger; a process known as hypertrophy. However, it is unknown if increasing the time that muscle is under tension will lead to greater increases in muscle protein synthesis. We report that leg extension exercise at 30% of the best effort (which is a load that is comparatively light), with a slow lifting movement (6 s up and 6 s down) performed to fatigue produces greater increases in rates of muscle protein synthesis than the same movement performed rapidly (1 s up and 1 s down). These results suggest that the time the muscle is under tension during exercise may be important in optimizing muscle growth; this understanding enables us to better prescribe exercise to those wishing to build bigger muscles and/or to prevent muscle loss that occurs with ageing or disease.

Diagnosis, Prevention, and Management of Statin Adverse Effects and Intolerance: Proceedings of a Canadian Working Group Consensus Conference

While the proportion of patients with significant statin-associated adverse effects or intolerance is very low, the increasing use and broadening indications have led to a significant absolute number of such patients commonly referred to tertiary care facilities and specialists. This report provides a comprehensive overview of the evidence pertaining to a broad variety of statin-associated adverse effects followed by a consensus approach for the prevention, assessment, diagnosis, and management. The overview is intended both to provide clarification of the untoward effects of statins and to impart confidence in managing the most common issues in a fashion that avoids excessive ancillary testing and/or subspecialty referral except when truly necessary. The ultimate goal is to ensure that patients who warrant cardiovascular risk reduction can be treated optimally, safely, and confidently with statin medications or alternatives when warranted.