Guayusa

Synopsis

Guayusa (Ilex guayusa Loes.)

1. Identity and Botanical Description

Taxonomic Classification and Nomenclature

Guayusa (Ilex guayusa Loes.) is a flowering plant in the family Aquifoliaceae, and one of over 800 holly (Ilex) species. One of four known caffeinated holly trees, the leaves of the guayusa tree are harvested fresh and brewed like a tea for their stimulative effects. It is known simply as guayusa in western languages like Spanish, as waisa in Kichwa, and as wayus or wais in Shuar. The name is commonly pronounced "gwhy-YOU-sah." The species was formally described and named by the German botanist Max Loesener, hence the authority abbreviation "Loes." appended to the binomial.

It is important to note that other unrelated plants share the common name "guayusa." There are other plants that have the common name of Guayusa that are in different plant families and genera, such as Siparuna eggersii in the Monimiaceae family, as well as other plants in the Piperaceae family. These plants are not the same as the Amazonian guayusa and may not have the same usage ethnobotanically or in herbalism, making it important to always seek out and confirm the scientific botanical name.

Morphology and Growth

Ilex guayusa is an evergreen dioecious tree which grows 6–30 m (20–98 ft) tall. The leaves are ovate, elliptic, oblong or lanceolate; 7–22 cm (2.8–8.7 in) long, 2.5–7 cm (0.98–2.76 in) wide; with serrate or dentate margin. The flowers are small and white, arranged in thyrses. Guayusa is a dioecious species. Despite the presence of seeds, guayusa is only known to reproduce asexually by human planting of the leafless hardwood stem cuttings extracted from the base of a stock plant. This near-exclusive reliance on vegetative propagation is consistent with the conclusion that the species has been domesticated over many generations of cultivation.

Geographic Distribution and Cultivation

(Ilex guayusa Aquifoliaceae) is a shrub or small tree native to the Neotropics, distributed along the Amazon region of Colombia, Ecuador, Peru, and Bolivia. It is commonly used to prepare tea-like infusions similar to other Amazonian beverages such as yerba mate (I. paraguariensis) and guaraná (Paullinia cupana). It grows at altitudes ranging from 200 to 2,000 m above sea level, and Ecuador appears to be the main center for its cultivation, especially towards the eastern Andean slopes and the adjacent Amazonian piedmont.

Its putative infertility and close association with human habitation have led to the conclusion that guayusa may be a domesticated species resulting from a long period of cultivation. For centuries, guayusa leaves have been grown and consumed as a traditional food by indigenous peoples in the western Amazon regions of Ecuador, Peru, Colombia, and Bolivia. It is traditionally cultivated in Amazonian chakra agroforestry systems, a diversified and sustainable land-use practice managed primarily by indigenous communities. These chakra systems integrate culturally significant plants for food, medicine, and ritual, preserving both biodiversity and traditional ecological knowledge.

Common Preparations and Commercial Forms

Guayusa is a traditional herbal tea of western Amazon regions and an international commodity of increasing importance. Its consumption is rapidly growing in the USA and Canada, and the authorization of guayusa extract as a novel food in Europe signals further international market growth of this antioxidant and stimulant tea. Commercial forms include dried whole leaves intended for infusion, powdered leaf extracts, standardized liquid concentrates, and encapsulated dietary supplements. Industrial processing applied to the leaves modifies the composition of bioactive compounds and antioxidant capacity. Blanched guayusa retained the concentration of phenolic compounds, some carotenoids, and similar antioxidant capacity to untreated green leaves. In contrast, fermentation reduced the content of bioactive compounds and showed the lowest antioxidant capacity.

