SHORT SCIENTIFIC ARTICLE Acute guarana poisoning: report of two cases Lara Leben, Miran Brvar Abstract Poison Control Unit, Guarana (Paullinia cupana) is a South American plant that contains twice more caffeine com- Division of Internal pared to coffee beans, and has a stimulatory effect. Thus guarana preparations in the form of Medicine, University capsules, tablets, powders, teas, syrups and energy drinks contain a lot of caffeine, which can Medical Centre Ljubljana, Ljubljana, Slovenia rapidly cause poisoning even when only slightly overdosed. Correspondence: Caffeine poisoning may result in irritability, insomnia, anxiety, restlessness, muscle twitching, Miran Brvar, e: miran. nausea or vomiting, rapid heart beat or cardiac arrhythmias, high blood pressure, sweating, [email protected] diuresis and gastroinestinal disturbance. Key words: This report presents two cases of guarana overdose with the common caffeine poisoning symp- stimulants; caffeine; overdose; adverse effects; toms and signs. Guarana in therapeutic doses can exacerbate underlying cardiac disease (espe- interactions cially cardiac arrhythmias, coronary heart disease, heart failure) and diabetes. Furthermore, children, pregnant and nursing women should avoid guarana as well. Received: 5. 2. 2018 Accepted: 30. 3. 2018 Treatment of guarana poisoning is symptomatic, mainly with benzodiazepines and by fluid and electrolyte substitution. Cite as: Leben L, Brvar M. [Acute guarana poisoning: report of two cases]. Zdrav Vestn. 2018;87(5–6):297– 303. DOI: 10.6016/ZdravVestn.2724 1 Introduction Over the last few years a marked in- on memory and concentration improve- crease in the number of patients with ment, lower degree of fatigue, increased health problems due to overconsumpti- energy and alertness, migraine pain re- on of products containing caffeine has lief, burning of body fat and on decre- been noticed. This has resulted from the asing appetite. Additionally, guarana is increased offer of energy drinks, stimu- ascribed antibacterial and antioxidati- lants and other preparations containing ve properties, therefore it is believed to caffeine (1,2). In the general population have beneficial effects on numerous in- the guarana plant has become increasin- flammatory diseases. For its stimulating gly popular in various forms: capsules, effect it has long been used as a substi- tablets, powder, teas, syrups, energy tute for coffee. For all the enumerated drinks and vitamin drinks (1,3). effects it has become attractive, increa- Guarana is being promoted as a na- singly used, and widely known all over tural ingredient having various effects the world since 1958 (1,4). Acute guarana poisoning online edition – 1 METABOLIC AND HORMONAL DISORDERS Guarana, technical term being caffeine poisoning after guarana consu- Paullinia cupana, is a South American mption. climbing plant, named after the Indian tribe Guarani from the Amazon basin. It 2 Presentation of clinical has large leaves and clusters of flowers, cases but it is mostly known for its brown red- dish fruit containing black seeds envelo- ped in white coats (Figure 1) (1,5). 2.1 Clinical case 1 Active ingredient is prepared from unripe seeds extracted from fruits, shel- In order to increase his concentration led, and then roasted and ground; the and alertness for his studies, an 18-year- obtained powder is modelled with wa- -old student prepared himself a drink. ter into sticks that are dried and roasted Instead of 1/3 of a tea spoonful he took again – the product is then called pasta 3–4 spoonfuls of guarana powder which guaranae (6). corresponds to approximately 600–900 The constituent components of gua- mg of caffeine or to 8–11 cups of espres- rana seeds are shown in Table 1 (7). The so (one 60-ml cup of espresso contains high content of caffeine giving guarana about 80 mg of caffeine) or to 2–3 li- its stimulating effects should be stressed. tres of energy drink (100 ml of energy High doses, however, may cause health drink contains about 30 mg of caffeine). problems triggered by caffeine overdo- Less than two hours after drink intake, se (1). restlessness, strong heart beat, excessive Quite a few cases of guarana overdose sweating, headache, abdominal distensi- have been registered worldwide (2). The on, and diuresis occurred. Examination purpose of this paper is to present the at the internal medicine clinic of the patients treated at the Centre of Clinical Emergency Service, University Medical Toxicology and Pharmacology of the Centre Ljubljana, revealed increased he- University Medical Centre Ljubljana for art rate (120 beats per minute), increased blood pressure (150/90 mm Hg) and sli- ghtly widened pupils, other parameters Table 1: Guarana seed components (7). were normal. ECG showed a borderline