| Ingredients | Amount Per Serving |
|---|---|
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(Ca)
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140 mg |
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(Na)
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10 mg |
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PureXen Green Coffee Blend
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800 mg |
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(Chlorogenic Acid, Coffea canephora var. robusta)
(standardized for 5% chlorogenic acids)
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(Chlorogenic Acid, Coffea canephora var. robusta)
(standardized for 45% chlorogenic acids)
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Microcrystalline Cellulose, Dicalcium Phosphate Dihydrate, Hydroxypropyl Cellulose (Alt. Name: HPC), Croscarmellose Sodium, Magnesium Stearate (Alt. Name: Mg Stearate), Stearic Acid (Alt. Name: C18:0), Silicon Dioxide (Alt. Name: SiO2), Hypromellose, Glycerin
Below is general information about the effectiveness of the known ingredients contained in the product Green Coffee+. 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
Below is general information about the safety of the known ingredients contained in the product Green Coffee+. 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 SAFE ...when used orally or intravenously and appropriately. Calcium is safe when used in appropriate doses (7555,12928,12946,95817). However, excessive doses should be avoided. The Institute of Medicine sets the daily tolerable upper intake level (UL) for calcium according to age as follows: Age 0-6 months, 1000 mg; 6-12 months, 1500 mg; 1-8 years, 2500 mg; 9-18 years, 3000 mg; 19-50 years, 2500 mg; 51+ years, 2000 mg (17506). Doses over these levels can increase the risk of side effects such as kidney stone, hypercalciuria, hypercalcemia, and milk-alkali syndrome. There has also been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI). Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these studies, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). Many of these trials also only included postmenopausal females. Other analyses report conflicting results, and have not shown that calcium intake affects the risk of CVD, CHD, or MI (92994,93533,97308,107231). Advise patients not to consume more than the recommended daily intake of 1000-1200 mg per day and to consider total calcium intake from both dietary and supplemental sources (17484). Also, advise patients taking calcium supplements to take calcium along with vitamin D (93533).
POSSIBLY UNSAFE ...when used orally in excessive doses. The National Academy of Medicine sets the daily tolerable upper intake level (UL) for calcium according to age as follows: 19-50 years, 2500 mg; 51 years and older, 2000 mg (17506). Doses over these levels can increase the risk of side effects such as kidney stones, hypercalciuria, hypercalcemia, and milk-alkali syndrome. There has also been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI). Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these studies, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). Many of these trials also only included postmenopausal females. Other analyses report conflicting results, and have not shown that calcium intake affects the risk of CVD, CHD, or MI (92994,93533,97308,107231). Advise patients to not consume more than the recommended daily intake of 1000-1200 mg per day and to consider total calcium intake from both dietary and supplemental sources (17484). Also, advise patients taking calcium supplements to take calcium along with vitamin D (93533).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Calcium is safe when used in appropriate doses (17506).
CHILDREN: POSSIBLY UNSAFE
when used orally in excessive doses.
The Institute of Medicine sets the daily tolerable upper intake level (UL) for calcium according to age as follows: 0-6 months, 1000 mg; 6-12 months, 1500 mg; 1-8 years, 2500 mg; 9-18 years, 3000 mg (17506). Doses over these levels can increase the risk of side effects such as kidney stones, hypercalciuria, hypercalcemia, and milk-alkali syndrome.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately (945,1586,3263,3264,17506).
The World Health Organization (WHO) recommends prescribing oral calcium supplementation 1.5-2 grams daily during pregnancy to those with low dietary calcium intake to prevent pre-eclampsia (97347).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses.
The Institute of Medicine sets the same daily tolerable upper intake level (UL) for calcium according to age independent of pregnancy status: 9-18 years, 3000 mg; 19-50 years, 2500 mg (17506). Doses over these amounts might increase the risk of neonatal hypocalcemia-induced seizures possibly caused by transient neonatal hypoparathyroidism in the setting of excessive calcium supplementation during pregnancy, especially during the third trimester. Neonatal hypocalcemia is a risk factor for neonatal seizures (97345).
LIKELY SAFE ...when used orally and appropriately. Drinking decaffeinated coffee or coffee containing caffeine in low to moderate amounts is safe (15,98806). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, drinking up to 4 cups of coffee daily providing caffeine 400 mg daily is 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 beverages such as coffee that contain caffeine 400 mg daily is not associated with increased risk of major chronic diseases, such as cardiovascular disease or cancer, in healthy adults (98806).
