Miroshnikov A.B., Rybakova P.D., Shevtsov A.V. The effect of dietary supplements containing ephedrine on body weight loss: an umbrella review of systematic reviews

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Publication date: 15.06.2024
DOI: 10.24412/2782-6570-2024_03_02_2
UDC 582.491; 613.2

THE EFFECT OF DIETARY SUPPLEMENTS CONTAINING EPHEDRINE ON BODY WEIGHT LOSS: AN UMBRELLA REVIEW OF SYSTEMATIC REVIEWS

A.B. Miroshnikov¹, P.D. Rybakova^1,2, A.V. Shevtsov¹

¹Russian University of Sport “GTSOLIFK”, Moscow, Russia
²Center for Sports Innovative Technologies and National Team Training, Department of Sports of Moscow, Moscow, Russia

Abstract. Ephedra or ephedrine are sometimes used to reduce weight or improve athletic performance, but the effectiveness and safety of these compounds is questionable. Aim of the study – to conduct a search and analysis of systematic reviews on the effects of dietary supplements containing ephedrine on weight loss. The study was conducted in accordance with the Development of the Preferred Reporting Items for Overviews of Reviews Statement. The methodological quality of included reviews was assessed using A MeaSurement Tool to Assess systematic Reviews. Duplication of components of primary studies included in all relevant reviews was assessed using the Corrected Covered Area formula. The literature search was carried out in the following databases: PubMed, MedNar, Epistemonikos, Cochrane Library, ResearchGate and Google Scholar (filter by date – from 2000 to June 2024). A total of 271 references were identified from the databases, with only 3 systematic reviews meeting the inclusion criteria. The overall confidence of the results was rated as “critically low”, with an area of ​​overlap of 4.55%. The authors of 3 systematic reviews came to a consensus on the effectiveness of using supplements containing ephedrine (ephedrine dose was 20-150 mg/day) to reduce weight (on average from 0.9 to 2.0 kg per month). Some concerns remain regarding the safety of this dietary supplement.

Keywords: ephedra, ephedrine, mahuang, obesity, weight loss, doping in sports, nutritional science.

Introduction. Overweight or obesity can predispose people to chronic diseases and metabolic disturbances, such as cardiovascular diseases, diabetes, Alzheimer’s disease and cancer, which are serious issues of healthcare and main causes of mortality around the world [1]. Change in lifestyle, including calorie restriction and physical exercise, are the main approach to weight loss. In addition to lifestyle changes, drug therapy is also used to combat obesity, especially if the body mass index (BMI) is more than 30 kg/m² or if there are comorbid diseases and BMI is more than 27 kg/m² [2]. Various herbal medicines and extracts are also available for weight loss, but unlike approved drugs, the clinical data for these products is currently unclear [3].

Ephedrae Herba (Ephedra), also known as “Mahuang” in China, grows mainly in deserts and is used in traditional Chinese medicine for more than 5000 years [4]. In modern medicine, ephedrine is mainly used as a bronchodilator in the treatment of asthma and as a vasoconstrictor in hypotension and shock. Ephedrine can also stimulate the central nervous system, which makes it useful in treating narcolepsy and asthma [5]. Also products with ephedra (ephedrine and caffeine) have become widely used in weight loss [6] and improvement of results in sports [7]. Due to the unfavorable cardiovascular side effects, the US Food and Drug Administration (FDA) banned the sale of supplements containing ephedrine alkaloids in 2004 [8]. However, a year later The United States district court lifted the FDA ban, and the safety of ephedrine for the cardiovascular system remains unclear. At the moment ephedrine is included into the Prohibited List of the World Anti Doping Agency (WADA), and dietary supplements containing ephedra are prohibited to sale in the Russian Federation. Based on the analysis of the problem, data of modern scientific literature and requests of sports nutritionists, nutritionists and anti-doping control experts, the aim of the study was formulated.

Aim of the study: to search and analyze systematic reviews on the effect of dietary supplements with ephedrine on weight loss.

Methods and organization. The study took place in the Department of Sports Medicine of the Russian University of Sport “GTSOLIFK”, Moscow. It was conducted in accordance with the Development of the Preferred Reporting Items for Overviews of Reviews Statement (PRIOR) [9]. The study’s protocol was designed before the search and did not change neither during nor after the search according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) [10]. The study’s protocol was also registered in the OSF base: https://doi.org/10.17605/OSF.IO/YGM­2H.

Prior to the search, it was decided that only systematic reviews and/or meta-analyses would be included in the review as they are the gold standard of evidence-based medicine.

Information sources and search strategies. The literature search was performed according to the Peer Review of Electronic Search Strategies (PRESS) [11]. The literature was searched in PubMed, MedNar, Epistemonikos, Cochrane Library, Research­Gate and Google Scholar using the following keywords (table 1).

