Ingredients | Amount Per Serving |
---|---|
Proprietary Blend
|
119.5 mg |
Bauhinia purpurea L. extract
(Bauhinia purpurea L.)
(leaf and pod)
|
|
(Bacopa monnieri )
(leaf)
|
|
Cirsium oligophyllum extract
(Cirsium oligophyllum )
(plant )
|
|
100 mg |
modified Starch, Gelatin, Vegetable Stearate, Silicon Dioxide (Alt. Name: SiO2), Red 3, Blue 1, Red 40, Titanium Dioxide color
This product contains 1,3-dimethylamylamine (DMAA), also known as methylhexanamine or geranium extract. There are serious safety concerns about DMAA. It is a stimulant that can potentially increase blood pressure and increase the risk of adverse cardiovascular events. DMAA-containing products have been linked to over 40 serious adverse event reports including adverse cardiovascular, metabolic, nervous system, and psychiatric events. Reports of death have also occurred (17660,17663,17904,17906,17907,17908,17958). In 2011, US Department of Defense (DoD) temporarily banned the sale of DMAA-containing supplements in military stores due to safety concerns. Sales of these products will be prohibited until the DoD investigates reports of potential serious adverse outcomes related to this product (17904,17909). On April 9, 2012, DMAA was also banned in New Zealand due to safety concerns (17960). Due to its stimulant effects, DMAA was added to the World Anti-Doping Agency's prohibited substances list for 2010. It is listed using the name methylhexaneamine on the prohibited list (17600).
Supplements that contain DMAA often list rose geranium oil, geranium oil, or geranium stems on the label. Some supplement manufacturers claim that this is because rose geranium oil contains a small amount of dimethylamylamine. However, this has not been verified by laboratory analysis. Some laboratories have not been able to detect dimethylamylamine in geranium oil. There is concern that some supplement manufacturers may be artificially spiking their supplements with this synthetic drug (17661,17662). In 2011, Health Canada determined that there is no credible evidence that DMAA is derived from the geranium plant. Therefore, DMAA is considered a drug and is not allowed in dietary supplements in Canada (17959).
For more information about DMAA, see the complete scientific monograph
This product has been discontinued by the manufacturer.
Below is general information about the effectiveness of the known ingredients contained in the product OxyElite Pro Super Thermogenic. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product OxyElite Pro Super Thermogenic. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY UNSAFE ...when used orally. 1,3-DMAA is a drug originally used as a stimulant nasal decongestant. There is concern that it increases the risk of serious adverse cardiovascular events, similar to other stimulants such as synephrine in bitter orange and ephedrine alkaloids from ephedra. There are several case reports linking 1,3-DMAA to serious adverse events including lactic acidosis, hemorrhagic stroke, heat stroke, and death (17599,17660,17662,17663,17904,94361,94369,94374). Although some supplement manufacturers claim that 1,3-DMAA is a natural compound found in geranium oil, this has not been verified by laboratory analysis. Some laboratories have not been able to detect 1,3-DMAA in geranium oil (94370,94372). There is concern that some supplement manufacturers may be artificially spiking their supplements with this synthetic drug (17661,17662). The New Zealand government restricted sales of supplements containing 1,3-DMAA to prevent the sale to people under 18 years of age due to concerns about safety (17599). The FDA has declared products containing 1,3-DMAA to be illegal and potential health risks (94383). Avoid using.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Bacopa has been used safely in clinical trials at a dose of up to 600 mg daily for up to 12 weeks (10058,10059,17946,97605).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Clinical research suggests bacopa extract might be safe to use at a dose of 225 mg daily for up to 6 months or 320 mg daily for up to 14 weeks in children aged 6-14 years (33304,97603,109625).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally, parenterally, or rectally and appropriately. Caffeine has Generally Recognized As Safe (GRAS) status in the US (4912,98806). Caffeine is also an FDA-approved product and a component of several over-the-counter and prescription products (4912,11832). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, doses of caffeine up to 400 mg daily are not associated with significant adverse cardiovascular, bone, behavioral, or reproductive effects in healthy adults (11733,98806). The US Dietary Guidelines Advisory Committee states that there is strong and consistent evidence that consumption of caffeine 400 mg daily is not associated with increased risk of major chronic diseases, such as cardiovascular disease or cancer, in healthy adults (98806). This amount of caffeine is similar to the amount of caffeine found in approximately 4 cups of coffee. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine from caffeine-containing natural ingredients such as coffee or green tea does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.
