Caffeine is a naturally occurring stimulant that promotes physiological arousal and dampens pain perception (10). In light of this, numerous investigators have established caffeine as an effective strategy to enhance exercise capacity and subsequent performance through reduction in fatigue and perception of exertion in young athletic populations. Although this ergogenic effect has been documented in older adults, evidence is scarce with equivocal findings.
Whereas some research groups report improved exercise capacity with caffeine in older and clinical populations (24,27), others have found no effect (16). Norager et al. (27) explored the acute effect of 6 mg·kg−1 of caffeine in a healthy, ≥70-year-old cohort. Caffeine significantly reduced perception of exertion after 5 min of cycling and increased aerobic and muscular endurance 1 h post-ingestion, but muscular strength and gait speed remained unchanged. In contrast, Jensen et al. (16) reported no significant effect of 6 mg·kg−1 of caffeine on aerobic endurance in healthy ≥70-yr-old citizens. The most recent study in ≥61-yr-old adults examined the acute effect of 3 mg·kg−1 of caffeine on mood, anticipation timing, perceived exertion, and muscular strength, reporting significant improvements in the former two outcomes, with no change in perceived exertion or muscular strength (36). It is not clear from the limited available research whether caffeine elicits an ergogenic effect on exercise capacity, muscular strength, or exercise-related fatigue in older populations. Furthermore, caffeine’s application in a clinical context remains unclear, including whether its ergogenic effect is observed in populations most affected by fatigue.
To date, only one study has examined the acute effect of caffeine on exercise performance in a clinical population. Momsen et al. (24) documented significant improvements in patients with intermittent claudication when 6 mg·kg−1 of caffeine was consumed 75 min before exercise participation namely, pain-free and maximal walking distance, muscular strength, and endurance. The increase in pain-free and maximal walking distance indicates that caffeine likely enhanced exercise tolerance although perceived exertion and fatigue during or immediately after exercise were not measured.
The effect of fatigue on cancer survivors remains a prominent area of exploration (23,39). Cancer-related fatigue (CRF) is a highly prevalent symptom that has been associated with several mental and physical comorbidities that detract from quality of life (QoL), hindering exercise participation and activities of daily living during (19) and beyond (12) cancer treatment. A recent publication proposed fatigue as the key mediator between physical fitness and QoL in cancer survivors; it was found that improvements in physical fitness (peak exercise capacity) corresponded to improvements in QoL and this could be attributed to reduction in fatigue (3). Indeed, the weight of research evidence suggests that exercise yields substantial improvements in CRF and reductions in associated comorbidities (5,29), although the optimal exercise prescription remains unclear. Thus, investigation and development of strategies to ameliorate the fatigue-related associations with exercise participation and, where possible, augment benefits are warranted. In this regard, caffeine, the world’s most commonly used stimulant known to reduce exercise-related fatigue and perception of exertion in healthy populations, has received no attention.
The aim of the present study was to examine the acute effect of caffeine on exercise capacity, exercise-related fatigue, and functional performance in prostate cancer survivors. It was hypothesized that an acute dose of caffeine would a) improve exercise capacity through reduction in timed performance of the 400-m walk, b) decrease immediate fatigue and perceived exertion after a battery of exercise tests, and c) improve measures of functional performance, including timed up-and-go (TUG), repeated chair stands, 6-m fast walk, and 6-m backward tandem walk.
Thirty-four community-dwelling prostate cancer survivors were recruited from the Prostate Cancer Foundation of Australia Support Groups across South East Queensland to participate in this randomized, double-blind, placebo-controlled crossover study. Prostate cancer survivors age >18 yr were eligible to participate, and the study requirements and protocol were explained to them before testing. Prospective participants completed a medical screening questionnaire and were excluded from the study if they had any musculoskeletal, neurological, respiratory, metabolic, or cardiovascular conditions that made it unsafe for them to complete the exercise testing. Ethical clearance was granted by the Medical Research Ethics Committee of The University of Queensland, and all participants completed a statement of written informed consent.
