Guarana, whose botanical name is Paullinia Cupana is a shrub grown in the Amazon which produces berries that have been used medicinally. Hardly any studies have been done with it alone to determine whether it has any health benefits. A few studies have been done combining guarana or guarana extract with other nutrients and herbs. Guarana and kola nut enjoy great popularity in their native lands because they are rich in caffeine which serves as a stimulant.

Potential uses for guarana or extract
Guarana offers protection against gastric lesions induced by ethanol and indomethacin in rats.
In combination with other herbs and nutrients, guarana may be helpful for weight loss. Other nutrients and herbs that influence appetite or may have thermogenic effects include:

Green tea extract may be effective in some people as a weight loss pill.
Citrus-Aurantium is a thermogenic appreciated by some people although it can increase body temperature and in very high doses can increase heart rate.
Caffeine is often found in weight loss pills but I personally don't like my patients taking extra caffeine since it can cause increased heart rate and anxiety. Most people already consume enough caffeine through coffee, tea, sodas, and chocolate.
Ginger may be helpful in some people but higher doses are required.
Hoodia has become quite popular over the past few years.
Chitosan has not been found to be very helpful as a weight loss pill.
Konjac is also known as Glucomannan, a fiber that has many health benefits.
Pyruvate in high doses, such as 20 to 40 gm a day, have been shown in some studies to lead to weight loss, but these high doses are impractical and expensive.
Alpha lipoic acid may also reduce appetite but it is primarily used as an antioxidant.
5-HTP is a nutrient that helps curb appetite in some individuals. This amino acid, by converting into serotonin, can be used temporarily to improve will power and decrease the urge to eat until more established weight loss habits are in place.
Yerba mate may work in combination with guarana and damiana.
Acetyl-l-carnitine is may reduce appetite in some individuals, a formula has been created by Ray Sahelian, M.D.

Guarana side effects, concerns
Guarana has a high concentration of caffeine and, in very high doses, may cause heart palpitations or heart rhythm irregularities in those who are sensitive to caffeine. Other guarana side effects include anxiety or restlessness.

Guarana extract is available in various extract potencies, including 16 percent caffeine and 22 percent caffeine.

Am J Emerg Med. 2013 Nov. Death of a young man after overuse of energy drink. A 28-year-old-man admitted to emergency department with ventricular tachycardia. Patient had drunk 3 cans of 250-mL energy drink 5 hours before the basketball match; he had palpitation and nausea before the match. After 30 minutes of the match, during the break, patient lost his consciousness. On admission, normal cardiac rhythm was achieved by cardioversion, and the patient was hospitalized and died on the third day. Energy drinks generally contain caffeine, taurine, various vitamins, glucose, and herbal extracts such as guarana and ginseng. Especially in high doses, caffeine can cause palpitations and supraventricular and ventricular arrhythmia. Energy drink consumers should be informed about their severe adverse effects in case of overuse.

Effect of guarana ingestion on mental function
A double-blind, placebo-controlled, multi-dose evaluation of the acute behavioural effects of guaranį in humans.
J Psychopharmacol. 2007. Human Cognitive Neuroscience Unit, Division of Psychology, Northumbria University, Newcastle upon Tyne, UK.
The present study aimed to systematically assess acute, dose-related effects of an extract of guaranį plant for the first time in humans. This double-blind, counterbalanced, placebo-controlled study assessed the acute mood and cognitive effects throughout the day of four different doses (37.5 mg, 75 mg, 150 mg and 300 mg) of a standardised guaranį extract (PC-102). Guaranį improved secondary memory performance and increased alert and content mood ratings. The two lower doses produced more positive cognitive effects than the higher doses. This research supports previous findings of cognitive improvements following 75 mg guaranį and provides the first exploration of different dose effects of guaranį in humans. The findings suggest that the effects cannot be attributed to caffeine alone.