2. Traditional and Historical Use

Historical Record and Time Depth

The plant has been consumed for thousands of years by the high Amazonian peoples of Ecuador and currently forms part of the gardens of ancestral peoples and mestizo settlers. Historical records suggest that leaves from guayusa have been used and traded since at least 500 CE. Guayusa is a caffeinated holly species that grows only in the upper Amazon basin of Colombia, Ecuador, and Peru. Traditionally, indigenous societies, such as the Amazonian Kichwa, brew guayusa leaves much like tea. Archaeological evidence reinforces this timeframe: the oldest finds of dried guayusa leaves date back more than 1,500 years. They were found in the tomb of a shaman in Bolivia. Today it is believed that guayusa originally came from Ecuador.

Indigenous Peoples and the Wayus Ritual

The Kichwa people use guayusa in the ritual known as "Wayus," the objective of which is to strengthen community ties, purify the body, and communicate with the material and spiritual worlds. Early in the morning, the preparation of the infusion is entrusted to the daughters-in-law of each family group, who serve the drink in natural containers. Guayusa was drunk mainly in the early morning hours to be prepared for the hunt and to talk about the dreams of the previous night. While drinking the guayusa brew, they shared creative thoughts, inspirational ideas, and stories about their ancestors.

The Kichwa Indians used the invigorating effects of guayusa before and during the hunt, which requires enormous concentration and strength. This relationship with guayusa is not limited to the Kichwa people living in the Amazon; Andean Kichwas of the Ecuadorian highlands adopted the use of guayusa as a medicinal plant to treat various ailments, focusing on pain relief, and also incorporated it in the preparation of alcoholic macerates like their lowland relatives.

Traditional Medicinal Applications

Within the context of Amazonian indigenous culture, I. guayusa has long been used as a medicinal plant by the indigenous Kichwa to help digestion, stimulate appetite, diuresis, clean blood and mouth, headache, treat diabetes and infertility, and also as a ritualistic plant by Jivaro Indians. They also use this decoction on the skin as an insect repellent, to prevent or treat snake bites, and to delay aging. In combination with ginger, lime juice, "chuchuwasi," and sugar cane liquor, the Kichwas use the guayusa infusion to treat colds. A health-promoting effect was attributed to guayusa tea for stomach problems and headaches, as well as for external use in injuries and against insects.

The ethnobotanical record also documents ritual uses among the Shuar (Jivaro) people, including consumption before and after drinking ayahuasca, uses related to gastritis relief, and as a relaxant. Guayusa has also been attributed with phytohormonal properties relevant to female fertility in traditional Amazonian medicine, though scientific investigation of these claims remains preliminary.

3. Phytochemical Composition and Key Constituents

Methylxanthine Alkaloids

Guayusa leaves contain caffeine (1.73–3.48%), theobromine and other dimethylxanthines (among them paraxanthine and theophylline). Guayusa leaves also contain L-theanine, gallic acid, guanidine, isobutyric acid, nicotinic acid, and ascorbic acid. The caffeine concentration is comparable to or higher than that found in green tea (Camellia sinensis) and approaches levels found in coffee beans. Theobromine has been reported in guayusa at 0.08–0.25 mg/g (0.008–0.025%), compared to 0.3% in dried yerba mate. Theophylline content is even more negligible, at levels of 0.002–0.005 mg/g.

The question of whether guayusa contains meaningful quantities of L-theanine has been a subject of debate. Guayusa also contains L-theanine (an amino acid that promotes a sense of calm). It has about 1.3 mg/g of dried leaf, compared to tea which contains about 20–50 mg/g of dried leaf. Some researchers note that the levels in guayusa are low relative to green tea.

Phenolic Compounds

The tea contains the methylxanthines caffeine and theobromine as well as chlorogenic acids, flavonoids, and sugars. In total, 14 phenolic compounds have been identified and quantified in guayusa leaves. Chlorogenic acid and quercetin-3-O-hexose are the main representatives of the hydroxycinnamic acids and flavonols respectively. Seven carotenoids have been quantified, with lutein being the main compound. Ripening affected phenolic content significantly, but there was no significant difference in carotenoid content. Antioxidant capacity, measured by the DPPH• method, was also significantly affected by leaf age.