On days when testing was scheduled, participants were asked to abstain from caffeine, alcohol, and substances that potentially affect the metabolism of caffeine (e.g., cruciferous vegetables, charcoal-broiled beef, aspirin, or cimetidine). Questionnaires were administered directly before both testing sessions to document and confirm the following: a) caffeine and alcohol abstinence, b) habitual caffeine consumption (33), c) presence and severity of CRF over the previous 24 h (Brief Fatigue Inventory BFI)) (22) and week (Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F scale)) (40), d) sleep quality over the previous month (Pittsburgh Sleep Quality Index (PSQI)) (4), e) current cancer treatment, and f) current medications to monitor potential changes between testing sessions. Twenty-four hour fatigue (Global BFI) was reported using an 11-point scale ranging from 0 to 10, with values closer to 10 indicative of greater severity of fatigue and impact on daily functioning. Weekly fatigue (Global FACIT-F) was reported using a scale ranging from 0 to 52, with values closer to 52 associated with increased QoL and values <30 indicative of severe fatigue. Sleep quality (Global PSQI) over the previous month was reported using a scale ranging from 0 to 21, with values >5 associated with poor sleep quality. Physical activity was assessed via a modified version of the Active Australia Survey (1) where continuous walking (≥10 min per occasion), moderate and vigorous activity were combined to form an approximation, in weighted minutes, of the participants’ total physical activity during a regular week. To avoid overreporting, two-level truncation was used so that the participants’ summed totals did not exceed 14 h·wk−1 for any one category or 28 h·wk−1 for combined physical activity. Participants were asked to provide information pertaining to their cancer diagnosis and were discouraged from practicing the exercise protocols between sessions. Individual results were not disclosed to the participants until the completion of the study. Of the 34 participants initially recruited, one did not adhere to the pretest protocol requirements and three were unable to attend their second testing session because of a timetable conflict; thus, 30 participants (age, 70.3 ± 7.7 yr; body mass, 80.5 ± 13.0 kg; mean ± SD) were included in the analyses.
Testing was conducted at The University of Queensland or the Prostate Cancer Foundation of Australia Support Group venues across South East Queensland. To minimize variation, the order of tests within the battery was identical between sessions for each participant. Furthermore, participants were required to perform subsequent sessions under the same test conditions where possible, specifically session time, location, and exercise tester. Treatment was randomized to each testing session by a person independent from the project using a random number-generating process. Participants were required to attend two testing sessions separated by 3–4 wk. Opaque capsules containing either 6.04 ± 0.16 mg·kg−1 of anhydrous caffeine (Sigma-Aldrich Co., St. Louis, MO) or placebo (calcium sulphate USG; Swift and Co., Ltd., Mulgrave, Victoria, Australia) were randomly allocated and consumed with 250-mL water 1 h before exercise participation. The order of administration was counterbalanced by the randomization of participants; 15 received caffeine in their first session and 15 in their second session.
A battery of exercise capacity and functional performance tests was replicated in both occasions; each test was first demonstrated by the supervising exercise tester, with the order of testing scheduled to minimize the influence of each performance on subsequent tests; all tests were performed in triplicate, except the 400-m walk. Assistance to maintain balance and safety during testing was provided where necessary and was mirrored across both testing sessions. Time taken to complete each test was recorded with an electronic stopwatch (with the exception of isometric grip strength, which was measured in kilograms), and the best result was included in the analyses. To assess blinding, participants were asked to report which treatment they believed they received after each testing session. Any adverse side effects were documented.
Functional Performance and Exercise Capacity Testing Battery
The following tests were administered in a sequential order to assess functional performance and exercise capacity.
As described by Podsiadlo and Richardson (28), the timed up-and-go (TUG) test was administered to assess basic functional mobility. The coefficient of variation (Cv) in our laboratory for TUG test is 3.4%.
Repeated chair stands
To assess functional leg strength, participants were instructed to perform the protocol as detailed by Gãlvao et al. (11). The Cv in our laboratory for repeated chair stands is 5.6%.
