Related Terms

• Brazilian cocoa, caffeine, caffeine-tannin complex, Dark Dog Lemon®, elixir of youth, gift of the gods, Go Gum®, guarana bread, guarana gum, guarana paste, Guarana Rush®, guarana seed paste, guaranin, guaranine, Guts®, Happy Motion®, Josta®, mysterious Puelverchen, pasta guarana, Paullinia, Paullinia cupana, Paullinia sorbilis, Sapindaceae (family), Superguarana, tetramethylxanthine, Uabano, Uaranzeiro, Zoom®.

Background

• Guarana is a native species of South America and has stimulating properties when taken by mouth. Guarana is also used to enhance athletic performance and to reduce fatigue. It has been used in the past as an aphrodisiac, diuretic, astringent, and to prevent malaria and dysentery, diarrhea, fever, headache, and rheumatism.

• The active ingredient in guarana was formerly called guaranine (tetramethylxanthine), but was later found to be caffeine. Guarana has one of the highest caffeine contents of all plants (up to 7%), and has been used by manufacturers for its caffeine content (e.g., Dark Dog Lemon®, Guts®, and Josta®).

• Although there is no scientific evidence that guarana itself increases mental alertness, its relationship to caffeine makes it probable that it would possess the same effects. It is proposed that the stimulatory effect of guarana is more gradual and sustained than caffeine due to the caffeine-tannin complex. Guarana is generally regarded as safe when not combined with other stimulatory agents, such as ephedra.

Scientific Evidence

Tradition/Theory

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious and should be evaluated by a qualified health care professional.

• Allergic rhinitis, aphrodisiac, apnea (pause in breathing), appetite suppressant, asthma, astringent, breathing difficulty (aid in removal of breathing tube), cancer, catalepsy (neuroleptic-induced), chronic diarrhea, cocaine withdrawal, colitis (necrotizing enterocolitis), diuretic, dysentery, enhanced athletic performance, fatigue, fertility, fever, fibromyalgia, flavoring agent, headache, heart conditions, hyperactivity, hypoglycemia (low blood sugar), kwashiorkor (severe malnutrition), low blood pressure (after eating), lung disease, malaria, migraine, pain, Parkinson's Disease, platelet aggregation inhibition, rheumatism, seizure, skin conditions, sore throat, stimulant, stress (heat), stroke, tonic (nerve).

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (over 18 years old)

• There is no proven effective dose for guarana. Teas, capsules and energy drinks are all commercially available. For cognitive enhancement, a single dose of 150 milligrams guarana dry extract, standardized to 11-13% alkaloid concentration has been used. One gram of guarana up to four times a day has been taken to relieve diarrhea or dysentery. As a diuretic, 486 milligrams of guarana daily has been used. One to two tablets or capsules (200-800 milligrams guarana extract) before breakfast or lunch, not to exceed 3 grams daily, has reportedly been used for energy enhancement.

Children (under 18 years old)

• There is no proven safe or effective dose for guarana in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

• Avoid in individuals with a known allergy or hypersensitivity to guarana (Paullinia cupana), caffeine, tannins or related species of the Sapindaceae family. Caffeine, a prominent constituent of guarana, may have an inhibitory effect on type-I allergic reactions.

Side Effects and Warnings

• Guarana is generally well-tolerated. A majority of information related to adverse effects of guarana is based in theory upon the adverse effect profile of caffeine. The effects of caffeine are likely more pronounced at age extremes, in the elderly and in children. The chronic use of caffeine, especially in large amounts, may produce tolerance, habituation, and psychological dependence. Abrupt discontinuation of caffeine can result in physical withdrawal symptoms including headache, irritation, nervousness, anxiety, and dizziness.

