The potential therapeutic effects of creatine supplementation on body composition and muscle function in cancer

Low muscle mass in individuals with cancer has a profound impact on quality of life and independence and is associated with greater treatment toxicity and poorer prognosis. Exercise interventions are regularly being investigated as a means to ameliorate treatment-related adverse effects, and nutritional/supplementation strategies to augment adaptations to exercise are highly valuable. Creatine (Cr) is a naturally-occurring substance in the human body that plays a critical role in energy provision during muscle contraction. Given the beneficial effects of Cr supplementation on lean body mass, strength, and physical function in a variety of clinical populations, there is therapeutic potential in individuals with cancer at heightened risk for muscle loss. Here, we provide an overview of Cr physiology, summarize the evidence on the use of Cr supplementation in various aging/clinical populations, explore mechanisms of action, and provide perspectives on the potential therapeutic role of Cr in the exercise oncology setting

Feasibility and preliminary efficacy of a 10-week resistance and aerobic exercise intervention during neoadjuvant chemoradiation treatment in rectal cancer patients

Background: Neoadjuvant chemoradiation treatment (CRT) in rectal cancer patients is associated with a reduction in physical capacity, lean mass and increased fatigue. As a countermeasure to these treatment-related adverse effects, we examined the feasibility and preliminary efficacy of a 10-week exercise program during CRT. Methods: Ten rectal cancer patients (7 men, aged 27-70 years, body mass index = 26.4 ± 3.8 kg/m2) receiving CRT undertook supervised resistance and aerobic exercise twice weekly. Assessments were undertaken pre- and post-intervention for upper and lower body muscle strength by 1-RM, muscle endurance, physical performance tests, body composition by dual X-ray absorptiometry, quality of life, and fatigue. Results: There was a significant loss in appendicular skeletal muscle (−1.1 kg, P =.012), and fat mass (−0.8 kg, P =.029) following CRT. Despite the loss in skeletal muscle, leg press (P =.030) and leg extension (P =.046) strength improved by 27.2% and 22.7%, respectively, and leg press endurance by 76.7% (P =.007). Changes in strength were accompanied by improved performance (P\u3c .05) in 6-m fast walking speed (6.9%) and dynamic balance as determined by the 6-m backwards walk (15.5%). There was minimal change in quality of life and fatigue, and no adverse events related to training. Conclusions: Exercise during neoadjuvant CRT appears to be feasible and well tolerated in rectal cancer patients and may enhance physical function while minimizing adverse changes in body composition and cancer-related fatigue. These initial findings need to be confirmed in randomized controlled trials

Feasibility and preliminary efficacy of a 10-week resistance and aerobic exercise intervention during neoadjuvant chemoradiation treatment in rectal cancer patients

Background: Neoadjuvant chemoradiation treatment (CRT) in rectal cancer patients is associated with a reduction in physical capacity, lean mass and increased fatigue. As a countermeasure to these treatment-related adverse effects, we examined the feasibility and preliminary efficacy of a 10-week exercise program during CRT. Methods: Ten rectal cancer patients (7 men, aged 27-70 years, body mass index = 26.4 ± 3.8 kg/m2) receiving CRT undertook supervised resistance and aerobic exercise twice weekly. Assessments were undertaken pre- and post-intervention for upper and lower body muscle strength by 1-RM, muscle endurance, physical performance tests, body composition by dual X-ray absorptiometry, quality of life, and fatigue. Results: There was a significant loss in appendicular skeletal muscle (−1.1 kg, P =.012), and fat mass (−0.8 kg, P =.029) following CRT. Despite the loss in skeletal muscle, leg press (P =.030) and leg extension (P =.046) strength improved by 27.2% and 22.7%, respectively, and leg press endurance by 76.7% (P =.007). Changes in strength were accompanied by improved performance (

Exercise medicine for cancer cachexia: targeted exercise to counteract mechanisms and treatment side effects

Purpose Cancer-induced muscle wasting (i.e., cancer cachexia, CC) is a common and devastating syndrome that results in the death of more than 1 in 5 patients. Although primarily a result of elevated inflammation, there are multiple mechanisms that complement and amplify one another. Research on the use of exercise to manage CC is still limited, while exercise for CC management has been recently discouraged. Moreover, there is a lack of understanding that exercise is not a single medicine, but mode, type, dosage, and timing (exercise prescription) have distinct health outcomes. The purpose of this review was to examine the effects of these modes and subtypes to identify the most optimal form and dosage of exercise therapy specific to each underlying mechanism of CC. Methods The relevant literatures from MEDLINE and Scopus databases were examined. Results Exercise can counteract the most prominent mechanisms and signs of CC including muscle wasting, increased protein turnover, systemic inflammation, reduced appetite and anorexia, increased energy expenditure and fat wasting, insulin resistance, metabolic dysregulation, gut dysbiosis, hypogonadism, impaired oxidative capacity, mitochondrial dysfunction, and cancer treatments side-effects. There are different modes of exercise, and each mode has different sub-types that induce vastly diverse changes when performed over multiple sessions. Choosing suboptimal exercise modes, types, or dosages can be counterproductive and could further contribute to the mechanisms of CC without impacting muscle growth. Conclusion Available evidence shows that patients with CC can safely undertake higher-intensity resistance exercise programs, and benefit from increases in body mass and muscle mass

