Systematic review and meta-analysis of bioactive hydrolysates derived from Saccharomyces cerevisiae on obesity management

Abstract

Background

Obesity is a major public health challenge. Pharmacological treatments are effective but limited by high cost, side effects, and restricted accessibility, particularly in low- and middle-income countries. Nutraceuticals may provide complementary or alternative approaches. Saccharomyces cerevisiae–derived bioactive hydrolysates have shown promise in clinical trials, but their efficacy has not previously been synthesized in a meta-analysis. Methods: We conducted a systematic review and meta-analysis following Cochrane and PRISMA 2020 guidelines (PROSPERO CRD420251024965). PubMed, SciELO, CENTRAL, ClinicalTrials.gov, Europe PMC, bioRxiv, medRxiv, and Preprints.org were searched (April–August 2025) for blinded, randomized, placebo-controlled trials in adults with overweight or obesity. Primary outcomes were changes in body weight, body mass index (BMI), fat mass, and waist circumference. Risk of bias was assessed using ROB-2, and certainty of evidence was graded with GRADE. Results: Six randomized controlled trials (n = 262) were included. Compared with placebo, S. cerevisiae bioactive hydrolysates significantly reduced body weight (MD − 3.08 kg; 95% CI − 4.02 to − 2.13; p < 0.001; I² = 10%), BMI (MD − 0.87 kg/m²; 95% CI − 1.32 to − 0.41; p < 0.01; I² = 50%), and fat mass (MD − 1.93 kg; 95% CI − 3.36 to − 0.49; p < 0.05; I² = 64%). A non-significant trend was observed for waist circumference (MD − 2.47 cm; 95% CI − 5.09 to 0.16; p = 0.06; I² = 78%). All trials were assessed as low risk of bias, but heterogeneity downgraded the certainty of evidence to low. Conclusions: This systematic review and meta-analysis demonstrate that S. cerevisiae–derived bioactive hydrolysates lead to statistically and clinically meaningful reductions in fat mass, BMI, waist circumference, and body weight. Their favorable safety and over-the-counter availability support their use as an accessible short-term option for obesity management. Further studies are warranted to evaluate long-term effects, durability of outcomes, and applicability in real-world settings.

Trial registration

PROSPERO: CRD420251024965

Supplementary Information

The online version contains supplementary material available at 10.1186/s12906-025-05139-8.

Background

Obesity is one of the greatest contemporary challenges in global public health, affecting 2.11 billion adults worldwide in 2021 [1]. To date, no country has effectively halted its increasing prevalence [1]. If current trends persist, it is estimated that by 2050 approximately 3.80 billion adults worldwide will be living with obesity, exacerbating the burden of associated non-communicable diseases [1].

Current therapeutic options for obesity management encompass lifestyle interventions, pharmacological therapies and surgical interventions [2–5]. Lifestyle modification remains the first-line strategy but typically produces modest, hard-to-maintain weight loss due to poor adherence and high rates of weight regain [6]. Pharmacological treatments are an established component of comprehensive obesity management and are endorsed by current clinical practice guidelines [3, 4]. Several drug classes have demonstrated clinical efficacy in promoting weight loss, improving outcomes, and decreasing the risk of obesity-related complications, particularly when combined with lifestyle interventions [7]. However, their effectiveness in real-world settings is often limited by factors such as variable individual response, early discontinuation, adverse effects, and barriers to access, including notably high costs [3, 4, 7]. For example, a recent analysis by the Congressional Budget Office estimated that authorizing Medicare coverage for anti-obesity medications (e.g., GLP-1 receptor agonists, GIP/GLP-1 dual agonists, and older agents like orlistat, bupropion/naltrexone, and phentermine/topiramate) starting in 2026 would increase federal spending by 35 billion dollars over nine years, while expected savings from improved health outcomes would remain comparatively modest [8]. The projected annual cost per user would substantially exceed the estimated savings during that period, highlighting the economic challenge of scaling these therapies despite their clinical potential [8].

