Guarana: Systematic Review with ☸️SAIMSARA.

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Review Stats

Generated: 2025-12-03 13:37:08 CET
Plan: Premium (expanded craft tokens; source: PubMed)
Source: PubMed
Scope: Titles/Abstracts (tiab)
Keyword Gate: Fuzzy (≥60% of required terms, minimum 2 terms matched in title/abstract)
Total Abstracts/Papers: 336
Downloaded Abstracts/Papers: 334
Included original Abstracts/Papers: 199
Total study participants (naïve ΣN): 12492

Outcome-Sentiment Meta-Analysis (OSMA): (LLM-only)
Frame: Effect-of Predictor → Outcome • Source: PubMed
Outcome: Outcome Typical timepoints: 11-day, 24-y. Reported metrics: %, CI, p.
Common endpoints: Common endpoints: complications, seizure, qol.
Predictor: guarana — exposure/predictor. Doses/units seen: 1000 μg, 50 mg, 300 mg. Routes seen: topical, oral. Typical comparator: placebo, a low dose of caffeine or, placebo groups, control….

1) Beneficial for patients — Outcome with guarana — [3], [6], [7], [9], [13], [14], [18], [20], [22], [23], [25], [26], [28], [30], [31], [33], [37], [38], [40], [42], [43], [44], [48], [51], [54], [58], [67], [68], [69], [70], [72], [75], [76], [78], [80], [81], [83], [84], [85], [90], [91], [93], [94], [95], [98], [99], [100], [103], [105], [106], [108], [109], [111], [112], [118], [121], [124], [125], [126], [127], [128], [131], [134], [135], [139], [146], [147], [149], [155], [172], [173], [174], [175], [177], [178], [180], [184], [186], [187], [190], [192], [194], [197], [198], [199] — ΣN=2164
2) Harmful for patients — Outcome with guarana — [11], [41], [55], [61], [77], [92], [116], [119], [122], [132], [133], [136], [138], [142], [148], [152], [168], [176], [181], [185], [188], [191] — ΣN=1880
3) No clear effect — Outcome with guarana — [1], [2], [4], [5], [8], [10], [12], [15], [16], [17], [19], [21], [24], [27], [29], [32], [34], [35], [36], [39], [45], [46], [47], [49], [50], [52], [53], [56], [57], [59], [60], [62], [63], [64], [65], [66], [71], [73], [74], [79], [82], [86], [87], [88], [89], [96], [97], [101], [102], [104], [107], [110], [113], [114], [115], [117], [120], [123], [129], [130], [137], [140], [141], [143], [144], [145], [150], [151], [153], [154], [156], [157], [158], [159], [160], [161], [162], [163], [164], [165], [166], [167], [169], [170], [171], [179], [182], [183], [189], [193], [195], [196] — ΣN=8448

1) Introduction
Guarana (Paullinia cupana) is a plant native to the Amazon basin, historically recognized for its stimulant properties and rich content of methylxanthines and polyphenols [35, 48, 146]. Recent research has expanded our understanding of guarana beyond its traditional use, revealing diverse applications across agriculture, industrial processes, and human health. Studies explore its potential in enhancing plant growth, developing sustainable materials, and modulating various physiological processes in biological systems. This paper synthesizes findings on guarana's multifaceted roles, from its rhizosphere microbiome interactions to its impact on cognitive function, metabolism, and therapeutic potential, alongside considerations for its safety and industrial applications.

2) Aim
The aim of this paper is to systematically review and synthesize the current scientific literature on guarana, extracting key findings related to its biological activities, health effects, and industrial applications, and to identify critical research gaps.

3) Methods
Systematic review with multilayer AI research agent: keyword normalization, retrieval & structuring, and paper synthesis (see SAIMSARA About section for details).

Bias: The included studies exhibit a range of designs, from experimental and cohort studies to randomized controlled trials (RCTs) and meta-analyses. Many studies are mixed-design, in vitro, or animal models, which may limit direct generalizability to human populations. Prospective RCTs provide higher certainty for human outcomes, but these are less frequent for all investigated aspects of guarana. Qualitative assessments of bias suggest a varied level of evidence, with a notable number of studies focusing on mechanisms and initial efficacy in non-human models.

4) Results
4.1 Study characteristics
The review encompassed a broad spectrum of study designs, including randomized controlled trials (RCTs), cohort studies, mixed-design investigations, and experimental studies. Populations ranged from human volunteers (e.g., students, athletes, cancer patients) to various animal models (e.g., Drosophila melanogaster, Wistar rats, mice, Caenorhabditis elegans, earthworms), and in vitro cellular systems (e.g., Caco-2 cells, human mesenchymal stem cells, neuronal cells). Agricultural settings included sugarcane, soybean, and guarana plants themselves. Follow-up periods varied widely, from acute observations over minutes or hours to longer durations of days, weeks, months, and in one case, up to 2 years for nanoparticle stability [8].

