Guarana and Health: Systematic Review with ☸️SAIMSARA.

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Review Stats

Generated: 2025-12-03 13:40:22 CET
Plan: Premium (expanded craft tokens; source: Europe PMC)
Source: Europe PMC
Scope: Titles/Abstracts (tiab)
Keyword Gate: Fuzzy (≥60% of required terms, minimum 2 terms matched in title/abstract)
Total Abstracts/Papers: 70
Downloaded Abstracts/Papers: 70
Included original Abstracts/Papers: 31
Total study participants (naïve ΣN): 5977

Outcome-Sentiment Meta-Analysis (OSMA): (LLM-only)
Frame: Effect-of Predictor → Outcome • Source: Europe PMC
Outcome: Outcome Typical timepoints: 6-y, 25-y. Reported metrics: %, p.
Common endpoints: Common endpoints: functional, seizure.
Predictor: guarana and health — exposure/predictor. Routes seen: sc. Typical comparator: soluble polyphenols.

1) Beneficial for patients — Outcome with guarana and health — [1], [2], [4], [5], [6], [7], [10], [11], [13], [14], [15], [16], [17], [24], [26], [29], [30], [31] — ΣN=126
2) Harmful for patients — Outcome with guarana and health — [12], [18], [19], [20], [21], [25], [27] — ΣN=4871
3) No clear effect — Outcome with guarana and health — [3], [8], [9], [22], [23], [28] — ΣN=980

1) Introduction
Guarana (Paullinia cupana) is a plant native to the Amazon basin, traditionally recognized for its stimulant properties and diverse health applications. Its seeds are rich in bioactive compounds, including caffeine, catechins, and other polyphenols, which contribute to its purported physiological effects. Recent scientific inquiry has explored guarana's potential benefits across various health domains, ranging from cognitive enhancement and metabolic regulation to antioxidant and antimicrobial activities. However, alongside these potential advantages, concerns regarding its safety profile, particularly in high concentrations or in combination with other stimulants, necessitate a comprehensive evaluation. This paper synthesizes current research on guarana and health, drawing insights from a structured extraction of scientific literature.

2) Aim
The aim of this paper is to systematically review the current evidence on the health effects of guarana, encompassing both its potential benefits and reported adverse outcomes, to identify key findings, research gaps, and implications for clinical practice and future research.

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

Bias: Qualitatively inferred from study design fields. Studies varied in design, from in vitro and animal models to small human trials (RCTs, cohort, cross-sectional), with many lacking specified directionality or blinding, suggesting a high potential for bias in many individual studies.

4) Results
4.1 Study characteristics
The included studies comprised a mixed array of designs, including in vitro analyses, animal models (Wistar rats, C. elegans, LDLr-/- mice, B6C3F1 mice, ICR mice, Chinese hamster ovary cells), and human investigations (students, healthy adults, truck drivers, overweight professionals, case reports, poison data system analyses). Follow-up periods varied significantly, from immediate observations to 2 years, with many studies not specifying a follow-up duration.

4.2 Main numerical result aligned to the query
Preventive treatment with guarana powder significantly mitigated paracetamol-induced liver damage in rats, resulting in a median reduction of 29% in elevated liver enzymes (ALT, AST, ALP), with a range of 24% to 44% [2].

4.3 Topic synthesis

Cognitive Enhancement & Energy Guarana consumption led to significant improvements in cognitive performance, with more participants reporting effects like increased energy and improved information retention [1].
Antioxidant & Organ Protection Guarana demonstrated high antioxidant capacity [5, 15, 17], significantly mitigating paracetamol-induced liver damage by reducing liver enzymes (24-44% reduction) and oxidative stress in rats [2, 31]. It also partially reversed oxidative and genotoxic alterations in retinal cells [6].
Metabolic Regulation & Weight Management Insoluble-bound polyphenols from guarana showed a 5.8-fold lower IC50 for alpha-glucosidase inhibition, suggesting potential for type 2 diabetes management [10]. Guarana supplementation attenuated weight gain and insulin resistance in rats [11], and a guarana-containing supplement induced significant weight loss (0.8 ± 0.05 kg over 10 days; 5.1 ± 0.5 kg over 45 days) and delayed gastric emptying (58 ± 15 min vs. 38 ± 7.6 min for placebo) in overweight patients [26, 29].
Antimicrobial & Cytotoxic Properties Guarana leaf extract synthesized silver nanoparticles (AgNPs) exhibited antibacterial activity and cytotoxic properties against cancer cells [4]. Guarana seed extracts also showed strong antimicrobial activity against tested microorganisms [17]. However, in vitro analysis suggested concentration-dependent cytotoxic activity, with high doses potentially being harmful [19].
Cardiovascular & Renal Health Guarana extracts possess strong anti-platelet aggregatory properties, attributed to caffeine-catechin complexes [16]. Aqueous extract of guarana attenuated renal and hematological adverse effects associated with ketoprofen administration in rats [13, 14]. However, consumption of normal guarana soft drinks worsened atherosclerosis (~60% increase) and hypercholesterolemia in dyslipidemic mice [12].
Product Formulation & Stability Metabolomic approaches identified specialized metabolites in guarana clones, supporting product development with specific metabolite levels [3]. Co-encapsulation with probiotics improved probiotic survivability and facilitated simultaneous delivery of bioactive compounds [7]. Encapsulation techniques significantly improved the stability of carotenoids from guarana byproducts against oxidation (e.g., 545-fold increase with SDC) [8, 9].
Adverse Effects & Safety Concerns Ephedra-guarana supplements increased heart rate (9.4 ± 8.6 beats/min), blood pressure (11.5 ± 10.7 mm Hg systolic, 7.3 ± 7.4 mm Hg diastolic), and postprandial glucose (41.0 ± 18.8 mg/dL) [18]. Non-alcoholic energy drinks containing guarana were associated with moderate to major adverse effects in 15.2% of cases in a poison data system [20]. A case report linked a high-caffeine guarana drink to ventricular fibrillation [21]. Guarana can exacerbate seizures in people with epilepsy [27] and is consumed by truck drivers to stay awake, often with other substances like amphetamines and alcohol [23].

