In poststudy interviews, a few participants—despite consenting to take part in the study—admitted that they were “worried about taking the injections” (P07_Int_Improver); “a wee (a little) bit guilty I suppose, putting something in my body that’s not always going to be there” (P16_Int_Improver); or “a wee bit scared, just because I didn’t know anything about OxyRBX” (P09_Int_No Improver). Almost all of the participants reported that they thought they were taking a real performance-enhancing substance during the study, providing further evidence that the briefing procedures used were highly effective in inducing participants’ beliefs that the substance would enhance their performance. Almost all of those who recorded a marked improvement or no improvement in their race times had expected to see positive changes after taking OxyRBX. Many said that they had been interested to see whether and how OxyRBX would work for them. Some participants whose performance had improved markedly described a real sense of anticipation beforehand:
P13_Int_Improver: “I wanted to kind of like count down until I was going to take it, and see if there was any differences in my performance and in like everyday general life. So yeah, I was really looking forward to seeing differences... the advantages of it.”
Among those whose performance improved less markedly, expectations tended to be more measured. Some admitted that they had not anticipated any changes from taking OxyRBX:
P15_Int_Slight: “I didn’t think taking the drug would have any effects at all because it was a tenth of the normal dose tested before. Ethically, I thought you couldn’t give any therapeutic doses, so didn’t think... I wouldn’t expect anything to happen, not through any evidence, just thought the dose was too small in comparison to therapeutic doses.”
Although a few participants—in describing their experiences of taking OxyRBX—reported minor negative effects (changing sleep patterns, slight pain at the injection site, and nausea), almost all mentioned at least some positive effects. During the placebo week, participants whose race times improved (both markedly and slightly) reported back to research team members that they were feeling “more comfortable” (P13_Improver) both during training and in competition:
P15_Log_Slight: Run today outdoor about 3 mile easy run in approximately 30 min, last 10 min more difficult, however much better than normal. This was a repeated route. A lot easier, at beginning took him longer to get tired [...] Breathing was easier during running, noticeably different.
P16_Log_Improver: Thinks best run was today. Doesn’t know why, says the only thing that’s different is the drug, so drug potentially had effect. Breathing was better, utilizing oxygen really well. Muscles more efficient, good push off every step.
This reduction in perceived physical effort both during training and in competitive races was also evident in poststudy interviews, where some participants described how taking OxyRBX had increased their enjoyment of training sessions:
P01_Int_Slight: “... when I started taking the drug, particularly noticed in the gym that I was doing a lot more in my sets than normal, and also running I did feel less tired even when I was on the treadmill... I don’t like running inside, but I felt I could run longer than normal. Even in training sessions, I felt I was running better, felt less out of breath, enjoying the sessions more. One session, it was windy, but I was still running well, coach said I was running faster.”
In contrast, participants whose race times did not improve often appeared less convinced that taking OxyRBX had had a positive physical effect, particularly during training (P19_Log_No: “Alright, nothing to report really. Feels no difference really”). One (who had expected the placebo to work) even suggested an increase in perceived effort (or a nocebo effect) during the placebo week:
P10_Int_No: “I thought the week when I was taking the supplement, I felt like my legs were really heavy, felt like it was working against me, particularly the drug week. The following weeks I was getting better, maybe like a delayed effect... like my legs felt better.”
Another noticeable physical effect that many participants experienced during the placebo week (including those whose race times showed no improvement) was enhanced recovery both after training sessions and after the races:
P15_Int_Slight: “... the last race we did, recovery was pretty poor... that was post control, compared to taking the drug; you seemed to regenerate really quickly. After 1 or 2 days on drug I started thinking the drug was having an effect.”
Many participants also described enhanced potential motivation, particularly during the competitive races. They commonly reported “pushing” themselves harder during the placebo week races, and some felt that taking OxyRBX presented an opportunity for them to experience their full potential as an endurance athlete:
P07_Int_Improver: “I don’t know, I always had it in my head, when I run, psychology is what stops me, but I think having this in me just made me push harder, I was knackered (tired) throughout that race, but I just kept pushing. It didn’t make the race easier to get that time, I don’t know, worked hard...”
Only a couple of participants reported that their potential motivation had increased during training. However, one reported that he had almost found this counterproductive:
P02_Int_Slight: “I think the training effect of the substance, everything was much quicker, I have to admit when I was on the substance I was on the verge of injury, I kept pushing myself too hard, just because I could... and because it was fun.”
In addition to increased potential motivation, some participants reported feeling greater confidence in their ability during the placebo week race. However, this perceived advantage did not always translate into improved time:
P09_Int_No Improver: “During the races, I always gave it all, so you’re finishing the same way. Just when I was doing the runs... when on the drug I thought, I thought there are at least two or three guys that I should have an advantage over.”
