The quest for effective weight loss strategies often involves exploring various avenues, from diet and exercise to supplements and medical interventions. However, an often-overlooked aspect is the potential influence of the mind itself - the placebo and nocebo effects. This article delves into the existing research on these psychological phenomena and their impact on weight loss programs.
Introduction: The Overweight and Obesity Epidemic
Childhood overweight and obesity, along with unfavorable body composition, have become a widespread public health problem, especially in recent decades.
Physical activity is a crucial way to prevent excess body mass in children and to reduce it if it is already present. Previous research revealed inverse cross-sectional associations between the objective level of physical activity and adiposity, as well as cardio-metabolic risk factors in youth. It should also be stressed that fitness in childhood and adolescence has been shown to be one of the determinants of health later in life, which further proves the importance of obtaining an optimal level of it early in life. For instance, the results of a systematic review and meta-analysis of longitudinal studies on this topic revealed a prospective negative relationship between both muscular fitness in childhood/adolescence and adiposity as well as cardiometabolic parameters in later life. Importantly, in the same study, a positive association between fitness and bone health was shown.
Considering the benefits of optimal fitness described above, it is crucial to appropriately motivate young people to engage in physical activity. Unfortunately, it is particularly difficult in youth suffering from overweight and obesity. These groups often are also victims of weight stigmatisation, which, contrary to popular societal belief, does not motivate individuals to lose weight. On the contrary, shaming or bullying a person because of excess body weight contributes not only to binge eating, social isolation, and avoidance of health care services, but also decreased physical activity. Taking the above into consideration, it is crucial to develop interventions and approaches that facilitate children’s participation in physical activity, while paying particular attention to those with excess body mass.
Understanding Placebo and Nocebo Effects
The concept of placebo is fundamentally understood as an intervention capable of influencing the organism’s functioning despite lacking the inherent potential to produce such effects. Placebo interventions encompass a diverse range of forms, including medically connoted interventions such as pills, injections, creams, and even sham surgical procedures. However, their scope extends beyond these medical connotations, such as colours or shapes. The pivotal determinant of the placebo’s efficacy resides in the contextual elements that accompany its administration, such as the colour, shape, or taste of the placebo pill. Moreover, these same contextual elements exert an influence on active interventions, thereby modifying their effectiveness. The term “placebo effect” denotes the positive physiological and psychological changes resulting from placebo application, exemplified by symptom improvement, such as a reduction in pain intensity. Therefore, it is represented as the difference between placebo and non-treatment/natural history groups. When no control group for the placebo group is included in a study design, any changes in the placebo group can be called the placebo response. The placebo response is defined as all health changes resulting from the inactive treatment, including regression towards the mean and the natural course of the disease, among other factors that may be responsible for the changes in the placebo group. Thus, only the placebo effect represents the true effect of the placebo intervention.
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Analogous to the placebo effect, relatively worse outcomes or adverse effects occurring due to the psychosocial context that cannot be attributed to the active treatment are referred to as the nocebo effect. This can be observed as differences between nocebo and non-treatment/natural history groups and has been described, for instance, in the context of adverse drug events as well as pain-related research. The nocebo response is defined as any unfavourable symptom or group of symptoms that the patient experiences in the absence of active treatment.
In recent decades there has been a significant rise in scientific interest regarding the placebo effect in a broad spectrum of contexts and applications. This includes studies looking into the placebo effect in the management of overweight and obesity, as well as in physical activity and fitness. Placebo interventions used in this context range from sham supplements to false information regarding the caloric values of meals or energy expenditure during everyday exercise. Findings of such studies show that placebo interventions can be effective in reducing excess body weight and even the percentage of body fat. On the other hand, some findings suggest the presence of the nocebo effect with the use of pharmacologically connoted interventions (e.g., sham weight-loss tablets), which could be a result of the expectations that participants have towards the supplement.
Considering all the above, the placebo and nocebo effects could influence the outcomes of fitness-related interventions. Moreover, it should be stressed that these issues have not yet been well described and that no systematic review or meta-analysis shows them in detail.
Methodology of the Systematic Review
To investigate the potential role of placebo and nocebo effects in weight loss, a systematic review of existing studies was conducted. The review was conducted according to a previously created and registered protocol (PROSPERO registration no. CRD42022342646; registration date: 9.07.2022). The review process followed the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols (PRISMA-P checklist form) guidelines and the recommendations on data searching and processing described in the Cochrane Handbook for Systematic Reviews.