5) Discussion
5.1 Principal finding
The central finding indicates that preventive treatment with guarana powder significantly mitigated paracetamol-induced liver damage in rats, resulting in a median reduction of 29% in elevated liver enzymes (ALT, AST, ALP) [2].

5.2 Clinical implications

Guarana may serve as a beneficial adjunct therapy for liver protection, particularly in cases of drug-induced damage, given its antioxidant properties [2, 31].
It could be considered for cognitive support and energy enhancement in specific populations, such as students, where improvements in information retention were observed [1].
Guarana-containing supplements might offer a complementary approach for weight management by delaying gastric emptying and promoting weight loss [26, 29].
Caution is warranted for individuals with pre-existing cardiovascular conditions or epilepsy, as guarana can increase heart rate and blood pressure, and exacerbate seizures [18, 21, 27].
The consumption of energy drinks containing guarana, especially by children, adolescents, and vulnerable populations, carries a risk of moderate to major adverse effects, necessitating careful consideration of intake [20, 25].

5.3 Research implications / key gaps

Dosage Optimization Studies — Future research should establish optimal dosages of guarana extracts for specific health benefits (e.g., cognitive enhancement, liver protection) in human populations [1, 2].
Long-Term Human Safety Trials — Longitudinal studies are needed to comprehensively assess the long-term safety profile of guarana consumption, particularly regarding cardiovascular and neurological effects [12, 18, 27].
Mechanistic Elucidation of Bioactive Compounds — Further investigation into the specific mechanisms of action of guarana's specialized metabolites, beyond caffeine, is required to understand their therapeutic potential [3, 16].
Drug-Guarana Interaction Assessments — Systematic studies are necessary to evaluate potential interactions between guarana and commonly prescribed medications, especially those affecting renal, cardiac, or neurological systems [13, 14, 27].
Clinical Efficacy in Metabolic Diseases — Randomized controlled trials are needed to confirm the efficacy of guarana in the prevention and management of metabolic conditions like type 2 diabetes and obesity in diverse human cohorts [10, 11].

5.4 Limitations

Small Sample Sizes — Many human studies involved very small cohorts (e.g., N=33 students, N=16 healthy adults) or were single case reports, limiting generalizability [1, 18, 21].
Heterogeneous Formulations — Guarana was administered in various forms (powder, extract, multi-ingredient supplements, energy drinks), making it difficult to attribute effects solely to guarana or to compare across studies [1, 4, 6, 18, 20].
Lack of Long-Term Human Data — Most human intervention studies were short-term, and long-term effects, particularly adverse ones, are largely inferred from observational data or animal models [1, 18, 23].
Confounding by Co-ingredients — Many studies evaluated guarana as part of multi-ingredient supplements (e.g., with ephedra, selenium, L-carnitine), making it challenging to isolate guarana's specific contribution to observed effects [6, 18, 20, 23, 26, 29, 31].
Qualitative Bias Inference — The assessment of bias was qualitatively inferred from study design descriptions rather than through a standardized, quantitative tool, potentially overlooking specific biases.

5.5 Future directions

Standardized Extract Trials — Conduct randomized controlled trials using chemically characterized and standardized guarana extracts to ensure reproducibility and isolate effects.
Longitudinal Safety Studies — Implement long-term prospective cohort studies to monitor the safety and efficacy of guarana consumption in diverse human populations.
Pharmacokinetic Profiling — Elucidate the absorption, distribution, metabolism, and excretion of guarana's key bioactive compounds in humans.
Drug Interaction Research — Systematically investigate potential pharmacokinetic and pharmacodynamic interactions between guarana and common pharmaceutical drugs.
Risk Assessment Guidelines — Develop evidence-based public health guidelines for safe guarana consumption, considering vulnerable populations and potential interactions.

6) Conclusion
Preventive treatment with guarana powder significantly mitigated paracetamol-induced liver damage in rats, resulting in a median reduction of 29% in elevated liver enzymes (ALT, AST, ALP), with a range of 24% to 44% [2]. While these findings suggest promising therapeutic potential, particularly in antioxidant and protective capacities, the generalizability to human populations is limited by the prevalence of animal studies and small sample sizes in human trials. The most significant limitation affecting certainty is the reliance on animal models and small, often unblinded, human studies, alongside the confounding presence of co-ingredients in many tested formulations. Therefore, clinicians should advise caution regarding guarana consumption, especially in individuals with pre-existing conditions, pending further robust human clinical trials.

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

Figure 4. Main extracted research topics

Figure 5. Limitations of current studies (topics)

Figure 6. Future research directions (topics)