• Caffeinism and caffeine withdrawal may be indistinguishable from anxiety neurosis (physical symptoms of anxiety), and caffeine intoxication may cause psychosis (mental disorder). In various cases, anxiety disorders and somatic dysfunctions could be linked to caffeine intake. However, in a study of schizophrenic inpatients, no correlation was found between levels of anxiety, depression or other behavior, and caffeine consumption. Caffeine has been reported to increase mental alertness, physical energy, enhanced mood and physical performance and endurance. Avoid use in patients with psychological or psychiatric disorders as guarana may exacerbate symptoms.

• Seizures, muscle spasms, and convulsions have been reported from caffeine overdose. Lifetime caffeinated coffee intake equivalent to two cups a day without daily milk consumption (or calcium intake below RDA) in women has been associated with significantly decreased bone density, and bone loss in older women. Use cautiously in individuals at risk for osteoporosis, as caffeine may increase urinary excretion of calcium. Cases of rhabdomyolysis and myoglobinuria have been related to toxic effects of caffeine. Caffeine-induced insomnia has also been extensively studied.

• Consuming large amounts of caffeine per day may increase the risk of breast disease, tachycardia (increased heart rate) or high blood pressure, although there is controversy in this area. Nevertheless, use cautiously in patients with pre-existing mitral valve prolapse, as intractable ventricular fibrillation has been reported in a case associated with high dosage caffeine consumption.

• Several studies have found no connection between coronary heart disease and habitual coffee drinking. The Framingham Study did not find an association between coffee-drinking and atherosclerotic (hardening of the blood vessels) cardiovascular disease in the general population. In another large study, there was no significant association between coffee consumption and angina (chest pain).

• An increase in blood glucose may occur after low caffeine ingestion. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.

• Theoretically, the caffeine in guarana may increase the bioavailability and absorption of tannins, and thus decrease the absorption of nutrients. Weight loss, delayed gastric emptying time, and perceived gastric fullness have been attributed to a combination guarana product also containing yerba maté and damiana. "Burning in the stomach," worsening of ulcer symptoms, and urticaria ("hives") have also been reported.

• Guarana may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.

• Adverse effects reported secondary to ingestion of a combination of ma huang and guarana included insomnia, anxiety, headache, irritability, poor concentration, blurred vision, and dizziness. Other symptoms include hyper-excitation, tremor, nervousness, cerebral infarction (stroke), changes in voice quality, and palpitations (with and without chest pain). Avoid use in combination with other stimulatory agents, especially ephedra, due to reports of death and permanent disability associated with this combination.

• Ingestion of caffeine has increased intraocular pressure in two glaucoma patients. Use cautiously in individuals with glaucoma.

• Guarana may produce a diuretic effect. A reduction of caffeine may reduce the episodes of leakage per day in patients with symptoms of urinary frequency, and/or urge incontinence. Caffeine may cause dysuria (difficulty or pain urinating). High caffeine intake has been shown to worsen the condition of detrusor instability (unstable bladder) in older women. Use cautiously in patients with impaired kidney function.

• Use cautiously in individuals with an iron deficiency due to possible association with the development of anemia.

• Avoid in patients with liver impairment, as the clearance of caffeine may be impaired.

Pregnancy and Breastfeeding

• Studies on caffeine, the active constituent in guarana, indicate that consumption of caffeine may increase certain risks in pregnant women, although there is controversy in this area. For instance, high levels of caffeine consumption may result in delayed conception among women who are nonsmokers. Several studies found an association between caffeine and low birth weight. Heavy caffeine intake throughout pregnancy may increase the risk for SIDS (sudden infant death syndrome). Three cases of birth defects have been associated with excessive caffeine intake. Studies in pregnant women drinking moderate amounts of caffeine have shown inconsistent results, with more recent studies reporting no adverse effects on the fetus.

• Caffeine consumption may increase the risk of an early spontaneous abortion among non-smoking women. Heavy caffeine consumers reporting nausea had a doubled risk for spontaneous abortion. Light caffeine use has been associated with risk for spontaneous abortion among women who aborted in their last pregnancy.