POSSIBLY UNSAFE ...when used orally in excessive amounts. Acute use of high doses of caffeine (more than 400 mg per day), which is found in more than 4 cups of caffeinated coffee, has been associated with significant adverse effects such as tachyarrhythmia and sleep disturbances (11832). Drinking caffeinated coffee in amounts greater than 6 cups per day (about 600 mg caffeine) short-term or long-term can also cause caffeinism, with symptoms of anxiety possibly progressing to delirium and agitation. Chronic use of caffeine, especially in large amounts, can sometimes produce tolerance, habituation, and psychological dependence (3719). 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 coffee, 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. ...when used rectally as an enema. Coffee enemas have been linked to cases of severe electrolyte abnormalities and septicemia leading to severe side effects including death (3026,3347,3349,6652).
CHILDREN: POSSIBLY SAFE
when coffee containing caffeine is consumed orally in moderate amounts.
Oral intake of caffeine in doses of less than 2.5 mg/kg daily is not associated with significant adverse effects in children and adolescents (11733,98806). However, higher doses should be avoided. The adverse effects typically associated with caffeine-containing coffee are usually more severe in children than adults (11733).
PREGNANCY: POSSIBLY SAFE
when used orally in moderate amounts.
Intake of caffeine from coffee and other sources should be monitored during pregnancy. Caffeine crosses the human placenta, but is not considered a teratogen. 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 effects (2708,2709,2710,2711,9606,11733,16014,16015). However, some research has also found that intrauterine exposure to even modest amounts of caffeine, based on maternal blood levels during the first trimester, is associated with a shorter stature in children ages 4-8 years (109846). In some studies, consuming amounts over 200 mg daily has been associated with a significantly increased risk of miscarriage (16014). This increased risk may be most likely to occur in people 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 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. 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 coffee, 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 caffeinated coffee providing more than 300 mg of caffeine daily is consumed orally.
Caffeine from coffee crosses the placenta, producing fetal blood concentrations similar to maternal levels (4260). 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 from all sources below 300 mg daily during pregnancy. This is similar to the amount of caffeine in about 3 cups of coffee. 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). Drinking more than 6 cups of coffee daily increases the risk of spontaneous abortion (2709). Drinking 8 or more cups of coffee daily doubles the risk of stillbirth when compared with those who do not drink coffee during pregnancy (10621).
LACTATION: POSSIBLY SAFE
when used orally.
Drinking one or two caffeine-containing beverages daily during lactation is not associated with unacceptable levels of caffeine in human milk (11734).
LACTATION: POSSIBLY UNSAFE
when used orally in large amounts.
Caffeine from coffee can cause wakefulness or irritability in breast-fed infants. Caffeine can also cause feeding intolerance and gastrointestinal irritation in infants (6026).
LIKELY SAFE ...when used orally and appropriately. Sodium is safe in amounts that do not exceed the Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams daily (100310). Higher doses can be safely used therapeutically with appropriate medical monitoring (26226,26227).
POSSIBLY UNSAFE ...when used orally in high doses. Tell patients to avoid exceeding the CDRR intake level of 2.3 grams daily (100310). Higher intake can cause hypertension and increase the risk of cardiovascular disease (26229,98176,98177,98178,98181,98183,98184,100310,109395,109396,109398,109399). There is insufficient reliable information available about the safety of sodium when used topically.
CHILDREN: LIKELY SAFE
when used orally and appropriately (26229,100310).
Sodium is safe in amounts that do not exceed the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310).
CHILDREN: POSSIBLY UNSAFE
when used orally in high doses.
Tell patients to avoid prolonged use of doses exceeding the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310). Higher intake can cause hypertension (26229).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Sodium is safe in amounts that do not exceed the CDRR intake level of 2.3 grams daily (100310).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in higher doses.
Higher intake can cause hypertension (100310). Also, both the highest and the lowest pre-pregnancy sodium quintile intakes are associated with an increased risk of hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, and the delivery of small for gestational age (SGA) infants when compared to the middle intake quintile (106264).
Below is general information about the interactions of the known ingredients contained in the product Green Coffee+. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Calcium citrate might increase aluminum absorption and toxicity. Other types of calcium do not increase aluminum absorption.
 Details
Calcium citrate can increase the absorption of aluminum when taken with aluminum hydroxide. The increase in aluminum levels may become toxic, particularly in individuals with kidney disease (21631). However, the effect of calcium citrate on aluminum absorption is due to the citrate anion rather than calcium cation. Calcium acetate does not appear to increase aluminum absorption (93006).
