A recent systematic review and network meta-analysis of 68 randomized controlled trials highlights the potential of several nutraceuticals for weight management. L-carnitine, inulin, and long-chain omega-3 fatty acids were associated with improvements in body weight and other anthropometric measures, with L-carnitine showing the most pronounced effect on weight reduction. In children, butyrate was the only supplement significantly associated with reductions in BMI and waist circumference. These findings provide valuable evidence for further research into nutraceutical-based approaches to weight management.
Obesity has become one of the most pressing global public health challenges, contributing to cardiometabolic complications, type 2 diabetes, hypertension, and other chronic diseases. As the prevalence of overweight and obesity continues to rise, consumers and the nutrition industry are increasingly seeking evidence-based nutritional strategies for weight management. Among the many dietary supplements marketed for weight control, however, their effectiveness and optimal dosages can vary considerably.
A recent systematic review and network meta-analysis published in Frontiers in Nutrition evaluated 68 randomized controlled trials conducted between January 2010 and May 2025, comparing the effects of several popular nutritional supplements in people with overweight or obesity. The supplements examined included L-carnitine, inulin, long-chain omega-3 polyunsaturated fatty acids, B vitamins, butyrates, and other nutritional interventions. The analysis found that L-carnitine, inulin, and long-chain omega-3 polyunsaturated fatty acids were associated with beneficial effects on several anthropometric measures, including body weight, BMI, waist circumference, hip circumference, fat mass, and fat-free mass. Among these interventions, L-carnitine showed the most pronounced effect on body weight.
The researchers also conducted a multivariable dose-response network meta-analysis to investigate the relationship between supplementation dosage and changes in key body measurements after 12 weeks. Using an average weight reduction of 2.5 kg compared with placebo as a common reference point, the estimated daily dosage was 458 mg for L-carnitine, compared with 5,751 mg for inulin and 6,000 mg for long-chain omega-3 polyunsaturated fatty acids.
The study also included a pediatric subgroup analysis. Interestingly, butyrate was the only supplement associated with significant reductions in BMI and waist circumference among children. These findings highlight the potential of specific nutraceutical ingredients as research-backed components of weight-management strategies, while also emphasizing the importance of dosage, population, and individual circumstances when interpreting nutritional evidence.
Obesity: A Growing Global Health Challenge
Obesity has long been an important threat to public health. It can contribute to a range of chronic conditions, including cardiometabolic complications, type 2 diabetes, and hypertension, making it one of the most serious public health challenges facing the world today.
Over the past several decades, the global prevalence of obesity has continued to rise. According to statistics from the World Health Organization (WHO), since 1990, the global prevalence of obesity among adults has more than doubled, while the prevalence among adolescents has increased fourfold. By 2022, approximately one in every eight people worldwide was living with obesity, highlighting the widespread and urgent nature of the problem.
World Obesity Report 2025
With a wide variety of weight-management supplements now available on the market, an important question remains: which nutritional supplements are supported by scientific evidence, and how do their effects compare?
A recent study published in Frontiers in Nutrition provides a systematic and comprehensive analysis of this question.
The study used a network meta-analysis to evaluate 68 randomized controlled trials published between January 2010 and May 2025. It specifically compared the effects of several popular weight-management supplements, including inulin, butyrates, long-chain omega-3 polyunsaturated fatty acids, B vitamins, and L-carnitine. The analysis provides a scientific basis for understanding the potential effects of different nutritional supplements in people with overweight or obesity.
Image source: Reference [1]
Which Supplements Showed Greater Weight-Management Effects?
The 68 randomized controlled trials included in the analysis investigated popular nutritional supplements as interventions. The study populations consisted of people with overweight or obesity, excluding pregnant women, and the reported outcomes included body weight, metabolic parameters, inflammatory markers, and other relevant measures.
For the statistical analysis, the researchers used a random-effects model for the network meta-analysis. Mean differences or standardized mean differences were used to evaluate the effects of different interventions compared with placebo, with the aim of providing a comprehensive and reliable comparison of the available evidence.
The analysis found that among the popular weight-management nutritional supplements evaluated, L-carnitine, inulin, and long-chain omega-3 polyunsaturated fatty acids were associated with beneficial effects on body weight, BMI, waist circumference, hip circumference, fat mass, and fat-free mass in people with obesity.
Compared with placebo, L-carnitine showed the most pronounced effect on body weight reduction.