POSSIBLY UNSAFE ...when used orally, long-term or in high doses (91063). Chronic use, especially in large amounts, can produce tolerance, habituation, psychological dependence, and other adverse effects (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). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine from caffeine-containing natural ingredients such as coffee or green tea does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.
LIKELY UNSAFE ...when used orally in very high doses. The fatal acute oral dose of caffeine is estimated to be 10-14 grams (150-200 mg/kg). Serious toxicity can occur at lower doses depending on variables in caffeine sensitivity such as smoking, age, or prior caffeine use (11832,95700,97454,104573). Caffeine products sold to consumers in highly concentrated or pure formulations are considered to a serious health concern because these products have a risk of being used in very high doses. Concentrated liquid caffeine can contain about 2 grams of caffeine in a half cup. Powdered pure caffeine can contain about 3.2 grams of caffeine in one teaspoon. Powdered pure caffeine can be fatal in adults when used in doses of 2 tablespoons or less. As of 2018, these products are considered by the FDA to be unlawful when sold to consumers in bulk quantities (95700).
CHILDREN: POSSIBLY SAFE
when used orally or intravenously and appropriately in neonates under the guidance of a healthcare professional (6371,38340,38344,91084,91087,97452).
...when used orally in amounts commonly found in foods and beverages in children and adolescents (4912,11833,36555). Daily intake of caffeine in doses of less than 2.5 mg/kg daily are not associated with significant adverse effects in children and adolescents (11733,98806). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine from caffeine-containing natural ingredients such as coffee or green tea 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 commonly found in foods.
Intakes of caffeine should be monitored during pregnancy. Caffeine crosses the human placenta, but is not considered a teratogen (38048,38252,91032). Fetal blood and tissue levels are similar to maternal concentrations (4260). The use of caffeine during pregnancy is controversial; however, moderate consumption has not been associated with clinically important adverse fetal or parenteral effects (2708,2709,2710,2711,9606,16014,16015,98806,108814). In some studies consuming amounts over 200 mg daily is associated with a significantly increased risk of miscarriage (16014,37960). This increased risk seems 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, up to 300 mg daily can be consumed during pregnancy without an increased risk of spontaneous abortion, stillbirth, preterm birth, fetal growth retardation, or congenital malformations (11733,98806). However, observational research in a Norwegian cohort found that caffeine consumption is associated with a 16% increased odds of the baby being born small for gestational age when compared with no consumption (100369,103707). The same Norwegian cohort found that low to moderate caffeine consumption during pregnancy is not associated with changes in neurodevelopment in children up to 8 years of age (103699). Advise patients to keep caffeine consumption below 300 mg daily during pregnancy. This is similar to the amount of caffeine in about 3 cups of coffee or tea.
PREGNANCY: POSSIBLY UNSAFE
when used orally in amounts over 300 mg daily.
Caffeine crosses the placenta, producing fetal blood concentrations similar to maternal levels (4260,98806). Consumption of caffeine in amounts over 300 mg daily is associated with a significantly increased risk of miscarriage in some studies (16014,98806). Advise patients to keep caffeine consumption below 300 mg daily during pregnancy. This is similar to the amount of caffeine in about 3 cups of coffee or tea. Additionally, 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).
LACTATION: POSSIBLY SAFE
when used orally in amounts commonly found in foods.
Caffeine intake should be closely monitored while breast-feeding. During lactation, breast milk concentrations of caffeine are thought to be approximately 50% of serum concentrations and caffeine peaks in breastmilk approximately 1-2 hours after consumption (23590).
LACTATION: POSSIBLY UNSAFE
when used orally in large amounts.
Caffeine is excreted slowly in infants and may accumulate. Caffeine can cause sleep disturbances, irritability, and increased bowel activity in breast-fed infants exposed to caffeine (2708,6026).
