Kate A. Bolam

The insulin-like growth factor axis: A biological mechanism linking physical activity to colorectal cancer survival

Physical activity (PA) is related to colorectal cancer (CRC) mortality, with approximately 15% of CRC deaths worldwide attributable to physical inactivity. Moreover, higher levels of PA in CRC survivors have been associated with a reduced risk of the disease recurring. Despite the recognised nexus between PA and the risk of CRC, the physiological mechanisms underlying the inverse relationship between PA and mortality following CRC diagnosis are less apparent, with evidence primarily drawn from epidemiological studies. The insulin-like growth factor (IGF) axis plays a central role in cellular growth, proliferation regulation, differentiation and apoptosis. Specifically, high levels of insulin-like growth factor 1 (IGF-1) have been consistently linked to the severity of CRC tumours. Further, insulin-like growth factor binding protein 3 (IGFBP-3) regulates the bioavailability of IGF-I and therefore plays a central role in CRC prognosis. Decreasing levels of IGF-1 and increasing levels of IGFBP-3 may thus be a plausible mechanism underlying the inverse association between PA and CRC survival.

Effects of Different Exercise Modalities on Fatigue in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: A Year-long Randomised Controlled Trial

BACKGROUND Physical exercise mitigates fatigue during androgen deprivation therapy (ADT); however, the effects of different exercise prescriptions are unknown. OBJECTIVES To determine the long-term effects of different exercise modes on fatigue in prostate cancer patients undergoing ADT. DESIGN, SETTING, AND PARTICIPANTS Between 2009 and 2012, 163 prostate cancer patients aged 43-90 y on ADT were randomised to exercise targeting the musculoskeletal system (impact loading+resistance training; ILRT; n=58), the cardiovascular and muscular systems (aerobic+resistance training; ART; n=54), or to usual care/delayed exercise (DEL; n=51) for 12 mo across university-affiliated exercise clinics in Australia. INTERVENTION Supervised ILRT for 12 mo, supervised ART for 6 mo followed by a 6-mo home program, and DEL received a printed booklet on exercise information for 6 mo followed by 6-mo stationary cycling exercise. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Fatigue was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 36 and vitality using the Short Form-36. Analysis of variance was used to compare outcomes for groups at 6 mo and 12 mo. RESULTS AND LIMITATIONS Fatigue was reduced (p=0.005) in ILRT at 6 mo and 12 mo (∼5 points), and in ART (p=0.005) and DEL (p=0.022) at 12 mo. Similarly, vitality increased for all groups (p≤0.001) at 12 mo (∼4 points). Those with the highest levels of fatigue and lowest vitality improved the most with exercise (ptrend<0.001). A limitation was inclusion of mostly well-functioning individuals. CONCLUSIONS Different exercise modes have comparable effects on reducing fatigue and enhancing vitality during ADT. Patients with the highest levels of fatigue and lowest vitality had the greatest benefits. PATIENT SUMMARY We compared the effects of different exercise modes on fatigue in men on androgen deprivation therapy. All exercise programs reduced fatigue and enhanced vitality. We conclude that undertaking some form of exercise will help reduce fatigue, especially in those who are the most fatigued.