The total phenolic content (TPC) was consistently higher than the total flavonoid content (TFC) in all samples studied. GC–MS identified 29 metabolites, and clustering analysis grouped samples from certain growing sites as rich in phenols and flavonoids, while others were richer in alcohols, aldehydes, and hydrocarbons. This variability underscores the influence of geographic origin and cultivation conditions on chemical composition.

Triterpenoids

The chemical constituents from the leaves of Ilex guayusa have been investigated, and sixteen triterpenoids were isolated from the 95% ethanol extract of dried leaves by silica gel, Sephadex LH-20, and ODS column chromatographies and semi-preparative HPLC. These include oleanolic acid, ursolic acid, and a range of structurally related pentacyclic triterpenoids. Triterpenoids such as oleanolic acid and ursolic acid, which have been isolated from Ilex guayusa, are known to enhance glucose tolerance and insulin secretion, further supporting its antidiabetic potential.

Carotenoids and Other Compounds

Five carotenoids have been identified in guayusa, with lutein showing the highest concentration. Guayusa leaves reveal high antioxidant capacity as determined by two analytical methods, DPPH and ORAC. The leaves additionally contain vitamins including ascorbic acid (vitamin C) and nicotinic acid (vitamin B3), as well as gallic acid, guanidine, and isobutyric acid.

Summary of Major Compound Classes

Methylxanthine alkaloids: Caffeine (1.73–3.48% dry weight), theobromine, theophylline, paraxanthine
Hydroxycinnamic acids: Chlorogenic acid (major), other caffeoylquinic and dicaffeoylquinic acid derivatives
Flavonols: Quercetin-3-O-hexose and related glycosides
Flavan-3-ols (catechins): Catechin, epicatechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate (EGCG)
Triterpenoids: Oleanolic acid, ursolic acid, and at least fourteen related pentacyclic compounds
Carotenoids: Lutein and at least six additional carotenoids
Amino acids: L-theanine (present at lower concentrations than in Camellia sinensis)
Other: Gallic acid, guanidine, isobutyric acid, ascorbic acid, nicotinic acid, sugars, saponins

4. Mechanisms of Action

Stimulant and Psychoactive Effects: Caffeine-Mediated Pathways

The primary pharmacological driver of guayusa's stimulant effects is caffeine, a non-selective adenosine receptor antagonist. By competitively blocking A1 and A2A adenosine receptors in the central nervous system, caffeine reduces the inhibitory neurotransmission mediated by adenosine, resulting in increased alertness, reduced fatigue perception, and enhanced psychomotor speed. This mechanism is well-established for caffeine across all botanical sources and is directly applicable to guayusa given its documented caffeine content.

The most relevant secondary metabolites that have been investigated are xanthine alkaloids, terpenes, and phenolic compounds, while from the pharmacological point of view, the following uses stand out: physical and mental stimulants, analgesic, antioxidant, antimicrobial, anti-inflammatory, anti-diabetic, and phytohormonal. Theobromine, also a methylxanthine, acts as a mild phosphodiesterase inhibitor and bronchodilator, though at the concentrations present in guayusa it likely contributes modestly to its overall effect profile.

Antioxidant Mechanisms

Due to the abundant presence of bioactive molecules, of which we highlight three groups of importance—alkaloids, terpenes, and phenolic compounds—guayusa exhibits a varied biological activity including stimulant, antioxidant, anti-diabetic, and antimicrobial properties, among others. The antioxidant activity of guayusa is primarily attributed to its high polyphenol content. Chlorogenic acids and flavonoids donate hydrogen atoms or electrons to neutralize free radicals, and chelate metal ions that catalyze oxidative reactions. In vitro assays (DPPH, ABTS, ORAC) consistently demonstrate potent free-radical scavenging capacity, though translation to in vivo relevance depends on bioavailability.