In low- and middle-income countries, these economic challenges are even more pronounced. In Mexico, for instance, a review of national clinical guidelines revealed that fewer than 2% of eligible patients receive pharmacotherapy for obesity, mainly due to high out-of-pocket costs, limited insurance coverage, and restricted drug availability in the public healthcare system [3]. These obstacles not only reinforce the existing inequities, but also underscore the need to identify complementary or alternative strategies that are effective, safe, financially sustainable, and better aligned with the economic realities of the broader population.

In this context, nutraceuticals have attracted increasing attention for their favorable tolerability profiles and potential health benefits [9, 10]. These products, which combine nutritional and pharmaceutical properties, have gained recognition for their potential to support health and manage various conditions, in addition to their advantages in terms of affordability and accessibility [9, 10]. This growing demand is reflected in their expanding market [9].

Obesity management is perceived as a promising area for nutraceuticals as therapeutic or complementary agents. However, evidence for these claims remains limited and subject to bias. For instance, a recent systematic review involving 18 different nutraceuticals across 111 studies revealed that they provide limited trivial benefits regarding weight loss with a low certainty in evidence [11].

Saccharomyces cerevisiae-derived hydrolysates are widely available nutraceuticals, with several brands on the market (Stetikal^®, Laboratorios Columbia; LipiGO^®, AB-biotics, Fytexia^®, ABF Ingredients, etc.). Clinical trials of these formulations have reported reductions in body weight and adiposity measurements, although the magnitude and consistency of effects are variable [12–20]. Study designs differ substantially in sample size, duration, outcome definitions, and populations evaluated, which complicates comparison and synthesis. This heterogeneity limits the strength of the available evidence and prevents clear conclusions regarding their efficacy. To address this gap, we conducted a systematic review and meta-analysis of bioactive S. cerevisiae-derived hydrolysates on body weight and adiposity.

Methods

The aim of this study was to evaluate the clinical efficacy of bioactive hydrolysates derived from Saccharomyces cerevisiae on body weight and adiposity. This systematic review and meta-analysis were conducted in accordance with standard Cochrane handbook recommendations and are reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines [21]. The study was prospectively registered in PROSPERO in March 2025 (CRD420251024965).

Search strategy

A systematic search was conducted in PubMed, SciELO, and the Cochrane Central Register of Controlled Trials (CENTRAL) between April and August 2025. Grey literature was searched in ClinicalTrials.gov, Europe PMC, bioRxiv, medRxiv, and Preprints.org. Additionally, a snowballing strategy and expert consultation were performed to identify additional studies. Full details of the search strategy are provided in Supplementary Material S1.

Study selection

Eligibility criteria were defined according to the Population, Intervention, Comparator, Outcomes, and Study design (PICOS) framework (Table 1). We included blinded, randomized, placebo-controlled trials evaluating S. cerevisiae–derived bioactive hydrolysates in adults with overweight or obesity. Exclusion criteria were non-human studies, formulations containing additional active components beyond yeast extracts, and studies in children or breastfeeding women.

Table 1.

PICOS criteria for inclusion and exclusion of studies

Parameters	Inclusion Criteria
Population	Adults with overweight or obesity
Intervention	Saccharomyces cerevisiae-derived bioactive hydrolysate
Comparison	Placebo
Outcomes	Changes in body weight, fat mass, BMI, and abdominal perimeter
Study Design	Blinded, randomized, placebo-controlled clinical trials

Data extraction, quality, and risk of bias assessment

Titles and abstracts were independently screened by two reviewers (YCJV, ARC) with discrepancies resolved through discussion or arbitration by an additional reviewer (MHR). Full-text articles or registry data were retrieved for detailed assessment. After duplicate removal, two additional reviewers (CTB, RRE) repeated the process with arbitration by a third reviewer (PGAA). Data were extracted using standardized forms and analyzed with Cochrane Review Manager (RevMan) software [22]. Risk of bias for each study was assessed using the Cochrane Risk of Bias 2.0 (ROB-2) tool [23]. Inter-reviewer agreement was calculated with Cohen’s kappa using a custom Python script (https://github.com/DrEdgarRamirez/Kappa). Certainty of evidence was graded according to GRADE.