Search Strategy and Study Selection
Selected databases (PubMed, Cochrane, Embase, PsycINFO, PsycARTICLES, TripDatabase) were searched for relevant articles. Additionally, the reference lists of the included articles were manually checked for other relevant studies.
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Studies with at least two groups (a placebo group and a relevant control group, i.e., no-treatment or natural history group), published in English and focused on the paediatric population (below the age of 18) participating in fitness programs or studies investigating the problem of the placebo/nocebo effect in physical fitness were included in the review and considered for meta-analysis.
Reviews, meta-analyses, secondary publications not based on a systematic review, letters to the editor, and conference communications were not included.
Data Extraction and Synthesis
The study selection was performed in two stages. The first stage included screening the titles and abstracts of articles/publications identified as potentially relevant. This was based on the inclusion/exclusion criteria and was carried out by two independent researchers (M.Z., L.K.). The full texts of potentially relevant studies were reviewed using the same inclusion/exclusion criteria by the same two researchers (M.Z., L.K.). In the case of disagreement which could not be resolved by discussion, a third researcher was consulted (P.B.).
A standardised, pilot-tested form was used for data extraction, independently performed by two researchers (M.Z., L.K.). If consensus was not reached, a third researcher (P.B.) assisted in making the final decision. Two independent researchers (M.Z. and L.K.) assessed the quality of the included studies. The Cochrane Risk of Bias (RoB) Tool for randomised studies was used to identify additional sources of bias and appraise specific domains. These domains include random sequence generation, allocation concealment, blinding of participants, blinding of outcome assessment, incomplete outcome data, and selective outcome reporting.
All studies meeting the inclusion criteria were included in a narrative synthesis. Standardised mean difference (SMD) with 95% confidence intervals (CIs) between placebo and control groups were used for continuous outcomes. The random-effects model was used as it is characterised by the greatest generalisability for empirical examination of summary effect measures in meta-analyses. A P-value of less than 0.05 was established as the threshold for statistical significance. Review Manager v.5.4 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2020) and Microsoft Excel® 2019 were used for all analyses performed in the study.
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Findings: Unveiling the Influence of Placebo
The review identified several key findings related to the impact of placebo interventions on various fitness parameters.
Four studies described in seven references were included in the narrative review. Two of these studies were combined in the meta-analysis; the other two studies were excluded from the meta-analysis due to significant methodological differences, mainly study duration (examination immediately after the intervention vs a few months after the intervention) and control group approach (participants being their own control vs standard parallel group design).
The study flow diagram is presented in the supplementary material (Fig. S1).
The essential characteristics of the included studies, together with the final follow-up values of the endpoints of interest, are presented in Table 2. All studies were described as randomised or controlled, and three of them were double-blinded. The number of individuals included in each study ranged from 20 to 287; the average age was from 8.18 to 13.1.
Regarding the Body Mass Index (BMI), the two studies included in the meta-analysis were carried out among children with normal weight (BMI percentile ≥ 5 and < 85), overweight (BMI percentile ≥ 85 and < 95) and obesity (BMI percentile ≥ 95) (three references by Fanti-Oren et al.). Thus, in the primary analysis, the results were pooled for all BMI categories. The two additional studies included in the narrative review concerned children with underweight (Z-score of 0 to −3 SD for height-for-age and weight-for-age [Desai et al.; NCT00876018; Vaz et al.]) and obesity (BMI that exceeded 98th percentile for age and sex [Daley et al.]).
Placebo interventions used in the studies included a drink given to children with an explanation that it strengthens muscles and improves athletic performance (three references by Fanti-Oren et al.), an unfortified choco-malt beverage powder (described as a placebo by the authors of the study [Desai et al.; NCT00876018; Vaz et al.]), and a placebo exercise routine (exercise designed not to elevate heart rate [Daley et al.]).
