| Ingredients | Each Capsule Contains |
|---|---|
| 100 mg | |
| 400 mg | |
|
(Theobroma cacao )
(seed)
|
67.7 mg |
|
(Theobroma cacao )
(seed)
|
2 Gram(s) |
|
(Eleutherococcus senticosus )
(root)
|
133.3 mg |
|
(Eleutherococcus senticosus )
(root)
|
2 Gram(s) |
|
(Rhodiola rosea )
(root)
|
93.8 mg |
|
(Rhodiola rosea )
(root)
|
750 mg |
|
(Glycyrrhiza glabra )
(root)
|
38.5 mg |
|
(Glycyrrhiza glabra )
(root)
|
500 mg |
|
(equiv. Pyridoxine 2.4mg)
|
3.5 mg |
|
(Se)
(Selenomethionine)
|
30 mcg |
Below is general information about the effectiveness of the known ingredients contained in the product PreDop Lift. 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
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 PreDop Lift. 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 and appropriately (13161,14306,14307,14308,15655,15752,17187,92271,92274,103247)(103250,108898). However, cocoa naturally contains caffeine, and caffeine may be unsafe when used orally in doses of more than 400 mg daily (11733,98806). While most cocoa products contain only small amounts of caffeine (about 2-35 mg per serving) (2708,3900), one cup of unsweetened, dry cocoa powder can contain up to 198 mg of caffeine (100515). To be on the safe side, cocoa should be used in amounts that provide less than 400 mg of caffeine daily. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine naturally found in ingredients such as cocoa does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. Cocoa and dark chocolate products worldwide also contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Advise patients to consume cocoa in moderation. ...when used topically. Cocoa butter is used extensively as a base for ointments and suppositories and is generally considered safe (11).
CHILDREN: POSSIBLY UNSAFE
when dark chocolate is used orally.
Cocoa and dark chocolate products worldwide contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Children are at increased risk of adverse effects from intake of lead and/or cadmium. There is insufficient reliable information available about the safety of other chocolate-based products that typically contain smaller quantities of cocoa.
PREGNANCY: POSSIBLY SAFE
when used orally in moderate amounts.
However, due to the caffeine content of cocoa preparations, intake should be closely monitored during pregnancy to ensure moderate consumption. Fetal blood concentrations of caffeine approximate maternal concentrations (4260). Some research has 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). While many cocoa products contain only small amounts of caffeine (about 2-35 mg per serving) (2708,3900), unsweetened, dry cocoa powder can contain up to 198 mg of caffeine per cup (100515). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, doses of up to 300 mg daily can be consumed during pregnancy without an increased risk of spontaneous abortion, still birth, preterm birth, fetal growth retardation, or congenital malformations (11733,98806). To be on the safe side, cocoa should be used in amounts that provide less than 300 mg of caffeine daily. 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 cocoa, 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 used orally in large amounts.
Caffeine found in cocoa 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). Additionally, high intake of caffeine during pregnancy have been associated with premature delivery, low birth weight, and loss of the fetus (6). While many cocoa products contain only small amounts of caffeine (about 2-35 mg per serving) (2708,3900), unsweetened, dry cocoa powder can contain up to 198 mg of caffeine per cup (100515). To be on the safe side, cocoa should be used in amounts that provide less than 300 mg of caffeine daily (2708). 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 cocoa, 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. Cocoa and dark chocolate products worldwide also contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Large doses or excessive intake of cocoa should be avoided during pregnancy.
LACTATION: POSSIBLY SAFE
when used in moderate amounts or in amounts commonly found in foods.
Due to the caffeine content of cocoa preparations, intake should be closely monitored while breastfeeding. During lactation, breast milk concentrations of caffeine are thought to be approximately 50% of serum concentrations. Moderate consumption of cocoa would likely result in very small amounts of caffeine exposure to a nursing infant (6). 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 cocoa, 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.
LACTATION: POSSIBLY UNSAFE
when used orally in large amounts.
Consumption of excess chocolate (16 oz per day) may cause irritability and increased bowel activity in the infant (6026). Cocoa and dark chocolate products worldwide also contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Large doses or excessive intake of cocoa should be avoided during lactation.
LIKELY SAFE ...when used orally and appropriately, short-term. Eleuthero root extract 300-2000 mg has been used safely in clinical trials lasting up to 3 months (730,1427,2574,7522,11099,15586,91509). There is insufficient reliable information available about the safety of eleuthero when used long-term.