Outcomes

The main outcomes were changes in body weight, BMI, abdominal circumference, and fat mass. All measures were standardized to international units, with conversions performed as needed. When standard deviations were not reported, they were calculated from available data. For outcomes reported only in graphical format, numerical values were extracted using the Plot Digitizer tool [24], and measures of dispersion were extrapolated as required.

Meta-analysis

Meta-analyses and forest plots were generated in RevMan [22]. Continuous variables were analyzed as mean differences with standard deviations. Random-effects models using the DerSimonian–Laird method were applied with inverse-variance weighting; 95% CIs used the Hartung–Knapp–Sidik–Jonkman adjustment. Confidence intervals for I² with 95% Cis were calculated with a custom Python script (https://github.com/DrEdgarRamirez/I2CI) utilizing the SciPy library. Additionally, Galbraith plots were generated with a custom Python script using the NumPy, Matplotlib, and Pandas libraries(https://github.com/DrEdgarRamirez/Galbraith-).

Ethical statement

No new studies involving human participants or animals were conducted by the authors; therefore, ethical approval was not required.

Use of large language models (LLMs)

An AI-based tool (ChatGPT, OpenAI) was used exclusively for grammar, spelling, and style suggestions. All content was subsequently reviewed and edited by the authors, who take full responsibility for the final manuscript

Results

Study selection

Between April and August 2025, the searcg strategy identified a total of 1,325 records (PubMed = 70; SciELO = 1055; CENTRAL = 123; ClinicalTrials.gov = 40; Europe PMC = 0; bioRxiv = 9; medRxiv = 28; Preprints.org = 0). After screening and duplicate removal, 1,317 records were excluded (κ = 0.935, all discrepancies resolved by consensus without third reviewer arbitration). Eight full texts were assessed for eligibility, of which four were included. An additional two studies were identified by snowballing, yielding a total of six randomized controlled trials comprising 262 participants (κ = 1.0; no discrepancies). The selection process is summarized in Fig. 1.

Fig. 1.

PRISMA flow diagram of study selection

Effects of a bioactive hydrolysate derived from Saccharomyces cerevisiae on weight and adiposity outcomes

Six randomized controlled trials assessed the effect of Saccharomyces cerevisiae–derived bioactive hydrolysates on weight and adiposity [13, 15–17, 19, 20]. Compared with placebo, the intervention significantly reduced body weight (Fig. 2), BMI (Fig. 3), and fat mass (Fig. 4). For abdominal circumference, a clear but non-significant trend towards reduction was observed (Fig. 5). All six studies included were judged as having a low overall risk of bias. Galbraith plots demonstrated notable heterogeneity, mostly influenced by the presence of outliers (Figs. 6, 7, 8 and 9). Certainty of evidence was deemed low for all outcomes due to residual, largely unexplained heterogeneity, primarily driven by Jung, et al. 2014 and Mosikanon, et al. 2017 outlier studies.

Fig. 2.

Forest plot showing the effect of Bioactive Hydrolysate on body weight loss. Green squares indicate individual effect sizes; diamond represents the pooled effect size. Jung_2014 refers to results from Jung, et al. [13]; Jung_2011 refers to results from Jung, et al. [20]; Jung_2017 refers to results from Jung, et al. [19]; Mosikanon_2017 refers to results from Mosikanon, et al. [17]; Santas_2017 refers results from Santas, et al. [16]

Fig. 3.