POSSIBLY UNSAFE ...when used orally. There is insufficient reliable information available about the safety of rauwolscine. However, it is structurally similar to yohimbine, which has been associated with serious adverse effects including cardiac arrhythmia, agitation, myocardial infarction, seizure, and others (17465).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product OxyElite Pro Super Thermogenic. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
1,3-DMAA strongly inhibits cytochrome P450 2D6 (CYP2D6) enzymes in vitro (91878). Theoretically, 1,3-DMAA can increase levels of CYP2D6 substrates. Some of drugs that are CYP2D6 substrates include amitriptyline (Elavil), clozapine (Clozaril), codeine, desipramine (Norpramin), donepezil (Aricept), fentanyl (Duragesic), flecainide (Tambocor), fluoxetine (Prozac), meperidine (Demerol), methadone (Dolophine), metoprolol (Lopressor, Toprol XL), olanzapine (Zyprexa), ondansetron (Zofran), tramadol (Ultram), trazodone (Desyrel), and others.
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1,3-DMAA is thought to have stimulant effects (94367). There is concern that taking 1,3-DMAA with stimulant drugs might increase the risk of adverse cardiovascular effects. Some preliminary research shows that taking 1,3-DMAA 50 mg daily in combination with caffeine 250 mg daily does not increase respiratory rate, blood pressure, or other cardiovascular outcomes compared to taking caffeine alone in healthy men (94364). However, a number of cardiovascular side effects have been reported for patients taking 1,3-DMAA in combination with other stimulants including caffeine (17660,91680,94362,94365,94371,94377). Theoretically, combining 1,3-DMAA with stimulant drugs might increase the risk of adverse cardiovascular effects. Some stimulant drugs include amphetamine, caffeine, diethylpropion (Tenuate), methylphenidate, phentermine (Ionamin), pseudoephedrine (Sudafed, others), and many others.
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Theoretically, concurrent use might decrease the effectiveness of both agents.
Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels, which could counteract the effects of anticholinergic drugs (17946). Similarly, anticholinergic drugs might counteract the cholinergic effects of bacopa.
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Theoretically, bacopa might increase the effects and adverse effects of cevimeline.
In one case, a 58-year-old female taking cevimeline long-term for Sjogren syndrome experienced hyperhidrosis, malaise, nausea, and tachycardia shortly after taking a single dose of bacopa. Symptoms resolved after two days. Cevimeline is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4, and researchers theorize that bacopa may have inhibited these isoenzymes (109627). However, it is unclear if bacopa causes clinically significant inhibition of either CYP2D6 or CYP3A4.
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Theoretically, concurrent use of bacopa with other cholinergic drugs might have additive effects.
Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels (17946). Theoretically, this could result in additive cholinergic effects when used with cholinergic drugs.
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Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.
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Theoretically, bacopa might increase the levels and adverse effects of CYP2C19 substrates.
In vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C19 enzymes (97606). It is not known whether this is clinically significant.
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Theoretically, bacopa might increase the levels and adverse effects of CYP2C9 substrates.
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Theoretically, bacopa might increase the levels and adverse effects of CYP3A4 substrates.
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Theoretically, bacopa might have additive effects when used with thyroid hormone.
Animal research suggests that bacopa increases thyroxine (T4) levels in mice by about 40% (33286).
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Theoretically, caffeine might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Some evidence shows that caffeine is a competitive inhibitor of adenosine and can reduce the vasodilatory effects of adenosine in humans (38172). However, other research shows that 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 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).
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Theoretically, concomitant use might increase levels and adverse effects of caffeine.
Alcohol reduces caffeine metabolism. Concomitant use of alcohol can increase caffeine serum concentrations and the risk of caffeine adverse effects (6370).
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Theoretically, caffeine may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Theoretically, taking caffeine with antidiabetes drugs might interfere with blood glucose control.
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Theoretically, large amounts of caffeine might increase the cardiac inotropic effects of beta-agonists (15).
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Theoretically, caffeine might reduce the effects of carbamazepine and increase the risk for convulsions.
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).
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Theoretically, cimetidine might increase the levels and adverse effects of caffeine.
Cimetidine decreases the rate of caffeine clearance by 31% to 42% (11736).
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Caffeine might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Caffeine might increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg per day inhibit clozapine metabolism (5051). Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Although researchers speculate that caffeine might inhibit CYP1A2, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients more sensitive to an interaction between clozapine and caffeine (13741). In one case report, severe, life-threatening clozapine toxicity and multiorgan system failure occurred in a patient with schizophrenia stabilized on clozapine who consumed caffeine 600 mg daily (108817).
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Theoretically, contraceptive drugs might increase the levels and adverse effects of caffeine.