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Calcium reduces the absorption of bisphosphonates.
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Advise patients to take bisphosphonates at least 30 minutes before calcium, but preferably at a different time of day. Calcium supplements decrease absorption of bisphosphonates (12937).
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Taking calcipotriene with calcium might increase the risk for hypercalcemia.
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Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia (12938). Theoretically, combining calcipotriene with calcium supplements might increase the risk of hypercalcemia.
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Intravenous calcium may decrease the effects of calcium channel blockers; oral calcium is unlikely to have this effect.
Details
Intravenous calcium is used to decrease the effects of calcium channel blockers in the management of overdose. Intravenous calcium gluconate has been used before intravenous verapamil (Isoptin) to prevent or reduce the hypotensive effects without affecting the antiarrhythmic effects (6124). But there is no evidence that dietary or supplemental calcium when taken orally interacts with calcium channel blockers (12939,12947).
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Co-administration of intravenous calcium and ceftriaxone can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys.
Details
Avoid administering intravenous calcium in any form, such as parenteral nutrition or Lactated Ringers, within 48 hours of intravenous ceftriaxone. Case reports in neonates show that administering intravenous ceftriaxone and calcium can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys. In several cases, neonates have died as a result of this interaction (15794,21632). So far there are no reports in adults; however, there is still concern that this interaction might occur in adults.
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Using intravenous calcium with digoxin might increase the risk of fatal cardiac arrhythmias.
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Theoretically, calcium may reduce the therapeutic effects of diltiazem.
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Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation (10574). Theoretically, calcium might increase this risk of hypercalcemia and reduce the effectiveness of diltiazem.
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Calcium seems to reduce levels of dolutegravir.
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Advise patients to take dolutegravir either 2 hours before or 6 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium carbonate 1200 mg concomitantly with dolutegravir 50 mg reduces plasma levels of dolutegravir by almost 40%. Calcium appears to decrease levels of dolutegravir through chelation (93578).
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Calcium seems to reduce levels of elvitegravir.
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Advise patients to take elvitegravir either 2 hours before or 2 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium along with elvitegravir can reduce blood levels of elvitegravir through chelation (94166).
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Calcium seems to reduce the absorption and effectiveness of levothyroxine.
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Theoretically, concomitant use of calcium and lithium may increase this risk of hypercalcemia.
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Clinical research suggests that long-term use of lithium may cause hypercalcemia in 10% to 60% of patients (38953). Theoretically, concomitant use of lithium and calcium supplements may further increase this risk.
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Calcium seems to reduce the absorption of quinolone antibiotics.
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Calcium may reduce levels of raltegravir.
Details
Pharmacokinetic research shows that taking a single dose of calcium carbonate 3000 mg along with raltegravir 400 mg twice daily modestly decreases the mean area under the curve of raltegravir, but the decrease does not necessitate a dose adjustment of raltegravir (94164). However, a case of elevated HIV-1 RNA levels and documented resistance to raltegravir has been reported for a patient taking calcium carbonate 1 gram three times daily plus vitamin D3 (cholecalciferol) 400 IU three times daily in combination with raltegravir 400 mg twice daily for 11 months. It is thought that calcium reduced raltegravir levels by chelation, leading to treatment failure (94165).
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Calcium seems to reduce the absorption of sotalol.
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Advise patients to separate doses by at least 2 hours before or 4-6 hours after calcium. Calcium appears to reduce the absorption of sotalol, probably by forming insoluble complexes (10018).
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Calcium seems to reduce the absorption of tetracycline antibiotics.
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Advise patients to take oral tetracyclines at least 2 hours before, or 4-6 hours after calcium supplements. Taking calcium at the same time as oral tetracyclines can reduce tetracycline absorption. Calcium binds to tetracyclines in the gut (1843).
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Taking calcium along with thiazides might increase the risk of hypercalcemia and renal failure.
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Thiazides reduce calcium excretion by the kidneys (1902). Using thiazides along with moderately large amounts of calcium carbonate increases the risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, renal failure). Patients may need to have their serum calcium levels and/or parathyroid function monitored regularly.
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Theoretically, calcium may reduce the therapeutic effects of verapamil.
Details
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation (10574). Theoretically, use of calcium supplements may increase this risk of hypercalcemia and reduce the effectiveness of verapamil.
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Theoretically, coffee might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Details
Coffee contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level (38172). 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 such as caffeine, as well as 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, alcohol might increase the levels and adverse effects of caffeine.