Forest plot showing the effect of Bioactive Hydrolysate on BMI. Green squares indicate individual effect sizes; diamond represents the pooled effect size. Jung_2014 refers to results from Jung, et al. [13]; Jung_2011 refers to results from Jung, et al. [20]; Jung_2017 refers to results from Jung, et al. [19]; Mosikanon_2017 refers to results from Mosikanon, et al. [17]; Santas_2017 refers results from Santas, et al. [16]. Valero_2020 refers to results from Valero-Perez, et al. [15]

Fig. 4.

Forest plot showing the effect of Bioactive Hydrolysate on fat mass loss. Green squares indicate individual effect sizes; diamond represents the pooled effect size. Jung_2014 refers to results from Jung, et al. [13]; Jung_2011 refers to results from Jung, et al. [20]; Jung_2017 refers to results from Jung, et al. [19]; Santas_2017 refers results from Santas, et al. [16]. Valero_2020 refers to results from Valero-Perez, et al. [15]

Fig. 5.

Forest plot showing the effect of Bioactive Hydrolysate on abdominal circumference. Green squares indicate individual effect sizes; diamond represents the pooled effect size. Jung_2014 refers to results from Jung, et al. [13]; Jung_2011 refers to results from Jung, et al. [20]; Mosikanon_2017 refers to results from Mosikanon, et al. [17]; Santas_2017 refers results from Santas, et al. [16]. Valero_2020 refers to results from Valero-Perez, et al. [15]

Fig. 6.

Galbraith plot showing the Heterogeneity of studies of Bioactive Hydrolysate on Body Weight. Green squares indicate individual effect sizes; diamond represents the pooled effect size. Jung 2014 refers to results from Jung, et al. [13]; Jung 2011 refers to results from Jung, et al. [20]; Mosikanon 2017 refers to results from Mosikanon, et al. [17]; Santas 2017 refers results from Santas, et al. [16]; Jung 2017 refers to results from Jung, et al. [19]

Fig. 7.

Galbraith plot showing the Heterogeneity of studies of Bioactive Hydrolysate on Body Mass Index. Green squares indicate individual effect sizes; diamond represents the pooled effect size. Jung 2014 refers to results from Jung, et al. [13]; Jung 2011 refers to results from Jung, et al. [20]; Mosikanon 2017 refers to results from Mosikanon, et al. [17]; Santas 2017 refers results from Santas, et al. [16]. Valero-Perez 2020 refers to results from Valero-Perez, et al. [15]; Jung 2017 refers to results from Jung, et al. [19]

Fig. 8.

Galbraith plot showing the Heterogeneity of studies of Bioactive Hydrolysate on Fat Mass. Green squares indicate individual effect sizes; diamond represents the pooled effect size. Jung 2014 refers to results from Jung, et al. [13]; Jung 2011 refers to results from Jung, et al. [20]; Santas 2017 refers results from Santas, et al. [16]; Jung 2017 refers to results from Jung, et al. [19]; Valero-Perez 2020 refers to results from Valero-Perez, et al. [15]

Fig. 9.

Galbraith plot showing the Heterogeneity of studies of Bioactive Hydrolysate on abdominal circumference. Green squares indicate individual effect sizes; diamond represents the pooled effect size. Jung 2014 refers to results from Jung, et al. [13]; Jung 2011 refers to results from Jung, et al. [20]; Mosikanon 2017 refers to results from Mosikanon, et al. [17]; Santas 2017 refers results from Santas, et al. [16]. Valero-Perez 2020 refers to results from Valero-Perez, et al. [15]