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Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
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Theoretically, caffeine might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Caffeine inhibits dipyridamole-induced vasodilation (11770,11772). It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests (11770). Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).
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Theoretically, disulfiram use might increase the levels and adverse effects of caffeine.
Disulfiram decreases the rate of caffeine clearance (11840).
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Theoretically, using caffeine with diuretic drugs might increase the risk of hypokalemia.
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Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Use of ephedrine with caffeine can increase the risk of stimulatory adverse effects. 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).
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Theoretically, estrogens might increase the levels and adverse effects of caffeine.
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Theoretically, caffeine might reduce the effects of ethosuximide and increase the risk for convulsions.
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.
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Theoretically, caffeine might reduce the effects of felbamate and increase the risk for convulsions.
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.
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Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
Fluconazole decreases caffeine clearance by approximately 25% (11022).
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Theoretically, caffeine might increase the levels and adverse effects of flutamide.
In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide (23553). However, this effect has not been reported in humans.
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Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Fluvoxamine reduces caffeine metabolism (6370).
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Theoretically, abrupt caffeine withdrawal might increase the levels and adverse effects of lithium.
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Theoretically, metformin might increase the levels and adverse effects of caffeine.
Animal research suggests that metformin can reduce caffeine metabolism (23571). However, this effect has not been reported in humans.
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Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.
Methoxsalen reduces caffeine metabolism (23572).
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Theoretically, mexiletine might increase the levels and adverse effects of caffeine.
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Theoretically, concomitant use might increase the risk of a hypertensive crisis.
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.
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Theoretically, concomitant use might increase the risk of hypertension.
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).
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Theoretically, caffeine might decrease the effects of pentobarbital.
Caffeine might negate the hypnotic effects of pentobarbital (13742).
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Theoretically, caffeine might reduce the effects of phenobarbital and increase the risk for convulsions.
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Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
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Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
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Theoretically, caffeine might reduce the effects of phenytoin and increase the risk for convulsions.
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Theoretically, caffeine might increase the levels and clinical effects of pioglitazone.
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.
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Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
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Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce the metabolism of one or both agents (11739).
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Theoretically, concomitant use might increase stimulant adverse effects.
Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects (11832).
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Theoretically, terbinafine might increase the levels and adverse effects of caffeine.
Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).
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Theoretically, caffeine might increase the levels and adverse effects of theophylline.
Large amounts of caffeine might inhibit theophylline metabolism (11741).
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Theoretically, caffeine might increase the levels and adverse effects of tiagabine.
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).
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Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.
In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.
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Theoretically, caffeine might reduce the effects of valproate and increase the risk for convulsions.
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Theoretically, verapamil might increase the levels and adverse effects of caffeine.
Verapamil increases plasma caffeine concentrations by 25% (11741).
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Theoretically, rauwolscine may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Theoretically, rauwolscine may have additive coronary vasodilatory effects if used with calcium channel blockers.
In vitro, rauwolscine inhibits calcium influx in aortic smooth muscle cells (103576).
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Theoretically, rauwolscine may inhibit the effects of clonidine.
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Theoretically, rauwolscine might increase levels of drugs metabolized by CYP2D6.
Rauwolscine is structurally related to yohimbine. In vitro research shows that yohimbine inhibits CYP2D6 enzyme activity (23117).
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Theoretically, taking rauwolscine with seizure threshold lowering drugs might increase the risk of adverse convulsant effects.
In animal research, intraperitoneal rauwolscine lowered the seizure threshold level of the drug metrazol (103574).
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Theoretically, taking rauwolscine with stimulant drugs might increase the risk of adverse stimulant effects.
Rauwolscine has demonstrated stimulant effects in animal research (103574).
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Below is general information about the adverse effects of the known ingredients contained in the product OxyElite Pro Super Thermogenic. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, taking 1,3-DMAA combination products (OxyELITE Pro, AmphetaLean, or Jack3d, USPlabs) has been reported to cause cardiac arrest, atrial fibrillation, chest pressure, angina, tachycardia, palpitations, hypertension, hypotension, myocardial infarction, and acute coronary syndrome (17660,91680,94361,94362,94365,94369,94371,94377).
