Guarana

Guarana is the seed of Paullinia cupana, and its tradition belongs to the Sateré-Mawé of the central Amazon, who domesticated the plant about 500 years ago ^{43Reference 43Peixoto et al. · 2017AnimalAnti-aging and antioxidant potential of Paullinia cupana var. sorbilis: findings in Caenorhabditis elegans indicate a new utilization for roasted seeds of guarana — in vivo (nematode)View study →}. The first written account is the Jesuit missionary João Felipe Bettendorf’s 1669 record of Sateré-Mawé use ^{1Reference 1Schimpl et al. · 2013ReviewGuarana: revisiting a highly caffeinated plant from the Amazon — reviewView study →}.

Across the Amazon the seed is used as a stimulant and astringent. It is taken for chronic diarrhoea, headache and migraine, neuralgia and fever, and to relieve fatigue and lift the spirits ^{41Reference 41FernTropical Plants Database: Paullinia cupana — species databaseView study →}.

The roasted seed is pounded into a paste and made into a stimulating drink ^{41Reference 41FernTropical Plants Database: Paullinia cupana — species databaseView study →}. In Sateré-Mawé practice the paste is shaped into cylinders and dried in the sun and smoke. The hard “stick” keeps for a year or more and is grated into water as needed. The drink made this way is çapó.

Women drink çapó during menstruation, through pregnancy and after giving birth. Men drink it at festivals, in mourning, before hunting trips and after their wives have given birth.

A 2023 systematic review and meta-analysis of eight placebo-controlled studies (328 participants, guarana 37.5–500 mg containing 4.3–100 mg caffeine) found a faster response time for guarana versus placebo (Hedge’s g = 0.20) but no benefit on accuracy, and no relationship with dose ^{2Reference 2Hack et al. · 2023Meta-analysisEffect of guarana (Paullinia cupana) on cognitive performance — systematic review and meta-analysisView study →}.

An early double-blind trial in 28 young adults reported faster attention-task performance after a single 75 mg dose of a dried extract, with some evidence of reduced accuracy. That dose held only about 9 mg of caffeine, and the authors judged the effect unlikely to come from caffeine alone ^{3Reference 3Kennedy et al. · 2004RCTImproved cognitive performance following guarana extract — randomised, placebo-controlled trialView study →}.

A randomised crossover trial around maximal-intensity cycling found faster reaction times with guarana than with placebo, but not than with an equivalent dose of caffeine ^{5Reference 5Gurney et al. · 2023RCTCognitive effects of guarana supplementation with maximal intensity cycling — randomised controlled trialView study →}.

A double-blind crossover trial in 20 adults comparing 500 mg guarana (130 mg caffeine) with 100 mg caffeine found reaction time and heart-rate variability unaffected by either ^{6Reference 6Talik et al. · 2024RCTAcute guarana ingestion on mental performance and vagal modulation — randomised controlled trialView study →}.

A 2025 controlled study assessed guarana alongside green tea on students’ intellectual performance ^{7Reference 7Amaritei et al. · 2025Effects of guarana and green tea consumption on students’ intellectual performance — controlled studyView study →}.

Several of the positive “guarana” cognition trials used vitamin and mineral complexes rather than the herb alone.

Gap: The pooled human effect is small and confined to reaction speed, and no trial has shown guarana outperforming an equivalent dose of plain caffeine.

This is guarana’s most consistent activity across study types. The ethanol seed extract shows strong radical-scavenging in vitro, closely correlated with its catechol content ^{8Reference 8Basile et al. · 2005In vitroAntibacterial and antioxidant activities of ethanol extract from Paullinia cupana — in vitroView study →}.

Condensed tannins isolated from the seed scavenge DPPH radicals potently ^{9Reference 9Yamaguti-Sasaki et al. · 2007In vitroAntioxidant capacity and in vitro prevention of dental plaque by extracts and condensed tannins of Paullinia cupana — in vitroView study →}. A tannin-rich, methylxanthine-free fraction keeps both antioxidant and anti-inflammatory activity, which places the effect in the polyphenols rather than the caffeine ^{11Reference 11Machado et al. · 2021In vitroTNF-α inhibition, antioxidant effects and chemical analysis of guaraná seed powder — in vitroView study →}.

