Safety Profile
Known Safety Concerns
- Highest natural caffeine + theophylline; dual-stimulant risk with Green Coffee Extract; contraindicated in hypertension, arrhythmia, anxiety, pregnancy
Contraindications
- Highest natural caffeine + theophylline; dual-stimulant risk with Green Coffee Extract; contraindicated in hypertension, arrhythmia, anxiety, pregnancy
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
Guarana (Paullinia cupana) seed extract contains the highest natural caffeine concentration of any plant source (4–6% caffeine vs 1–2% in coffee beans), plus theophylline and theobromine — a full methylxanthine triad. Thermogenic, stimulant, lipolytic (fat mobilisation via beta-adrenergic activation), and appetite-suppressive. Caffeine half-life 4–6 hours; theophylline 6–12 hours. Critical safety concern when combined with Green Coffee Extract: dual caffeine source — total caffeine from both sources in a single supplement is frequently undisclosed on labels and may exceed 100–200 mg per serving or more, significantly above safe thresholds for sensitive individuals. Contraindicated in: caffeine sensitivity, hypertension, cardiac arrhythmia, tachycardia, anxiety disorders, insomnia, hyperthyroidism, pregnancy, and nursing. Interactions with MAOIs (hypertensive crisis risk), stimulant medications (additive), anticoagulants (platelet inhibition at high doses). High-dose consumption associated with rhabdomyolysis case reports. Not for children.
Biological and Chemical Classification
- Scientific Name
- Paullinia cupana
Mechanism of Action
Information not yet available for this ingredient profile.
Clinical Evidence of Effectiveness
Information not yet available for this ingredient profile.
Pharmacokinetics
Information not yet available for this ingredient profile.
Recommended Dosage
Information not yet available for this ingredient profile.
SETI — Scientific Evidence Transparency Index
Executive Summary — Ingredient Assessment
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or RCT)
- Main clinical benefit observed: Botanical
- Evidence consistency: High consistency across studies (100%)
- Highest natural caffeine + theophylline; dual-stimulant risk with Green Coffee Extract; contraindicated in hypertension, arrhythmia, anxiety, pregnancy
The available scientific evidence for Guarana indicates notable safety signals that warrant caution. Use should be considered carefully and monitored, particularly in sensitive populations or alongside other medications.
Total SETI Score
High risk| Evidence quality | 10/40 |
| Evidence consistency | 20/20 |
| Safety signals | 0/20 |
| Study recency | 10/10 |
| Evidence transparency | 10/10 |
Evidence Summary
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or systematic review)
- 0 studies identified benefits or no safety concern (GREEN)
- 10 studies reported limited or advisory safety evidence (YELLOW)
Evidence Policy
Only peer-reviewed scientific literature indexed in PubMed or comparable databases is included in this evaluation. Commercial websites, blogs, and marketing materials are excluded. All references include direct traceable links to source documents.
Last updated: 06 აპრ 2026, 12:09
Evidence Distribution
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Observational / other LOW evidence YELLOWGenetic variability among guarana (Paullinia cupana var. sorbilis (Mart.) Ducke) provenances to support breeding strategies. ↗Escobar RJB et al.. Genetic variability among guarana (Paullinia cupana var. sorbilis (Mart.) Ducke) provenances to support breeding strategies.. Braz J Biol. 2026. PMID:41810625.PMID 41810625 ↗Journal Braz J BiolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41810625/
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Observational / other LOW evidence YELLOWEfficacy of Phytotherapy for Cancer-Related Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. ↗Matsas S et al.. Efficacy of Phytotherapy for Cancer-Related Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Diseases. 2026. PMID:41745077.PMID 41745077 ↗Journal DiseasesYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41745077/
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Observational / other LOW evidence YELLOWAntimicrobial Potential of Three Native Plant Species From the Brazilian Amazon: A Review. ↗de Lara NOT et al.. Antimicrobial Potential of Three Native Plant Species From the Brazilian Amazon: A Review.. Chem Biodivers. 2026. PMID:41355715.PMID 41355715 ↗Journal Chem BiodiversYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41355715/
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Observational / other LOW evidence YELLOWHigh-throughput screening identifies paullinic acid as an antiviral agent against Bombyx mori nucleopolyhedrovirus. ↗Jia Z et al.. High-throughput screening identifies paullinic acid as an antiviral agent against Bombyx mori nucleopolyhedrovirus.. Pestic Biochem Physiol. 2026. PMID:41350064.PMID 41350064 ↗Journal Pestic Biochem PhysiolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41350064/
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Observational / other LOW evidence YELLOWBiosynthesis of Silver Nanoparticles from Paullinia cupana Kunth Leaf: Effect of Seasonality and Preparation Method of Aqueous Extracts. ↗Lima AKO et al.. Biosynthesis of Silver Nanoparticles from Paullinia cupana Kunth Leaf: Effect of Seasonality and Preparation Method of Aqueous Extracts.. Pharmaceuticals (Basel). 2025. PMID:41599672.PMID 41599672 ↗Journal Pharmaceuticals (Basel)Year 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41599672/