CHILDREN: POSSIBLY SAFE
when used orally in adolescents aged 12-17 years, short-term.
Eleuthero 750 mg three times daily was used for 6 weeks with apparent safety in one clinical trial (75028). There is insufficient reliable information available about the safety of eleuthero in children or adolescents when used long-term.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Licorice has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes. Licorice flavonoid oil 300 mg daily for 16 weeks, and deglycyrrhizinated licorice products in doses of up to 4.5 grams daily for up to 16 weeks, have been used with apparent safety (6196,11312,11313,17727,100984,102960). ...when licorice products containing glycyrrhizin are used orally in low doses, short-term. Licorice extract 272 mg, containing glycyrrhizin 24.3 mg, has been used daily with apparent safety for 6 months (102961). A licorice extract 1000 mg, containing monoammonium glycyrrhizinate 240 mg, has been used daily with apparent safety for 12 weeks (110320). In addition, a syrup providing licorice extract 750 mg has been used twice daily with apparent safety for 5 days (104558). ...when applied topically. A gel containing 2% licorice root extract has been applied to the skin with apparent safety for up to 2 weeks. (59732). A mouth rinse containing 5% licorice extract has been used with apparent safety four times daily for up to one week (104564).
POSSIBLY UNSAFE ...when licorice products containing glycyrrhizin are used orally in large amounts for several weeks, or in smaller amounts for longer periods of time. The European Scientific Committee on Food recommends that a safe average daily intake of glycyrrhizin should not exceed 10 mg (108577). In otherwise healthy people, consuming glycyrrhizin daily for several weeks or longer can cause severe adverse effects including pseudohyperaldosteronism, hypertensive crisis, hypokalemia, cardiac arrhythmias, and cardiac arrest. Doses of 20 grams or more of licorice products, containing at least 400 mg glycyrrhizin, are more likely to cause these effects; however, smaller amounts have also caused hypokalemia and associated symptoms when taken for months to years (781,3252,15590,15592,15594,15596,15597,15599,15600,16058)(59731,59740,59752,59785,59786,59787,59792,59795,59805,59811)(59816,59818,59820,59822,59826,59828,59849,59850,59851,59867)(59882,59885,59888,59889,59895,59900,59906,97213,110305). In patients with hypertension, cardiovascular or kidney conditions, or a high salt intake, as little as 5 grams of licorice product or 100 mg glycyrrhizin daily can cause severe adverse effects (15589,15593,15598,15600,59726).
PREGNANCY: UNSAFE
when used orally.
Licorice has abortifacient, estrogenic, and steroid effects. It can also cause uterine stimulation. Heavy consumption of licorice, equivalent to 500 mg of glycyrrhizin per week (about 250 grams of licorice per week), during pregnancy seems to increase the risk of delivery before gestational age of 38 weeks (7619,10618). Furthermore, high intake of glycyrrhizin, at least 500 mg per week, during pregnancy is associated with increased salivary cortisol levels in the child by the age of 8 years. This suggests that high intake of licorice during pregnancy may increase hypothalamic-pituitary-adrenocortical axis activity in the child (26434); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when L-phenylalanine is consumed in amounts typically found in foods (11120).
POSSIBLY SAFE ...when L-phenylalanine is used orally in doses up to 100 mg/kg daily for up to 3 months (2463,2464,2466,2467,2469). ...when D-phenylalanine is used orally in doses up to 1 gram daily for up to 4 weeks, or as a single dose of 4-10 grams (2455,2456,2459,68795,104792). ...when DL-phenylalanine is used orally in doses up to 200 mg daily for up to 4 weeks (2468,68795,68825). ...when phenylalanine cream is applied topically, short-term (2461,92704).
PREGNANCY: LIKELY SAFE
when L-phenylalanine is consumed in amounts typically found in foods by pregnant patients with normal phenylalanine metabolism (2020,11120).
PREGNANCY: UNSAFE
when L-phenylalanine is consumed in amounts typically found in foods by pregnant patients with high serum phenylalanine concentrations, such as those with phenylketonuria (PKU).
Serum levels of phenylalanine greater than 360 micromol/L increase the risk of birth defects (1402,11468). Experts recommend that patients with high phenylalanine serum concentrations follow a low phenylalanine diet for at least 20 weeks prior to conception to decrease the risk for birth defects (1402).