Increased heart rate and blood pressure have also been reported. Other reported adverse effects associated with the use of 1,3-DMAA-containing products have included life-threatening lactic acidosis (17660), nausea, vomiting, diarrhea, and abdominal pain (17663,17907,17908,94365,94371,94377), urinary changes (17663,94365,94371,94377), liver injury (94367,94368,94369), anaphylaxis (94365), muscle symptoms such as spasm or weakness (94377), neurological symptoms including tremors, insomnia, sweating, tiredness, confusion, headache, and chills (17907,17663), hemorrhagic stroke (17663,90318), pupil dilation or tinnitus (94365,94371), psychiatric symptoms such as anxiety, agitation, paranoia, and aggression (17660,17907,94365,94371,94377), or rapid breathing (17660,94371). The dose of 1,3-DMAA at which such adverse effects occur is not clear (94368).
Death has occurred in some cases following organ failure and cardiac arrest (17904,94361,94369,94374).
Topically, rubbing an eye while mixing a drink with a 1,3-DMAA-containing combination product (Jack3d) has caused pupil dilation (94368).
Cardiovascular
...Due to the stimulant effects of 1,3-DMAA, there is concern that it might increase the risk of adverse cardiovascular events similar to synephrine from bitter orange or ephedrine from ephedra.
Cardiovascular outcomes have rarely been assessed in patients taking 1,3-DMAA alone. Most adverse effects are linked to 1,3-DMAA-containing combination products. Palpitations and tachycardia are some of the most common side effects reported for adults and children taking 1,3-DMAA-containing combination products (17660,91680,94365,94371). Other less common adverse effects have included chest pressure, angina, atrial fibrillation, hypertension, hypotension, myocardial infarction, and acute coronary syndrome (17660,91680,94362,94365,94371,94377).
There is inconsistent data about the effects of 1,3-DMAA on heart rate and blood pressure (94368). For example, some research suggests that taking specific 1,3-DMAA-containing combination products (OxyELITE Pro or Jack3d, USPlabs) significantly increases systolic blood pressure and increases heart rate within 1-2 hours of taking a dose. These increases appear to be dose dependent (17906,17907,17908). However, in an 8-week study, heart rate was significantly increased, but blood pressure was not (17907). Other research shows that neither acute nor chronic intake of 1,3-DMAA increases heart rate or blood pressure (17908,94364,94368,94376). Overall, it seems that oral intake of a single dose of a 1,3-DMAA-containing product is more likely to increase systolic blood pressure. Resting blood pressure is less likely to remain increased following chronic use (94368,94379). Higher doses are more likely to increase heart rate and blood pressure. Although most sports supplements contain 25-65 mg/dose, some contain as much as 285 mg/dose (94377).
In case reports of healthy young adults taking 1,3-DMAA-containing combination products prior to exercise, cardiac arrest causing death has occurred (94361,94369).
Endocrine ...In one report, a patient who took a specific combination product containing 1,3-DMAA (Jack3d by USP Labs) prior to intense exercise experienced life-threatening lactic acidosis (17660).
Gastrointestinal ...Orally, taking 1,3-DMAA-containing combination products has been reported to cause nausea (17907,17908,94365,94371,94377), vomiting (17663,94365,94371,94377), diarrhea (94365), vomiting blood (94371), and abdominal pain (94371).
Genitourinary ...Urinary hesitancy (94365), urinary retention (94371), and uncontrolled urination (94377), have been reported following ingestion of 1,3-DMAA-containing combination products.
Hepatic ...Acute liver injury, in some cases requiring a liver transplant, has been reported following oral intake of 1,3-DMAA-containing products (94367,94368,94369).
Immunologic ...An anaphylactic reaction has been reported following oral intake of 1,3-DMAA-containing products (94365).
Musculoskeletal ...Orally, dimethylamine-containing products have caused muscle spasm (94365), muscle weakness (94377), and leg pains (94377).
Neurologic/CNS ...Orally, taking specific 1,3-DMAA-containing combination products (OxyELITE Pro or Jack3d, USPlabs) has been reported to cause feelings of jitters, sleeplessness, shakiness, chills, sweating, fatigue, tingling, and lack of focus in clinical trials (17907). Other adverse effects reported for products containing 1,3-DMAA have included headache, dizziness, tremor, numbness, flushing, seizure, blacking out, visual disturbances, confusion, and lethargy (17660,17908,94365,94368,94371,94377). In a case report, a 26 year old male reported with a hemorrhagic stroke linked to taking the supplement Jack3d, which contains 1,3-DMAA, schizandrol A, caffeine, beta-alanine, creatine, and L-arginine alpha-ketoglutarate (90318). In another report, a patient experienced a hemorrhagic stroke after taking two tablets of a product containing 1,3-DMAA 278 mg each along with caffeine 150 mg and a can of beer (17663).