Discussion

This systematic review and meta-analysis is, to our knowledge, the first to evaluate Saccharomyces cerevisiae–derived bioactive hydrolysates for obesity management in humans using clinical endpoints of weight and adiposity. A previous systematic review by Canaan et al. examined yeast-derived compounds in animal feed and found no significant effect on weight gain, but those findings are not generalizable to clinical practice [25]. Our analysis indicates that S. cerevisiae hydrolysates significantly reduce body weight, BMI, and fat mass, with a non-significant trend toward reductions in abdominal circumference. While the direction of effect was consistent across trials, heterogeneity was considerable, driven in part by outlier studies (Jung et al. 2014; Mosikanon et al. 2017) and methodological differences in study design, sample size, and population characteristics [13, 17]., Consequently, the certainty of evidence was downgraded to low. Nevertheless, the overall consistency across diverse conditions supports a potential role in obesity management Previous trials evaluated different nutraceuticals containing S. cerevisiae-derived bioactive hydrolysates, reporting reductions in abdominal circumference [12, 18]. However, they did not show significant effects on body weight or BMI. Variability in product formulation may account for these discrepancies, although further research is required to substantiate this hypothesis When compared with pharmacological therapies, the magnitude of effect was more modest. For example, a recent meta-analysis reported mean weight reductions of 7.98% with phentermine–topiramate and 5.79% with GLP-1 receptor agonists, whereas reductions with S. cerevisiae hydrolysates averaged 3–4% [26]. However, pharmacotherapies are associated with higher rates of adverse events and treatment discontinuation (OR for treatment discontinuation: 2.69 for naltrexone–bupropion, 2.40 for phentermine–topiramate, 2.22 for GLP-1 receptor agonists, 1.71 for orlistat, 1.42 for SGLT2 inhibitors, 1.19 for metformin), while the nutraceutical trials reported minimal attrition [26]. This favorable tolerability may enhance adherence, particularly in patients unwilling or unable to use pharmacological agents. This may be compared to similar strategies such as symbiotics, which have also demonstrated an effect on reducing body weight, BMI, and waist perimeter [27, 28]. Potential mechanisms include appetite suppression and immunomodulation. β-glucans reduce caloric intake in animal models and may lower ghrelin; [19, 29]. one included trial reported reduced caloric intake [13]. In addition, Mosikanon et al. observed reductions in proinflammatory cytokines (IL-6, TNF-α) and increases in the anti-inflammatory cytokine IL-10, suggesting a dectin-1–mediated regulatory effect on inflammatory signaling [17]. These findings suggest an immunomodulatory effect, possibly mediated through β-glucan binding to the dectin-1 receptor in the intestinal epithelium, leading to downstream regulation of inflammatory signaling. However, these mechanisms warrant confirmation in larger mechanistic studies Although the exact biological mechanisms remain uncertain and multiple hypotheses have been proposed separately in the literature (appetite suppression, inflammatory modulation, lipid absorption reduction, etc.), additional mechanistic studies are required to confirm these pathways Our findings indicate that Saccharomyces cerevisiae–derived bioactive hydrolysates produce measurable reductions in body weight and adiposity in adults with overweight or obesity, independent of cointerventions such as diet, exercise, or intervention duration. Although their effects are less pronounced than those of pharmacological therapies, they are notable for their favorable safety profile and low rates of treatment discontinuation, making them promising candidates as adjunctive options or alternatives for patients unwilling or unable to use pharmacological agents. However, the high degree of heterogeneity and the influence of outlier studies reduce the certainty of the evidence, underscoring the need for larger, well-controlled trials with standardized outcomes and timepoints Our study is strengthened by a rigorous methodology, including prospective PROSPERO registration, adherence to Cochrane and PRISMA standards, use of blinded placebo-controlled trials, and low assessed risk of bias However, several limitations of this study should be acknowledged. First, the small number of available trials and modest sample sizes limit the statistical power of the analysis and reduce the generalizability of the findings. This is compounded by the fact that most included studies had relatively short intervention periods, which may not adequately capture the long-term effects of S. cerevisiae–derived hydrolysates on weight and adiposity. Second, heterogeneity was substantial across outcomes, persisting even after sensitivity analyses. Although partly explained by outlier studies (e.g., Jung et al. 2014; Mosikanon et al. 2017), heterogeneity remained unexplained in several comparisons. Likely contributors include differences in study populations, intervention durations, baseline BMI ranges, and the small sample sizes of some trials. Variability in product formulations and dosing regimens may also have influenced treatment effects, further complicating cross-study comparisons. Third, while the included studies were well designed and judged at low risk of bias, reporting quality was uneven. Some outcomes (e.g., caloric intake, inflammatory markers) were reported in only a subset of studies, limiting the ability to conduct pooled analyses for mechanistic insights. Additionally, in several instances outcome data were available only in graphical form, requiring digital extraction, which may introduce minor measurement error despite standardized procedures. Fourth, this meta-analysis did not evaluate safety outcomes in a systematic way. Although trial reports suggest a low rate of adverse events and treatment discontinuation, the absence of uniform reporting precludes firm conclusions about tolerability or long-term safety. Similarly, patient-centered outcomes such as satisfaction, adherence, or quality of life were not consistently assessed, yet these are highly relevant for obesity management. Finally, the generalizability of the findings is limited. All included studies were conducted in Asian populations, and to date no randomized controlled trials have been performed in Latin America or other low- and middle-income regions, where these nutraceuticals are already commercially available. Region-specific differences in diet, genetic background, microbiota composition, and health system access may influence the effectiveness and acceptability of such interventions. Post-marketing surveillance and regionally tailored clinical trials will be essential to determine external validity. Taken together, these limitations justify downgrading the certainty of evidence to low and underscore the need for larger, longer, and more methodologically homogeneous studies that incorporate standardized endpoints, mechanistic assessments, and diverse populations Despite these limitations, the results support the clinical applicability of S. cerevisiae–derived bioactive hydrolysates as a promising option in obesity management. While their effect size is smaller than that of pharmacological agents, their favorable safety profile and low discontinuation rates position them as valuable adjuncts to existing therapies and as a stand-alone alternative for patients unwilling or unable to use pharmacological treatments. Larger, longer, and more methodologically homogeneous trials are warranted to confirm these benefits and reduce uncertainty.