There is insufficient reliable information available about the safety of L-phenylalanine when taken by mouth in large doses during pregnancy; avoid using.
There is insufficient reliable information available about the safety of oral D-phenylalanine during pregnancy; avoid using.
LACTATION: LIKELY SAFE
when L-phenylalanine is consumed in amounts typically found in foods by breast-feeding patients with normal phenylalanine metabolism (2020,11120).
There is insufficient reliable information available about the safety of L-phenylalanine when taken by mouth in medicinal amounts during lactation; avoid using. There is insufficient reliable information available about the safety of oral D-phenylalanine during lactation; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. There is some clinical research showing that taking rhodiola extract up to 300 mg twice daily has been used without adverse effects for up to 12 weeks (13109,16410,17616,71172,96459,102283,103269).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. Selenium appears to be safe when taken short-term in amounts below the tolerable upper intake level (UL) of 400 mcg daily (4844,7830,7831,7836,7841,9724,9797,14447,17510,17511)(17512,17513,17515,17516,97087,97943,109085); however, there is concern that taking selenium long-term might not be safe. Some evidence shows that consuming a diet containing more than the recommended dietary allowance (RDA) of selenium, which is 55 mcg daily for most adults, is associated with an increased risk for developing type 2 diabetes (99661). Some evidence also shows that taking a selenium supplement 200 mcg daily for an average of 3-8 years increases the risk of developing type 2 diabetes (97091,99661). Higher serum levels of selenium are also associated with an increased risk of developing diabetes and increased mortality (16710,99661). ...when used intravenously. Selenium, as selenious acid, is an FDA-approved drug. Sodium selenite intravenous infusions up to 1000 mcg daily have been safely used for up to 28 days (90347,92910).
POSSIBLY UNSAFE ...when used orally in high doses or long-term. Doses above 400 mcg daily can increase the risk of developing selenium toxicity (4844,7825). Additionally, some evidence shows that consuming a diet containing more than the recommended dietary allowance (RDA) of selenium, which is 55 mcg daily for most adults, is associated with an increased risk for developing type 2 diabetes (99661). There is also concern that taking a selenium supplement 200 mcg daily long-term, for an average of 3-8 years, increases the risk of developing type 2 diabetes (99661). Higher serum levels of selenium are also associated with an increased risk of developing diabetes and increased mortality (16710,99661).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately.
Selenium seems to be safe when used short-term in doses below the tolerable upper intake level (UL) of 45 mcg daily for infants up to age 6 months, 60 mcg daily for infants 7 to 12 months, 40-90 mcg daily for children 1 to 3 years, 100-150 mcg daily for children 4 to 8 years, 200-280 mcg daily for children 9 to 13 years, and 400 mcg daily for children age 14 years and older (4844,86095); however, there is some concern that long-term use might not be safe. ...when used via a nasogastric tube in premature infants (7835,9764).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately.
Selenium appears to be safe when used short-term in amounts that do not exceed the tolerable upper intake level (UL) of 400 mcg daily (4844,17507,74419,74481,74391); however, there is concern that long-term use might not be safe.
PREGNANCY: POSSIBLY UNSAFE
when used orally in excessive doses.
Doses above 400 mcg daily may cause significant toxicity (4844).
LACTATION: POSSIBLY SAFE
when used orally and appropriately.
Selenium appears to be safe when used short-term in amounts that do not exceed the tolerable upper intake level (UL) of 400 mcg daily when taken short-term (4844,74467); however, there is concern that long-term use might not be safe.
LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses.
Doses above 400 mcg daily may cause significant toxicity (4844,7838). ...when used orally in HIV-positive women. Selenium supplementation in HIV-positive women not taking highly active antiretroviral therapy may increase HIV-1 levels in breast milk (90358).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Tyrosine has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Tyrosine has been used safely in doses up to 150 mg/kg daily for up to 3 months (7210,7211,7215). ...when used topically and appropriately (6155).
PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of tyrosine during pregnancy and lactation when used in medicinal amounts.
Some pharmacokinetic research shows that taking a single dose of tyrosine 2-10 grams orally can modestly increase levels of free tyrosine in breast milk. However, total levels are not affected, and levels remain within the range found in infant formulas. Therefore, it is not clear if the increase in free tyrosine is a concern (91467).
