Kola Nut-V by Douglas Laboratories

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Obesity. Oral cola nut has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in overweight and obese adults shows that taking cola nut 1500 mg daily for 3 months, in combination with ephedra and willow bark, modestly increases weight loss (12811). Other preliminary clinical research shows that taking an herbal treatment containing ephedra and cola nut for 6 months reduces body weight by 2.7 kg and body fat by 1.6 kg when compared with placebo in overweight and obese individuals (8647). Ephedra is banned in the US due to the risk for severe adverse effects (10055). More evidence is needed to rate cola nut for this use.

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LIKELY SAFE ...when used in amounts commonly found in foods. Cola nut extract has Generally Recognized As Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately, short-term. Cola nut has been used with apparent safety for up to 12 weeks (12811).

POSSIBLY UNSAFE ...when used orally, long-term, or in large amounts. Chewing cola nut is associated with an increased risk of mouth cancer and gastrointestinal cancer (11963). Cola nut also contains caffeine. Chronic use of caffeine, especially in large amounts, can sometimes produce tolerance, habituation, and psychological dependence (3719). Acute use of high doses, typically above 400 mg daily, has been associated with significant adverse effects such as tachyarrhythmia and sleep disturbances (11832). Abrupt discontinuance of caffeine can cause physical withdrawal symptoms (11733). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as cola nut, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.

PREGNANCY: POSSIBLY SAFE
when used orally in amounts found in foods. Due to the caffeine content of cola nut, pregnant patients should closely monitor their intake to ensure moderate consumption. Fetal blood concentrations of caffeine approximate maternal concentrations (4260). The use of caffeine during pregnancy is controversial; however, moderate consumption has not been associated with clinically important adverse fetal effects (2708,2709,2710,2711,9606,11733,16014,16015). In some studies, consuming amounts over 200 mg daily is associated with a significantly increased risk of miscarriage (16014). This increased risk may be most likely to occur in those with genotypes that confer a slow rate of caffeine metabolism (98806). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, most healthy pregnant patients can safely consume caffeine in doses up to 300 mg daily without an increased risk of spontaneous abortion, stillbirth, preterm birth, fetal growth retardation, or congenital malformations (11733,98806). Advise keeping caffeine consumption below 300 mg daily. This is similar to the amount of caffeine in about 3 cups of coffee or tea. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as cola nut, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.

PREGNANCY: POSSIBLY UNSAFE
when caffeine, a constituent of cola nut, is used orally in amounts over 300 mg daily. Caffeine crosses the placenta, producing fetal blood concentrations similar to maternal levels (4260). Advise keeping caffeine consumption from all sources below 300 mg daily (2708). High doses of caffeine throughout pregnancy have resulted in symptoms of caffeine withdrawal in newborn infants (9891). High doses of caffeine have also been associated with spontaneous abortion, premature delivery, and low birth weight (2709,2711,91033,91048,95949). Keep in mind that only the amount of added caffeine must be stated on product labels. The amount of caffeine found in ingredients such as cola nut, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. In a study that included 2 large cohorts of mother/infant pairs, the first cohort with a median maternal plasma caffeine level of 168.5 ng/mL (range 29.5-650.5 ng/mL) during pregnancy, suggests birth weights and lengths were lower in the 4th quartile of caffeine intake compared with the 1st. By age 7, heights and weights were lower by 1.5 cm and 1.1 kg, respectively. In the second cohort of mother/infant pairs with higher maternal pregnancy plasma caffeine levels, median 625.5 ng/mL (range 86.2 to 1994.7 ng/mL), heights at age 8 were 2.2 cm lower, but there was no difference in weights (109846).

LACTATION: POSSIBLY SAFE
when used orally in amounts found in foods. Due to the caffeine content of cola nut, caffeine intake should be closely monitored while nursing. Breast milk concentrations of caffeine are thought to be approximately 50% of maternal serum concentrations. Minimal consumption would likely result in limited exposure to a nursing infant (9892).

LACTATION: POSSIBLY UNSAFE
when used orally in large amounts. Consumption of cola nut might cause sleep disturbances, irritability, and increased bowel activity in nursing infants due to its caffeine content (6026). Large doses or excessive intake of cola nut should be avoided during lactation. It is unknown whether potentially carcinogenic constituents of cola nut are transferred via breast milk.

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ADENOSINE (Adenocard) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, cola nut might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.  Details Cola nut contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine (11771). It is recommended that methylxanthines and methylxanthine-containing products (including cola nut) be stopped 24 hours prior to pharmacological stress tests (11770). However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).