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Coffee reduces alendronate bioavailability.
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Separate coffee ingestion and alendronate administration by two hours. Coffee reduces alendronate bioavailability by 60% (11735).
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Theoretically, coffee may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
Coffee contains caffeine. Caffeine is reported to have antiplatelet activity (8028,8029). Theoretically, the caffeine in coffee might increase the risk of bleeding when used concomitantly with these agents. However, this interaction has not been reported in humans. There is some evidence that caffeinated coffee might increase the fibrinolytic activity in blood (8030).
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Theoretically, concomitant use of coffee and antidiabetes drugs might interfere with blood glucose control.
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Theoretically, concomitant use of large amounts of coffee might increase cardiac inotropic effects of beta-agonists.
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Coffee contains caffeine. Caffeine can increase cardiac inotropic effects of beta-agonists (15).
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Theoretically, cimetidine might increase the effects and adverse effects of caffeine in coffee.
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Theoretically, coffee might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
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Coffee 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 be more sensitive to the interaction between clozapine and caffeine (13741).
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Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in coffee.
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Theoretically, coffee might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Details
Coffee contains caffeine. Caffeine is a methylxyanthine that may inhibit dipyridamole-induced vasodilation (11770,11772,24974,37985,53795). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products such as coffee, 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 might increase the risk of adverse effects from caffeine.
Details
Coffee contains caffeine. In human research, disulfiram decreases the clearance and increases the half-life of caffeine (11840).
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Theoretically, concomitant use might increase the risk of hypokalemia.
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Theoretically, concomitant use might increase the risk of stimulant adverse effects.
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Coffee 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 (1275,6486,9740,10307). Tell patients to avoid taking caffeine with ephedrine and other stimulants.
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Theoretically, estrogens might increase the levels and adverse effects of caffeine.
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Coffee contains caffeine. Estrogen inhibits caffeine metabolism (2714).
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Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
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Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
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Coffee consumption can decrease the levels and clinical effects of lamotrigine.
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A pharmacokinetic study in patients taking lamotrigine shows that consumption of coffee, both caffeinated and decaffeinated, can decrease the area under the concentration-time curve (AUC) and the peak plasma level (Cmax) of lamotrigine. Each additional cup of coffee reduced the AUC and Cmax by 4% and 3%, respectively. It is unclear whether this interaction is due to induction of lamotrigine metabolism or inhibition of lamotrigine absorption (107837).
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Coffee can reduce the absorption of levothyroxine.
Details
In some patients, coffee can reduce levothyroxine absorption, possibly through the formation of non-absorbable complexes. A pharmacokinetic study in these patients found that 25-30 mL of espresso coffee consumed with levothyroxine tablets delayed the time to peak plasma levels by 38-43 minutes, reduced the peak plasma level (Cmax) by 19% to 36%, and reduced the area under the curve (AUC) by 27% to 36%. Coffee consumed one hour after levothyroxine did not affect absorption (16401). It is not known whether this interaction occurs with other types of coffee. Tell patients to avoid drinking coffee at the same time that they take their levothyroxine, and for up to an hour afterwards.
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Theoretically, abrupt coffee withdrawal might increase the levels and adverse effects of lithium.
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Coffee contains caffeine. Abrupt caffeine withdrawal can increase serum lithium levels (609). Two cases of lithium tremor that worsened with abrupt coffee withdrawal have been reported (609,610). There is also one case of a 2.8-fold increase in blood lithium levels after a patient taking lithium reduced his coffee consumption from 13-20 cups daily to 10 cups daily (97369).
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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.
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Coffee 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.
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Theoretically, concomitant use might increase the risk of hypertension.
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Coffee 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).
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Theoretically, coffee might reduce the effects of pentobarbital.
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Coffee contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).
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Theoretically, phenothiazines might increase the levels and adverse effects of caffeine. Also, coffee may bind to phenothiazines and reduce their absorption.
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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, coffee might increase the levels and clinical effects of pioglitazone.
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Coffee 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.
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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.
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Coffee contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce metabolism of one or both agents (11739).
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Theoretically, concomitant use might increase stimulant adverse effects.
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Coffee 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).
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Theoretically, terbinafine might increase the levels and adverse effects of caffeine.
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Coffee contains caffeine. Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).
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Theoretically, coffee might increase the levels and adverse effects of theophylline.
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Theoretically, TCAs might bind with coffee constituents when taken at the same time.