In healthy subjects a 5-day treatment with a commercial preparation of guarana used according to labelled instructions provided no evidence for any major effects on psychological well-being, anxiety and mood. J Negat Results Biomed. 2013. Effects of a commercial product containing guaranį on psychological well-being, anxiety and mood: a single-blind, placebo-controlled study in healthy subjects.

The effects of long-term administration of guarana on the cognition of normal, elderly volunteers.
Federal University of Sao Paulo, Brazil.
Rev Paul Med. 1996.
Paulinia cupana (guarana) is a Brazilian plant given great prestige in popular medicine, for example as being a potent stimulator of brain functions. The authors assessed the effects of the long-term administration of guarana on the cognition of normal, elderly volunteers. Forty-five volunteers were studied, with a random distribution in three experimental groups: placebo, caffeine, and guarana, in a double-blind study. There were no significant cognitive alterations in these volunteers.

Influence of guarana on weight loss
Supplements that contain ephedra and caffeine-rich guarana, used for weight loss, result in significant cardiovascular and metabolic changes. These changes could be harmful in people with high blood pressure, atherosclerosis (clogged arteries), or glucose intolerance, a precursor to diabetes marked by elevated blood sugar. Guarana is an herb containing caffeine. Researchers at the University of California, San Francisco tested the effects of Xenadrine RFA (a supplement containing 25.4 mg ephedra alkaloids and 185 mg caffeine) and ephedra extract (23.2 mg total ephedra alkaloids) plus guarana (167 mg caffeine), compared with placebo, in 16 healthy adults. Repeated dosing of ephedra and guarana produced elevated ephedrine blood concentrations, increased heart rate and blood pressure, and had unfavorable effects on glucose and potassium homeostasis. These effects could exacerbate obesity-related conditions such as insulin resistance and metabolic syndrome. Clinical Pharmacology and Therapeutics June 2005.

Weight loss and delayed gastric emptying following a South American herbal preparation in overweight patients.
J Hum Nutr Diet. 2001.
Among the herbal preparations known to non-western cultures are materials which may have applications in modulating physiological processes which influence gut motility, food intake and energy balance. One such mixed herbal preparation is 'YGD' containing Yerbe Mate (leaves of Ilex paraguayenis), Guarana (seeds of Paullinia cupana) and Damiana (leaves of Turnera diffusa). This study had two distinct aims: to determine the effect of a herbal preparation 'YGD' containing Yerbe Mate, Guarana and Damiana on gastric emptying; to determine the effect of the same preparation on weight loss over 10 days and 45 days and weight maintenance over 12 months. Gastric emptying was observed using ultrasound scanning in seven healthy volunteers following YGD and placebo capsules taken with 420 mL apple juice. Body weight was observed before and after 10 days of treatment with three YGD capsules or three placebo capsules before each meal for 10 days in 44 healthy overweight patients attending a primary health care centre. Forty-seven healthy overweight patients entered a double-blind placebo-controlled parallel trial of three capsules of YGD capsules before each main meal for 45 days compared with three placebo capsules on body weight. Body weight was monitored in 22 patients who continued active (YGD capsules) treatment for 12 months. The herb preparation YGD was followed by a prolonged gastric emptying time of 58 compared to 38 min after placebo. Body weight reductions were 0.8 kg after YGD capsules compared to 0.3 kg after placebo capsules over 10 days, and 5 kg after PGD capsules compared to 0.3 kg after placebo over 45 days. Active treatment with YGD capsules resulted in weight maintenance of the group (73 kg at the beginning and 72.5 kg at the end of 12 months). The herbal preparation, YGD capsules with guarana significantly delayed gastric emptying, reduced the time to perceived gastric fullness and induced significant weight loss over 45 days in overweight patients treated in a primary health care context. Maintenance treatment given in an uncontrolled context resulted in no further weight loss, nor weight regain in the group as a whole. The herbal preparation with guarana is thus shown to be one that significantly modulates gastric emptying. Further clinical studies with dietetic monitoring of energy intake, dietary quality, satiety ratings, body weight and body composition are now indicated, and examination of the active principles contained in the three herbal components may prove.