Antidiabetic Mechanisms

Chlorogenic acid, a major compound in Ilex guayusa, has been shown to improve insulin sensitivity and reduce blood glucose levels by inhibiting glucose-6-phosphatase, an enzyme involved in hepatic glucose production. These mechanisms suggest that the polyphenolic and flavonoid content of Ilex guayusa may play a significant role in its antidiabetic effects. Complementary mechanisms include α-glucosidase inhibition (which slows carbohydrate absorption from the gut) and stimulation of β-cell function by triterpenoids. In vitro testing of guayusa extracts has shown α-glucosidase inhibition with an IC50 of 68.05 µg/mL, while no α-amylase inhibition or hemolysis was observed.

Molecular docking analysis has provided mechanistic evidence at the molecular level supporting the reported bioactivity of I. guayusa extracts. The free binding energy values and the nature of interactions identified allow establishment of a structure-activity relationship for the inhibition of α-glucosidase and catalase enzymes, which are related to antidiabetic and antioxidant properties, respectively.

5. Scientific Evidence by Area of Use

5.1 Cognitive Function and Mood

The most clinically developed area of guayusa research concerns its acute effects on cognitive performance and mood. The key human study is a randomized, double-blind, placebo-controlled crossover trial published in 2024.

Researchers conducted a randomized, double-blind, placebo-controlled crossover trial in young adults to examine the dose-dependent (600 mg versus 1200 mg), acute effects of consumption of an Ilex guayusa tea extract (GLE) on mood, cognitive and motor-cognitive performance, as well as its acute cardiovascular effects. Twenty-five adults (mean ± SD, age = 28 ± 7 years; 9 M/16 F) completed familiarization and then three randomly ordered experimental visits where they consumed either 600 mg (GLE600) or 1200 mg (GLE1200) GLE or placebo. Following supplement consumption, participants completed a mood state survey, assessments of perceived jitteriness, energy, and focus, and neurocognitive and motor-cognitive testing.

Overall, findings demonstrated that GLE600 was effective for improving motor and psychomotor speed, mood, and perceived energy, whereas GLE1200 was effective for enhancing psychomotor speed and reaction time in a neurocognitive hop test. This dose-response pattern suggests outcome-specific effects that varied with dose, an important nuance for interpretation.

A separate industry-funded study also provides supporting clinical data. A double-blind, randomized, placebo-controlled crossover study included 40 healthy adults to evaluate attention, working memory, mental processing speed, and mood. The study examined a single dose of 650 mg guayusa extract (AmaTea® Max). The study compared the 650 mg guayusa extract versus 1 g of lion's mane extract versus placebo. Testing occurred at three intervals: baseline (pre-ingestion), 60 minutes, and 120 minutes post-ingestion. Many scores improved at the 60- and 120-minute marks, indicating a positive impact on cognitive performance and mood. These results demonstrate that guayusa not only provides short-term stimulation, but also produces sustained cognitive improvements over a period of at least two hours.

Additionally, a double-blind crossover randomized human clinical trial of 12 adult males compared the CNS effects of guayusa extract and synthetic caffeine, each dose containing 200 mg of caffeine. The study reported no adverse effects.

Evidence assessment: Human clinical evidence for acute cognitive and mood effects is present but limited. The existing studies are small (n = 12–40), acute in design (single dose), and at least one was funded by a commercial supplier of a proprietary guayusa extract (AmaTea® Max). No long-term cognitive trials have been published. It is not possible to disentangle how much of the observed effect is attributable to caffeine (a well-established cognitive enhancer) versus other guayusa-specific constituents.

5.2 Antioxidant Activity

Guayusa leaves reveal high antioxidant capacity as determined by two analytical methods, DPPH and ORAC. Multiple analytical studies have consistently reported high polyphenol and flavonoid content and strong radical-scavenging capacity in both aqueous and hydroalcoholic extracts. Antioxidant potential was demonstrated across hydroethanolic extracts from multiple geographic sites, with ABTS and DPPH assays confirming significant radical-scavenging activity.