Table 1

Keywords for literature search

Научная база	Search input
PubMed	All Fields ((((Ephedrine) AND (Mahuang)) AND (“Ephedra sinica”)) AND (“Weight Loss”)) AND (Obesity)
Epistemonikos	(title:(Ephedrine) OR abstract:(Ephedrine)) AND (title:(Mahuang) OR abstract:(Mahuang)) AND (title:(“Ephedra sinica”) OR abstract:(“Ephedra sinica”)) AND (title:(“Weight Loss”) OR abstract:(“Weight Loss”)) AND (title:(Obesity) OR abstract:(Obesity))
Google Scholar	Ephedrine AND Mahuang AND “Ephedra sinica” AND “Weight Loss” AND Obesity AND Systematic Review AND Meta-Analysis
Cochrane Library	Ephedrine in Title Abstract Keyword AND Mahuang in Title Abstract Keyword AND “Ephedra sinica” in Title Abstract Keyword AND “Weight Loss” in Title Abstract Keyword AND Obesity in Title Abstract Keyword
MedNar	Full Record: Ephedrine AND Mahuang AND “Ephedra sinica” AND “Weight Loss” AND Obesity AND Systematic Review AND Meta-Analysis / Title: Ephedrine AND Mahuang AND “Ephedra sinica” AND “Weight Loss” AND Obesity AND Systematic Review AND Meta-Analysis
ResearchGate	Ephedrine AND Mahuang AND “Ephedra sinica” AND “Weight Loss” AND Obesity AND Systematic Review AND Meta-Analysis

Studies over the past ~24 years were examined (filter by date – from 2000 to June 2024). The language barrier was not set. The reference lists of retrieved studies were then manually searched to identify potentially relevant studies not covered by the electronic search. In order to be included in the review, the study should comply with the inclusion criteria based on the PICOS system [12]. P (Population) – healthy people (men and women) over 18; I (Intervention) – intake of dietary supplements containing ephedrine (ephedra, ephedrine, ephedrine+caffeine) for weight loss; C (Comparison) – comparison with the control group; O (Outcomes) – any analysis of body weight or composition; S (Study) – only systematic reviews and/or meta-analyses.

Choice of studies. Initially, two authors of the review (A.V. Shevtsov and P.D. Rybakova) independently and at the same time checked the titles, abstracts and, if needed, full texts of the articles from the databases in accordance with the eligibility criteria. Duplicates and articles that did not comply with the criteria were excluded from the search. Any discrepancies were resolved by consensus discussion, and any disagreements were resolved by the third reviewer (A.B. Miroshnikov).

Retraction of studies. After the search, the two authors (A.V. Shevtsov and P.D. Rybakova) independently and at the same time retracted the full texts in accordance with the inclusion criteria. Duplicates and articles that did not comply with the criteria were excluded. In case of any disagreements between the assessments of the authors, consensus was reached either through discussion or with the help of the third reviewer (A.B. Miroshnikov). Interrater (kappa) reliability varied from 0.51 (week) to 1.00 (almost ideal), as recommended by M. McHugh [13].

Methodological quality assessment. The methodological quality of the reviews included was rated with A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) [14] consisting of 16 points. The quality of each eligible article was independently analyzed by the two researchers (A.V. Shevtsov and P.D. Rybakova). In case of any disagreements between the assessments of the authors, consensus was reached either through discussion or with the help of the third reviewer (A.B. Miroshnikov). In this review, we thoroughly examined initial fields that can critically affect reliability of the review and its findings, as suggested by Shea et al [14]. Since the data in this study are descriptive, the statistical analysis was conducted according to SWiM (Synthesis Without Meta-analysis) [15].

Umbrella review synthesis methods. Duplication of components of primary studies included in all relevant reviews was assessed using the Corrected Covered Area (CCA) formula [16]: CCA=(N−R)/(RC−R), where N – sum of the total number of the primary stidues, included in all reviews, R – a number of unique primary studies, С – a total number of reviews. CCA varies from 0% to 100%, with 100% indicating that all reviews in an umbrella review include the same original research, and 0% indicating that each review includes completely unique original research. CCA was classified based on the following threshold values: 0-5% as slight overlap; 6-10% – moderate overlap; 11-15% – high overlap; >15% – very high overlap [17].

Results and discussion. A total of 271 references were identified in the databases. The figure below shows a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart of the research selection process. Only 3 systematic reviews [18-20] met the inclusion criteria, with one systematic review [20] found by manual search (fig.).

Characteristics of the included reviews. The number of studies included in the reviews ranged from 10 [19] to 20 [20] (table 2).

Quality of the reviews. Methodological quality of 3 included reviews is shown in table 2. Based on the overall validity assessment using AMSTAR-2, the overall reliability of the results of 3 (100%) reviews was rated as “critically low”. For this reason, and because systematic reviews and meta-analyses are a recent method of research in the field of sports nutritional science, we did not exclude any of the studies from further analysis based on quality assessment. Also, no review reported conflicts of interest and funding of studies included in the meta-analysis. The selected systematic reviews and meta-analyses did not mention criteria limiting the type of experimental design adopted in the studies.

