Exercise-based, multimodal rehabilitation programming similar to that used in the existing models of cardiac or pulmonary rehabilitation or prehabilitation is a holistic potential solution to address the range of physical, psychological, and existential (e.g., as their diagnosis relates to potential death) stressors associated with a cancer diagnosis and subsequent treatment. The purpose of this study was to systematically evaluate the structure and format of any type of exercise-based, multimodal rehabilitation programs used in individuals with cancer and the evidence base for their real-world effectiveness on metrics of physical (e.g., cardiorespiratory fitness, blood pressure) and psychological (e.g., health-related quality of life) health. Very few of the 33 included exercise-based, multimodal rehabilitation programs employed intervention components, education topics, and program support staff that were multi-disciplinary or cancer-specific. In particular, a greater emphasis on nutrition care, and the evaluation and management of psychosocial distress and CVD risk factors, with cancer-specific adaptations, would broaden and maximize the holistic health benefits of exercise-based rehabilitation. Despite these opportunities for improvement, exercise-based, multimodal rehabilitation programs utilized under real-world settings in individuals with cancer produced clinically meaningful and large effect sizes for cardiorespiratory fitness (VO2peak, ±2.9 mL/kg/min, 95% CI = 2.6 to 3.3) and 6-minute walk distance (+47 meters, 95% CI = 23 to 71), and medium effect sizes for various measures of cancer-specific, health-related quality of life. However, there were no changes to blood pressure, body mass index, or lung function. Overall, these findings suggest that exercise-based, multimodal rehabilitation is a real-world therapy that improves physical and psychological health among individuals with cancer, but the holistic health benefits of this intervention would likely be enhanced by addressing nutrition, psychosocial concerns, and risk factor management through education and counselling with consideration of the needs of an individual with cancer.

Metabolic dysfunction and excess accumulation of adipose tissue are detrimental side effects from breast cancer treatment. Diet and physical activity are important treatments for metabolic abnormalities, yet patient compliance can be challenging during chemotherapy treatment. Time-restricted eating (TRE) is a feasible dietary pattern where eating is restricted to 8 hours/day with water-only fasting for the remaining 16 hours. The objective of this study is to evaluate the effect of a multimodal intervention consisting of TRE, healthy eating, and reduced sedentary time during chemotherapy treatment for early-stage (I-III) breast cancer on accumulation of visceral fat (primary outcome), other fat deposition locations, metabolic syndrome, and CVD risk (secondary outcomes) compared to usual care. The study will be a two-site, two-arm, parallel-group superiority randomized control trial enrolling 130 women scheduled for chemotherapy for early-stage breast cancer. The intervention will be delivered by telephone including 30-60-minute calls with a registered dietitian who will provide instructions on TRE, education and counselling on healthy eating, and goal setting for reducing sedentary time. The comparison group will receive usual cancer and supportive care including a single group-based nutrition class, and healthy eating and physical activity guidelines. Magnetic resonance imaging, blood draws, and assessment of blood pressure will be performed at baseline, after chemotherapy (primary end-point), and 2-year follow-up. If our intervention is successful in attenuating the effect of chemotherapy on visceral fat accumulation and cardiometabolic dysfunction, it has the potential to reduce risk of cardiometabolic disease and related mortality among breast cancer survivors.

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This commentary highlights the challenges of clinical trials, especially as related to trials on exercise for older adults with advanced cancer, and comments on the study by Mikkelsen et al.

Exercise is a commonly prescribed therapy for patients with established cardiovascular disease or those at high risk for de novo disease. Exercise-based, multidisciplinary programs have been associated with improved clinical outcomes post myocardial infarction and is now recommended for patients with cancer at elevated risk for cardiovascular complications. Imaging studies have documented numerous beneficial effects of exercise on cardiac structure and function, vascular function and more recently on the cardiovascular risk profile. In this contemporary review, we will discuss the effects of exercise training on imaging-derived cardiovascular outcomes. For cardiac imaging via echocardiography or magnetic resonance, we will review the effects of exercise on left ventricular function and remodeling in patients with established or at risk for cardiac disease (myocardial infarction, heart failure, cancer survivors), and the potential utility of exercise stress to assess cardiac reserve. Exercise training also has salient effects on vascular function and health including the attenuation of age-associated arterial stiffness and thickening as assessed by Doppler ultrasound. Finally, we will review recent data on the relationship between exercise training and regional adipose tissue deposition, an emerging marker of cardiovascular risk. Imaging provides comprehensive and accurate quantification of cardiac, vascular and cardiometabolic health, and may allow refinement of risk stratification in select patient populations. Future studies are needed to evaluate the clinical utility of novel imaging metrics following exercise training.