Factors influencing serum caffeine concentrations following caffeine ingestion

OBJECTIVES To determine whether differences in training status, body composition and/or habitual caffeine intake influenced serum caffeine concentrations following caffeine ingestion. DESIGN Single-blind. METHODS Trained cyclists/triathletes (n=14) and active (n=14) males consumed 6 mg kg(-1) anhydrous caffeine. Peak, total and time to peak serum caffeine concentrations were determined from venous blood samples at baseline and 6 time-points over 4h following intake. Body composition was assessed by dual energy X-ray absorptiometry and habitual caffeine intake by a questionnaire. RESULTS Trained cyclists/triathletes had 16% lower peak caffeine concentrations following caffeine ingestion compared to active individuals, although this was not statistically significant (p=0.066). There was no significant difference between trained cyclists/triathletes and active males in total (p=0.131) or time to peak (p=0.249) serum caffeine concentrations. Fat mass was significantly associated with total (r=0.427, p=0.038) but not peak (r=0.343, p=0.101) or time to peak serum caffeine concentration (β=0.00008, p=0.961). There were no associations between habitual caffeine intake and peak, total or time to peak serum caffeine concentrations. CONCLUSIONS Following caffeine ingestion three findings from the study were evident: (1) endurance-trained athletes trended towards lower peak caffeine concentrations compared to active males; (2) higher fat mass was associated with higher concentrations of caffeine in the blood over 4h, and (3) habitual caffeine intake does not appear to influence serum caffeine concentrations. Identification of the optimal conditions to ensure peak availability of caffeine within the blood and/or overcoming some of the variation in how individuals respond to caffeine requires consideration of the training status and body composition of the athlete.

The Osteogenic Effect of Impact-Loading and Resistance Exercise on Bone Mineral Density in Middle-Aged and Older Men: A Pilot Study

Background: Regular exercise has been recommended as a potential strategy to counteract the age-related bone loss experienced by men; however, the optimal exercise prescription is not known. Objective: To perform a pilot study to examine the osteogenic effect, safety and feasibility of a combined program of upper body resistance exercise and two doses of impact-loading exercise on bone mineral density (BMD) of middle-aged and older men. Methods: Forty-two community-dwelling men aged 50-74 years were randomly assigned to either an exercise program of combined upper body resistance exercise and either high-dose impact-loading (HI; 80 jumps per session) or moderate-dose impact-loading (MOD; 40 jumps per session) or a control (CON) group. The 9-month intervention involved 4 sessions each week: 2 supervised clinic-based and 2 home-based. BMD of the lumbar spine, femoral neck, total hip, trochanter and whole body as well as lean and fat mass were assessed at baseline and 9 months by dual-energy X-ray absorptiometry. Bone turnover markers, hormone levels, physical function and muscle strength were also assessed. Results: Following 9 months of training, significant differences in BMD among groups were found at the total hip (p = 0.010) and trochanter (p = 0.047) with BMD in the MOD group decreasing relative to the HI group. Although not significant, the HI group consistently preserved BMD, whereas BMD of the MOD and CON groups declined at the hip sites. Mean change for all groups at all skeletal sites was approximately within ±1%. There was no change in bone turnover markers. There were no adverse events as a result of the intervention; however, overall attendance for the HI and MOD groups was 53% (clinic: 68%, home: 38%) and 65% (clinic: 74%, home: 55%), respectively. Conclusions: This study indicates that while impact-loading exercise can be safely undertaken in middle-aged and older men, the current combined program did not elicit significant improvements in BMD.

SCAPIS Pilot Study : Sitness, Fitness and Fatness - Is Sedentary Time Substitution by Physical Activity Equally Important for Everyone's Markers of Glucose Regulation?

BACKGROUND Although moderate-to-vigorous physical activity (MVPA) is mainly recommended for glucose control, light physical activity (LIPA) may also have the potential to induce favorable changes. We investigated sedentary time (SED) substitution with equal time in LIPA and MVPA, and the association with markers of glucose regulation and insulin sensitivity after stratification by waist circumference, fitness and fasting glucose levels. METHODS A total of 654 men and women, 50 to 64 years, from the SCAPIS pilot study were included. Daily SED, LIPA and MVPA were assessed using hip-worn accelerometers. Fasting plasma glucose, insulin and HOMA-IR were determined. RESULTS Substituting 30 min of SED with LIPA was significantly associated with 3.0% lower fasting insulin values and 3.1% lower HOMA-IR values, with even lower levels when substituting SED with MVPA. Participants with lower fitness and participants with high fasting glucose levels benefited significantly more from substituting 30 min of SED with LIPA compared with participants with normal to high fitness levels and participants with normal glucose levels, respectively. CONCLUSIONS LIPA, and not only MVPA, may have beneficial associations with glucose regulation. This is of great clinical and public health importance, not least because it may confer a higher compliance rate to regular PA.