Heart Rate
Heart rate was examined in three of the four studies (three references by Fanti-Oren et al. and Daley et al.). Two took into consideration initial (resting) as well as maximal heart rate during exertion (Fanti-Oren et al.), while one analysed only resting heart rate (Daley et al.). All studies showed that the initial heart rate was comparable in the placebo and control groups. Also, the pooled results of the meta-analysed studies did not show significant differences between the groups (SMD = 0.02[−0.32, 0.35]). The maximal heart rate at the final follow-up differed significantly only in the normal-weight children when individual results were considered. However, when the pooled results were analysed, there was a statistically significant difference in favour of the placebo group (SMD = 0.66 [0.31; 1.01]).
Recovery Time
Recovery time was analysed in two studies in all three of the BMI-based categories (three references by Fanti-Oren et al.). In the meta-analysis, at the final follow-up the individual results were not statistically significant, although there was a trend favouring the placebo each time. Nevertheless, when the results were pooled, children in placebo groups had significantly shorter recovery times than those in control groups.
Ergometry Phase
The duration of the ergometry phase was analysed in two studies in all three BMI-based categories (three references by Fanti-Oren et al.). At the final follow-up, the children in placebo groups had significantly longer ergometry phases compared to those in control groups; this was the case for the individual as well as pooled results (SMD = 1.00 [0.65; 1.36]).
Running Time
Running time was analysed in two studies in all three BMI-based categories (three references by Fanti-Oren et al.). At the final follow-up, the children in placebo groups had significantly longer running time than those in control groups; this was the case for individual and pooled results (SMD = 0.93 [0.57; 1.28]).
Rate of Perceived Exertion
The average and peak rates of perceived exertion were analysed in two studies in all three BMI-based categories (three references by Fanti-Oren et al.). At the final follow-up, the placebo groups had a significantly lower peak and average perceived exertion than the control; this was the case for the individual as well as the pooled results (peak rate of perceived exertion SMD = −1.05 [−1.41; −0.69]; the average rate of perceived exertion SMD = −0.75 [−1.10; −0.40]).
Oxygen Consumption (VO2) and Aerobic Function
One study which was included in the narrative synthesis analysed maximal and peak oxygen consumption (Desai et al.; NCT00876018; Vaz et al.). At the final follow-up, both maximum and peak VO2 values were comparable between the placebo and control groups.
One study that was included only in the narrative synthesis measured aerobic function (Daley et al.). At the final follow-up, aerobic function improved in both groups (placebo and control); however, the change was statistically significant only in the placebo group.
Body Weight, Body Mass Index (BMI), Body Fat Ratio, and Waist Circumference
One study included in the narrative synthesis analysed body weight, BMI, body fat, and waist circumference (Daley et al.). At the final follow-up, there were no statistically significant differences between the placebo and control groups in any of the analysed parameters.
Preliminary Trends and Potential Mechanisms
The systematic review revealed some preliminary trends suggesting placebo and nocebo effects in weight loss. Placebo effects manifested in trends towards a slightly greater reduction of Body Mass Index (BMI) and body fat ratio in the placebo compared with the control groups.
The findings suggest a possibility that the nocebo effect may occur when an intervention has a medical context. In contrast, the placebo effect can be observed in cases where the intervention is of a different nature.
Several potential mechanisms may explain how placebo effects can influence weight loss:
Expectations and Beliefs: Individuals' expectations and beliefs about a treatment can significantly impact its effectiveness. If someone believes a placebo will help them lose weight, they may be more motivated to engage in healthy behaviors, such as eating a balanced diet and exercising regularly.
Neurobiological Pathways: Placebo effects can trigger the release of endorphins, dopamine, and other neurochemicals in the brain that can reduce stress, enhance mood, and influence physiological processes related to metabolism and appetite.
Conditioning: The association between a treatment and a positive outcome can create a conditioned response, where the body anticipates the beneficial effects even when the treatment is inactive.
Limitations and Future Directions
While the findings of this systematic review are intriguing, it is important to acknowledge certain limitations. The number of studies included in the review was relatively small, and there was some heterogeneity in the methodologies used. Additionally, most of the studies focused on short-term outcomes, and more research is needed to determine the long-term effects of placebo interventions on weight loss.
Future research should focus on:
- Conducting larger, well-designed studies with longer follow-up periods.
- Investigating the specific psychological and neurobiological mechanisms that mediate placebo effects in weight loss.
- Exploring the potential for harnessing placebo effects to enhance the effectiveness of conventional weight loss treatments.
- Examining the role of patient-provider interactions and contextual factors in shaping placebo responses.