• Caffeine is readily transferred into breast milk. Infant caffeine ingestion can lead to infant sleeping disturbances. The effect of other substances contained in guarana is unknown. Breastfeeding may inhibit the caffeine metabolism in infants due to human milk components. Babies from mothers who consumed large amounts of caffeine daily have experienced tremors, and some experienced cardiac rhythm disturbances.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

• Although the interactions for guarana are quite limited, there are numerous theoretical interactions based on guarana's caffeine content.

• Caffeine combined with analgesics (pain relievers) has been reported to increase analgesic effects. For example, in treatment of migraine, a combination of N-acetyl-para-aminophenol acetaminophen (APAP), aspirin, and caffeine was found to be highly effective. Caffeine may also be beneficial when taken with ibuprofen or propyphenazone. Caffeine increases the peak plasma concentration, rate of absorption and bioavailability of aspirin. The addition of caffeine to aspirin has significant benefits on mood and performance. An aspirin/butalbital/caffeine/codeine combination is considered superior to acetaminophen/codeine in relieving oral surgery pain.

• Caffeine is an adenosine antagonist and inhibits A1-receptors. Therefore the actions of caffeine are directly negated by adenosine and adenosine directly negates the effects of caffeine.

• Alcohol consumption may increase caffeine serum concentrations and the risk of caffeine adverse effects.

• There is one case report of ischemic stroke after the nasal ingestion of amphetamine and caffeine. Caution is advised with this combination.

• Caffeine has been reported to have antiplatelet activity, and may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®). Caffeine was also shown to attenuate the hemodynamic response to dipyridamole, a rheologic agent that inhibits platelet aggregation.

• Caffeine may also alter blood sugar levels. Caution is advised when using medications that may also alter blood sugar. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.

• Caffeine may interact with benzodiazepines. When lorazepam and caffeine were given and mental performance tests were administered and compared, the effect of caffeine counteracted both the effect of reducing anxiety and the reduction in mental performance caused by lorazepam alone. Caffeine with diazepam (Valium®) may produce similar results by counteracting the drowsy effects and mental slowness of diazepam. The caffeine in guarana may also negate the hypnotic effects of pentobarbital. Sedative doses may need to be monitored.

• Concomitant use of guarana may increase the inotropic effects of beta-adrenergic agonists.

• Caffeine may alter the effects of carbamazepine (Tegretol®) and reduce the bioavailability. Consult with a qualified healthcare professional, including a pharmacist, as dosing adjustments may be necessary.

• The antihistamine cimetidine (Tagamet®) may decrease caffeine clearance by inhibiting the microsomal metabolism of caffeine. Caution is advised in patients taking cimetidine along with caffeine or guarana.

• The antibiotic ciprofloxacin (Cipro®) significantly inhibits caffeine elimination. Caution is advised in patients taking certain antibiotics and caffeine.

• Caffeine taken with the antipsychotic clozapine (Clozaril®, Leponex®) may increase the risk of unwanted side effects, such as tardive dyskinesia, hallucinations, and akathisia. Caution is advised.

• Concomitant use of central nervous system stimulants and caffeine may increase the risk of stimulant adverse effects.

• Caffeine may interfere with the way the body processes certain drugs using the liver's "cytochrome P450" enzyme system. As a result, the levels of these drugs may be decreased or increased in the blood, and alter the intended effects. Patients taking any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions. Examples of agents that may interact include riluzole or fluvoxamine

• Numerous agents alter the clearance, metabolism, and pharmacokinetics of caffeine when taken concurrently. For instance, when caffeine is taken with the steroid agent dexamethasone (Decadron®), the clearance of caffeine may increase. Antibacterial agents such as enoxacin may significantly inhibit caffeine elimination. Impaired iron metabolism and microcytic anemia may occur in infants of breastfeeding women consuming caffeine. Methoxsalen and mexiletine have been shown to decrease the clearance of caffeine. Concomitant use of birth control pills and caffeine may increase serum caffeine concentrations and increase the risk of adverse effects, as birth control pills decrease the rate of caffeine clearance. Disulfiram decreased clearance of caffeine in normal volunteers. Caffeine administration in patients pretreated with quinolones (norfloxacin or pipemidic acid) may result in decreased caffeine clearance. Caffeine degradation may be impaired by phenytoin (Dilantin®), an anticonvulsant drug.