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Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
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Coffee contains caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).
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Theoretically, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.
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Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.
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Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone (4425).
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Altering dietary intake of sodium might alter the levels and clinical effects of lithium.
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High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion (26225). Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate (26224,26225). Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L (112909). Patients taking lithium should avoid significant alterations in their dietary intake of sodium.
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Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related complications.
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The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population (100310). Some medications contain high quantities of sodium. When used in conjunction with sodium supplements or high-sodium diets, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.
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Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.
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Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia (29406). Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.
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Below is general information about the adverse effects of the known ingredients contained in the product Green Coffee+. 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 and intravenously, calcium is well-tolerated when used appropriately.
Most Common Adverse Effects:
Orally: Belching, constipation, diarrhea, flatulence, and stomach upset.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about calciphylaxis and kidney stones.
Cardiovascular
...There has been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI).
Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these results, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). Many of these trials also only included postmenopausal females. Other analyses report conflicting results, and have not shown that calcium intake affects the risk of CVD, CHD, or MI (92994,93533,97308,107231). Reasons for these discrepancies are not entirely clear. It may relate to whether calcium is taken as monotherapy or in combination with vitamin D. When taken with vitamin D, which is commonly recommended, calcium supplementation does not appear to be associated with an increased risk of CVD, CHD, or MI (93533,107231). Also, the association between calcium supplementation and CVD, CHD, or MI risk may be influenced by the amount of calcium consumed as part of the diet. Supplementation with calcium may be associated with an increased risk of MI in people with dietary calcium intake above 805 mg daily, but not in those with dietary calcium intake below 805 mg daily (17482). To minimize the possible risk of CVD, CHD, or MI, advise patients not to consume more than the recommended daily intake of 1000-1200 mg and to consider total calcium intake from both dietary and supplemental sources (17484). While dietary intake of calcium is preferred over supplemental intake, advise patients who require calcium supplements to take calcium along with vitamin D, as this combination does not appear to be associated with an increased risk of MI (93533).
Rarely, calcium intake can increase the risk of calciphylaxis, which usually occurs in patients with kidney failure. Calciphylaxis is the deposition of calcium phosphate in arterioles, which causes skin ulcers and skin necrosis. In a case report, a 64-year-old female with a history of neck fracture, sepsis, and ischemic colitis presented with painful leg ulcers due to calciphylaxis. She discontinued calcium and vitamin D supplementation and was treated with sodium thiosulfate and supportive care (95816).
Gastrointestinal ...Orally, calcium can cause belching, flatulence, nausea, gastrointestinal discomfort, and diarrhea (1824,1843,12950,38803). Although constipation is frequently cited as an adverse effect of calcium, there is no scientific substantiation of this side effect (1824,1843,1844,1845,12950,38978). Calcium carbonate has been reported to cause acid rebound, but this is controversial (12935,12936).
Oncologic ...There is some concern that very high doses of calcium might increase the risk of prostate cancer. Some epidemiological evidence suggests that consuming over 2000 mg/day of dietary calcium might increase the risk for prostate cancer (4825,12949). Additional research suggests that calcium intake over 1500 mg/day might increase the risk of advanced prostate cancer and prostate cancer mortality (14132). Consumption of dairy products has also been weakly linked to a small increase in prostate cancer risk (98894). However, contradictory research suggests no association between dietary intake of calcium and overall prostate cancer risk (14131,14132,104630). More evidence is needed to determine the effect of calcium, if any, on prostate cancer risk.
Renal ...Kidney stones have been reported in individuals taking calcium carbonate 1500 mg daily in combination with vitamin D 2000 IU daily for 4 years (93943).
General
...Orally, caffeinated or decaffeinated coffee is well tolerated in moderate amounts.
Most Common Adverse Effects:
Orally: Drinking coffee containing caffeine can cause agitation, anxiety, chest pain, diuresis, gastric distress, headache, insomnia, nervousness, premature heart rate, ringing in the ears, and vomiting. These effects are more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly). With chronic caffeine use, especially in large amounts, habituation, tolerance, and psychological dependence can occur.
Abrupt discontinuation of caffeine may result in physical withdrawal symptoms, including anxiety, decreased physical energy, depressed mood, difficulty concentrating, drowsiness, fatigue, headache, irritability, reduced alertness, and rhinorrhea.
Rectally: Coffee enemas have been linked to proctocolitis, severe electrolyte abnormalities, and septicemia leading to death.
