Guarana is an Amazonian fruit-bearing plant that has been used traditionally by natives of the Amazons and Brazil. You can find Guarana in many soft drinks and energy drinks because of its energy-boosting properties. Its benefits extend beyond being a tool for wakefulness, and modern science has helped uncover some of the benefits of Guarana, including its use as a powerful antioxidant and cognitive and exercise enhancer. It is recognized as a GRAS substance, but it does have interactions with diseases, conditions, medications, herbs, supplements, and laboratory tests because of its high caffeine content.
What is Guarana?
Guarana (Paullinia cupana) is a woody vine which grows in South America. It belongs to the Sapindaceae family, which also contains the flowering plants horse chestnut, lychee, and maple. Guarana’s leaves are evergreen and it produces reddish brown fruits which contain one black seed per fruit. These fruits contain five times more caffeine than coffee beans, and although it is prized by humans for its energy boosting properties, the extremely high concentration of caffeine in the berry and seeds is actually a toxin which the plant uses for self-defense against pathogens. 
Guarana grows in the Amazon basin and Brazil. The origins of the word guarana are derived from the Guarani word guara-na, meaning “fruit like the eyes of the people”. Guarani is a language indigenous to South America. [2, 3]
Guarana is still produced in Brazil, primarily in Amazonas and Bahia, and about 70% of the guarana produced is for energy drinks and soft drinks, while the rest is either sold for direct consumption or for raw material for pharmaceutical or cosmetics industries. 
What is the history of Guarana?
The natives in the Amazon Basin used Guarana for thousands of years before the Europeans arrived in South America. The Tupi and Guarani people of Brazil valued Guarana for its medicinal benefits, and its name is rooted in mythology. When the fruit is mature, it splits open and reveals the black seed inside, which resembles eyes. The Satere-Maue tribe believes that this is because a village child was killed by a diety, and another kinder diety was aware of their grief, so the god took the left eye from the child, planted it in the forest, and caused wild guarana to grow. The god then took the right eye from the child and planted it in the village, which caused domesticated guarana to grow. [1, 5]
Father Felip Betendorf (also known as Johannes Philippus Bettendorf), a seventeenth century Jesuit missionary, discovered the use of Guarana by the natives in 1669 and introduced it to western civilization. Father Betendorf observed that the natives drank Guarana and they used it to treat headaches, cramps, and fevers, and it was a diuretic. [1, 5]
The first compound isolated from guarana was named guaranine in 1826. Guaranine is a tetramethylxanthine which is the same class of compound as caffeine. Guarana became a commercial commodity by 1958. [1, 5]
What are the traditional uses of Guarana?
- Amazon basin: The Guaranis made tea from the seeds, after washing them and grinding them into a powder. They made guarana bread by taking the powder, kneading it into a dough, and rolling it out into loaves. The bread could then be grated and put in hot water with sugar, which then made Brazillian cocoa.
- Traditional tribal uses: The natives use Guarana for a pain reliever, stimulant, to prevent arteriosclerosis and cardiovascular conditions, to treat migraine, diarrhea, fever, high blood pressure, and dysentery. 
What is Guarana made of?
Guarana seeds contain bioactive xanthines, purine alkaloids, phenolics, polysaccharides, fibers, and essential oil. There are two groups of phenolics: catechins and tannins. The catechins are epicatechin chains and catechin itself; the tannins are not further characterized but are still considered active components. [6, 7]
The seeds of guarana contain:
- Catechins: 4% dry weight (including epicatechin)
- Polysaccharides (glucose and xylose in high amounts)
- Procyanidins B1, B2, B3, B4, A2, C1
- Dietary fibers pectin and xylan: 6% of seed weight 
The essential oil from guarana seeds contains:
- Carvacol: 5 to 15%
- 4-(dimethylpropyl)-phenol 
- Cis-11-eiocsenoic acids
- Cis-11-octadeenoic, or cis-vaccenic acid
- Oleic acid
- Paullinic acid
- Cyclic sesquiterpene and monoterpene hydrocarbons
- Alkylphenol derivatives 
What are the benefits of Guarana?
Guarana regulates fat cells
This study in mice found that guarana prevents fat tissue accumulation, increases energy, and stimulates mitochondrial biogenesis in brown fat tissue. Animals fed with a high fat diet and supplemented with guarana had lower body weight, lower fat, and more energy.
