The global obesity epidemic necessitates exploring all factors influencing weight loss interventions. While placebo and nocebo effects are known to significantly impact various health conditions, their role in weight loss remains poorly understood. This study aimed to systematically review and meta-analyze existing research to determine the presence, magnitude, and potential differences between placebo and nocebo effects on adult weight loss. The rising prevalence of obesity, particularly central obesity, highlights the urgent need to understand the multifaceted factors contributing to successful weight management. Psychological factors are increasingly recognized as important in this context, with placebo and nocebo effects potentially playing a significant, yet under-researched role. Placebo effects represent improvements in health outcomes not attributable to the active treatment but rather to the psychosocial context, while nocebo effects represent negative outcomes or adverse effects also stemming from the psychosocial context. This study aims to address this gap by rigorously investigating the evidence for placebo and nocebo effects in weight loss interventions across various methodologies.

Existing literature suggests a potential role for placebo effects in weight reduction interventions. Some studies indicate that positive expectations and beliefs about an intervention can lead to greater weight loss, even if the intervention itself is inactive. However, this area of research remains largely unexplored. Furthermore, there’s a lack of systematic reviews and meta-analyses specifically focused on placebo and nocebo effects in adult weight loss, necessitating a comprehensive review of the available evidence to fully understand this phenomenon. This review aims to systematically evaluate the available data on placebo and nocebo effects in interventions aimed at weight reduction to better inform future research and clinical practice.

This systematic review and meta-analysis followed a pre-registered protocol (PROSPERO registration no. [Number]). A comprehensive search of PubMed, Cochrane, PsycINFO, PsycARTICLES, TripDatabase, and Embase databases was conducted using PICOS framework-based search terms. Studies included were those: 1) with at least two groups (placebo and control); 2) published in English; and 3) focusing on adult weight loss programs or placebo/nocebo effects in weight loss. Two independent researchers screened titles/abstracts and full texts. Disagreements were resolved through consultation with a third researcher. The Cochrane Risk of Bias tool was used to assess study quality. Data extracted included sample size, age, sex, body weight/derived indicators before and after intervention, intervention description, and subjective satisfaction (where reported). A narrative synthesis was performed for all included studies. Meta-analysis using a random-effects model was conducted for studies with comparable outcome measures and methodology, calculating standardized mean differences (SMDs) with 95% confidence intervals (CIs). Statistical significance was set at p<0.05. Review Manager v.5.4 and Microsoft Excel were used for analyses. Sensitivity analyses were performed by excluding studies with the smallest sample sizes.

Five studies were included in the review, four of which were included in the meta-analysis. The meta-analysis revealed non-significant differences between placebo and control groups for body weight (SMD [95% CI]: -0.07 [-0.38, 0.24]), BMI (-0.24 [-0.58, 0.11]), and body fat percentage (-0.27 [-0.61, 0.07]). However, individual studies showed trends toward greater weight loss (or improvement in body composition measures) in placebo groups compared to controls for BMI and body fat percentage. One study reported a possible nocebo effect where expectancy of taking oral weight-loss agents led to less weight loss. Sensitivity analyses, excluding a study with a small sample size, yielded similar results. The analysis of body weight, BMI, body fat percentage, waist circumference, and waist-to-hip ratio revealed some interesting trends. For instance, several studies observed greater reductions in BMI and body fat percentage in the placebo groups compared to control groups. In one study that examined waist-to-hip ratio (WHR), a greater reduction was found in the placebo group. The magnitude of these effects, however, wasn’t always statistically significant, likely due to the limited sample sizes of some studies. These findings suggest a potential role for placebo interventions in weight loss, especially considering that improvements in body composition measures (reduction in fat tissue) rather than overall weight were observed in placebo groups in several studies.

The findings suggest a possible role for placebo and nocebo effects in weight loss, with placebo interventions potentially leading to improved outcomes in certain contexts. The observed trends toward greater weight loss in placebo groups for certain body composition measures indicate that improvements in weight management might not be solely dependent on active interventions. The potential for a nocebo effect, particularly with pharmacologically-based placebos, warrants further investigation. The study highlights the complex interplay between psychological and physiological factors in weight loss. The context of the intervention, expectations, and beliefs might significantly influence the outcome. Future research should explore the mechanisms underlying these effects and consider utilizing more nuanced methods to understand and maximize placebo effects in weight loss interventions. Future research should include larger sample sizes and more consistent methodology to enhance the power and reliability of the results.

This systematic review and meta-analysis provide preliminary evidence suggesting potential placebo and nocebo effects in adult weight loss. While the meta-analysis did not yield statistically significant differences between placebo and control groups for all outcomes, individual studies showed trends favoring placebo interventions, particularly in terms of body composition changes. The possibility of a nocebo effect associated with pharmacologically-connoted interventions needs further investigation. The limitations of the current research highlight the need for larger, well-designed studies using consistent methodologies to confirm these findings and elucidate the mechanisms driving placebo and nocebo effects in weight loss.

The review's limitations include a small number of included studies, heterogeneity in study designs and interventions, and a high proportion of studies with unknown risk of bias in several domains. The limited number of participants in some studies might have reduced the power to detect statistically significant differences between groups. The use of final values instead of changes from baseline in the meta-analysis, due to limited data availability, is another limitation. Despite these limitations, this is the first systematic review exploring the placebo and nocebo effects on weight loss, providing valuable initial insight into this under-researched area.