In 42 healthy elderly people, habitual guarana drinkers showed 27% lower LDL oxidation than non-drinkers, and the extract also suppressed conjugated-diene and TBARS formation in vitro ^{10Reference 10Portella et al. · 2013In vitroGuaraná effects on LDL oxidation in elderly people — in vitro and in vivo studyView study →}.

Reported potency varies widely with origin and processing ^{1Reference 1Schimpl et al. · 2013ReviewGuarana: revisiting a highly caffeinated plant from the Amazon — reviewView study →}.

Gap: The human data are limited to an LDL-oxidation marker in an observational sample. No trial has shown that guarana’s antioxidant activity changes a clinical outcome, and sugary commercial guarana drinks were pro-oxidant in mice ^{16Reference 16Chisté et al. · 2019AnimalWorsening of oxidative stress, DNA damage and atherosclerotic lesions with guarana soft drinks in LDLr-knockout mice — animal modelView study →}.

Guarana inhibits platelet aggregation through a mechanism that appears independent of caffeine. Aqueous extracts reduced ADP- and arachidonate-induced aggregation of human and rabbit platelets in vitro and in vivo, with the active material being water-soluble, heat-resistant and distinct from known xanthines ^{14Reference 14Bydlowski et al. · 1988In vitroInhibition of platelet aggregation by aqueous guaraná extract — in vitro and in vivo (rabbit)View study →}, and decreased platelet thromboxane synthesis in rabbit platelets ^{13Reference 13Bydlowski et al. · 1991In vitroAn aqueous extract of guaraná decreases platelet thromboxane synthesis — animal/in vitroView study →}.

HPLC/MS fractionation identified catechin, epicatechin and their dimers, with a small amount of caffeine, as the likely antiaggregatory factors ^{12Reference 12Subbiah et al. · 2008In vitroAnti-platelet aggregatory factors in guarana seeds — in vitroView study →}.

In an elderly Amazonian population in Maués, habitual guarana drinkers had lower rates of hypertension, obesity and metabolic syndrome than non-drinkers ^{15Reference 15Krewer et al. · 2011ObservationalHabitual intake of guaraná and metabolic morbidities — observational epidemiological studyView study →}. Habitual drinkers also showed reduced LDL oxidation ^{10Reference 10Portella et al. · 2013In vitroGuaraná effects on LDL oxidation in elderly people — in vitro and in vivo studyView study →}.

Gap: All direct cardiovascular data are in vitro, animal or observational — no randomised trial has tested a cardiovascular endpoint. The epidemiological association may be confounded, and guarana’s caffeine acutely raises blood pressure.

Guarana’s best-studied clinical application is also its most contested. In a crossover RCT of 75 women with breast cancer on chemotherapy, 50 mg twice daily improved FACIT-F and Brief Fatigue Inventory scores versus placebo ^{19Reference 19de Oliveira Campos et al. · 2011RCTGuarana improves fatigue in breast cancer patients undergoing systemic chemotherapy — randomised controlled trialView study →}.

An earlier pilot crossover trial of 75 mg daily in 36 women with breast cancer during radiotherapy found no benefit over placebo for fatigue or depression ^{20Reference 20da Costa Miranda et al. · 2009RCTGuaraná for postradiation fatigue and depression — randomised, double-blind pilot trial (null)View study →}. Two later double-blind RCTs of a standardised purified extract (PC-18) failed to beat placebo, which the authors attributed partly to an unexpectedly strong placebo response ^{21Reference 21Sette et al. · 2018RCTPurified dry Paullinia cupana (PC-18) extract for chemotherapy-induced fatigue — two double-blind randomised trials (null)View study →}.

A phase II study in 60 patients with head-and-neck cancer found worse quality of life in the guarana arm after the second cycle of chemoradiotherapy ^{23Reference 23Martins et al. · 2017RCTDry guarana extract in head-and-neck tumour patients undergoing chemoradiotherapy — placebo-controlled, double-blind, randomised studyView study →}.

A 2021 meta-analysis of three breast-cancer trials found no benefit, with very low GRADE certainty ^{17Reference 17de Araujo et al. · 2021Meta-analysisGuarana as a dietary supplement for fatigue in cancer patients — systematic review with meta-analysisView study →}. A 2024 meta-analysis of five studies (229 patients) reported a significant effect (SMD −0.77) despite high heterogeneity ^{18Reference 18Maselli-Schoueri et al. · 2024Meta-analysisNatural supplementation to treat cancer-induced fatigue: meta-analysis on guaraná — systematic review and meta-analysisView study →}.