• Caffeine may increase urination, urinary sodium, and potassium excretion. Caution is advised in patients taking other diuretics (water pills), due to possible additive effects.

• Ephedrine in combination with guarana may increase blood pressure and therefore the risk of stroke and other cardiovascular events. Thermogenic synergism between ephedrine and caffeine may enhance the activity of ephedrine. Theoretically, pseudoephedrine (Sudafed®) would be expected to have the same effect on blood pressure when used in combination with guarana.

• Caffeine may enhance the effectiveness of ergotamine tartrate (Cafergot®) in the treatment of migraine headaches. Caffeine may enhance topically applied (on the skin) hydrocortisone in the treatment of atopic dermatitis.

• In preterm infants, caffeine has been found to be equivalent to theophylline in altering erythropoietin production, a hormone made in the kidneys. Theophylline is also used as a bronchodilator agent, and given to asthmatics. Caffeine may decrease total body clearance and elimination rate of theophylline. Caution is advised.

• In a case report, esmolol was an effective treatment of caffeine toxicity resulting from a suicide attempt of ingesting excessive amounts of caffeine.

• Caffeine may increase the renal (kidney) clearance of lithium and may reduce the plasma levels in stabilized patients. Abrupt discontinuation of a consistent caffeine intake may cause an increase in lithium tremors and an increase in serum lithium levels. Monitoring of doses may be necessary.

• Although not well studied in humans, caffeine and monoamine oxidase inhibitors (MAOIs) may cause encephalopathy (degenerative brain disease), neuromuscular irritability, hypotension (low blood pressure), sinus tachycardia (increased heartbeat), rhabdomyolysis (potentially fatal disease involving destruction or degeneration of skeletal muscle) and hyperthermia (abnormally high body temperature). Consult with a qualified healthcare professional, including a pharmacist, to check for any interactions.

• Caffeine may have additive effects on cardiovascular parameters when taken with nicotine. Concomitant consumption of caffeine and cigarettes during pregnancy may place the developing fetus at higher risk for diminished growth.

• The combination of phenylpropanolamine and caffeine caused a manic psychosis in one woman with no previous history of mental disturbances. It is noted that phenylpropanolamine can increase the peak levels reached by caffeine by almost four-fold. An additive increase in blood pressure has occurred when using the combination of phenylpropanolamine and caffeine. Caution is advised.

• Terbinafine (Lamisil®) is an antifungal agent that may increase serum caffeine concentrations and increase the risk of adverse effects. Caution is advised when taking terbinafine concurrently with caffeine.

• Verapamil is a calcium channel blocker agent. When taken with caffeine, verapamil may increase the risk of side effects.

Interactions with Herbs and Dietary Supplements

• Herb and supplement interactions associated with guarana are predominantly theoretical and generally based upon the adverse effect profile of caffeine.

• Caffeine may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

• Caffeine might increase or decrease blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

• Bitter orange may add to the possible hypertensive (blood pressure increasing) effects of caffeine. Caution is advised in patients with high blood pressure or those taking other herbs that have blood pressure altering effects.

• Other caffeine containing products (black tea, cocoa, coffee, cola nut, green tea, yerba mate, etc.) used in combination with guarana may have additive effects.

• Caffeine may interfere with the way the body processes certain herbs or supplements using the liver's "cytochrome P450" enzyme system. As a result, the levels of other herbs or supplements may become too low in the blood. It may also alter the effects that other herbs or supplements potentially may have on the P450 system.

• Caffeine may increase the flow of urine (diuresis), and may have additive effects with other herbs or supplements that have diuretic effects.