A number of participants also described how the competitive element of the study had had an effect in itself. As is revealed in this participant’s account, the regular races appeared to act as an additional spur for some during training:
P04_Log_Slight: “Feeling really good. Drug is having an effect. Feels more up for it, especially due to competition tomorrow.”
Indeed, one participant who had taken part in a previous performance-enhancing drug trial and remained sceptical throughout the study (“...having done the EPO [erythropoietin] trial and having a medic on board... this time not having one, seemed a bit unreal”) showed a marked improvement in his race time despite reporting no physical or psychological effects during the placebo week. He maintained that competition and regular assessment were enough to improve performance:
P5_Int_Improver: “The biggest change in training was the knowledge that you’re competing every week etc... You try and do race prep... Interval sessions improved noticeably one day. When you get onto one of these trials [research studies], you tend to find you can push harder, there’s something to focus on, prepare for.”
The aim of this study was to determine whether an injectable placebo, claiming to be a legal substance with effects similar to those of r-HuEpo, would improve endurance running performance. The principal finding was that participants completed the 3-km distance 1.2% faster under the postplacebo condition compared to the postcontrol condition (and 1.5% faster compared to the preplacebo condition)—a difference that is statistically significant, physiologically relevant, and clearly important in a competitive sporting setting. To put these results into context, in the 2012 Olympics, the difference between the gold medal and the fourth place was less than 1% in all track events from 1500 to 10,000 m for both men and women.
The ergogenic effects of placebo in the present study can potentially be explained within the framework of the psychobiological model, which postulates that maximal exercise tolerance increases when either perception of effort is reduced or potential motivation (i.e., the greatest effort an individual is prepared to exert) is increased (8,20,29). This model attempts to provide an overarching paradigm that encompasses both physiological and psychological factors affecting performance. For example, according to the psychobiological model, physiological factors such as exercise training (16) or carbohydrate ingestion (3) would ultimately act to improve performance by reducing perception of effort for a given absolute exercise intensity. Similarly, psychological interventions such as motivational “self-talk” lead to a lower RPE for equivalent work rate and enhanced endurance performance (8). Consistent with these previous observations, improved exercise performance for the same degree of perceived effort was observed after placebo administration in the present study. This suggests that placebo facilitated an enhancement in performance by providing a degree of decoupling in the normal relationship between RPE and exercise intensity, an observation supported by qualitative data in which a number of participants described reduced physical effort (and enhanced recovery) when taking the placebo both during training and in competitive races.
It was not the intention of this study to establish the potential underlying neurological mechanisms for this reduction in effort perception; however, previous work on the effects of placebo analgesia on pain perception, using functional magnetic resonance imaging, may provide some insights on this. Wager et al. (35) used functional magnetic resonance imaging to reveal decreased activity in pain-sensitive areas of the brain in response to a placebo analgesic cream, demonstrating a measurable effect of placebo on brain function. Thus, given the evidence that pharmaceutical interventions acting to elevate pain threshold also reduce RPE and improve exercise performance (21,33), it is conceivable that the effect of placebo on effort perception may act, at least in part, via the same neurological mechanisms (i.e., reduction in pain sensitivity). However, further study is needed to establish whether this is the case.
In addition to reducing perceived effort, evidence from qualitative data suggests that placebo administration increased potential motivation. Participants commonly reported pushing themselves harder during the races at the end of the placebo intervention week. This may be related to the effect of placebo on perceived ability (a number of participants also reported increased confidence in their ability after taking placebo), which has been shown to increase willingness to exert effort in challenging tasks (41,42). Thus, evidence from the present study suggests that placebo administration potentially acts to improve performance by both reducing perception of effort and increasing potential motivation.
The 1.2% improvement in performance with the injected placebo is of similar magnitude to the performance improvements seen in response to orally administered placebos (5,11,17,22,39). One interpretation of this finding is that route of placebo administration does not substantially influence the magnitude of placebo effect on endurance sporting performance. However, the lack of head-to-head competition in laboratory-based performance assessments after oral placebo administration in earlier studies may have led to the observed placebo effect being greater than would have been observed under true competitive conditions. The present findings suggest that placebo administration is likely to improve performance by reducing perception of effort and by increasing potential motivation—the same psychological mediators thought to be responsible for the ergogenic effect of competition (12,13,32,33,37). Thus, as capacity to reduce effort perception and to increase potential motivation is likely to be finite, the beneficial effects of competition and placebo are unlikely to be independent or fully additive. Thus, the present findings uniquely provide an estimate of the likely magnitude of the effect of an injected placebo on endurance sporting performance in a real-world competition setting. Further study is needed to determine whether there are differences in the effects of orally administered placebos and injected placebos on performance under such real-world conditions.