4.2 Main numerical result aligned to the query
Guarana-associated microbes demonstrate significant plant growth-promoting capabilities. Specifically, studies show that Bacillus paramycoides RZ3MS14 improved sugarcane growth by increases ranging from 225.92% to 520.89% [1], while rhizobacteria isolated from guarana promoted corn root dry weight increases of 136.9% and 247.8% [103]. Across these comparable metrics, the median increase in plant growth and root dry weight attributed to guarana-associated microbes was 242.25% (range: 136.9% to 520.89%) [1, 103].

4.3 Topic synthesis

Cognitive Enhancement & Performance: Guarana ingestion improved rapid visual information processing and multitasking [18], reaction times [26, 28, 38], alertness [38], and information processing speed during exercise [85]. One study noted a stronger correlation with improvements in energy and information retention compared to green tea [6]. However, some studies found no significant effect on cognitive performance compared to caffeine or placebo [27].
Antioxidant & Anti-inflammatory Effects: Guarana consistently enhanced endogenous antioxidant defenses [4, 9, 35, 39, 40, 58, 68, 93, 105, 175, 190] and demonstrated anti-inflammatory properties by modulating cytokine levels [72, 75, 78, 80] and ameliorating oxidative stress in various models, including osteoarthritis [4], hepatotoxicity [9], and testicular dysfunction [37].
Metabolic Regulation & Weight Management: Guarana treatment reduced body weight, white fat, and liver weight in obese rats, alleviating dyslipidemia and liver steatosis by regulating lipid metabolism [20]. It also inhibited pancreatic lipase, bound bile acids, and decreased cholesterol micellar solubilization [22]. Formulations containing guarana significantly reduced food and energy intake [139], improved fatty acid oxidation during exercise [121], and promoted short-term weight and fat loss in overweight humans [187].
Antimicrobial & Antifungal Properties: Guarana extracts and guarana-synthesized silver nanoparticles exhibited significant antibacterial [8, 15, 109, 118, 134, 175] and antifungal activities against various pathogenic microorganisms and phytopathogenic fungi [10, 36, 73, 97, 115]. This suggests potential for diverse applications, including food preservation [30, 33, 36, 70, 84].
Plant Growth Promotion & Biocontrol: Bacteria isolated from the guarana rhizosphere, such as Bacillus paramycoides RZ3MS14 [1] and Bacillus thuringiensis RZ2MS9 [5], significantly improved plant growth (sugarcane, soybean, corn) and root architecture [103], and demonstrated entomopathogenic activity [5] and antifungal potential [10, 73, 79, 115].
Safety & Adverse Event Profile: While generally recognized as safe when consumed properly and within caffeine intake guidelines [71, 153], guarana has been associated with adverse events, particularly when consumed in high doses or in energy drinks. These include cardiac issues (cardiomyopathy, myocardial infarction) [41, 92, 176], rhabdomyolysis [181], and potential drug interactions (e.g., with phenytoin [11], amiodarone [136], and CYP3A substrates [64]). Abuse and misuse among adolescents have been reported [101, 113, 132, 148].
Anticancer & Chemoprotective Potential: Guarana extracts demonstrated antiproliferative effects on breast cancer cells [127, 23, 44], reduced tumor growth in mice [51, 155], and exhibited nephroprotective [13] and intestinal protective [54] effects against chemotherapy-induced toxicity. However, meta-analyses did not show a significant reduction in cancer-related fatigue with guarana supplementation [21, 56].

5) Discussion
5.1 Principal finding
The most striking and consistently quantifiable positive effect of guarana, as evidenced by this review, is its role in agriculture: plant growth promotion by guarana-associated microbes showed a median increase of 242.25% (range: 136.9% to 520.89%) in plant growth and root dry weight [1, 103].

5.2 Clinical implications

Cognitive Enhancement: Guarana can acutely improve cognitive performance, reaction times, and alertness in healthy individuals and athletes [6, 18, 26, 38, 85], suggesting its utility in settings requiring sustained mental focus.
Metabolic Health: Guarana shows promise in weight management and metabolic regulation, potentially reducing body fat, improving lipid profiles, and aiding in cholesterol management [20, 22, 81, 187].
Antioxidant Support: Its strong antioxidant and anti-inflammatory properties suggest a role in mitigating oxidative stress and inflammation in various physiological contexts [4, 9, 37, 72, 78].
Adverse Event Risk: Clinicians should be aware of potential adverse cardiovascular effects, especially with high doses or in energy drink formulations [41, 92, 176], and counsel patients on potential drug interactions with medications like phenytoin or amiodarone [11, 136].
Cancer-Related Fatigue: Despite some early promising results, current meta-analyses indicate that guarana does not significantly reduce cancer-related fatigue [21, 56], suggesting it should not be routinely recommended for this indication.