Cardiovascular
...Orally, coffee containing caffeine can cause chest pain and premature heartbeat (8042,111045).
These effects are more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly) (8042). Excessive doses of caffeine can cause massive catecholamine release and subsequent sinus tachycardia (11832,11838,13734,13735).
Although acute administration of caffeine can cause increased blood pressure, regular consumption does not seem to increase either blood pressure or pulse, even in hypertensive patients (1451,1452,2722,13739,105312). Drinking one or more cups of caffeinated coffee daily also doesn't seem to increase the risk of developing hypertension in habitual coffee drinkers (8033,13739,111037).
Epidemiological research has found that regular caffeine intake of up to 400 mg daily, or approximately 4 cups of caffeinated coffee, is not associated with an increased incidence of atrial fibrillation (38018,38076,91028,91034,97451,97453,105310), atherosclerosis (38033), cardiac ectopy (91127), stroke (37804), ventricular arrhythmia (95948,97453,105310), or cardiovascular disease (CVD) in general (37805,98806,104882). However, some observational research suggests that drinking at least 1 cup of coffee per week is associated with a 40% increased risk of atrial fibrillation, with the highest incidence of atrial fibrillation occurring in adults consuming at least 6 cups daily (111042). Also, one large, observational study found a J-shaped association between regular coffee consumption and the risk of developing acute coronary syndromes. Moderate consumption of less than 300 mL daily (about 1.3 cups) was associated with a lower risk of developing acute coronary syndromes, whereas regular consumption of 300 mL daily or more was associated with an increased risk (11318). In contrast, other observational research in people without a history of CVD has found that drinking more than 6 cups of coffee daily does not appear to be associated with an increased risk of developing coronary heart disease (14343). Also, in people with a history of CVD, population research has found that coffee consumption is associated with a reduction in CVD-related mortality (97373,97374,103997,103998,104594,104595,104882,105308,105311,105313,105314); however not all research agrees (112735). However, in current smokers with a history of acute coronary syndrome, consuming more than 3 cups of coffee daily is associated with more than a two-fold increased risk of overall mortality (105313). Also, population research in patients with severe hypertension, but not mild hypertension, suggests that drinking at least two cups of coffee daily is associated with a 2-fold increase in CVD mortality compared with non-coffee drinkers (111027).
Caffeine intake may pose a greater cardiovascular risk to subjects who are not regular caffeine users. Population research suggests that drinking caffeinated coffee might trigger a myocardial infarction (MI) in some people. People who drink one or fewer cups of coffee daily and are sedentary and have multiple risk factors for heart disease have a significantly increased risk of MI within an hour after drinking coffee. However, this risk appears diminished in people who routinely consume greater amounts of coffee on a daily basis (14497). In another population study, caffeinated coffee consumption was associated with an increased risk of ischemic stroke in subjects who didn't regularly drink coffee (38102).
Boiled coffee that is prepared without a filter appears to increase serum cholesterol and triglyceride levels (1353,4200,8036,8539). Drinking one liter of strong, unfiltered coffee daily for two weeks can raise serum cholesterol by 10% and serum triglycerides by 36% (1353). Tell patients to use coffee filters since these effects do not seem to occur with filtered coffee (4200,8036,8539).
Coffee can adversely affect homocysteine levels. Higher homocysteine levels have been associated with CVD. One liter of unfiltered strong coffee daily for two weeks can increase plasma homocysteine levels by 10% (1353). The same amount of filtered strong coffee appears to raise plasma homocysteine levels by 20%, although there have been no head-to-head comparisons of filtered versus unfiltered coffee (3344).
Dermatologic ...Some researchers suggest symptoms such as flushed face occur during caffeine withdrawal. However, withdrawal symptoms may be due to nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).
Endocrine
...Orally, excessive doses of caffeine can cause massive catecholamine release and subsequent metabolic acidosis, hyperglycemia, and ketosis (13734).
Other symptoms include hypokalemia and respiratory alkalosis (11832,11838,13735).
Some evidence shows that caffeine, a constituent of coffee, is associated with fibrocystic breast disease, breast cancer, and endometriosis in females; however, this is controversial since findings are conflicting (8043). Restricting caffeine intake in patients with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain (8996). Population research suggests that exposure to caffeine is not associated with an increased risk of endometriosis (91035).
A population analysis of the Women's Health Initiative observational study has found no association between consumption of caffeine-containing beverages, such as coffee, 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).
Gastrointestinal
...Orally, coffee containing caffeine can cause gastric distress and vomiting.