Feasibility of Presurgical Exercise in Men with Prostate Cancer Undergoing Prostatectomy

Background: Prostatectomy is associated with short- and long-term morbidity, which includes attenuation of muscle function and deterioration of lean body mass. Physical function is a known predictor of morbidity and mortality, with initial evidence indicating that presurgical exercise is associated with fewer postsurgical complications and shorter hospitalization. The aim was to determine the feasibility of a supervised presurgical exercise program for prostate cancer (PCa) patients scheduled for prostatectomy. Methods: Ten men (68+6.4 years old) with localized PCa undertook a 6-week resistance and aerobic exercise program prior surgery. Training was undertaken twice weekly and patients were assessed at baseline, presurgery, and 6 weeks postsurgery. Outcome measures included muscle and physical performance, body composition, urinary incontinence and questionnaire. Results: Muscle strength increased by 7.5% to 24.3% (P \u3c .05) from baseline to presurgery but decreased to pretraining levels postsurgery, except for knee extensor strength (P =.247). There were significant improvements (P \u3c .05) in the 6-m fast walk (9.3%), 400-m walk (7.4%), and chair rise (12.3%) at presurgery. Following surgery, improvements in physical performance were maintained. There was no change in lean or fat mass prior to surgery, but lean mass declined by 2.7 kg (P =.014) following surgery. There were no adverse effects from the exercise program. Conclusions: Exercise undertaken prior to prostatectomy improved muscle and physical performance, with functional benefits maintained 6 weeks postsurgery. Presurgical exercise for PCa patients has the potential to facilitate recovery by improving physical reserve capacity, especially in men with poor muscle nd physical performance

Exercise intervention and sexual function in advanced prostate cancer: A randomised controlled trial

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objectives: Treatments for prostate cancer such as androgen deprivation therapy (ADT), surgery and radiation therapy can adversely affect sexual, urinary and bowel function. Preliminary research has demonstrated the efficacy of exercise to preserve sexual function in men with localised prostate cancer receiving ADT, though this has yet to be investigated in a metastatic setting. We examined the effects of a 12-week exercise programme comprising resistance, aerobic and flexibility training on sexual health and function in men with advanced prostate cancer. Methods: Patients with prostate cancer (70.0±8.4 year; body mass index 28.7±4.0 kg/m2) with bone metastases (rib/thoracic spine, 66.7%; lumbar spine, 43.9%; pelvis, 75.4%; femur, 40.4%; humerus, 24.6%; other sites, 70.2%) were randomly assigned to supervised exercise 3 days/week (n=28) or usual care (n=29). Sexual health and function were assessed using the International Index of Erectile Function, the Expanded Prostate Cancer Index Composite and the EORTC-PR25 at baseline and 12 weeks. Results: Patients attended 89% of planned sessions and there were no adverse events. After adjusting for baseline values, there was no significant difference between groups for any measure of sexual function and activity (p \u3e 0.05). Additionally, there was no significant difference between groups for urinary and bowel function assessed by the EORTC-PR25 (p \u3e 0.05). Conclusions: A short-Term programme of supervised exercise does not appear to enhance indices of sexual health and function in men with advanced prostate cancer. Limitations of the intervention included the conservative modular exercise programme, which deliberately avoided loading bone metastatic sites

Timing of exercise for muscle strength and physical function in men initiating ADT for prostate cancer

© 2020, The Author(s). Background: Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) results in adverse effects, including reduced muscle strength and physical function, potentially compromising daily functioning. We examined whether it was more efficacious to commence exercise at the onset of ADT rather than later in treatment to counter declines in strength and physical function. Methods: One-hundred-and-four men with PCa (68.3 ± 7.0 years) initiating ADT were randomised to immediate exercise (IMX, n = 54) or delayed exercise (DEL, n = 50) for 12 months. IMX comprised 6 months of supervised resistance/aerobic/impact exercise initiated at the onset of ADT with a 6-month follow-up. DEL comprised 6 months of usual care followed by 6 months of resistance/aerobic/impact exercise. Upper and lower body muscle strength and physical function were assessed at baseline, 6 and 12 months. Results: There was a significant difference for all strength measures at 6 months favouring IMX (P \u3c 0.001), with net differences in leg press, seated row and chest press strength of 19.9 kg (95% CI, 12.3–27.5 kg), 5.6 kg (3.8–7.4 kg) and 4.3 kg (2.7–5.8 kg), respectively. From 7 to 12 months, DEL increased in all strength measures (P \u3c 0.001), with no differences between groups at 12 months. Similarly, physical function improved (P \u3c 0.001) in IMX compared with DEL at 6 months for the 6-m fast walk (−0.2, 95% CI −0.3 to −0.1 s), 400-m walk (−9.7, −14.8 to −4.6 s), stair climb (−0.4, −0.6 to −0.2 s) and chair rise (−1.0, −1.4 to −0.7 s), with no differences between groups by 12 months, except for the 6-m fast walk (P \u3c 0.001). Conclusion: Exercise either at the onset or after 6 months of ADT preserves/enhances muscle strength and physical function. However, to avoid initial treatment-related adverse effects on strength and function, exercise therapy should be implemented with initiation of ADT