ALCOHOL (Ethanol) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, alcohol might increase the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Concomitant use of alcohol and caffeine can increase caffeine serum concentrations and the risk of caffeine adverse effects. Alcohol reduces caffeine metabolism (6370).

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, cola nut may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Cola nut contains caffeine. Caffeine is reported to have antiplatelet activity (8028,8029). This interaction has not been reported in humans.

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, taking cola nut with antidiabetes drugs might interfere with blood glucose control.  Details Cola nut contains caffeine. Some conflicting reports claim that caffeine might increase or decrease blood sugar (6024,8646).

BETA-ADRENERGIC AGONISTS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, the caffeine in cola nut might increase the clinical effects of beta-adrenergic agonists.  Details Cola nut contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase the cardiac inotropic effects of beta-agonists (15).

CARBAMAZEPINE (Tegretol) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cola nut might reduce the effects of carbamazepine and increase the risk for convulsions.  Details Cola nut contains caffeine. Animal research suggests that taking caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when taken in doses above 400 mg/kg (23559,23561). Human research has shown that taking caffeine 300 mg in three divided doses along with carbamazepine 200 mg reduces the bioavailability of carbamazepine by 32% and prolongs the plasma half-life of carbamazepine 2-fold in healthy individuals (23562).

CIMETIDINE (Tagamet) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, cimetidine might increase the effects and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Cimetidine decreases the rate of caffeine clearance by 31% to 42% (11736).

CLOZAPINE (Clozaril) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, cola nut might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.  Details Cola nut contains caffeine. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism (5051). Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients more sensitive to the interaction between clozapine and caffeine (13741).

CONTRACEPTIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, contraceptive drugs might increase the effects and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Oral contraceptives can decrease the rate of caffeine clearance by 40% to 65% (2714,11737).

CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, CYP1A2 inhibitors might increase the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Caffeine is metabolized by CYP1A2 (3941,5051,11741,23557,23573,23580,24958,24959,24960,24962), (24964,24965,24967,24968,24969,24971,38081,48603).

DIPYRIDAMOLE (Persantine) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, cola nut might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.  Details Cola nut contains caffeine. Caffeine may inhibit dipyridamole-induced vasodilation (11770,11772). It is recommended that methylxanthines and methylxanthine-containing products, such as cola nut, be stopped 24 hours prior to pharmacological stress tests (11770). Methylxanthines appear more likely to interfere with dipyridamole than with adenosine-induced stress testing (11771).

DISULFIRAM (Antabuse) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, disulfiram might increase the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. In human research, disulfiram decreases the rate of caffeine clearance (11840).

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, using cola nut with diuretic drugs might increase the risk of hypokalemia.  Details Cola nut contains caffeine. In excessive amounts, caffeine can reduce potassium levels due to stimulation of the sodium-potassium pump (23579,37905,37953,38003,38034). Certain diuretics can also lower potassium levels.

EPHEDRINE Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the risk for stimulant adverse effects.  Details Cola nut contains caffeine. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death (1275,6486,10307).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, estrogens might increase the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Estrogen inhibits caffeine metabolism (2714).

ETHOSUXIMIDE (Zarontin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cola nut might reduce the effects of ethosuximide and increase the risk for convulsions.  Details Cola nut contains caffeine. Animal research suggests that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide (23560). However, this effect has not been reported in humans

FELBAMATE (Felbatol) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cola nut might reduce the effects of felbamate and increase the risk for convulsions.  Details Cola nut contains caffeine. Animal research suggests that a high dose of caffeine 161.7 mg/kg can decreases the anticonvulsant activity of felbamate (23563). However, this effect has not been reported in humans.

FLUCONAZOLE (Diflucan) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, fluconazole might increase the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022).

FLUTAMIDE (Eulexin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cola nut might increase the levels and adverse effects of flutamide.  Details Cola nut contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide (23553). This effect has not been reported in humans.

FLUVOXAMINE (Luvox) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Theoretically, fluvoxamine might increase the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Fluvoxamine reduces caffeine metabolism (6370).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, abrupt cola nut withdrawal might increase the levels and adverse effects of lithium.  Details Cola nut contains caffeine. Abrupt caffeine withdrawal can increase serum lithium levels. There are two case reports of lithium tremor that worsened upon abrupt coffee withdrawal (609,610).

METFORMIN (Glucophage) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, metformin might increase the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Animal research suggests that metformin can reduce caffeine metabolism (23571).