These effects are more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly) (8042,13734). There is also some evidence that consumption of three or more cups of caffeinated coffee might increase the risk of Helicobacter pylori infection (8034).
Caffeine withdrawal symptoms such as nausea and vomiting have been described. However, these symptoms may be due to nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).
Rectally, at least 5 cases of proctocolitis related to the use of coffee enemas have been reported (96868,103273).
Genitourinary ...The caffeine found in coffee is a known diuretic and 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). Excessive caffeine consumption may worsen premenstrual syndrome. Consumption of up to 10 cups of caffeinated drinks daily has been associated with increased severity of premenstrual syndrome (38177).
Hematologic
...There is evidence that coffee containing caffeine shortens whole blood fibrinolysis time (8030).
Rectally, coffee enemas have been linked to severe electrolyte abnormalities leading to death (3026,3347,3349,6652)
Hepatic ...Boiled coffee that is prepared without a filter appears to increase liver aminotransferase enzymes. Tell patients to use coffee filters since these effects do not seem to occur with filtered coffee (8539).
Immunologic
...Caffeine can cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).
Rectally, coffee enemas have been linked to septicemia leading to death (3026,3347,3349,6652).
Musculoskeletal
...Orally, there is preliminary evidence that use of greater than four cups of coffee daily can increase the risk of rheumatoid factor positive rheumatoid arthritis, but this association has not been confirmed (6482).
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).
Caffeine withdrawal symptoms, such as muscle tension and muscle pains, have been described. However, these symptoms may be due to nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).
Neurologic/CNS
...Orally, coffee containing caffeine can cause agitation, headache, insomnia, and nervousness, .
These effects are more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly) (8042,11832,11838,13734,13735).
Combining ephedra with coffee can increase the risk of adverse effects, due to the caffeine contained in coffee. Jitteriness, seizures, and temporary loss of consciousness have been associated with the combined use of ephedra and caffeine (2729).
Some researchers suggest that symptoms such as headache; tiredness and fatigue; decreased energy, alertness, and attentiveness; drowsiness; decreased contentedness; difficulty concentrating; irritability; and lack of clear-headedness are typical of caffeine withdrawal (13738). Withdrawal symptoms such as delirium, nervousness, and restlessness have also been described. However, these symptoms may be due to nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).
Ocular/Otic ...Orally, coffee containing caffeine can cause ringing in the ears. This is more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly) (8042,13734). Coffee containing caffeine also increases intraocular pressure, starting about 30 minutes after consumption and persisting for at least 90 minutes. Decaffeinated coffee does not appear to affect intraocular pressure (8540).
Oncologic
...The association between consumption of coffee and pancreatic cancer is controversial.
Coffee may increase the incidence of some types of pancreatic cancers, but it may decrease other types (8535,8536,8537). Some studies do not support this association, especially in patients that have never smoked (8038,8040,93878,103999). Patients who are at risk of pancreatic cancer (pancreatitis) should limit their consumption of coffee.
People who consume 2-4 or more cups of caffeinated coffee dail might have a significantly increased risk of developing lung cancer (13191,90177). But drinking decaffeinated coffee seems to be associated with a decreased risk of lung cancer (13191).
Coffee consumption has also been associated at various times with an increased risk of breast cancer, bladder cancer, colon cancer, and other types of cancers, but there's no good evidence that coffee consumption increases cancer risk (8039,8040,8041). Most human studies that have examined caffeine or coffee intake have found that they do not play a role in the development of various cancers, including breast or most gastric cancers (91054,91076,98806). However, drinking caffeinated coffee might increase the risk of gastric cardia cancer (91076).
Psychiatric ...Orally, coffee containing caffeine can cause anxiety. This is more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly) (8042,13734). With chronic use, especially in large amounts, habituation, tolerance, and psychological dependence can occur (3719). Other researchers suggest symptoms such as depressed mood are typical of caffeine withdrawal (13738). However, withdrawal symptoms may be due to nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).
Pulmonary/Respiratory ...Caffeine withdrawal symptoms such as rhinorrhea have been described. However, these symptoms may be due to nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).
Renal ...Orally, coffee containing caffeine can cause diuresis. This is more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly) (8042,13734).
General
...Orally, sodium is well tolerated when used in moderation at intakes up to the Chronic Disease Risk Reduction (CDRR) intake level.
Topically, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Worsened cardiovascular disease, hypertension, kidney disease.