Ocular/Otic ...Orally, dimethylamine-containing products have caused tinnitus (94365) and pupil dilation (94371). Pupil dilation also occurred after rubbing an eye while mixing a drink with the specific product Jack3d, containing 1,3-DMAA (94368).
Psychiatric ...Orally, taking 1,3-DMAA-containing combination products has been reported to cause feelings of anxiety (17907,94365), suicidal behavior (94365), agitation or irritability (94365,94371,94377), paranoia (94377), depression (94377), panic (94377), and aggression or combativeness (17660,94365).
Pulmonary/Respiratory ...Orally, combination products containing 1,3-DMAA have caused rapid breathing and hyperventilation (17660,94371).
Other ...There are at least two reports of death in US Army soldiers who took 1,3-DMAA supplements and suffered heat stroke and related complications following physical fitness training (17904).
General
...Orally, bacopa is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, diarrhea, dry mouth, headache, nausea.
Cardiovascular ...Orally, bacopa has been reported to cause palpitations (10058).
Gastrointestinal ...Orally, bacopa has been reported to cause increased stool frequency in 30% of patients, nausea in 18% of patients, and abdominal cramps in 16% of patients in clinical trials (17946). It has also been reported to cause dry mouth, excessive thirst, indigestion, diarrhea, flatulence, bloating, and decreased appetite (10058,17946,97605). About 20% of patients taking an aqueous bacopa extract experienced abdominal pain and gastrointestinal disturbance in the early period of a 16-week trial (33295). In a 12-month clinical trial, around 18% and 12% of patients taking bacopa reported diarrhea and nausea, respectively (109623).
Musculoskeletal ...Orally, bacopa has been reported to cause arthralgia and muscle fatigue (10058,109623).
Neurologic/CNS ...Orally, bacopa has been reported to cause drowsiness, headache, insomnia, and vivid dreams (10058,10059,17946,109623).
Other ...Orally, bacopa has been reported to cause flu like symptoms and fatigue (10058,97605).
General
...Caffeine in moderate doses is typically well tolerated.
Most Common Adverse Effects:
Orally: Anxiety, dependence with chronic use, diarrhea, diuresis, gastric irritation, headache, insomnia, muscular tremors, nausea, and restlessness.
Serious Adverse Effects (Rare):
Orally: Stroke has been reported rarely.
Cardiovascular
...Caffeine can temporarily increase blood pressure.
Usually, blood pressure increases 30 minutes after ingestion, peaks in 1-2 hours, and remains elevated for over 4 hours (36539,37732,37989,38000,38300).
Although acute administration of caffeine can cause increased blood pressure, regular consumption does not seem to increase either blood pressure or pulse, even in mildly hypertensive patients (1451,1452,2722,38335). However, the form of caffeine may play a role in blood pressure increase after a more sustained caffeine use. In a pooled analysis of clinical trials, coffee intake was not associated with an increase in blood pressure, while ingesting caffeine 410 mg daily for at least 7 days modestly increased blood pressure by an average of 4.16/2.41 mmHg (37657). In one case, a 42-year-old male taking Hydroxycut, a product containing caffeine, garcinia, gymnema, green tea, glucomannan, guarana extract, and willow bark, 8 tablets daily for 3 weeks, presented with malignant hypertension and hypertensive retinopathy. He was stabilized after discontinuation of Hydroxycut and symptom management with metoprolol and hydralazine; hypertension was resolved at a four-week follow-up. The suspected causal agent was caffeine 800 mg daily, although the other ingredients cannot be ruled out (16527).
When used prior to intensive exercise, caffeine can increase systolic blood pressure by 7-8 mmHg (38308). The blood pressure-raising effects of caffeine are greater during stress (36479,38334) and after caffeine-abstinence of at least 24 hours (38241).