A review revealed that I. guayusa leaves contain significant concentrations of polyphenols, caffeine, carotenoids, and other bioactive compounds with antioxidant, anti-inflammatory, antimicrobial, and potentially neuroprotective properties.

Evidence assessment: Antioxidant activity is well-characterized in vitro. However, there are no published randomized controlled trials in humans measuring biomarkers of oxidative stress following guayusa consumption. The in vitro data are robust but insufficient on their own to establish clinical antioxidant efficacy.

5.3 Glycemic Regulation and Antidiabetic Effects

The antidiabetic potential of guayusa has been explored in preclinical models. A 2025 animal study is the most recent published investigation:

Streptozotocin (STZ)-induced diabetic rats, untreated with insulin, exhibit human-like symptoms such as hyperglycemia, polydipsia, polyuria, weight loss, cardiomyopathy, neuropathy, and oxidative stress. A study evaluated the effects of Ilex guayusa tea on cardiovascular, autonomic, metabolic, and oxidative stress parameters in diabetic rats, as well as its antioxidant and phytochemical properties. Triterpenoids such as oleanolic acid and ursolic acid, which have been isolated from Ilex guayusa, are known to enhance glucose tolerance and insulin secretion, further supporting its antidiabetic potential. These compounds, along with the antioxidant and anti-inflammatory properties of Ilex guayusa, contribute to its multifaceted role in diabetes management.

At the in vitro level, guayusa extracts demonstrated α-glucosidase inhibition, with the best activity at an IC50 of 68.05 µg/mL, though no α-amylase inhibition was observed.

Evidence assessment: Antidiabetic evidence is currently confined to animal models and in vitro mechanistic work. No human clinical trials specifically investigating guayusa's effects on blood glucose or insulin sensitivity have been published. The identified mechanisms (α-glucosidase inhibition, chlorogenic acid-mediated glucose-6-phosphatase inhibition, triterpenoid effects on β-cells) are plausible but require human validation.

5.4 Antimicrobial Activity

Promising biological activities have been detected in guayusa, especially as a new source of antioxidant agents due to the presence of phenolic compounds. A preliminary study as an antidiabetic natural product also accounts for new research directions. Ethnobotanical records document its traditional use for skin infections and as an insect repellent, and preliminary laboratory work has identified activity against some fungal strains, including Microsporum canis. However, antimicrobial data for guayusa are limited to in vitro and preclinical studies; no human clinical trials have been conducted in this area.

Evidence assessment: Preliminary in vitro data only. Clinical evidence is absent.

5.5 Anti-inflammatory Effects

The anti-inflammatory potential of guayusa is linked mechanistically to its chlorogenic acid and flavonoid content. Chlorogenic acid has documented anti-inflammatory properties in preclinical studies, including reduction of pro-inflammatory cytokines. However, no human clinical studies have been conducted to evaluate guayusa-specific anti-inflammatory effects.

Evidence assessment: Mechanistically plausible based on constituent pharmacology, but direct human evidence for guayusa as an anti-inflammatory agent is absent.

5.6 Cardiovascular Effects

A randomized, double-blind, placebo-controlled crossover trial examined the dose-dependent, acute effects of consumption of an Ilex guayusa tea extract on mood, cognitive performance, as well as its acute cardiovascular effects including blood pressure, heart rate, and QT interval length. The study measured these outcomes in 25 adults who consumed either 600 mg or 1200 mg guayusa leaf extract or placebo. Following supplement consumption, participants completed cardiovascular measurements including blood pressure, heart rate, and QT interval length determined before and after supplementation. The results indicated no significant adverse cardiovascular signals at the doses tested in this short-term study.

In the streptozotocin-induced diabetic rat model, no differences in arterial pressure, heart rate, or linear heart rate variability were detected between guayusa-treated and control groups.