Cardiovascular
...Orally, intake of sodium above the CDRR intake level can exacerbate hypertension and hypertension-related cardiovascular disease (CVD) (26229,98176,100310,106263).
A meta-analysis of observational research has found a linear association between increased sodium intake and increased hypertension risk (109398). Observational research has also found an association between increased sodium salt intake and increased risk of CVD, mortality, and cardiovascular mortality (98177,98178,98181,98183,98184,109395,109396,109399). However, the existing research is unable to confirm a causal relationship between sodium intake and increased cardiovascular morbidity and mortality; high-quality, prospective research is needed to clarify this relationship (100312). As there is no known benefit with increased salt intake that would outweigh the potential increased risk of CVD, advise patients to limit salt intake to no more than the CDRR intake level (100310).
A reduction in sodium intake can lower systolic blood pressure by a small amount in most individuals, and diastolic blood pressure in patients with hypertension (100310,100311,106261). However, post hoc analysis of a small crossover clinical study in White patients suggests that 24-hour blood pressure variability is not affected by high-salt intake compared with low-salt intake (112910). Additionally, the available research is insufficient to confirm that a further reduction in sodium intake below the CDRR intake level will lower the risk for chronic disease (100310,100311). A meta-analysis of clinical research shows that reducing sodium intake increases levels of total cholesterol and triglycerides, but not low-density lipoprotein (LDL) cholesterol, by a small amount (106261).
It is unclear whether there are safety concerns when sodium is consumed in amounts lower than the adequate intake (AI) levels. Some observational research has found that the lowest levels of sodium intake might be associated with increased risk of death and cardiovascular events (98181,98183). However, this finding has been criticized because some of the studies used inaccurate measures of sodium intake, such as the Kawasaki formula (98177,98178,101259). Some observational research has found that sodium intake based on a single 24-hour urinary measurement is inversely correlated with all-cause mortality (106260). The National Academies Consensus Study Report states that there is insufficient evidence from observational studies to conclude that there are harmful effects from low sodium intake (100310).
Endocrine ...Orally, a meta-analysis of observational research has found that higher sodium intake is associated with an average increase in body mass index (BMI) of 1. 24 kg/m2 and an approximate 5 cm increase in waist circumference (98182). It has been hypothesized that the increase in BMI is related to an increased thirst, resulting in an increased intake of sugary beverages and/or consumption of foods that are high in salt and also high in fat and energy (98182). One large observational study has found that the highest sodium intake is not associated with overweight or obesity when compared to the lowest intake in adolescents aged 12-19 years when intake of energy and sugar-sweetened beverages are considered (106265). However, in children aged 6-11 years, usual sodium intake is positively associated with increased weight and central obesity independently of the intake of energy and/or sugar-sweetened beverages (106265).
Gastrointestinal ...In one case report, severe gastritis and a deep antral ulcer occurred in a patient who consumed 16 grams of sodium chloride in one sitting (25759). Chronic use of high to moderately high amounts of sodium chloride has been associated with an increased risk of gastric cancer (29405).
Musculoskeletal
...Observational research has found that low sodium levels can increase the risk for osteoporosis.
One study has found that low plasma sodium levels are associated with an increased risk for osteoporosis. Low levels, which are typically caused by certain disease states or chronic medications, are associated with a more than 2-fold increased odds for osteoporosis and bone fractures (101260).
Conversely, in healthy males on forced bed rest, a high intake of sodium chloride (7.7 mEq/kg daily) seems to exacerbate disuse-induced bone and muscle loss (25760,25761).
Oncologic ...Population research has found that high or moderately high intake of sodium chloride is associated with an increased risk of gastric cancer when compared with low sodium chloride intake (29405). Other population research in patients with gastric cancer has found that a high intake of sodium is associated with an approximate 65% increased risk of gastric cancer mortality when compared with a low intake. When zinc intake is taken into consideration, the increased risk of mortality only occurred in those with low zinc intake, but the risk was increased to approximately 2-fold in this sub-population (109400).
Pulmonary/Respiratory ...In patients with hypertension, population research has found that sodium excretion is modestly and positively associated with having moderate or severe obstructive sleep apnea. This association was not found in normotensive patients (106262).
Renal ...Increased sodium intake has been associated with impaired kidney function in healthy adults. This effect seems to be independent of blood pressure. Observational research has found that a high salt intake over approximately 5 years is associated with a 29% increased risk of developing impaired kidney function when compared with a lower salt intake. In this study, high salt intake was about 2-fold higher than low salt intake (101261).