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Observational / other LOW evidence YELLOWSystematic review and network meta-analysis of the effects of plant active substance on quality of life in breast cancer patients. ↗Wang L et al.. Systematic review and network meta-analysis of the effects of plant active substance on quality of life in breast cancer patients.. Front Pharmacol. 2025. PMID:41394145.PMID 41394145 ↗Journal Front PharmacolYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41394145/
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Observational / other LOW evidence YELLOWCharacterization of a Drosophila model to study functions of guarana seeds. ↗Manica-Cattani MF et al.. Characterization of a Drosophila model to study functions of guarana seeds.. PLoS One. 2025. PMID:40742986.PMID 40742986 ↗Journal PLoS OneYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40742986/
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Observational / other LOW evidence YELLOWEffects of Guarana and Green Tea Consumption on Students' Intellectual Performances. ↗Amaritei V et al.. Effects of Guarana and Green Tea Consumption on Students' Intellectual Performances.. Nutrients. 2025. PMID:40290036.PMID 40290036 ↗Journal NutrientsYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40290036/
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Observational / other LOW evidence YELLOWSynergistic Neuroprotective and Immunomodulatory Effects of Cocoa Seed Husk and Guarana Extract: A Nutraceutical Approach for Parkinson's Disease Management. ↗Azzolin VF et al.. Synergistic Neuroprotective and Immunomodulatory Effects of Cocoa Seed Husk and Guarana Extract: A Nutraceutical Approach for Parkinson's Disease Management.. Antioxidants (Basel). 2025. PMID:40227469.PMID 40227469 ↗Journal Antioxidants (Basel)Year 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40227469/
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Observational / other LOW evidence YELLOWGreen Synthesis of Silver Nanoparticles Using Paullinia cupana Kunth Leaf Extract Collected in Different Seasons: Biological Studies and Catalytic Properties. ↗Lima AKO et al.. Green Synthesis of Silver Nanoparticles Using Paullinia cupana Kunth Leaf Extract Collected in Different Seasons: Biological Studies and Catalytic Properties.. Pharmaceutics. 2025. PMID:40143020.PMID 40143020 ↗Journal PharmaceuticsYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40143020/
Score Transparency
0 of 10 approved references (score saturates at 10). More peer-reviewed studies = stronger evidence base.
Method: Q = number of approved references ÷ 10 (capped at 1.0)
Limited — mostly case reports or animal studies
Method: L = mean study-level weight across approved references. Level 1 (meta-analysis / systematic review) = 1.0; Level 2 (RCT) = 0.8; Level 3 (cohort/case-control) = 0.6; Level 4 (case report) = 0.4; Level 5 (animal / in-vitro) = 0.2.
Mixed or neutral — roughly equal benefit and risk signals
Method: D = (sum of risk-scored references − sum of benefit-scored references) ÷ total evidence score, then scaled from [−1, 1] to [0, 1]. 0.0 = pure benefit; 0.5 = neutral; 1.0 = pure risk.
One or more monitoring-level safety signals active
Method: S = 0.5 (neutral baseline) + sum of active signal severity deltas ÷ 10. Severity deltas: Critical = +2.0, High = +1.5, Moderate = +1.0, Low = +0.5. Capped at 1.0.
Final GIRI Score for Guarana. Risk level thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
Full methodology & data sources
The GIRI Score is computed entirely from structured data — no editorial scoring or subjective weighting is applied at any step.
- References: Only approved references are counted. Each reference is assigned an evidence level (L1–L5) and a direction (risk / neutral / benefit) by the reference manager or AI classifier.
- Safety Signals: Sourced from regulatory agencies (FDA, EMA, Health Canada, TGA, and others) and pharmacovigilance databases. Only active signals count toward the score.
- Formula version: GIRI Score v3.7.0 — Q × L × D × S × 10.
- Limitations: The score reflects published evidence and recorded signals as of the last update date. It is not a clinical risk assessment and should not replace advice from a qualified healthcare professional.
Risk Level Classification
Based on available regulatory signals and scientific evidence, this ingredient presents a moderate safety concern. Caution is advised, particularly at high doses or in sensitive populations.
0–3.0
3.0–5.5
5.5–7.5
7.5–10
The score pin shows exactly where this ingredient falls on the fixed risk scale.
What drove the Moderate classification for Guarana
A score of 4.5 places this ingredient in the Moderate band. Thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
0 approved references.
Limited — mostly case reports or animal studies (Level 4–5).
Neutral or mixed — benefit and risk signals roughly balanced.
No active signals — S component is at neutral baseline (0.5), contributing no extra risk weight.
No major regulatory restrictions or advisories recorded across monitored jurisdictions (FDA, EMA, Health Canada, TGA, and others).
How are the Low / Moderate / High / Critical thresholds defined?
The four risk levels are fixed score bands. A score is assigned to exactly one level based on where it falls:
| Level | Score | Meaning |
|---|---|---|
| LOW | 0.0 – 2.9 | Sparse or predominantly beneficial evidence. No active safety alerts. |
| MODERATE | 3.0 – 5.4 | Mixed signals — some risk alongside benefit. Caution at high doses or in sensitive groups. |
| HIGH | 5.5 – 7.4 | Multiple studies or regulatory alerts documenting adverse effects. Professional oversight recommended. |
| CRITICAL | 7.5 – 10 | Regulatory restrictions in one or more major jurisdictions. Serious documented harm. Avoid without specialist supervision. |
Thresholds are fixed constants (GIRI_Score_Utils::LEVEL_THRESHOLDS). They do not change per ingredient and are never subject to editorial adjustment.