Guarana reduces fatigue
This study determined that guarana reduces fatigue in breast cancer patients undergoing chemotherapy with no negative effects on sleep quality or worsening of depression or anxiety.
Another study focused on patients receiving chemotherapy determined that Guarana extract was an effective treatment for fatigue related to chemotherapy.
Guarana improves cognition and reduces mental fatigue
A double-blind, placebo-controlled, randomized study with 129 healthy adults concluded that guarana, combined in a vitamin and mineral supplement, enhanced cognition and reduced mental fatigue.
Guarana can increase physical exercise performance
This study focused on the perceived exertion during moderate-intensity exercise in a double-blind, placebo-controlled, randomized cross-over study and found that it reduced the perceived exertion during exercise, as well as improving memory performance.
Guarana improves cognitive performance
This double-blind, placebo-controlled study focused on standardized guarana extract administered to volunteers before cognitive tests. Guarana improves secondary memory performance and alertness.
Guarana supports a positive mood
The same study referenced above found that Guarana not only improved cognitive performance but improved feelings of well-being and supported a positive, content mood.
Guarana improves memory
A study in rats with cognitive deficits found that guarana improved memory impairment.
Guarana is a powerful antioxidant
This study focused on the polysaccharide content of guarana powder and isolated pectin and xylan. The polysaccharides are strong free radical scavengers, especially for DPPH radicals (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radicals.
This study focused on the antioxidant effects of Guarana against LDL oxidation in elderly people. LDL oxidation is associated with the onset of atherosclerosis.
This in-vitro, animal-based study found that roasted guarana seeds enhance the ability to reduce oxidative stress and promote anti-aging markers such as polyQ40 aggregation and muscle function decline.
Guarana may fight cancer cells
This in-vitro study with colorectal cancer cells discovered that guarana kept the cells from multiplying and induced cell death.
Guarana is protective against DNA damage
In this study with mice, Guarana had a protective effects against DNA damage in the liver.
Guarana may support healthy vision
This study found that elderly people with high consumption of guarana had better self-reported eyesight.
Guarana is antibacterial
This study found that guarana is antibacterial against E. coli and Salmonella typhimurium.
Guarana prevents wrinkling
How to Use Guarana
Guarana is commercially available in powder, capsules, extracts and whole seeds.
For Guarana powder:
- Mix into hot water for a tea
- Mix into smoothies
- Mix into protein drinks
- Pack into capsules
For Guarana extract:
- For short-term use, mix 0.5-1 ml with water and take 2-3 times daily
How much Guarana should I take? Dosage information
There is no standard dose for guarana. Guarana extract is often standardized with tannin and caffeine content, but these standardizations also vary. Most people find results with 50-75 mg once daily before noon, or 2 doses of 50 mg (taken one time after waking up and once again around noon). 
- Cancer-related inappetence: 50 mg of Guarana extract twice daily for 4 weeks
- Fatigue from chemotherapy: 75-50 mg of Guarana extract twice daily for 3 weeks
- Cognitive function: 5-75 mg of Guarana extract as a single dose:
- 2 mg of a Guarana product (standardized to 40 mg caffeine) as a single dose, combined with vitamins B1, B2, niacinamide, pantothenic acid, vitamin B6, biotin 150 mcg, folic acid 200 mcg, vitamin B12 1 mcg, vitamin C 60 mg, calcium 100 mg, magnesium 100 mg, and zinc 9.5 mg
- 300 mg of Guarana, combined with 100 mg ginseng, 7490 mg zinc, 1003 mg vitamin B6, 9005 mg vitamin B3, 0.798 mg vitamin B2, 0.705 mg vitamin B1, 180 mg vitamin C
- Athletic performance: 2 mg of a Guarana product (standardized to 40 mg caffeine) as a single dose, combined with vitamins B1, B2, niacinamide, pantothenic acid, vitamin B6, biotin 150 mcg, folic acid 200 mcg, vitamin B12 1 mcg, vitamin C 60 mg, calcium 100 mg, magnesium 100 mg, and zinc 9.5 mg 
Safety and Side Effects of Guarana
Guarana is considered a GRAS substance (Generally Recognized as Safe) by the U.S. FDA in appropriate quantities, but there are side effects that are associated with Guarana. 
Guarana contains a high amount of caffeine and the quantity of the stimulant can cause side effects. It is not recommended for people who have a sensitivity to caffeine or people who have anxiety, bleeding disorders, cardiac (heart) conditions, diabetes, epilepsy, glaucoma, high blood pressure, incontinence, irritable bowel syndrome (IBS), osteoporosis, or schizophrenia. 