Time on androgen deprivation therapy and adaptations to exercise: secondary analysis from a 12-month randomized controlled trial in men with prostate cancer

Objectives To explore if duration of previous exposure to androgen deprivation therapy (ADT) in men with prostate cancer (PCa) undertaking a year-long exercise programme moderates the exercise response with regard to body composition and muscle performance, and also to explore the moderator effects of baseline testosterone, time since ADT, and baseline value of the outcome. Patients and Methods In a multicentre randomized controlled trial, 100 men who had previously undergone either 6 months (short-term) or 18 months (long-term) of ADT in combination with radiotherapy, as part of the TROG 03.04 RADAR trial, were randomized to 6 months supervised exercise, followed by a 6-month home-based maintenance programme, or to printed physical activity educational material for 12 months across 13 university-affiliated exercise clinics in Australia and New Zealand. The participants were long-term survivors of PCa with a mean age of 71.7 ± 6.4 years, and were assessed for lower extremity performance (repeated chair rise), with a subset of men (n = 57) undergoing additional measures for upper and lower body muscle strength and body composition (lean mass, fat mass, appendicular skeletal muscle [ASM]) by dual X-ray absorptiometry. Data were analysed using generalized estimating equations. Results Time on ADT significantly moderated the exercise effects on chair rise (βinteraction = −1.3 s, 95% confidence interval [CI] −2.6 to 0.0), whole-body lean mass (βinteraction = 1194 g, 95% CI 234 to 2153) and ASM mass (βinteraction = 562 g, 95% CI 49 to 1075), and approached significance for fat mass (βinteraction = −1107 g, 95% CI −2346 to 132), with greater benefits for men previously on long-term ADT. At 6 months, the intervention effects on chair rise time −1.5 s (95% CI −2.5 to −0.5), whole-body lean mass 824 g (95% CI 8 to 1640), ASM mass 709 g (95% CI 260 to 1158), and fat mass −1377 g (95% CI −2156 to −598) were significant for men previously on long-term ADT, but not for men on short-term ADT. At 12 months, the intervention effects for men on long-term ADT remained significant for the chair rise, with improved performance (−2.0 s, 95% CI −3.0 to −1.0) and increased ASM (537 g, 95% CI 153 to 921). Time on ADT did not moderate the exercise effects on muscle strength, nor did time since ADT cessation moderate any intervention effects. Similarly, testosterone and baseline values of the outcome had negligible moderator effects. Conclusions Men with PCa previously treated long-term with ADT respond more favourably to exercise in terms of lower body muscle performance and body composition (lean and fat mass, and ASM) than those with short-term ADT exposure. As a result, men who were formerly on long-term androgen suppression regimens should be especially prescribed exercise medicine interventions to alleviate residual treatment-related adverse effects

Musculoskeletal comparison of patients with localised versus metastatic prostate cancer

Abstract of a presentation at the 2nd Prostate Cancer World Congress, Australia, 17-21 August 201

Adjusting bone mass for differences in projected bone area and other confounding variables: an allometric perspective.

The traditional method of assessing bone mineral density (BMD; given by bone mineral content [BMC] divided by projected bone area [Ap], BMD = BMC/Ap) has come under strong criticism by various authors. Their criticism being that the projected bone "area" (Ap) will systematically underestimate the skeletal bone "volume" of taller subjects. To reduce the confounding effects of bone size, an alternative ratio has been proposed called bone mineral apparent density [BMAD = BMC/(Ap)3/2]. However, bone size is not the only confounding variable associated with BMC. Others include age, sex, body size, and maturation. To assess the dimensional relationship between BMC and projected bone area, independent of other confounding variables, we proposed and fitted a proportional allometric model to the BMC data of the L2-L4 vertebrae from a previously published study. The projected bone area exponents were greater than unity for both boys (1.43) and girls (1.02), but only the boy's fitted exponent was not different from that predicted by geometric similarity (1.5). Based on these exponents, it is not clear whether bone mass acquisition increases in proportion to the projected bone area (Ap) or an estimate of projected bone volume (Ap)3/2. However, by adopting the proposed methods, the analysis will automatically adjust BMC for differences in projected bone size and other confounding variables for the particular population being studied. Hence, the necessity to speculate as to the theoretical value of the exponent of Ap, although interesting, becomes redundant