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 found that regular caffeine intake of up to 400 mg daily is not associated with increased incidence of atrial fibrillation (38018,38076,91028,91034,97451,97453,103708), atherosclerosis (38033), cardiac ectopy (91127), stroke (37804), ventricular arrhythmia (95948,97453), and cardiovascular disease in general (37805,98806). One clinical trial shows that in adults with diagnosed heart failure, consumption of 500 mg of coffee does not result in an increased risk for arrhythmia during exercise (95950). However, caffeine intake may pose a greater cardiovascular risk to subjects that are not regular users of caffeine. For example, in one population study, caffeinated coffee consumption was associated with an increased risk of ischemic stroke in subjects that don't regularly drink coffee (38102). In a population study in Japanese subjects, caffeine-containing medication use was modestly associated with hemorrhagic stroke in adults that do not consume caffeine regularly (91059).
The most common side effect of caffeine in neonates receiving caffeine for apnea is tachycardia (98807).
Dermatologic ...There are several case reports of urticaria after caffeine ingestion (36546,36448,36475).
Endocrine
...Some evidence shows caffeine is associated with fibrocystic breast disease or breast cancer in females; however, this is controversial since findings are conflicting (8043,108806).
Restricting caffeine in females with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain (8996). 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 2 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 an increase consumption of caffeine results in increased insulin resistance (91023).
Gastrointestinal ...Gastrointestinal upset, nausea, diarrhea, abdominal pain, and fecal incontinence may occur with caffeine intake (36466,37755,37806,37789,37830,38138,38136,38223,95956,95963). Also, caffeine may cause feeding intolerance and gastrointestinal irritation in infants (6023). Perioperative caffeine during cardiopulmonary bypass surgery seems to increase the rate of postoperative nausea and vomiting (97451). Caffeine and coffee consumption have been associated with an increase in the incidence of heartburn (37545,37575,38251,38259,38267) and gastrointestinal esophageal reflux disease (GERD) (38329,37633,37631,37603).
Genitourinary ...Caffeine, a known diuretic, may increase voiding, give a sense of urgency, and irritate the bladder (37874,37961,104580). In men with lower urinary tract symptoms, caffeine intake increased the risk of interstitial cystitis/painful bladder syndrome (38115). Excessive caffeine consumption may worsen premenstrual syndrome. Consumption of up to 10 cups of caffeinated drinks daily was associated with increased severity of premenstrual syndrome (38177). Finally, population research shows that exposure to caffeine was not associated with an increased risk of endometriosis (91035).
Immunologic ...Caffeine can cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).
Musculoskeletal
...Caffeine can induce or exacerbate muscular tremors (38136,37673,38161).
There has also been a report of severe rhabdomyolysis in a healthy 40-year-old patient who consumed an energy drink containing 400 mg of caffeine (4 mg/kg) and then participated in strenuous weightlifting exercise (108818).
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, less than 300 mg daily, does not seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317).
Neurologic/CNS ...Caffeine can cause headaches, anxiety, jitteriness, restlessness, and nervousness (36466,37694,37755,37806,37865,37830,37889,38223,95952). In adolescents, there is an inverse correlation between the consumption of caffeine and various measurements of cognitive function (104579). Insomnia is a frequent adverse effect in children (10755). Caffeine may result in insomnia and sleep disturbances in adults as well (36445,36483,36512,36531,37598,37795,37819,37862,37864,37890)(37968,37971,38091,38242,91022,92952). Additionally, caffeine may exacerbate sleep disturbances in patients with acquired immunodeficiency syndrome (AIDS) (10204). Combining ephedra with caffeine can increase the risk of adverse effects. Jitteriness, hypertension, seizures, temporary loss of consciousness, and hospitalization requiring life support has been associated with the combined use of ephedra and caffeine (2729). Finally, epidemiological research suggests that consuming more than 190 mg of caffeine daily is associated with an earlier onset of Huntington disease by 3.6 years (91078).
Ocular/Otic
...In individuals with glaucoma, coffee consumption and caffeine intake has been found to increase intraocular pressure (8540,36464,36465,37670).
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 ...Most human studies which have examined caffeine or methylxanthine intake have found that they do not play a role in the development of various cancers, including breast, ovarian, brain, colon, rectal, or bladder cancer (37641,37737,37775,37900,38050,38169,38220,91054,91076,108806).
Psychiatric
...Caffeine may lead to habituation and physical dependence (36355,36453,36512,36599), with amounts as low as 100 mg daily (36355,36453).