Guarana and blood thinning, anti platelet activity, anti thrombosis
Studies on the nature of anti-platelet aggregatory factors in the seeds of the Amazonian Herb Guarana (Paullinia cupana).
Int J Vitam Nutr Res. 2008. Ravi Subbiah MT, Yunker R, Yunker R. Department of Internal Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
Extracts derived from the dried seeds of guarana possess strong anti-platelet aggregatory properties. In this study, an active fraction was extracted containing catechins, epicatechins, and their dimers, with a small amount of caffeine. Complexes containing caffeine and catechins (and their dimers) might be responsible for anti-platelet aggregatory activity in guarana seeds and might offer health benefits towards decreasing risk of thrombosis and cardiovascular disease.

Combining with other herbs
Andrology (Los Angeles). 2015. Treatment with a combination of ginger, L-citrulline, muira puama and Paullinia cupana can reverse the progression of corporal smooth muscle loss, fibrosis and veno-occlusive dysfunction in the aging rat. Aging associated erectile dysfunction is characterized within the corpora by a progressive apoptosis of the smooth muscle cells and their replacement by collagen. Nitric oxide from iNOS has been shown to inhibit these histological changes in the corpora while PDE5 inhibitors as well as certain nutraceuticals such as ginger, paullinia cupana, muira puama and L-citrulline are known to enhance the effects of NO. We evaluated whether the daily oral administration for 2 months with a combination of ginger, paullinia cupana, muira puama and L-citrulline (COMP-4) can effectively delay the ongoing corporal fibrosis, smooth muscle cell apoptosis and cavernosal veno-occlusive dysfunction (CVOD) seen in middle aged rats similar to that seen with tadalafil. 10 Month old Fisher 344 rats were treated or not for two months with COMP-4, tadalafil or a combination of tadalafil plus COMP-4. CVOD was determined by dynamic infusion cavernosometry. Penile sections of the corpora cavernosa were subjected to Masson trichrome staining to evaluate fibrosis and immunohistochemistry for desmin as a marker of smooth muscle content and inducible nitric oxide synthase (iNOS) followed by image analysis. Oxidative stress levels were determined by GSH/GSSG ratio in whole blood. A decline in the non-treated rat's erectile function is evident by 10-12 months of age and is accompanied by a decrease in the corporal smooth muscle content determined by desmin expression and an increase in corporal fibrosis. The daily treatment for two months with COMP-4 reverses this process by reducing systemic oxidative stress and increasing desmin and iNOS expression, similar to that seen with tadalafil or the combination of COMP-4 plus tadalafil. An oral combination of ginger, muira puama, Paullinia cupana and L-citrulline seems to be as effective as daily PDE5 inhibitor therapy in either delaying or reversing the onset of the histological and functional characteristics of aging related erectile dysfunction.

Emails about caffeine and guarana
I keep hearing of the ills of caffeine, its risks, etc. I also hear of the ills of coffee. But I was wondering, isn't the coffee bean a natural source of caffeine? If that's the case then why is it a problem? And additionally, what of a herb like guarana, which is also supposed to have natural caffeine in it? Isn't guarana safe? I want to buy a guarana diet pill but I am concerned about safety.
   Caffeine, in large amounts, whether from coffee, tea, guarana, or other sources, can cause restlessness, insomnia, anxiety, perhaps rapid heart beat, elevated blood pressure, irregular heart beats, etc. Therefore, a small amount is fine, and coffee has some antioxidants, but it is the excess that is the problem.

Can guarana be taken the same day as lyprinol, the Ayurvedic herb ashwagandha, or the prostate herbs saw palmetto and Africanum pygeum? I am considering a product called System-Six.
   As long as the dosage of the guarana is kept low, it should be okay. Many supplements can be combined if the dosages are kept low.