prolonged QTc interval (464 ms), whe- Guarana seed components Number of particles of each component (parts per million; ppm) reas laboratory tests showed a slightly decreased potassium concentration (3.7 Caffeine 25.000–76.000 mmol/L). The patient was otherwise he- Theophylline 570 althy not taking any medications. Tannin 85.000–120.000 He was admitted to the ward where he received diazepam 5 mg perorally, Theobromine 200–400 other therapeutic measures were not Fats < 30.000 required. The next day he was free of any Proteins < 98.600 subjective health problems, the sings of Resin < 70.000 poisoning resolved and he was dischar- ged from hospital. Starch 50.000–60.000 Adenine, guanine, hypoxanthine, > 100.000 choline, D-catehcin 2 – online edition Zdrav Vestn | May – June 2018 | Volume 87 SHORT SCIENTIFIC ARTICLE predominant; guarana was just a supple- ment to overdosing. 3 Discussion The effect of guarana is mostly rela- ted to caffeine activity. Guarana contains twice as much caffeine as coffee beans (guarana seeds contain 2–4.5 % caffeine, coffee beans 1–2 % only). Guarana seeds contain numerous other substances, mo- stly theophylline and theobromine that increase caffeine activity. Due to conju- Figure 1: Guarana fruit (27). gation of caffeine with tannins that form hardly soluble complexes, caffeine from guarana is released into the blood circu- 2.2 Clinical case 2 lation much more slowly than caffeine from coffee. Therefore, its effect is more A 23-year-old man was consuming steady and long lasting; it perseveres for preparations for fitness containing gua- about 6 hours (1,8,9). rana over one week. Additionally, he was In therapeutic concentrations, caffe- extremely physically active that week. ine inhibits adenosine receptors, thus After one week he felt nauseous, had ir- increasing adenylate cyclase activity regular and strong heart beat, felt squee- and plasma cAMP concentration, which zing chest pain with tingling on both si- leads to increased activity of the sym- des of the body lasting for some seconds. pathetic nervous system, and this in- He did not report any other problems. creases the release of neurotransmitter ECG showed a slowed down heart transporters, catecholamines in particu- rhythm and non-specific elevation of the lar. The systemic vascular resistance and ST segment in leads V2-V4. Additionally, blood pressure increase, and alertness, an ultrasound scan of the heart and chest vigilance and concentration are more roentgenogram were made revealing no intense (1). Also, caffeine increases the abnormality. Toxicological analysis of synthesis of thromboxane and inhibits biological samples was not made. The thrombocyte aggregation (10). Blocking problems resolved in approximately adenosine receptors on juxtaglomerular two hours after the occurrence of symp- cells in the kidney, it affects increased toms; ECG normalized. The patient was renin release, which further increases advised to discontinue using the prepa- angiotensin and aldosterone concentra- rations that may trigger heart rhythm tions. This usually results in diuresis (1). problems (caffeine, theine, guarana and Adrenaline and caffeine act synergi- other stimulants). stically in increasing metabolism which There have been two cases of attemp- affects weight loss. In the liver, an addi- ted suicide with guarana overdose in tional amount of sugar is released into combination with other psychoactive the blood circulation and the body gets substances treated. In these two cases, more energy. Besides, caffeine activa- poisoning with other substances was tes hormone-sensitive lipase in the adi- pose tissue thus stimulating lipolysis. Acute guarana poisoning online edition – 3 METABOLIC AND HORMONAL DISORDERS Additionally, it stimulates peristalsis and flushing, excessive sweating, diuresis, ir- the activity of gall bladder, which results ritability of the intestines with frequent in quicker dissolution of fats, in increa- defecation (Table 2). Should the patient sed concentrations of free short-chain have at least 5 of the enumerated signs fatty acids in the large intestines which and symptoms, the diagnosis of poiso- may lead to diarrhoea, nausea, abdomi- ning with caffeine is in place (14,15,16). nal cramps and dehydration (11). As the cases we managed presented In toxic concentrations caffeine com- with most of the enumerated symptoms petitively inhibits phosphodiesterase, and signs, we presume that caffeine po- therefore its effects are more markedly isoning occurred, although toxicology expressed. Due to inhibition of this en- analysis of caffeine in the blood was not zyme in vascular smooth muscle cells, made. the amount of cAMP increases, which In excessive doses, caffeine affects car- increases the renin production and inhi- diac