Gap: The signal is unstable and depends on the preparation. Several individual RCTs were null, placebo responses are large, and pooled estimates swing with which trials are included. No definitive dose or extract has emerged.

Two double-blind crossover RCTs suggest a small ergogenic effect. In 11 endurance-trained adults, 500 mg guarana (130 mg caffeine) increased the work done in a 15-minute cycling time trial versus placebo. The effect was graded trivial-to-small, did not differ significantly from 100 mg caffeine, and was linked to lower perceived exertion ^{26Reference 26Penna et al. · 2024RCTGuarana but not low-dose caffeine improves cycling time-trial performance — randomised controlled trialView study →}.

In 27 under-17 soccer players, 3 g of seed powder improved intermittent-exercise capacity (Yo-Yo test) but not jump, sprint or agility ^{27Reference 27Estrázulas et al. · 2024RCTAcute ingestion of guarana on soccer player performance — randomised controlled trialView study →}.

Gap: Effects are small, inconsistent across performance domains, and appear centrally mediated (reduced perceived effort) rather than metabolic; there is no clear advantage over plain caffeine.

A tannin-rich, methylxanthine-free guarana fraction inhibited TNF-α in vitro alongside its antioxidant activity, indicating a polyphenol-driven anti-inflammatory action ^{11Reference 11Machado et al. · 2021In vitroTNF-α inhibition, antioxidant effects and chemical analysis of guaraná seed powder — in vitroView study →}.

In rodent models, guarana prevented rises in IL-1β and IL-6 during methotrexate toxicity ^{29Reference 29Aldhahrani · 2023AnimalPaullinia cupana seed extract ameliorates methotrexate-induced testicular dysfunction — mouse modelView study →} and blunted lipotoxicity-associated inflammation on a high-fat background ^{34Reference 34Ruchel et al. · 2021Lipotoxicity-associated inflammation is prevented by guarana — comparative animal studyView study →}.

The active fraction here is the tannins rather than the caffeine-rich material most people consume, and no human anti-inflammatory endpoint has been measured.

Guarana powder (300 mg/kg for seven days) given to rats before a toxic paracetamol dose prevented serum ALT, AST and ALP elevations (by 44%, 29% and 24%), reduced necrotic liver area, preserved glutathione and modulated SOD and catalase ^{28Reference 28Teixeira et al. · 2025AnimalPreventive guarana powder mitigates acute paracetamol-induced hepatotoxicity in rats — animal modelView study →}.

A seed extract likewise ameliorated methotrexate-induced organ toxicity through antioxidant and anti-apoptotic pathways ^{29Reference 29Aldhahrani · 2023AnimalPaullinia cupana seed extract ameliorates methotrexate-induced testicular dysfunction — mouse modelView study →}.

Both designs pre-treat before an acute chemical insult, and there is no human liver data.

Guarana inhibited the AKT/mTOR/S6K and MAPK pathways and reduced colony formation in colorectal (HT-29) and breast (MCF-7) cancer cells without harming normal cells ^{30Reference 30Cadoná et al. · 2017In vitroGuaraná presents in vitro antitumour activity in colorectal and breast cancer cell lines via AKT/mTOR/S6K and MAPK pathways — in vitroView study →}, and increased HT-29 sensitivity to oxaliplatin while up-regulating p53 and the Bax/Bcl-2 ratio ^{31Reference 31Cadoná et al. · 2016In vitroGuaraná increases oxaliplatin sensitivity of colorectal HT-29 cells — in vitroView study →}. In vivo, guarana reduced proliferation and increased apoptosis of B16/F10 melanoma lung metastases in mice ^{32Reference 32Fukumasu et al. · 2008AnimalPaullinia cupana var. sorbilis reduces cell proliferation and increases apoptosis of B16/F10 melanoma lung metastases in mice — animal modelView study →}.

Gap: The human oncology trials on guarana address fatigue, anorexia and hot flashes rather than the tumour itself. Antitumour efficacy has never been tested in people ^{24,25Reference 24Palma et al. · 2016Clinical trialGuarana improves anorexia in patients with advanced cancer — phase II clinical trialView study →Reference 25Oliveira et al. · 2013Clinical trialPaullinia cupana for control of hot flashes in breast cancer patients — pilot clinical trialView study →}.