Evidence assessment: Acute cardiovascular safety appears acceptable in small-scale studies, but long-term cardiovascular outcome data in humans do not exist.

6. Body Systems and Health Areas

Central nervous system / cognition: Adenosine receptor antagonism via caffeine; acute psychomotor and mood effects documented in small human trials.
Metabolic / glycemic regulation: α-Glucosidase and glucose-6-phosphatase inhibition; triterpenoid effects on insulin secretion — documented in vitro and in animal models only.
Antioxidant / redox: High polyphenol-mediated free-radical scavenging; well characterized in vitro.
Cardiovascular system: Acute cardiovascular parameters measured in one small human trial; modest effects observed.
Gastrointestinal system: Traditional uses for stomach complaints and gastritis; no controlled human data.
Immune / inflammatory response: Anti-inflammatory mechanisms linked to chlorogenic acid and flavonoids; preclinical data only.
Antimicrobial: In vitro activity against select pathogens; no human trial data.
Skin / external use: Traditional topical applications (insect repellent, wound care); not scientifically validated.

7. Dosage Forms and Reported Dosages

Traditional Preparation

Traditionally, guayusa is prepared as a decoction by simmering leaves in water, or as a simple aqueous infusion (steep). In a tea-like beverage, it is mainly made by picking and drying leaves. The traditional preparation involves large volumes of relatively dilute infusion consumed collectively over extended morning gatherings.

Caffeine Content Per Serving

Published estimates for caffeine content per prepared cup vary by source and preparation method. Guayusa leaves contain caffeine at 1.73–3.48% by dry weight. Based on this range and typical brewing quantities, prepared beverages contain variable caffeine levels. One composition study reported a typical cup contains approximately 40–90 mg of caffeine. Another analysis estimated approximately 66 mg per 8-oz serving.

Dosages Used in Clinical and Preclinical Studies

600 mg and 1200 mg standardized guayusa leaf extract (GLE): used in a randomized, double-blind, placebo-controlled crossover trial of 25 healthy adults assessing cognitive, motor-cognitive, and cardiovascular outcomes.
650 mg guayusa extract (AmaTea® Max): used in a double-blind, randomized, placebo-controlled crossover study of 40 healthy adults evaluating attention, working memory, mental processing speed, and mood.
Dose equivalent to 200 mg caffeine from guayusa extract: used in a double-blind crossover randomized human clinical trial of 12 adult males comparing CNS effects to synthetic caffeine.
1,200 mg/kg/day, 2,500 mg/kg/day, and 5,000 mg/kg/day of guayusa concentrate, plus a caffeine-positive control at 150 mg/kg/day: used in a 90-day subchronic study in male and female rats.

No established human therapeutic dose has been formally defined by any regulatory or pharmacopoeial body. The doses used in clinical studies reflect proprietary extract preparations and are not necessarily equivalent to infusions prepared from dried leaf.

8. Safety Considerations and Interactions

General Toxicology

Various studies were performed to evaluate the general and genetic toxicology of a standardized liquid concentrate of guayusa (GC). Guayusa concentrate was found to be negative in in vitro genotoxicity tests including the Ames test and a chromosome aberration study in human lymphocytes. The oral median lethal dose (LD50) of GC was greater than 5,000 mg/kg for female rats.

Effects observed in the GC-treated rat groups were comparable to those in the caffeine control group and included reductions in body weights, food efficiency, triglyceride values, and fat pad weights, and increases in blood chemistry values for serum aspartate aminotransferase, serum alanine aminotransferase, cholesterol, and adaptive salivary gland hypertrophy. No signs of incremental toxicity due to any other components of guayusa were observed. The studies indicate no harmful effects of GC in these test systems.