LIKELY SAFE ...when used orally and appropriately in doses that do not exceed the tolerable upper intake level (UL) of 100 mg daily for adults (15). ...when used parenterally and appropriately. Injectable vitamin B6 (pyridoxine) is an FDA-approved prescription product (15).
POSSIBLY SAFE ...when used orally and appropriately in doses of 101-200 mg daily (6243,8558).
POSSIBLY UNSAFE ...when used orally in doses at or above 500 mg daily. High doses, especially those exceeding 1000 mg daily or total doses of 1000 grams or more, pose the most risk. However, neuropathy can occur with lower daily or total doses (6243,8195). ...when used intramuscularly in high doses and frequency due to potential for rhabdomyolysis (90795).
CHILDREN: LIKELY SAFE
when used orally and appropriately (3094).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately in amounts exceeding the recommended dietary allowance (5049,8579,107124,107125,107135).
CHILDREN: POSSIBLY UNSAFE
when used orally in excessive doses, long-term (3094).
PREGNANCY: LIKELY SAFE
when used orally and appropriately.
A special sustained-release product providing vitamin B6 (pyridoxine) 75 mg daily is FDA-approved for use in pregnancy. Vitamin B6 (pyridoxine) is also considered a first-line treatment for nausea and vomiting in pregnancy by the American College of Obstetrics and Gynecology (111601). However, it should not be used long-term or without medical supervision and close monitoring.
PREGNANCY: POSSIBLY UNSAFE
when used orally in excessive doses.
There is some concern that high-dose maternal vitamin B6 (pyridoxine) can cause neonatal seizures (4609,6397,8197).
LACTATION: LIKELY SAFE
when used orally in doses not exceeding the recommended dietary allowance (RDA) (3094).
The RDA in lactating women is 2 mg daily. There is insufficient reliable information available about the safety of vitamin B6 when used in higher doses in breast-feeding women.
Below is general information about the interactions of the known ingredients contained in the product PreDop Lift. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, taking cocoa with ACEIs might increase the risk of adverse effects.
 Details
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Theoretically, cocoa might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Details
Cocoa contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. However, methylxanthines appear more likely to interfere with dipyridamole than adenosine-induced stress testing (11771).
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Theoretically, concomitant use might increase levels and adverse effects of caffeine.
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Cocoa contains 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, cocoa may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
Clinical research shows that intake of cocoa can inhibit platelet adhesion, aggregation, and activity (6085,17076,41928,41948,41957,41958,41995,42014,42070,42145)(111526) and increase aspirin-induced bleeding time (23800). For patients on dual antiplatelet therapy, cocoa may enhance the inhibitory effect of clopidogrel, but not aspirin, on platelet aggregation (111526).
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Theoretically, taking cocoa with antihypertensive drugs might increase the risk of hypotension.
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Theoretically, large amounts of cocoa might increase the cardiac inotropic effects of beta-agonists.
Details
Cocoa contains caffeine. Theoretically, large amounts of caffeine might increase cardiac inotropic effects of beta-agonists (15). A case of atrial fibrillation associated with consumption of large quantities of chocolate in a patient with chronic albuterol inhalation abuse has also been reported (42075).
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Theoretically, concomitant use might increase the effects and adverse effects of caffeine in cocoa.
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Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in cocoa.
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Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Caffeine is metabolized by cytochrome P450 1A2 (CYP1A2) (3941,5051,11741,23557,23573,23580,24958,24959,24960,24962), (24964,24965,24967,24968,24969,24971,38081,48603). Theoretically, drugs that inhibit CYP1A2 may decrease the clearance rate of caffeine from cocoa and increase caffeine levels.
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Theoretically, cocoa might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Details
Cocoa contains caffeine. Caffeine may inhibit 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 than adenosine-induced stress testing (11771).
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Theoretically, disulfiram might increase the risk of adverse effects from caffeine.
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Cocoa contains caffeine. In human research, disulfiram decreases the rate of caffeine clearance (11840).
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Theoretically, using cocoa with diuretic drugs might increase the risk of hypokalemia.
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Theoretically, concomitant use might increase the risk for stimulant adverse effects.
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Theoretically, estrogens might increase the levels and adverse effects of caffeine.
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Cocoa 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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Cocoa contains caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022).