Image source: Reference [1]
The research team further conducted a multivariable dose-response network meta-analysis to clarify the relationship between the dosage of different supplements and changes in key anthropometric measurements after 12 weeks of intervention.
The results showed that, when an average reduction of 2.5 kg in body weight compared with placebo was used as a common reference point, a daily intake of only 458 mg of L-carnitine was estimated to achieve this level of weight reduction. By comparison, the estimated daily amounts were 5,751 mg of inulin and 6,000 mg of long-chain omega-3 polyunsaturated fatty acids to achieve the same reference level of weight reduction. The doses required for the latter two interventions were therefore substantially higher than that estimated for L-carnitine.
L-Carnitine: A Promising Ingredient for Weight Management
L-carnitine, also known simply as carnitine, is an amino-acid-like compound naturally present in the human body, particularly in the liver and kidneys. The human body can synthesize L-carnitine from lysine and methionine with the involvement of nutrients including vitamin C, vitamin B6, niacin, and iron. It can also be obtained from animal-based foods, particularly meat.
In 1958, Fritz and colleagues first demonstrated the important role of L-carnitine in the oxidation of long-chain fatty acids in muscle and heart tissues. L-carnitine can increase the rate of fatty-acid β-oxidation and facilitate the utilization of fatty acids by mitochondria for energy production.
More specifically, L-carnitine binds to fatty acids and helps transport them from the cytoplasm into mitochondria, where they can undergo oxidation and contribute to energy production.
These physiological functions have made L-carnitine a long-standing ingredient of interest in sports nutrition, weight-management supplements, and metabolic health products. The findings of the recent network meta-analysis further highlight its potential role among nutritional ingredients investigated for weight management.
Butyrate: An Emerging Ingredient for Pediatric Weight Management
Adult obesity is not the only issue requiring attention. Overweight and obesity among children are also increasingly concerning. According to available data, the global number of overweight children under five years of age reached approximately 35 million in 2024.
The systematic review and network meta-analysis titled “Nutraceuticals for the management of weight and inflammation-related complications in obesity: a pediatric perspective. Systematic review and network meta-analysis” included a specific pediatric subgroup analysis to evaluate the effects of different nutritional supplements on body weight, BMI, and waist circumference in children.
The analysis showed that butyrate was the only intervention associated with significant reductions in BMI and waist circumference in children, while the other evaluated supplements did not demonstrate statistically significant improvements in these outcomes.
Image source: Reference [1]
Butyrate is a short-chain fatty acid (SCFA) that is primarily produced by the gut microbiota through the fermentation of dietary fiber. It also serves as a major energy source for colon cells.
Multiple studies have demonstrated that butyrate can significantly inhibit the activity of histone deacetylase 3 (HDAC3), thereby regulating the expression of genes involved in metabolic processes.
In a diet-induced obesity mouse model, researchers observed that HDAC3 in intestinal epithelial cells could promote the development of obesity. Butyrate, by inhibiting HDAC3 activity, may therefore help prevent diet-induced obesity at the intestinal epithelial level.
Further mechanistic research has provided additional insights into the relationship between butyrate and energy expenditure. When researchers knocked out HDAC3 in the intestinal epithelial cells of mice, the animals showed a significant increase in overall energy expenditure despite maintaining similar food intake and activity levels.
These findings suggest that butyrate may promote weight reduction, at least in part, through mechanisms associated with increased energy expenditure and metabolic regulation.
In addition to its potential role in weight management, butyrate has demonstrated a range of other health-related effects, including potential roles in immune regulation, metabolic regulation, intestinal health, and cardiovascular protection.
Overall, current evidence suggests that L-carnitine and butyrate represent two nutraceutical ingredients of particular interest in the field of weight management, although their effects may differ according to age, dosage, physiological conditions, and other factors. The findings of network meta-analyses can help identify promising nutritional strategies, but they should be interpreted within the context of the available clinical evidence rather than as a substitute for individualized medical or nutritional advice.
References
[1] Zuccotti G, Gatti A, Rossi V, Cordaro E, Calcaterra V. Nutraceuticals for the management of weight and inflammation-related complications in obesity: a pediatric perspective. Systematic review and network meta-analysis. Frontiers in Nutrition. 2026;13.
[2] WeChat article. Available at: https://mp.weixin.qq.com/s/J4zf8by13glGmptb2pUJeA
[3] Whitt J, et al. Disruption of Epithelial HDAC3 in Intestine Prevents Diet-Induced Obesity in Mice. Gastroenterology. 2018.