5.3 Research implications / key gaps

Standardized Extract Efficacy: Future RCTs are needed to compare the efficacy of standardized guarana extracts versus pure caffeine or placebo for specific cognitive and metabolic endpoints in diverse human populations [27, 28].
Long-term Safety Profiling: Longitudinal studies are required to assess the long-term safety profile of chronic guarana consumption, particularly concerning cardiovascular health and potential cumulative toxicities [41, 66, 77, 92, 132, 176].
Mechanistic Elucidation: Detailed mechanistic studies using multi-omics approaches (e.g., metabolomics, proteomics) are needed to fully understand how guarana's complex chemical profile contributes to its observed biological effects, especially beyond caffeine [19, 39, 50, 52].
Drug-Herb Interactions: Further in vivo studies are crucial to comprehensively map potential drug interactions, particularly with cytochrome P450 enzymes (e.g., CYP3A) and drug transporters, to inform clinical guidelines [11, 64, 136].
Agricultural Optimization: Research could explore optimizing the application of guarana rhizosphere microbes for sustainable enhancement of crop yields and pest control in various agricultural systems beyond sugarcane and corn [1, 5, 10, 103].

5.4 Limitations

Heterogeneity of Study Designs — The diverse range of study designs (in vitro, animal, human, agricultural) and methodologies limits direct comparability and generalizability of findings across different contexts.
Variability in Guarana Preparations — Studies often used different forms of guarana (e.g., crude extract, powder, specific formulations, or as an ingredient in complex beverages), making it difficult to attribute effects to specific compounds or doses.
Limited Human Clinical Trials — While some RCTs exist for cognitive and metabolic effects, many health claims are supported by animal or in vitro data, necessitating more rigorous human trials to confirm efficacy and safety.
Inconsistent Reporting of Outcomes — The lack of standardized outcome measures and reporting across studies, especially for non-numerical results, complicates systematic synthesis and quantitative comparison.
Risk of Adverse Events — The presence of caffeine and other bioactive compounds means that high doses or combinations with other stimulants can lead to adverse effects, which may not be fully captured in all study designs.

5.5 Future directions

Standardized Extract Characterization — Develop and test standardized guarana extracts with precisely quantified bioactive compounds to enable reproducible research and clinical application.
Longitudinal Human Trials — Conduct large-scale, long-term randomized controlled trials to evaluate the chronic effects of guarana on cognitive function, metabolic health, and overall safety in diverse human populations.
Mechanistic Pathway Elucidation — Utilize advanced molecular and cellular biology techniques to fully unravel the specific molecular pathways and targets through which guarana exerts its beneficial and adverse effects.
Drug Interaction Profiling — Systematically investigate potential pharmacokinetic and pharmacodynamic interactions between guarana and commonly prescribed medications to enhance patient safety.
Sustainable Agricultural Practices — Explore the commercial viability and environmental impact of utilizing guarana-associated plant growth-promoting microbes as biofertilizers and biocontrol agents in large-scale agriculture.

6) Conclusion
Plant growth promotion by guarana-associated microbes showed a median increase of 242.25% (range: 136.9% to 520.89%) in plant growth and root dry weight [1, 103]. This remarkable agricultural potential contrasts with the more varied and sometimes contradictory findings in human health, where guarana demonstrates promise in cognitive enhancement and metabolic regulation but also carries risks of adverse events, particularly when consumed in high doses or in combination with other stimulants. The high variability in guarana preparations and study designs across human and animal models significantly limits the generalizability of its direct physiological effects. Future research should focus on standardized guarana extracts and rigorous human clinical trials to clarify its efficacy and safety for specific health applications.

References
SAIMSARA Session Index — session.json

Figure 1. Publication-year distribution of included originals

Figure 1. Publication-year distribution of included originals

Figure 2. Study-design distribution of included originals

Figure 2. Study-design distribution

Figure 3. Study-type (directionality) distribution of included originals
Figure 3. Directionality distribution

Figure 3. Directionality distribution

Figure 4. Main extracted research topics

Figure 4. Main extracted research topics (Results)

Figure 5. Limitations of current studies (topics)

Figure 5. Limitations of current studies (topics)

Figure 6. Future research directions (topics)

Figure 6. Future research directions (topics)