Isometric grip strength
Dominant and nondominant handgrip was assessed using a spring-loaded grip dynamometer (TTM, Tokyo, Japan) to estimate physical performance (35) and muscular strength (25). Participants were required to perform a maximal contraction with each hand, maintaining a 90° elbow flexion and limit accessory movements. A brief rest period (approximately 10 s) was provided between subsequent attempts. The Cv in our laboratory for isometric grip strength is 3.6%.
Six-meter backward tandem walk
To evaluate dynamic balance, participants were asked to walk backward as quickly and safely as possible along a 6-m line using a toe-to-heel protocol (14). The Cv in our laboratory for the 6-m backward tandem walk is 9.4%.
Six-meter fast walk
Gait speed was measured via the 6-m fast walk (11). Participants were asked to walk a marked 10-m distance as quickly and safely as possible, with performance timed over the middle 6-m distance to minimize the influence of acceleration and deceleration. The Cv in our laboratory for the 6-m fast walk is 6.7%.
Four hundred-meter walk
The 400-m walk was used to estimate exercise capacity according to the method described by Newman et al. (26), with slight modifications composed of exclusion of the 2-min warm-up (with the previous tests performed as part of the battery acting as the warm-up) and a 10-m shuttle track. The Cv in our laboratory for 400-m walk is 2.5%.
Upon arrival for testing and after a 5-min rest period, resting HR and blood pressure (BP) were measured. Immediate postexercise and recovery HR and BP were recorded upon completion of the 400-m walk and 5 min after completion of the testing battery. Height and body mass were recorded to determine each participants’ body mass index (BMI) (kg·m−2); height was measured to the nearest centimeter at the first testing session, whereas body mass was measured in duplicate at the beginning of each testing session. Participants reported their rating of perceived exertion (RPE) (2) using the 15-point Borg scale and immediate fatigue via the BFI using an 11-point scale ranging from 0 (“no fatigue”) to 10 (“as bad as you can imagine”) on three occasions, as follows: a) on arrival after a 5-min rest period, b) 5 min before the commencement of the testing battery, and c) immediately upon completion of the 400-m walk. For the latter measure, participants reported their fatigue and exertion as experienced during the final 20-m lap of the 400-m walk test.
A sample size calculation indicated that to detect a 2.0% difference in performance (assuming 4.5 min to complete 400-m walk = 5.4 s) with an SD of 10 s with alpha = 0.05 and power = 80%, 29 participants would be required (paired t-test) (Power and Sample Size Software, Vanderbilt University, TN).
Data were analyzed using Microsoft Excel 2010 and IBM SPSS statistical software package (version 21.0; IBM Corp., Armonk, NY). The Kolmogorov–Smirnov test was used to assess normality of distribution for all outcome measures. Analyses included standard descriptive statistics and paired t-tests. Where data was not normally distributed, the related samples (Wilcoxon signed-rank) test was used. All tests were two tailed, and a P value of <0.05 was required for statistical significance. Results are given as mean ± SD, unless stated otherwise.
Participant characteristics are summarized in Table 1. The average time since diagnosis was 5.7 ± 4.1 yr before participation in this study. Caffeine consumption was 237 ± 84 mg·d−1 and primarily accrued through coffee and tea. Baseline 24-h fatigue (Global BFI) and baseline weekly fatigue (Global FACIT-F) were 2.5 ± 2.2 and 41.1 (33.1–49.1), respectively. The PSQI median global score was 5.0 (2.0–8.0). The average time since prostate cancer treatment was 3.8 ± 4.5 yr, and treatments included radical prostatectomy (66%), past androgen deprivation therapy (ADT) (17%), external beam radiation therapy (30%), and brachytherapy (20%). None of the participants reported previous or concurrent chemotherapy treatment. Eight participants (27%) were receiving ADT at the time of the study. All participants reported walking (>10 min), moderate or vigorous activity, or a combination of the aforementioned; the median physical activity participation during a regular week was 375 (190–520) weighted minutes. The average BMI for all participants was 26.1 ± 3.5 kg·m−2, and all but seven participants took prescribed medications on a daily basis for treatment of hypertension (36%), hypercholesterolemia (33%), depression (13%), and other conditions (gout, reflux, erectile dysfunction, hyperuricemia, and restless leg syndrome) (50%). All participants included in the analyses (n = 30) reported adherence to protocol requirements, including abstinence from caffeine, alcohol, and products that potentially influence the metabolism of caffeine on the day of testing. Two participants required the aid of the exercise tester to maintain balance while performing the backward walk test.