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Theoretically, cocoa might increase the levels and adverse effects of flutamide.
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Cocoa contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide (23553).
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Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Fluvoxamine reduces caffeine metabolism (6370).
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Theoretically, abrupt cocoa withdrawal might increase the levels and adverse effects of lithium.
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Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Methoxsalen can reduce caffeine metabolism (23572).
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Theoretically, metformin might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Animal research suggests that metformin can reduce caffeine metabolism (23571).
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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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Cocoa contains caffeine. Large amounts of caffeine with MAOIs might precipitate a hypertensive crisis (15).
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Theoretically, concomitant use might increase the risk of hypertension.
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Cocoa 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, cocoa might decrease the effects of pentobarbital.
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Cocoa contains caffeine. Caffeine might negate the hypnotic effects of pentobarbital (13742).
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Theoretically, cocoa 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, cocoa might reduce the effects of phenytoin and increase the risk for convulsions.
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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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Cocoa contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2, 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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Cocoa contains caffeine. Concomitant use might increase the risk of stimulant adverse effects (11832).
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Theoretically, terbinafine might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Terbinafine decreases the rate of caffeine clearance (11740).
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Theoretically, cocoa might increase the levels and adverse effects of theophylline.
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Theoretically, cocoa tea might increase the levels and adverse effects of tiagabine.
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Cocoa contains caffeine. Animal research suggests that chronic caffeine administration can increase the serum concentrations of tiagabine. However, concomitant use does not seem to reduce the antiepileptic effects of tiagabine (23561).
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Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.
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Cocoa contains 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, cocoa 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.
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Cocoa contains caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).
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Theoretically, eleuthero may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Theoretically, eleuthero might have additive effects when used with antidiabetes drugs.
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Animal research suggests that certain constituents of eleuthero have hypoglycemic activity in both healthy and diabetic animals (7591,73535,74932,74956,74988,74990). A small study in adults with type 2 diabetes also shows that taking eleuthero for 3 months can lower blood glucose levels (91509). However, one very small study in healthy individuals shows that taking powdered eleuthero 3 grams, 40 minutes prior to a 75-gram oral glucose tolerance test, significantly increases postprandial blood glucose levels when compared with placebo (12536). These contradictory findings might be due to patient-specific variability and variability in active ingredient ratios.
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Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.
Details
In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2 (7532). This effect has not been reported in humans.
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Theoretically, eleuthero might increase levels of drugs metabolized by CYP2C9.
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In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2C9 (7532). This effect has not been reported in humans.
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Theoretically, eleuthero might increase levels of drugs metabolized by CYP2D6.
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Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.
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Eleuthero might increase serum digoxin levels and increase the risk of side effects.
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In one case report, a 74-year-old male who was stabilized on digoxin presented with an elevated serum digoxin level after starting an eleuthero supplement, without symptoms of toxicity. After stopping the supplement, serum digoxin levels returned to normal (543). It is not clear whether this was due to a pharmacokinetic interaction or to interference with the digoxin assay (15585). Although the product was found to be free of digoxin and digitoxin (543), it was not tested for other contaminants (797).
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Theoretically, eleuthero might interfere with immunosuppressive drugs because of its immunostimulant activity.
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Theoretically, eleuthero might decrease levels of drugs metabolized by OATP.
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In vitro research suggests that eleuthero inhibits OATP2B1, which might reduce the bioavailability of oral drugs that are substrates of OATP2B1 (35450). Due to the weak inhibitory effect identified in this study, this interaction is not likely to be clinically significant.
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Theoretically, eleuthero might increase levels of P-glycoprotein substrates.
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Theoretically, licorice might reduce the effects of antihypertensive drugs.
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Theoretically, licorice might reduce the effects of cisplatin.
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In animal research, licorice diminished the therapeutic efficacy of cisplatin (59763).
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Theoretically, concomitant use of licorice and corticosteroids might increase the side effects of corticosteroids.
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Case reports suggest that concomitant use of licorice and oral corticosteroids, such as hydrocortisone, can potentiate the duration of activity and increase blood levels of corticosteroids (3252,12672,20040,20042,48429,59756). Additionally, in one case report, a patient with neurogenic orthostatic hypertension stabilized on fludrocortisone 0.1 mg twice daily developed pseudohyperaldosteronism after recent consumption of large amounts of black licorice (108568).