Fig. The PRISMA flowchart

Note: PRISMA – Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Table 2

Systematic reviews evaluating the effects of dietary supplements containing ephedrine on weight loss

Review authors/year	Included studies	Key findings of the systematic reviews	AMSTAR-2
Shekelle et al, 2003 [18]	20	Ephedrine and ephedra promote slight short-term weight loss (≈0.9 kg/month more than placebo). There are no data on long-term weight loss, and there is insufficient evidence to support the use of ephedra to improve athletic performance.	CL
Yoo et al, 2021 [19]	10	Compared to placebo, the products containing ephedrine revealed better effect on weight loss. The products with ephedrine may be useful for patients with obesity or overweight.	CL
Jo et al, 2017 [20]	16	Effect of mahuang and ephedrine on weight loss was better (ephedrine dose was 20~90 mg/day) than in the control group	CL

Note: AMSTAR – A MeaSurement Tool to Assess systematic Reviews; CL – critically low

The meta-analysis of Shekelle et al [18] included studies on people with the observation period of not less than 8 weeks. The authors classified 20 studies by 6 categories: ephedrine vs placebo, ephedrine and caffeine vs placebo, ephedrine and caffeine vs ephedrine only, ephedrine vs other drug for weight loss, ephedra vs placebo, ephedra with herbs containing caffeine vs placebo. As a result, the researchers concluded that short-term usage of ephedrine at high doses or ephedrine and caffeine, ephedra and ephedra with herbs containing caffeine contributes to weight loss in selected groups of patients by at least 5% of pre-intervention body weight. According to the meta-analysis by Yoo et al [19], the products with ephedrine compared to placebo at a daily dose of 60 to 150 mg for 4 to 24 weeks significantly reduced weight by an average of 2.0 kg. A systematic review by Jo et al [20] concluded that the effect of mahuang and ephedrine on weight loss was better (ephedrine dose was ~20-90 mg/day) than in the control group.

Regarding the safety of ephedrine supplements, although we did not aim to review this aspect, all systematic reviews have shown the following (table 3).

Table 3

Data on side effects

Review authors/year	Key findings of the systematic reviews	Conflict of interest
Shekelle et al, 2003 [18]	Use of ephedra or ephedrine and caffeine is associated with an increased risk of mental, autonomic or gastrointestinal symptoms, as well as palpitations.	ND
Yoo et al, 2021 [19]	Products with ephedrine at a daily dose of 60 to 150 mg for 4 to 24 weeks increased heart rate to 5.8 beats/min.	None
Jo et al, 2017 [20]	No serious side effects associated with mahuang and ephedrine use were found in all studies.	ND

Note: ND – no data

A systematic review of Cho et al [21] that united the data from 6 randomized controlled trials (RCTs), on the safety of supplements with ephedrine concluded that, that in most studies the heart rate in the experimental group was higher than in the placebo group, and the difference was statistically significant. Systolic and diastolic arterial pressure had no statistically significant differences between both groups, and most adverse events reported in the experimental group included dry mouth, constipation, diarrhea, palpitations, and insomnia. No serious adverse events were reported.

Conclusion. Overlap in meta-analyses is a methodological issue, which, if ignored or solved incorrectly, can lead to false assumptions in relation to the presented evidence [22]. In the analysis of the CCA of the primary studies (ССА: 4.55%) we note the low overlap, which increases our confidence in the results. In addition to potential shortcomings (small sample size, lack of randomization rules etc), revealed in the original studies, this umbrella review of systematic reviews and meta-analyses revealed a critically low methodological quality of the studies, reflecting a need to significantly improve methodological procedures. Authors of 3 systematic reviews included in our umbrella review, concluded the effectiveness of using dietary supplements with ephedrine (ephedrine dose was 20-150 mg/day) for weight loss (on average from 0.9 to 2.0 kg per month). However, these data should be interpreted with caution, as the reviews and the original studies themselves did not analyze body composition. It is known that the use of drug-based interventions influences muscle tissue [32], and this should be taken into account when designing RCTs protocols. Some concerns remain about the safety of ephedrine supplements. High-quality RCTs in this field are required.

Conflict of interest. The authors declare no conflict of interest.

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INFORMATION ABOUT THE AUTHORS:
Aleksandr B. Miroshnikov – Doctor of Biological Sciences, Associate Professor, Professor of the Department of Sports Medicine, Russian University of Sport “GTSOLIFK”, Moscow, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: https://orcid.org/0000-0002-4030-0302.
Polina D. Rybakova – Analyst of the Department of Sports Nutrition, Center for Sports Innovative Technologies and Training of National Teams, Department of Sports of Moscow; Post-Graduate Student of the Department of Sports Medicine, Russian University of Sport “GTSOLIFK”, Moscow, e-mail: rybakova. This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: https://orcid.org//0000-0003-1165-6518.
Aleksej V. Shevtsov – Candidate of Pedagogical Sciences, Professor, Professor of the Department of Theory and Methodology of Martial Arts, Russian University of Sport “GTSOLIFK”, Moscow, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID: https://orcid.org/0000-0002-1406-8079.

For citation: Miroshnikov A.B., Rybakova P.D., Shevtsov A.V. The effect of dietary supplements containing ephedrine on body weight loss: an umbrella review of systematic reviews. Russian Journal of Sports Science: Medicine, Physiology, Training, 2024, vol. 3, no. 2. DOI: 10.24412/2782-6570-2024_03_02_2