METHOXSALEN (Oxsoralen) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, methoxsalen might increase the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Methoxsalen can reduce caffeine metabolism (23572).

MEXILETINE (Mexitil) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, mexiletine might increase the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Mexiletine can decrease caffeine elimination by 50% (1260,11741).

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the risk of a hypertensive crisis.  Details Cola nut contains caffeine. Caffeine has been shown to inhibit monoamine oxidase (MAO) A and B in laboratory studies (37724,37877,37912,38108). Concomitant intake of large amounts of caffeine with MAOIs might precipitate a hypertensive crisis (15). In a case report, a patient that consumed 10-12 cups of caffeinated coffee and took the MAOI tranylcypromine presented with severe hypertension (91086). Hypertension was resolved after the patient switched to drinking decaffeinated coffee.

NICOTINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use might increase the risk of hypertension.  Details Cola nut contains caffeine. Concomitant use of caffeine and nicotine has been shown to have additive cardiovascular effects, including increased heart rate and blood pressure. Blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly (36549).

PENTOBARBITAL (Nembutal) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, cola nut might decrease the effects of pentobarbital.  Details Cola nut contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).

PHENOBARBITAL (Luminal) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, cola nut might reduce the effects of phenobarbital and increase the risk for convulsions.  Details Cola nut contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital (23558,23559,23561). However, this effect has not been reported in humans.

PHENOTHIAZINES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, phenothiazines might increase the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Phenothiazines can reduce the metabolism of caffeine by inhibiting cytochrome P450 1A2 (CYP1A2) (23573,23574).

PHENYLPROPANOLAMINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure (11738). Phenylpropanolamine also seems to increase caffeine serum levels (13743).

PHENYTOIN (Dilantin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cola nut might reduce the effects of phenytoin and increase the risk for convulsions.  Details Cola nut contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenytoin (23559,23561). The effect does not seem to be related to the seizure threshold-lowering effects of caffeine. However, the exact mechanism of this interaction is unclear.

PIOGLITAZONE (Actos) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cola nut might increase the levels and clinical effects of pioglitazone.  Details Cola nut contains caffeine. Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This increased the antidiabetic effects of pioglitazone (108812). However, the exact mechanism of this interaction is unclear.

QUINOLONE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, quinolone antibiotics might increase the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Quinolones (also called fluoroquinolones) can decrease caffeine clearance by inhibiting cytochrome P450 1A2 (CYP1A2) (606,607,608,23554,23555,23556).

RILUZOLE (Rilutek) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.  Details Cola nut contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2, and concomitant use might reduce metabolism of one or both agents (11739).

STIMULANT DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Theoretically, concomitant use might increase stimulant adverse effects.  Details Cola nut contains caffeine. Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects (11832).

TERBINAFINE (Lamisil) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, terbinafine might increase the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. Terbinafine decreases the rate of intravenous caffeine clearance by 19% (11740).

THEOPHYLLINE Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, cola nut might increase the levels and adverse effects of theophylline.  Details Cola nut contains caffeine. Large amounts of caffeine might inhibit theophylline metabolism (11741).

TIAGABINE (Gabitril) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, cola nut might increase the levels and adverse effects of tiagabine.  Details Cola nut contains caffeine. Animal research suggests that chronic caffeine administration can increase the serum concentrations of tiagabine. However, concomitant use does not seem to reduce the antiepileptic effects of tiagabine (23561).

TICLOPIDINE (Ticlid) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, ticlopidine might increase the levels and adverse effects of the caffeine in cola nut.  Details Cola nut contains caffeine. In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.

VALPROATE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cola nut might reduce the effects of valproate and increase the risk for convulsions.  Details Cola nut contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of valproate (23558,23559,23561,37882). However, this effect has not been reported in humans.

VERAPAMIL (Calan, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the levels and adverse effects of both verapamil and caffeine.  Details Cola nut contains caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).

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General ...Orally, cola nut is well tolerated when eaten in the amounts found in food. It seems to be well tolerated when used medicinally and appropriately, short-term. However, the caffeine found in cola nut may cause adverse effects when taken in large amounts.
Most Common Adverse Effects:
Orally: Dyspepsia, skin discoloration.
Serious Adverse Effects (Rare):
Orally: Increased risk of oral cancer, gastrointestinal cancer, and West African crystalline retinopathy with long-term use.