Guarana can also interact with many medications and can interfere with some laboratory tests. Generally, the side effects seen for people with no conditions and who are not taking medication are:
- Dizziness, insomnia, restlessness, nervousness, nausea, gastric irritation, vomiting, high heart rate, fast breathing, tremors, convulsions, delirium
- Headache, agitation, anxiety, ringing in the ears, low potassium blood levels, respiratory alkalosis, high blood glucose levels, ketosis, high blood pressure, irregular heartbeat (arrhythmia), premature heartbeat, chest pain
- Some side effects of high caffeine consumption include some conflicting accounts of fibrocystic breast disease, endometriosis, and breast cancer 
Drug Interactions with Guarana
Combining Guarana with street drugs, ephedra products, or herbs and supplements which contain caffeine or can make Guarana stronger, is dangerous. Medications and supplements which can also interact negatively with Guarana are listed below.
Major interactions can occur between Guarana and:
Amphetamines, cocaine, ephedrine 
Moderate interactions can occur between Guarana and:
Adenosine, anticoagulant/antiplatelet medications, beta-adrenergic agonists (such as albuterol, metaprotenerol, isoproterenol, and terbutaline), MAOI (monoamine oxidase inhibitors), carbamazepine, Tagamet (cimetidine), Clozaril (clozapine), Persantine (dipyridamole), Antabuse (disulfiram), diuretic drugs, estrogens, Zarontin (ethosuximide), Felbatol (felbamate), Luvox (fluvoxamine), lithium, nicotine, Nembutal (pentobarbital), Luminal (phenobarbital), phenylpropanolamine, Dilantin (phenytoin), Rilutek (riluzole), stimulants (such as nicotine, sympathomimetic amines, amphetamines, and cocaine), theophylline, Parnate (tranylcypromine), valproate, Calan (verapamil) 
Minor interactions can occur between Guarana and:
Alcohol, anti-diabetes drugs, contraceptive drugs, CYP1A2 Inhibitors, Diflucan (fluconazole), Oxsoralen (methoxsalen), Mexitil (mexiletine), phenothiazines, quinolone antibiotics, Lamisil (terbinafine), Gabitril (tiagabine), Ticlid (ticlopidine) 
Herbs and Supplements which may Interact with Guarana:
Herbs and supplements which have anticoagulant/antiplatelet properties:
Caffeine-containing herbs and supplements:
Black tea, oolong tea, green tea, cocoa, cola nut , coffee, and mate
Herbs and Supplements to avoid using with guarana:
Laboratory Tests, Bloodwork, and Diagnostics Interactions with Guarana:
Guarana may have interactions between some laboratory tests, diagnostics, and bloodwork. Some of these tests include: 5-Hydroxyindoleacetic acid, bleeding time, catecholamines, creatine, dipyridamole thallium imaging, functional magnetic resonance imaging (fMRI), glucose, lactate, neuroblastoma tests, pharmacological stress tests, pheochromocytoma tests, pulmonary function tests, technetium-99M (Tc-99m) labelling, theophylline, urate, urinary calcium, and vanillylmandelic acid (VMA). 
Toxicity of Guarana
The specific toxicity of guarana has not been determined yet, but the toxicity associated with the caffeine content has been noted. A case study of a man who consumed 20 tablets of Guaranax, a guarana extract equivalent to 1600 mg of caffeine, experienced caffeine toxicity.
Caffeine toxicity can range in symptoms from heart palpitations and chest pain to ventricular fibrillation, high blood pressure, low potassium levels, high blood sugar, elevated creatinine, vomiting, and nausea; to fatality and death. 
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- Schimpl, Flavia Camila, et al. “Guarana: Revisiting a Highly Caffeinated Plant from the Amazon.” Journal of Ethnopharmacology, vol. 150, no. 1, 28 Oct. 2013, pp. 14–31., doi:https://doi.org/10.1016/j.jep.2013.08.023.
- Marques, Leila Larisa Mederios, et al. “Paullinia Cupana: a Multipurpose Plant – a Review.” Revista Brasileira De Farmacognosia, vol. 29, no. 1, 2019, pp. 77–110., doi:https://doi.org/10.1016/j.bjp.2018.08.007.
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- “Guarana.” Drugs.com, 9 Jan. 2019, www.drugs.com/npp/guarana.html.