Optitrain: a randomised controlled exercise trial for women with breast cancer undergoing chemotherapy

BackgroundWomen with breast cancer undergoing chemotherapy suffer from a range of detrimental disease and treatment related side-effects. Exercise has shown to be able to counter some of these side-effects and improve physical function as well as quality of life. The primary aim of the study is to investigate and compare the effects of two different exercise regimens on the primary outcome cancer-related fatigue and the secondary outcomes muscle strength, function and structure, cardiovascular fitness, systemic inflammation, skeletal muscle gene activity, health related quality of life, pain, disease and treatment-related symptoms in women with breast cancer receiving chemotherapy. The second aim is to examine if any effects are sustained 1, 2, and 5 years following the completion of the intervention and to monitor return to work, recurrence and survival. The third aim of the study is to examine the effect of attendance and adherence rates on the effects of the exercise programme.MethodsThis study is a randomised controlled trial including 240 women with breast cancer receiving chemotherapy in Stockholm, Sweden. The participants are randomly allocated to either: group 1: Aerobic training, group 2: Combined resistance and aerobic training, or group 3: usual care (control group). During the 5-year follow-up period, participants in the exercise groups will receive a physical activity prescription. Measurements for endpoints will take place at baseline, after 16 weeks (end of intervention) as well as after 1, 2 and 5 years.DiscussionThis randomised controlled trial will generate substantial information regarding the effects of different types of exercise on the health of patients with breast cancer undergoing chemotherapy. We expect that dissemination of the knowledge gained from this study will contribute to developing effective long term strategies to improve the physical and psychosocial health of breast cancer survivors.Trial registrationOptiTrain - Optimal Training Women with Breast Cancer (OptiTrain), NCT02522260; Registration: June 9, 2015, Last updated version Feb 29, 2016. Retrospectively registered.

Effect of caffeine on exercise capacity and function in prostate cancer survivors

PURPOSE This study aimed to examine the acute effect of caffeine on exercise capacity, exercise-related fatigue, and functional performance in prostate cancer survivors. METHODS In this randomized, placebo-controlled, double-blind crossover study, 30 prostate cancer survivors (age, 70.3 ± 7.7 yr; body mass, 80.5 ± 13.0 kg; mean ± SD) consumed 6.04 ± 0.16 mg·kg(-1) of anhydrous caffeine or a placebo 1 h before completing a battery of exercise capacity and functional performance tests. Testing sessions were separated by 3-4 wk. Immediate fatigue and perceived exertion were measured directly pre- and postexercise at both testing sessions. RESULTS Caffeine increased exercise capacity by 7.93 s (+3.0%; P = 0.010); however, postexercise fatigue and perception of exertion were comparable with the placebo session (P = 0.632 and P = 0.902, respectively). Increases in isometric grip strength trended toward significance in both dominant (+2.9%; P = 0.053) and nondominant (+2.1%; P = 0.061) hands in the caffeine trial compared with placebo. Caffeine ingestion did not result in improvements in performance for any of the remaining functional measures, including the timed up-and-go test, repeated chair stands, 6-m fast walk, and 6-m backward tandem walk. Systolic blood pressure and HR were significantly increased (P = 0.006 and P = 0.040, respectively) upon completion of the testing battery when compared with placebo. CONCLUSIONS Consumption of caffeine 1 h before exercise induced improvements in exercise capacity and muscular strength in prostate cancer survivors. However, there was no change in exercise-related fatigue when compared with placebo despite reduction in timed performance of the 400-m walk. Caffeine seems to enhance exercise tolerance through improved performance with no subsequent increase in fatigue or perception of exertion and may be an appropriate strategy to promote exercise participation in prostate cancer survivors.