Conclusions

This systematic review and meta-analysis demonstrate that a Saccharomyces cerevisiae–derived bioactive hydrolysates lead to statistically and clinically meaningful reductions in fat mass, BMI, abdominal circumference, and weight. Its favorable safety profile and over-the-counter availability support its use as an accessible short-term option for obesity management. Further studies are warranted to assess its long-term impact, the durability of weight-related outcomes, and its applicability in broader, real-world settings.

Abbreviations

BMI

Body mass index

CI

Confidence interval

GIP

Glucose-dependent insulinotropic polypeptide

GLP-1

Glucagon-like peptide-1

ITT

Intention-to-treat

PICOS

Population, intervention, comparison, outcomes, study design

PP

Per protocol

RoB-2

Risk of bias tool version 2

SMD

Standarized mean difference

XML

Extensible markup language

Authors’ contributions

Conceptualization: A.A.P.-G., B.C.-T. and E.R.-R; data curation: J.V.Y.-C., C.A.-R., R.M.H., B.C.-T. and E.R.-R; formal analysis: B.C.-T. and E.R.-R; project administration: A.A.P.-G. and R.M.H.; software, B.C.-T. and E.R.-R; writing—original draft: A.A.P.-G., J.V.Y.-C., C.A.-R., R.M.H., B.C.-T. and E.R.-R; writing—review and editing: A.A.P.-G., J.V.Y.-C., C.A.-R., R.M.H., B.C.-T. and E.R.-R. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by Laboratorios Columbia Comercial, S.A. de C.V., through unrestricted sponsorship, which also covered the article processing charge (APC). The sponsor had no role in the design of the study; in the collection, analysis or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Data availability

All data generated or analysed during this study are included in this published article.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

Palacios-García AA and Moreno-Higareda R, are full time employees of Laboratorios Columbia. Cerón-Trujillo B holds shares at Aequitas Medica. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.