History of Safe Use in Ecuador

Within a three-year surveillance period in Ecuador there was one minor adverse effect reported nationally, related to the stimulant properties of guayusa. However, there were no hospital presentations, no product safety notifications, and no disease register records of guayusa-related illness. Comprehensive records demonstrate that Ecuador's surveillance and reporting system has sufficient rigour to identify risks should they exist. This single reported adverse effect is consistent with the known caffeine composition of guayusa, which like coffee has a metabolic stimulant effect.

Guayusa's moisture content, caffeine concentration, amino acid complement and elemental profile, including heavy metals, present no greater risk to human health than the consumption of tea or yerba mate. It is also established that there is a low risk of mycotoxin, bacterial or pesticide residue contamination of guayusa. The chemical composition of guayusa presents no barrier to the authorization of guayusa as a novel food in accordance with European Union novel food guidelines.

Regulatory Status

There is intense commercial activity to expand the consumption of guayusa as a healthy energy drink in Europe, where it is classified by law as a novel food. European Union novel food legislation permits traditional foods to be placed on the market if a history of safe use in a non-EU country can be established. The EFSA evaluation of guayusa for novel food status has involved examination of its caffeine content in the context of established safe caffeine intake thresholds. The European Food Safety Authority (EFSA) formally adopted the position that less than 400 mg of caffeine per day is not associated with adverse effects in healthy adults.

Caffeine-Related Adverse Effects and Interactions

Because caffeine is guayusa's dominant pharmacologically active constituent, all known caffeine-related adverse effects apply. These include insomnia, tachycardia, anxiety, gastrointestinal discomfort, and increased blood pressure at high doses. Guayusa should be used with care alongside other caffeine-containing products to avoid exceeding established safe daily caffeine thresholds.

Caffeine interacts with a number of drugs and substances. It is a substrate of CYP1A2, and agents that inhibit this enzyme (such as fluvoxamine, quinolone antibiotics, and others) can increase plasma caffeine concentrations. Caffeine also potentiates the effects of sympathomimetic agents and may reduce the sedative effects of adenosine-receptor-mediated drugs. These interactions apply to guayusa by virtue of its caffeine content.

Populations Requiring Particular Attention

The 90-day rat toxicology study found that observed adverse signals were attributable to caffeine rather than to other guayusa constituents. The putative phytohormonal properties attributed to guayusa in traditional medicine — including historical use as an emmenagogue and effects on fertility — have not been evaluated in controlled human studies, and the safety profile during pregnancy and lactation has not been formally characterized beyond the general caffeine-intake guidance applicable to all caffeinated foods.

Limitations of Current Safety Data

One published study provides the first scientific evidence for the lack of acute pathophysiological in vivo toxicity of a functional drink based on Ilex guayusa. However, additional toxicological studies, such as sub-acute and chronic toxicity studies, are necessary to strengthen its long-term use as a safe, functional nutraceutical beverage. Long-term human safety data from controlled studies are not available.

9. State of the Evidence: Overall Summary

Guayusa is a well-characterized botanical with a documented multi-millennial history of safe use by Amazonian indigenous peoples. Its phytochemical profile — dominated by caffeine and a diverse array of polyphenols, triterpenoids, and carotenoids — is now reasonably well described in the peer-reviewed literature. Due to the abundant presence of bioactive molecules, including alkaloids, terpenes, and phenolic compounds, guayusa exhibits varied biological activity. This makes it possible for it to be projected as one of the bioproducts with the greatest commercialization potential in industries such as functional food, pharmaceuticals, and cosmetics.

Nevertheless, while many findings are promising, it is important to recognize the preliminary nature of some studies, particularly those conducted on a small scale or in preclinical settings. Continued research is essential to fully understand guayusa's mechanisms of action and to validate its efficacy and safety in different populations. The body of human clinical trial evidence remains small, acute in its temporal scope, and in part derived from industry-funded research using proprietary extracts. Claims related to antidiabetic, antimicrobial, anti-inflammatory, and reproductive effects remain unvalidated in human populations.