Compared with placebo, participants performed the 400-m walk test 7.93 s faster (3.0%; P = 0.010) when caffeine was administered (Table 2). As shown in Figure 1, improvements in isometric grip strength were observed and approached statistical significance with caffeine supplementation, as measured in dominant (P = 0.053) and nondominant hands (P = 0.069). However, no significant difference between sessions was found for the remaining functional measures, including TUG test (P = 0.821), repeated chair stands (P = 0.894), 6-m backward walk (P = 0.530) and 6-m fast walk (P = 0.434) (Table 2).
Baseline weekly fatigue did not significantly differ between caffeine and placebo (Global FACIT-F, P = 0.767). One hour after ingestion and before testing, there was no statistical difference between caffeine and placebo for immediate fatigue (BFI, P = 0.521) or perception of exertion (RPE, P = 0.267), and this was maintained postexercise, upon completion of the 400-m walk (P = 0.632 and P = 0.902 for BFI and RPE, respectively) (Table 2).
Systolic BP (SBP) and HR were significantly higher during the caffeine session (SBP, P = 0.017; HR, P = 0.040), as measured upon completion of the 400-m walk, and this was sustained 5 min postexercise (P = 0.006 and P = 0.009 for SBP and HR, respectively) (Table 2). There was no significant difference for diastolic BP (DBP) at either time point (P = 0.149 and P = 0.209, respectively).
Participants correctly identified their allocation in 36/60 sessions; 11/30 correctly identified the caffeine session and 25/30 correctly identified the placebo session. Across the 60 sessions, participants reported adverse side effects on nine occasions (caffeine, n = 5; placebo, n = 4), including restlessness and blurred vision when they had received caffeine and headache and dry mouth when they had received the placebo. Light-headedness was reported during caffeine and placebo sessions.
This is the first study to investigate the acute effect of caffeine on exercise capacity and exercise-related fatigue in prostate cancer survivors. The findings support the primary hypothesis that caffeine would significantly increase exercise capacity as determined by reduction in time taken to complete the 400-m walk test. In contrast to our secondary hypothesis, caffeine did not reduce immediate postexercise fatigue (BFI) or RPE. There were no significant differences between caffeine and placebo for any of the other functional measures; however, isometric grip strength trended toward significance for dominant and nondominant hands. These results indicate that caffeine may be beneficial for prostate cancer survivors who struggle with exercise participation because of fatigue.
Exercise capacity was significantly increased by 3.0% (7.93 s; P = 0.010) after consumption of 6 mg·kg−1 of caffeine 1 h before exercise participation. This ergogenic effect is consistent with previous research that documented a significant ergogenic effect of 6 mg·kg−1 of caffeine in older adults (27) and clinical populations (24) where participants were required to perform exercise capacity tasks until volitional exhaustion; investigators reported 25.0% improvement for steady-state (65% estimated HRmax) cycling endurance in healthy ≥70-yr-old adults and 26.0% improvement for maximal walking distance in patients >40 yr with intermittent claudication. In contrast, Jensen et al. (16) used steady-state cycling to volitional exhaustion and documented no significant differences (+10.6%, P = 0.123) between caffeine and placebo. Of the 30 participants in the study by Jensen et al. (16), 18 performed the same workload for both sessions whereas 11 cycled at a resistance 25 W higher (seven during their caffeine session and four during their placebo session). Exclusion of the latter participants still did not yield a significant effect of caffeine on exercise capacity (P = 0.536); however, this analysis was conducted for 18 participants, with one participant unaccounted for. Thus, there may have been too few participants to establish an effect. Furthermore, the ecological validity of the aforementioned studies is questionable given the population group under investigation; steady-state cycling to exhaustion is likely an uncommon task for older adults and therefore may lack transferability from research to practice. Whereas the pain-free and maximal walking distance protocol used by Momsen et al. (24) is more likely to reflect a functionally important measure, time to voluntary termination tests are less reliable, have a larger Cv, and more likely to be affected by caffeine supplementation than constant-distance or time protocols such as the 400-m walk test used in the present study (9,15).