An estimated 9% to 30% of caffeine consumers could be considered addicted to caffeine (36355). Higher doses of caffeine have caused nervousness, agitation, anxiety, irritability, delirium, depression, sleep disturbances, impaired attention, manic behavior, psychosis and panic attacks (36505,37717,37818,37839,37857,37982,38004,38017,38028,38072)(38079,38138,38306,38325,38331,38332,97464). Similar symptoms have been reported in a caffeine-naïve individual experiencing fatigue and dehydration after a dose of only 200 mg, with resolution of symptoms occurring within 2 hours (95952).
Withdrawal: The existence or clinical importance of caffeine withdrawal is controversial. Some researchers think that if it exists, it appears to be of little clinical significance (11839). Headache is the most common symptom, due to cerebral vasodilation and increased blood flow (37769,37991,37998). Other researchers suggest symptoms such as tiredness and fatigue, decreased energy, alertness and attentiveness, drowsiness, decreased contentedness, depressed mood, difficulty concentration, irritability, and lack of clear-headedness are typical of caffeine withdrawal (13738). Withdrawal symptoms typically occur 12-24 hours after the last dose of caffeine and peak around 48 hours (37769,36600). Symptoms may persist for 2-9 days. Withdrawal symptoms such as delirium, nausea, vomiting, rhinorrhea, nervousness, restlessness, anxiety, muscle tension, muscle pains, and flushed face have been described. However, these symptoms may be from nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839). In a case report, caffeine consumption of 560 mg daily was associated with increased suicidality (91082).
Renal ...Clinical research shows that caffeine consumption may increase the risk of calcium oxalate stone formation (37634).
Other ...People with voice disorders, singers, and other voice professionals are often advised against the use of caffeine; however, this recommendation has been based on anecdotal evidence. One small exploratory study suggests that caffeine ingestion may adversely affect subjective voice quality, although there appears to be significant intra-individual variability. Further study is necessary to confirm these preliminary findings (2724).
General
...Orally, no adverse effects have been reported.
However, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: A related chemical, yohimbine, has been reported to cause serious adverse effects, such as loss of consciousness, paralysis, seizures, and vertigo.
Dermatologic ...Since rauwolscine is structurally related to yohimbine, rauwolscine might theoretically cause similar adverse effects. Yohimbine may cause rash, erythrodermic skin eruption, and exanthema (3312,3971,86878,86896).
Gastrointestinal ...Since rauwolscine is structurally related to yohimbine, rauwolscine might theoretically cause similar adverse effects. Nausea, vomiting, increased salivation, diarrhea, and gastrointestinal distress may occur with yohimbine use (3970,17465,86780,86786,86804,86827,86896).
Genitourinary ...Since rauwolscine is structurally related to yohimbine, rauwolscine might theoretically cause similar adverse effects. Orally, yohimbine may cause dartos contraction or decreased libido in some patients (86786,86882).
Immunologic ...Since rauwolscine is structurally related to yohimbine, rauwolscine might theoretically cause similar adverse effects. There is one report of a hypersensitivity reaction including fever, chills, malaise, itchy and scaly skin, progressive renal failure, and lupus-like syndrome associated with ingestion of a one-day dose of yohimbine (6169).
Neurologic/CNS ...Since rauwolscine is structurally related to yohimbine, rauwolscine might theoretically cause similar adverse effects. Orally, yohimbine has been associated with reports of tremulousness, head twitching, seizures, loss of consciousness, enhanced brain norepinephrine release, decreased energy, dizziness, vertigo, headache, feeling cold, flushing, diaphoresis, and paralysis (11,18,3312,3971,17465,86786,86801,86804,86827,86896).
Psychiatric ...Since rauwolscine is structurally related to yohimbine, rauwolscine might theoretically cause similar adverse effects. Orally, yohimbine may cause anxiety (17465) and impulsivity (86784,86810).
Pulmonary/Respiratory ...Since rauwolscine is structurally related to yohimbine, rauwolscine might theoretically cause similar adverse effects. Orally, yohimbine may cause bronchospasm, tachypnea, cough, sinusitis, and rhinorrhea (17465,86825,86850,94112).
Renal ...Since rauwolscine is structurally related to yohimbine, rauwolscine might theoretically cause similar adverse effects. A case of acute renal failure related to yohimbine-induced systemic lupus erythematosus has been reported (6169).