Molecular and clinical effects of aromatase inhibitor therapy on skeletal muscle function in early-stage breast cancer.

We evaluated biochemical changes in skeletal muscle of women with breast cancer initiating aromatase inhibitors (AI), including oxidation of ryanodine receptor RyR1 and loss of stabilizing protein calstabin1, and detailed measures of muscle function. Fifteen postmenopausal women with stage I-III breast cancer planning to initiate AI enrolled. Quadriceps muscle biopsy, dual-energy x-ray absorptiometry, isokinetic dynamometry, Short Physical Performance Battery, grip strength, 6-min walk, patient-reported outcomes, and serologic measures of bone turnover were assessed before and after 6 months of AI. Post-AI exposure, oxidation of RyR1 significantly increased (0.23 ± 0.37 vs. 0.88 ± 0.80, p < 0.001) and RyR1-bound calstabin1 significantly decreased (1.69 ± 1.53 vs. 0.74 ± 0.85, p < 0.001), consistent with dysfunctional calcium channels in skeletal muscle. Grip strength significantly decreased at 6 months. No significant differences were seen in isokinetic dynamometry measures of muscle contractility, fatigue resistance, or muscle recovery post-AI exposure. However, there was significant correlation between oxidation of RyR1 with muscle power (r = 0.60, p = 0.02) and muscle fatigue (r = 0.57, p = 0.03). Estrogen deprivation therapy for breast cancer resulted in maladaptive changes in skeletal muscle, consistent with the biochemical signature of dysfunctional RyR1 calcium channels. Future studies will evaluate longer trajectories of muscle function change and include other high bone turnover states, such as bone metastases.

The Influence of a Total Body Resistance Training Program on Autonomic Modulation and Strength Variables in Young Adults.

The purpose of this study was to examine autonomic modulation using multiple quantitative measures before and after a resistance training (RT) intervention. Seventeen young adults (age 18-35 years) were tested for body composition, muscular strength, and autonomic activity. The RT protocol targeted total-body large muscle groups, which were performed three days a week for eight-weeks. Autonomic assessments included respiratory sinus arrhythmia (RSA), static handgrip exercise, Valsalva maneuver, heart rate variability (HRV), and tilt-table testing. The main finding was that tilt-table duration increased by 68 seconds (p = 0.05) after RT. Upper body strength increased by 11.2 kg (p = 0.001) and lower body strength increased by 68.3 kg (p < 0.001) following completion of the RT intervention. The average total lean mass increased by 1.5 kg (p < 0.01), while total fat mass was unchanged (Δ = 0.5 kg, p = 0.23). RSA (Δ = 0.4, p = 0.89), Valsalva ratio (Δ = -0.09, p = 0.48), static handgrip (Δ = 8 mm Hg, p = 0.07), and HRV (Δ = -0.4, p = 0.53) were not affected by RT. The results from this study suggest that RT improves tilt-table tolerance in a young healthy population as evidence by improved tilt-table duration. However, RT seemed to have no effect on cardio-vagal or adrenergic function.

Regular Resistance Training Enhances Fibrinolytic Potential but Does Not Affect Coagulation.

PURPOSE: This study aimed to identify effects of an 8-wk, whole-body RT program on coagulation and fibrinolysis. METHODS: Sixteen healthy women and men (23 ± 5 yr) completed an RT program three times per week for 8 wk. Exercises included 2-3 sets of 8-12 repetitions performed at approximately 60%-80% of a one repetition maximum. Strength, body composition, and body circumferences were assessed before and after training. Plasma samples were obtained before and after training, and analyzed for active tissue plasminogen activator (tPA activity), total tissue plasminogen activator (tPA antigen), active plasminogen activator inhibitor-1 (PAI-1 activity), total plasminogen activator inhibitor-1 (PAI-1 antigen), fibrinogen, and coagulation factors VII (FVII) and VIII (FVIII). RESULTS: Significant increases in lean mass, arm and thigh circumferences, maximal chest press (PRE: 57.8 ± 37.5 kg, POST: 73.3 ± 43.2 kg), and leg press (PRE: 189.5 ± 96.0 kg, POST: 256.7 ± 97.9 kg) were observed (P < 0.05 for all). PAI-1 activity (PRE: 20.3 ± 32.5 IU·mL-1, POST 9.5 ± 20.9 IU·mL-1) and PAI-1 antigen decreased (PRE: 10.2 ± 9.0 ng·dL-1, POST: 7.2 ± 5.7 ng·dL-1; both, P < 0.05). No change in tPA activity or tPA antigen occurred. Fibrinogen, FVII, and FVIII did not change after training. CONCLUSIONS: Inhibition of fibrinolysis was decreased after training, and coagulation was unaffected. These results suggest that regular RT may beneficially influence the risk of a thrombotic event. More research is warranted to understand the mechanisms through which RT affects hemostasis.

Beetroot supplementation in women enjoying exercise together (BEE SWEET): Rationale, design and methods.

BACKGROUND: Postmenopausal women exhibit higher rates of disability and cardiovascular disease (CVD) with aging compared to men. Whereas habitual exercise training is a known strategy to enhance physiologic function in men and premenopausal women, exercise-related adaptations are often modest in postmenopausal women. We propose dietary nitrate (beetroot juice) administered prior to exercise training may be a feasible approach to improve mobility and cardio-metabolic health outcomes in postmenopausal women. METHODS: Our randomized, placebo-controlled study aims to determine preliminary effects sizes for changes in functional mobility and endothelium-dependent vasodilation across three study arms: exercise only (EX), exercise + placebo (EX + PL), and exercise + beetroot (EX + BR). Thirty-six postmenopausal women are recruited in small cohorts wherein group exercise is implemented to facilitate social support and adherence to an 8-week training progression. Participants are randomized to one of three study arms (n = 12 per group) following baseline assessments. Post-intervention assessments are used to determine pre-post changes in outcome measures including distance covered during a 6 min walk test, walking economy, muscle speed and power, and endothelial-dependent vasodilation as determined by flow-mediated dilation. Measures of feasibility include recruitment, retention, adherence to exercise prescription, perceived exercise session difficulty, and adverse event rates. DISCUSSION: Evidence-based, translational strategies are needed to optimize exercise training-related adaptations in postmenopausal women. Findings will inform larger randomized clinical trials to determine if pre-exercise consumption of beetroot juice is an efficacious strategy to promote mobility and attenuate CVD disease risk.

Dietary Nitrate Supplementation and Exercise-Related Performance.

Over the last decade, there has been a growing interest in the utility of nitrate (NO3-) supplementation to improve exercise-related performance. After consumption, dietary NO3- can be reduced to nitric oxide, a free radical gas involved in numerous physiological actions including blood vessel vasodilation, mitochondrial respiration, and skeletal muscle contractile function. Emerging evidence indicates that dietary NO3- supplementation has a small but nevertheless significant beneficial effect on endurance performance through the combined effects of enhanced tissue oxygenation and metabolic efficiency in active skeletal muscle. There is further evidence to suggest that dietary NO3- exerts a direct influence on contractile mechanisms within the skeletal muscle through alterations in calcium availability and sensitivity. Response heterogeneity and sizeable variability in the nitrate content of beetroot juice products influence the effectiveness of dietary NO3- for exercise performance, and so dosing and product quality, as well as training history, sex, and individual-specific characteristics, should be considered.