Conversely, the 400-m walk test provides an indication of exercise capacity in older adults (32), with performance associated with and predictive of mortality, cardiovascular disease, mobility limitation, and disability in well-functioning older adults (26,37). This functional mobility measure has also been correlated with survival and 2-yr progression to disability or death in a population with cancer (18). Therefore, it is reasonable to conclude that improvements in walking performance, as observed in this study, would result in decreased risk of developing an assortment of physical comorbidities. In addition, previous research (5,29) has established that increased exercise capacity, as a consequence of exercise participation, has been associated with improved QoL, mobility, and fatigue in cancer survivors. Thus, on the basis of the findings of this study, caffeine is a plausible strategy to facilitate improvements in exercise capacity, thereby enhancing the associated exercise adaptations of walking. Further research is required to substantiate the aforementioned claims, including investigation of the following: a) a dose–response effect to determine whether caffeine-induced improvements in exercise capacity can be replicated at lower doses and, subsequently, via the consumption of common caffeinated food and beverages, b) the effect of caffeine on brisk walking activities of longer (>5 min) duration more consistent with current physical activity guidelines (i.e., ≥30-min duration), and c) the ergogenic effect of caffeine on exercise capacity after chronic (>1 wk) supplementation.
For the caffeine group, significant improvements in exercise capacity were found despite the lack of change in postexercise fatigue (BFI, P = 0.632) or perceived exertion (RPE, P = 0.902). Therefore, the participants were able to produce a greater amount of effort and exercise faster during their caffeine session, as evidenced by the reduction in timed performance of the 400-m walk; however, fatigue and exertion were equivalent to the placebo session. Thus, it would seem that the participants’ perceptions of fatigue and exertion were positively altered by caffeine supplementation. Consistent with previous research (10), caffeine’s acute amelioration of exercise-related fatigue has been verified and is typically attributed to its preferential antagonism of adenosine receptors. Increased self-determined exercise duration was recently documented in sedentary adults (31) after the acute ingestion of 3 mg·kg−1 of caffeine, 1 h before performing treadmill walking exercise at 60%–70% of HRmax. Participants performed six subsequent sessions; exercise duration was not increased after chronic caffeine administration, and caffeine did not reduce perception of exertion at any of these sessions when compared with the placebo group. Recently, in apparently healthy older adults, Tallis et al. (36) reported no change in perception of exertion after a maximal isokinetic knee extension task. In the present study, participants reported the same exertion and fatigue despite increased exercise intensity. This effect may be particularly beneficial for cancer survivors. Indeed, increased exercise tolerance could enhance exercise participation, which is favorable in this population because they are at greater risk of developing an array of comorbidities that have been attributed to decreased physical fitness (19,23,39).