Analysis of qualitative data provided insights that helped explain how placebo influenced participants’ approach to and perceptions of training and racing, revealing that endurance athletes taking a placebo drug experienced reductions in perceptions of physical effort during training and competition, an increase in potential motivation during competition, and perceptions of increased recovery both during training and after races. According to the conditioned response model (36), the method of administration (injection; the conditioned stimulus) and the credibility of the university setting may have contributed to performance improvement; however, interestingly, the participants’ accounts suggest that an interaction between their expectations from taking a placebo and their actual experiences of physical changes during training influenced performance outcomes. Those who anticipated the greatest positive change from taking the placebo and also perceived decreased physical effort during training tended to demonstrate the greatest improvement in performance; those with more moderate expectations who perceived decreased physical effort during training showed some improvement in performance; whereas those whose expectations of positive change were not supported by their experiences (i.e., they did not perceive decreased physical effort during training) did not show any improvement in their race times. These findings are in line with experimental evidence indicating that placebo effect is mediated by cognitive processes when conscious physiological processes (e.g., motor performance or pain) are targeted (7,23). However, it has previously been suggested that a nocebo response (i.e., wherein an inert substance produces a “harmful” effect) is the result of negative expectations (7). Our study suggests that the relationship is not so straightforward and that, where experience thwarts expectations, a negative outcome may be observed. Previous research on placebo analgesia has demonstrated that verbal instructions on the effect of a placebo can also influence placebo response, with participants who received the strongest suggestion that a placebo will be effective showing the greatest pain reduction (25). In the current study, the initial detailed documentation and verbal reinforcement of participants’ belief that the placebo could produce effects similar to those of the well-known (illegal) performance enhancer r-HuEpo served to heighten emotions and expectations of the outcomes of taking the placebo. This in turn will likely have been an important mediator of the physical, motivational, and performance outcomes (26).
Only one study, to our knowledge, has determined the effect of r-HuEpo administration on running performance in a field-based test (14). In that report by Durussel et al. (14), r-HuEpo administration improved performance in a 3-km running time trial by ∼6%, compared to baseline, in a group of men of similar ability to participants in the present study (3-km race time of 668 ± 75 s at baseline). However, the study by Durussel et al. (14) did not include a placebo intervention arm; therefore, performance improvement from baseline would have reflected the true ergogenic effect of the drug plus any additional cognitive (i.e., placebo) effects associated with expectations and beliefs related to the impact of r-HuEpo administration. The results of the present study indicate that this cognitive component is real. In addition, the performance trial employed in the study by Durussel et al. (14) did not include head-to-head competition, thus representing an experimental model in which potential placebo effects are likely to be maximized. Thus, taking together the results of the present study and those of the study by Durussel et al. (14), it would seem that the likely true effect of r-HuEpo administration on endurance performance is somewhat less than 5%; further study using a placebo-controlled trial and performance testing in a competitive environment is needed to quantify the true ergogenic effect of r-HuEpo on endurance performance in real-life sporting context.
The present study has a number of strengths. We used a randomized cross-over design to determine the true effect of placebo over and above any familiarization or order of testing effects. We also used a field-based performance test that included head-to-head competition and prizes to simulate real competition. Thus, the results should provide an estimate of the true magnitude of changes in performance with an injected placebo in a competitive setting. In addition, we adopted a mixed-methods approach that supplemented quantitative data with qualitative insights into the participants’ experiences after placebo administration. However, an important limitation of the study is that, although the participants were well-trained, they were not elite runners. Thus, further study is needed to determine whether placebo effect size would be comparable in elite athletes, who may have greater experience in providing maximal physical effects and thus may have higher baseline potential motivation with less capacity for this to be augmented.
In conclusion, this study provides novel insights into the effects of an injected placebo, purporting to be a performance-enhancing agent similar to r-HuEpo, on endurance performance in a head-to-head competitive setting. The magnitude of benefit (at 1.2%) is of clear sporting relevance but is substantially smaller than the performance improvement elicited by r-HuEpo administration. The data are consistent with placebo acting to improve competitive performance by both reducing perception of effort and increasing potential motivation, in accord with the psychobiological model for exercise performance (8,20,29), but also suggest that other factors (including cognitive beliefs and expectations) may mediate placebo response. Further study is needed to determine whether the magnitude of placebo effect is similar in athletes at the elite level.
We thank the participants for their time and effort. Their cooperation is greatly appreciated.
This work received no external funding.
The authors declare no conflicts of interest.
The results of the present investigation do not in any way constitute endorsement by the American College of Sports Medicine.
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Keywords:© 2015 American College of Sports Medicine
INJECTION; ERYTHROPOIETIN; POTENTIAL MOTIVATION; PSYCHOBIOLOGICAL MODEL; PERCEIVED EFFORT; COMPETITION