Cardiovascular ...Orally, acute administration of caffeine can cause increased blood pressure. However, regular consumption of caffeine does not seem to increase either blood pressure or pulse, even in mildly hypertensive patients (1451,1452,2722). Epidemiological research suggests there is no association of caffeine consumption with incidence of hypertension (38190). Habitual coffee consumption also doesn't seem to be related to hypertension, but habitual consumption of sugared or diet cola is associated with development of hypertension (13739).
Epidemiological research has also found that regular caffeine intake of up to 400 mg daily is not associated with an increased incidence of atrial fibrillation (38018,38076,91028,91034,97451,97453), atherosclerosis (38033), cardiac ectopy (91127), stroke (37804), ventricular arrhythmia (95948,97453), or cardiovascular disease in general (37805,98806).

Dermatologic ...Orally, chewing cola nut has been reported to cause bright yellow skin pigmentation (57680).

Endocrine ...Some evidence shows that caffeine, which is found in cola nut, is associated with fibrocystic breast disease, breast cancer, and endometriosis; however, this is controversial since findings are conflicting (8043). Restricting caffeine in people with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain (8996). Also, a population analysis of the Women's Health Initiative observational study has found no association between consumption of caffeine-containing beverages and the incidence of invasive breast cancer in models adjusted for demographic, lifestyle, and reproductive factors (108806). Also, a dose-response analysis of two low-quality observational studies has found that high consumption of caffeine is not associated with an increased risk of breast cancer (108807).
Clinical research in healthy adults shows that increased consumption of caffeine results in increased insulin resistance (91023).

Gastrointestinal ...Orally, cola nut may induce gastric acid secretion and cause dyspepsia and peptic ulceration (57672,57674,57683). The caffeine found in cola nut may cause feeding intolerance and gastrointestinal irritation in infants (6023).

Genitourinary ...Orally, the caffeine in cola nut may increase voiding, give a sense of urgency, and irritate the bladder (37874,37961,104580). In males with lower urinary tract symptoms, caffeine intake increased the risk of interstitial cystitis/painful bladder syndrome (38115).

Immunologic ...Cola nut contains caffeine. Caffeine can cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).

Musculoskeletal ...Cola nut contains caffeine. Epidemiological evidence regarding the relationship between caffeine use and the risk for osteoporosis is contradictory. Caffeine can increase urinary excretion of calcium (2669,10202,11317). Females identified with a genetic variant of the vitamin D receptor appear to be at an increased risk for the detrimental effect of caffeine on bone mass (2669). However, moderate caffeine intake of less than 400 mg daily does not seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317,98806).

Neurologic/CNS ...Orally, cola nut may prolong sleep latencies and suppress REM and 3rd and 4th stages of sleep (57697). Cola nut has also been reported to cause insomnia in children (10755) and may exacerbate sleep disturbances in patients with acquired immunodeficiency syndrome (AIDS) (10204). Caffeine, a constituent of cola nut, can cause headaches, anxiety, jitteriness, restlessness, and nervousness (36466,37694,37755,37806,37865,37830,37889,38223,95952).

Ocular/Otic ...Orally, cola nut has been associated with an increased risk for West African crystalline retinopathy in one retrospective, observational case series (57667).
Cola nut contains caffeine. In individuals with glaucoma, caffeine intake has been found to increase intraocular pressure. This did not occur in patients without glaucoma (36462,36464,36465,37670). The magnitude of this effect seems to depend on individual tolerance to caffeine. Some research in healthy young adults shows that caffeine increases intraocular pressure to a greater degree in low-consumers of caffeine (i.e., 1 cup of coffee or less daily) when compared to high-consumers (i.e., those consuming 2 cups of coffee or more daily) (100371). The peak increase of intraocular pressure seems to occur at about 1.5 hours after caffeine ingestion, and there is no notable effect 4 hours after ingestion (36462,100371).

Oncologic ...Orally, chewing cola nut has been associated with an increased risk of oral and gastrointestinal cancer. Cola nut contains high amounts of tannins and N-nitroso compounds, which are carcinogenic. The risk may be even higher in smokers (11963).

Psychiatric ...Cola nut contains caffeine. Caffeine may lead to habituation and physical dependence with amounts as low as 100 mg daily (36353,36355). Higher doses of caffeine have caused nervousness, agitation, anxiety, irritability, delirium, depression, sleep disturbances, impaired attention, psychosis, and panic attacks (36505,37717,37818,37839,37857,37982,38004,38017,38028,38072). Abrupt discontinuation of caffeine may result in physical withdrawal symptoms, including headache, fatigue, drowsiness, decreased physical energy, difficulty concentrating, depression, anxiety, irritability, and reduced alertness (13738).

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