Caffeine has been documented to elicit improvements in muscular strength and endurance for older (27), clinical (24), and athletic populations (38); however, the present study did not establish significance when comparing caffeine and placebo performance for strength-based measures. Forearm strength, as measured by isometric grip strength, trended toward significance with caffeine supplementation, with improvements of 2.9% and 2.1% for dominant and nondominant hands, respectively. In contrast to the findings of the present study, Norager et al. (27) established no significant difference between caffeine and placebo for maximal voluntary isometric contraction (arm flexion) in older adults. Similarly, Tallis et al. (36) found no effect of acute caffeine intake in healthy older adults on maximal isokinetic knee extension force when compared with placebo. At present, the one available study in clinical populations (24) documented a 9.8% significant improvement in maximal isometric knee extension strength after caffeine ingestion. Importantly, 1-kg improvements in grip strength, as documented in this study, have been associated with increased physical performance for older adults (35). Furthermore, poor handgrip strength performance has been identified as a clinical marker for sarcopenia (20) and dynapenia (21) and associated with decreased health-related QoL in older adults (30). Hence, the increased handgrip strength noted in this study may be clinically significant for this population with cancer. Finally, functional leg strength and power, as measured in the present study, did not improve with caffeine (P = 0.894). Thus, further investigation may be warranted to differentiate whether caffeine’s lack of effect on lower body muscle strength holds true for activities of extended duration, which require muscle endurance as opposed to short-duration submaximal tasks.
Immediately postexercise, caffeine increased SBP (P = 0.017) and HR (P = 0.040) whereas DBP remained unchanged between sessions (P = 0.149). Because there was no difference between postingestion, preexercise SBP (P = 0.318) and HR (P = 0.618), it is plausible that the increased postexercise SBP and HR resulted from the participants walking faster during the caffeine session (P = 0.010). This known transient increase in BP after acute ingestion of caffeine (34) has been shown to have minimal long-term effects with regard to chronic elevations in BP (13). Nevertheless, the reported transitory increase in SBP cautions use with populations where uncontrolled medical conditions or comorbidities exist. No studies have explored the effect of caffeine on physiological parameters of BP and HR, at rest or during exercise, in clinical populations that declare uncontrolled medical conditions. Although it is generally understood that an acute ingestion of caffeine increases BP (34), the chronic effect of caffeine on the aforementioned parameters, and associated health outcomes, remains poorly understood; a recent meta-analysis did not find a significant effect of chronic (>1 wk) caffeine consumption (via coffee) on BP or development of hypertension but highlighted that the available literature consisted of low-quality data (17). Specific to populations with cancer, there have been three studies (6–8) that have examined the chronic effect of guarana, a caffeine-containing stimulant, on fatigue in breast cancer survivors. However, none of the studies monitored cardiovascular parameters. Further research examining the chronic effect of caffeine on BP, HR, and exercise performance in cancer survivors is warranted.
The recruited sample was a good representation of the wider prostate cancer population, with markedly heterogeneous disease-related factors, particularly current and former cancer treatment, current levels of fatigue, and time since diagnosis. Recently, a systematic review (19) explored fatigue prevalence and severity in men with prostate cancer; ADT, radiotherapy, and surgical intervention via prostatectomy (up to 6 wk after operation) were strongly associated with increased fatigue severity, with the combination of radiotherapy and ADT documented to produce a cumulative effect on fatigue severity. If fatigue severity is strongly associated with these treatments, it is plausible that the participants’ relatively low baseline fatigue may be explained by their increased time since cancer diagnosis (5.7 ± 4.1 yr) and/or lack of concurrent treatment. Given this, it remains unknown whether the ergogenic effect of caffeine on exercise-related fatigue, as seen in our study, would be further enhanced in prostate cancer survivors that collectively report severe fatigue due to concurrent therapy. Finally, it is difficult to determine whether the participants in this study experienced low, moderate, or high levels of fatigue when compared with other fatigue studies in men with prostate cancer, as those available have used a wide array of questionnaires and self-report measures to assess fatigue (19).
This study demonstrated that caffeine can enhance exercise tolerance through improved performance, with no subsequent increase in fatigue or perception of exertion in prostate cancer survivors. Therefore, caffeine supplementation may be an appropriate fatigue management strategy to ameliorate difficulties associated with exercise participation and tolerance to increasing exercise intensities and/or duration in this population with cancer. Further investigations are required to determine whether this effect is maintained at doses <6 mg·kg−1 of caffeine and in other populations with cancer.
No funding was received for this work.
The authors declare no conflicts of interest.
The results of the present study do not constitute endorsement by the American College of Sports Medicine.
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