In obese rats, guarana reduced body weight, white fat and hepatic steatosis by suppressing fatty-acid and triglyceride synthesis and increasing β-oxidation ^{33Reference 33Liang et al. · 2023AnimalEffect of guarana on lipid metabolism in obese rats: a lipidomics study — animal modelView study →}.

Guarana seed powder inhibited pancreatic lipase and reduced cholesterol micellar solubilization and Caco-2 absorption in vitro ^{35Reference 35Figueira et al. · 2022In vitroEffect of guarana seed powder on cholesterol absorption in vitro and in Caco-2 cells — in vitroView study →}.

Human weight-loss data come from combinations. Caffeine-containing ephedra-guarana formulas raised heart rate, blood pressure, glucose and insulin ^{36Reference 36Haller et al. · 2005RCTShort-term metabolic and hemodynamic effects of ephedra and guarana combinations — randomised controlled trialView study →}, and guarana’s own contribution cannot be isolated from them.

Gap: There are no human weight-loss trials of guarana alone. The human data come from products that also contain ephedra, yerba maté or green tea.

In rodents with induced hyperlipidemia, guarana powder prevented memory impairment and normalized brain acetylcholinesterase activity while lowering total and LDL cholesterol ^{37Reference 37Ruchel et al. · 2017AnimalGuarana ameliorates memory impairment and modulates acetylcholinesterase in hyperlipidemic rat brain — animal modelView study →}. In human neuronal-like cells, guarana prevented protein glycation, β-amyloid aggregation and acrolein-induced toxicity — hallmarks relevant to Alzheimer’s pathology ^{38Reference 38Bittencourt et al. · 2014In vitroGuarana prevents β-amyloid aggregation, AGE generation and acrolein-induced cytotoxicity in neuronal-like cells — in vitroView study →}.

Gap: Cell and rodent data only, at doses and in disease models far removed from human use, with no clinical cognitive-decline or neurodegeneration data.

The ethanol extract of guarana seeds showed antibacterial activity in vitro against both gram-negative and gram-positive organisms, most strongly Pseudomonas aeruginosa, Proteus mirabilis, Proteus vulgaris and Escherichia coli ^{8Reference 8Basile et al. · 2005In vitroAntibacterial and antioxidant activities of ethanol extract from Paullinia cupana — in vitroView study →}.

It is one in vitro report, with no data on whether inhibitory concentrations are reachable in the body.

Caffeine load. Guarana seed contains up to about 6% caffeine ^{1Reference 1Schimpl et al. · 2013ReviewGuarana: revisiting a highly caffeinated plant from the Amazon — reviewView study →}. Its main risks are those of caffeine: sleeplessness, anxiety, palpitations, a fast or irregular heartbeat and a rise in blood pressure. The effects add to those of coffee, tea, energy drinks and other stimulants. Keep total caffeine intake under about 400 mg a day, and avoid guarana with uncontrolled high blood pressure, heart disease, heart-rhythm problems or an anxiety disorder.

Stimulant combinations. In a controlled human study, combinations of ephedra and guarana raised heart rate, blood pressure, blood glucose and insulin and lowered serum potassium. Stimulant combinations of this kind have been linked to serious adverse events ^{36Reference 36Haller et al. · 2005RCTShort-term metabolic and hemodynamic effects of ephedra and guarana combinations — randomised controlled trialView study →}.

Sugary guarana drinks. In mice prone to high cholesterol, sweetened guarana soft drinks worsened oxidative stress, atherosclerosis and liver and stomach damage. The authors attributed this largely to the added sugar rather than the guarana ^{16Reference 16Chisté et al. · 2019AnimalWorsening of oxidative stress, DNA damage and atherosclerotic lesions with guarana soft drinks in LDLr-knockout mice — animal modelView study →}.

Drug interactions. In rats, guarana delayed the absorption of the anti-seizure drug phenytoin ^{39Reference 39Alves et al. · 2026AnimalImpact of Paullinia cupana extract on the pharmacokinetics of phenytoin in rats — animal modelView study →}. Caffeine’s own interactions apply by extension: with CYP1A2 inhibitors such as fluvoxamine and ciprofloxacin, other stimulants, theophylline, lithium, clozapine and MAO inhibitors. These have not been tested with guarana specifically.