• Avoid use of combination products of ma huang (ephedra) and guarana due to the reports of death and permanent disability associated with this combination (such as Metabolife-356®).

• Caffeine may interact with herbs with estrogenic effects; caffeine metabolism was inhibited in postmenopausal women using hormone replacement estrogen.

• Impaired iron metabolism and microcytic anemia may occur in infants of breastfeeding women consuming caffeine. Caution is advised.

• Caffeine and monoamine oxidase inhibitors (MAOIs) may cause encephalopathy (degenerative brain disease), neuromuscular irritability, hypotension (low blood pressure), sinus tachycardia (increase heartbeat), rhabdomyolysis (potentially fatal disease involving destruction or degeneration of skeletal muscle), and hyperthermia (abnormally high body temperature).

• Additive effects on cardiovascular parameters may occur with nicotine or tobacco. Concomitant consumption of caffeine and cigarettes during pregnancy may place the developing fetus at higher risk for diminished growth.

Author Information

• This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. Berube-Parent S, Pelletier C, Dore J, et al. Effects of encapsulated green tea and Guarana extracts containing a mixture of epigallocatechin-3-gallate and caffeine on 24 h energy expenditure and fat oxidation in men. Br J Nutr 2005;94(3):432-436. View Abstract

2. Boutroy MJ, Vert P, Monin P, et al. Methylation of theophylline to caffeine in premature infants. Lancet 4-14-1979;1(8120):830. View Abstract

3. Cheraskin E, Ringsdorf WM, Jr. Blood-glucose levels after caffeine. Lancet 9-21-1968;2(7569):689. View Abstract

4. Cole P. Coffee-drinking and cancer of the lower urinary tract. Lancet 6-26-1971;1(7713):1335-1337. View Abstract

5. Debrah K, Sherwin RS, Murphy J, et al. Effect of caffeine on recognition of and physiological responses to hypoglycaemia in insulin-dependent diabetes. Lancet 1-6-1996;347(8993):19-24. View Abstract

6. Fraumeni JF Jr, Scotto J, Dunham LJ. Coffee-drinking and bladder cancer. Lancet 11-27-1971;2(7735):1204. View Abstract

7. Fukumasu H, Silva TC, Avanzo JL, et al. Chemopreventive effects of Paullinia cupana Mart var. sorbilis, the guarana, on mouse hepatocarcinogenesis. Cancer Lett. 5-7-2005; View Abstract

8. Haller CA. Jacob P, Benowitz NL. Short-term metabolic and hemodynamic effects of ephedra and guarana combinations. Clin Pharmacol.Ther. 2005;77(6):560-571. View Abstract

9. Hess AM, Sullivan DL. Potential for toxicity with use of bitter orange extract and guarana for weight loss. Ann.Pharmacother. 2005;39(3):574-575. View Abstract

10. Jacobson MF, Goldman AS, Syme RH. Coffee and birth defects. Lancet 6-27-1981;1(8235):1415-1416. View Abstract

11. James JE. Is habitual caffeine use a preventable cardiovascular risk factor? Lancet 1-25-1997;349(9047):279-281. View Abstract

12. Joesoef MR, Beral V, Rolfs RT, et al. Are caffeinated beverages risk factors for delayed conception? Lancet 1-20-1990;335(8682):136-137. View Abstract

13. Nyska A, Murphy E, Foley JF, et al. Acute hemorrhagic myocardial necrosis and sudden death of rats exposed to a combination of ephedrine and caffeine. Toxicol.Sci. 2005;83(2):388-396. View Abstract

14. Roberts AT, Jonge-Levitan L, Parker CC, et al. The effect of an herbal supplement containing black tea and caffeine on metabolic parameters in humans. Altern Med Rev 2005;10(4):321-325. View Abstract

15. Shapiro P. Caffeine for allergic rhinitis. Lancet 4-3-1982;1(8275):793. View Abstract