AST-induced bone loss in men with prostate cancer: exercise as a potential countermeasure

Androgen suppression treatment (AST) for men with prostate cancer is associated with a number of treatment-related side effects including an accelerated rate of bone loss. This loss of bone is greatest within the first year of AST and increases the risk for fracture. Pharmaceutical treatment in the form of bisphosphonates is currently used to counter the effects of hormone suppression on bone but is costly and associated with potential adverse effects. Recently, exercise has been shown to be an important adjuvant therapy to manage a range of treatment-related toxicities and enhance aspects of quality of life for men receiving AST. We propose that physical exercise may also have an important role in not only attenuating the bone loss associated with AST but in improving bone health and reducing fracture risk. In this review, the rationale underlying exercise as a countermeasure to AST-induced bone loss is provided.

The Effect of Nutrition Therapy and Exercise on Cancer-Related Fatigue and Quality of Life in Men with Prostate Cancer: A Systematic Review

Background: Improvements in diet and/or exercise are often advocated during prostate cancer treatment, yet the efficacy of, and optimal nutrition and exercise prescription for managing cancer-related fatigue and quality of life remains elusive. The aim of this study is to systematically review the effects of nutrition and/or exercise on cancer-related fatigue and/or quality of life. Methods: A literature search was conducted in six electronic databases. The Delphi quality assessment list was used to evaluate the methodological quality of the literature. The study characteristics and results were summarized in accordance with the review’s Population, Intervention, Control, Outcome (PICO) criteria. Results: A total of 20 articles (one diet only, two combined diet and exercise, and seventeen exercise only studies) were included in the review. Soy supplementation improved quality of life, but resulted in several adverse effects. Prescribing healthy eating guidelines with combined resistance training and aerobic exercise improved cancer-related fatigue, yet its effect on quality of life was inconclusive. Combined resistance training with aerobic exercise showed improvements in cancer-related fatigue and quality of life. In isolation, resistance training appears to be more effective in improving cancer-related fatigue and quality of life than aerobic exercise. Studies that utilised an exercise professional to supervise the exercise sessions were more likely to report improvements in both cancer-related fatigue and quality of life than those prescribing unsupervised or partially supervised sessions. Neither exercise frequency nor duration appeared to influence cancer-related fatigue or quality of life, with further research required to explore the potential dose-response effect of exercise intensity. Conclusion: Supervised moderate-hard resistance training with or without moderate-vigorous aerobic exercise appears to improve cancer-related fatigue and quality of life. Targeted physiological pathways suggest dietary intervention may alleviate cancer-related fatigue and improve quality of life, however the efficacy of nutrition management with or without exercise prescription requires further exploration.

The influence of exercise on the insulin-like growth factor axis in oncology: physiological basis, current and future perspectives

Exercise and physical activity have been shown to reduce the risk of many common cancers and strongly influence tumor biology. A cause–effect mechanism explaining this relationship is dependent on cellular pathways that can influence tumor growth and are exercise responsive. The insulin-like growth factor (IGF) axis is reported to promote the development and progression of carcinomas through cellular signaling in cancerous tissues. This review summarizes the physiologic basis of the role of the IGF axis in oncology and the influence of exercise on this process. We examined the effects of exercise prescription on the IGF axis in cancer survivors by evaluating the current scope of the literature. The current research demonstrates a remarkable heterogeneity and inconsistency in the responses of the IGF axis to exercise in breast, prostate, and colorectal cancer survivors. Finally, this review presents an in-depth exploration of the physiologic basis and mechanistic underpinnings of the seemingly disparate relationship between exercise and the IGF axis in oncology. Although there is currently insufficient evidence to categorize the effects of exercise prescription on the IGF axis in cancer survivors, the inconsistency of results suggests a multifaceted relationship, the complexities of which are considered in this review. Cancer Epidemiol Biomarkers Prev; 25(2); 239–49. ©2015 AACR.