Individuals with high physical activity levels, such as athletes and military personnel, are likely to experience periods of low muscle glycogen content. Reductions in glycogen stores are associated with impaired physical performance. Lower glycogen stores in these populations are likely due to sustained aerobic exercise coupled with suboptimal carbohydrate or energy intake. Consuming exogenous carbohydrate during aerobic exercise may be an effective intervention to sustain physical performance during periods of low glycogen. However, research is limited in the area of carbohydrate recommendations to fuel performance during periods of suboptimal carbohydrate and energy intake. Additionally, the studies that have investigated the effects of low glycogen stores on exogenous carbohydrate oxidation have yielded conflicting results. Discrepancies between studies may be the result of glycogen stores being lowered by restricting carbohydrate or restricting energy intake. This narrative review discusses the influence of low glycogen status, resulting from carbohydrate restriction versus energy restriction, on exogenous carbohydrate oxidation and examines the potential mechanism resulting in divergent responses in exogenous carbohydrate oxidation. Results from this review indicate that rates of exogenous carbohydrate oxidation can be maintained when glycogen content is lower following carbohydrate restrictions but may be reduced following energy restriction. Reductions in exogenous carbohydrate oxidation following energy restriction appear to result from lower insulin sensitivity and glucose uptake. Exogenous carbohydrate may thus be an effective intervention to sustain performance following short-term energy-adequate carbohydrate restriction but may not be an effective ergogenic aid when glycogen stores are low due to energy restriction.

Background The impact of gut microbiota-targeted interventions on the incidence, duration, and severity of respiratory tract infections (RTI) in non-elderly adults, and factors moderating any such effects, are unclear. Objectives This systematic review and meta-analysis aimed to determine the effects of orally ingested probiotics, prebiotics, and synbiotics versus placebo on RTI incidence, duration, and severity in non-elderly adults, and to identify potential sources of heterogeneity. Methods Studies were identified by searching CENTRAL, PubMed, Scopus, and Web of Science up to December 2021. English-language peer-reviewed publications of randomized, placebo-controlled studies that tested an orally ingested probiotic, prebiotic or synbiotic intervention of any dose for ≥ 1 week in adults 18–65 yr were included. Results were synthesized using intention-to-treat and per protocol random effects meta-analysis. Heterogeneity was explored by sub-group meta-analysis and meta-regression. Risk of bias (RoB) was assessed using the Cochrane RoBv.2 tool for randomized trials. Results Forty-two manuscripts reporting effects of probiotics (n = 38), prebiotics (n = 2), synbiotics (n = 1) or multiple -biotic types (n = 1) were identified (n = 9,179 subjects). Probiotics reduced the risk of experiencing ≥ 1 RTI (relative risk = 0.91 [95%CI: 0.84, 0.98] P = 0.01), and total days (rate ratio = 0.77 [0.71, 0.83] P < 0.001), duration (Hedges's g = -0.23 [-0.39, -0.08] P = 0.004) and severity (Hedges's g = -0.16 [-0.29, -0.03] P = 0.02) of RTI. Effects were relatively consistent across different strain combinations, doses and durations, though reductions in RTI duration were larger with fermented dairy as the delivery matrix, and beneficial effects of probiotics were not observed in physically active populations. Overall RoB was rated as “some concerns" for most studies. Conclusions Orally ingested probiotics, relative to placebo, modestly reduce the incidence, duration and severity of RTI in non-elderly adults. Physical activity and delivery matrix may moderate some of these effects. Whether prebiotic and synbiotic interventions confer similar protection remains unclear due to few relevant studies. PROSPERO registration: CRD42020220213

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