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Theoretically, licorice might increase levels of drugs metabolized by CYP2B6.
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In vitro research shows that licorice extract and glabridin, a licorice constituent, inhibit CYP2B6 isoenzymes (10300,94822). Licorice extract from the species G. uralensis seems to inhibit CYP2B6 isoenzymes to a greater degree than G. glabra extract in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2B6; however, these interactions have not yet been reported in humans.
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Theoretically, licorice might increase levels of drugs metabolized by CYP2C19.
Details
In vitro, licorice extracts from the species G. glabra and G. uralensis inhibit CYP2C19 isoenzymes in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C19; however, this interaction has not yet been reported in humans.
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Theoretically, licorice might increase levels of drugs metabolized by CYP2C8.
Details
In vitro, licorice extract from the species G. glabra and G. uralensis inhibits CYP2C8 isoenzymes (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C8; however, this interaction has not yet been reported in humans.
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Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP2C9.
Details
There is conflicting evidence about the effect of licorice on CYP2C9 enzyme activity. In vitro research shows that extracts from the licorice species G. glabra and G. uralensis moderately inhibit CYP2C9 isoenzymes (10300,94822). However, evidence from an animal model shows that licorice extract from the species G. uralensis can induce hepatic CYP2C9 activity (14441). Until more is known, licorice should be used cautiously in people taking CYP2C9 substrates.
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Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.
Details
Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity (59808). Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity (14441). However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species (10300,94822). Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.
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Theoretically, concomitant use of licorice with digoxin might increase the risk of cardiac toxicity.
Details
Overuse or misuse of licorice with cardiac glycoside therapy might increase the risk of cardiac toxicity due to potassium loss (10393).
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Theoretically, concomitant use of licorice with diuretic drugs might increase the risk of hypokalemia.
Details
Overuse of licorice might compound diuretic-induced potassium loss (10393,20045,20046,59812). In one case report, a 72-year-old male with a past medical history of hypertension, type 2 diabetes, hyperlipidemia, arrhythmia, stroke, and hepatic dysfunction was hospitalized with severe hypokalemia and uncontrolled hypertension due to pseudohyperaldosteronism. This was thought to be provoked by concomitant daily consumption of a product containing 225 mg of glycyrrhizin, a constituent of licorice, and hydrochlorothiazide 12.5 mg for 1 month (108577).
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Theoretically, licorice might increase or decrease the effects of estrogen therapy.
Details
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Theoretically, loop diuretics might increase the mineralocorticoid effects of licorice.
Details
Theoretically, loop diuretics might enhance the mineralocorticoid effects of licorice by inhibiting the enzyme that converts cortisol to cortisone; however, bumetanide (Bumex) does not appear to have this effect (3255).
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Theoretically, licorice might increase levels of methotrexate.
Details
Animal research suggests that intravenous administration of glycyrrhizin, a licorice constituent, and high-dose methotrexate may delay methotrexate excretion and increase systemic exposure, leading to transient elevations in liver enzymes and total bilirubin (108570). This interaction has not yet been reported in humans.
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Theoretically, licorice might decrease levels of midazolam.
Details
In humans, the licorice constituent glycyrrhizin appears to moderately induce the metabolism of midazolam (59808). This is likely due to induction of cytochrome P450 3A4 by licorice. Until more is known, licorice should be used cautiously in people taking midazolam.
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Theoretically, licorice might decrease the absorption of P-glycoprotein substrates.
Details
In vitro research shows that licorice can increase P-glycoprotein activity (104561).
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Theoretically, licorice might decrease plasma levels and clinical effects of paclitaxel.
Details
Multiple doses of licorice taken concomitantly with paclitaxel might reduce the effectiveness of paclitaxel. Animal research shows that licorice 3 grams/kg given orally for 14 days before intravenous administration of paclitaxel decreases the exposure to paclitaxel and increases its clearance. Theoretically, this occurs because licorice induces cytochrome P450 3A4 enzymes, which metabolize paclitaxel. Notably, a single dose of licorice did not affect exposure or clearance of paclitaxel (102959).
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Theoretically, licorice might decrease plasma levels and clinical effects of warfarin.
Details
Licorice seems to increase metabolism and decrease levels of warfarin in animal models. This is likely due to induction of cytochrome P450 2C9 (CYP2C9) metabolism by licorice (14441). Advise patients taking warfarin to avoid taking licorice.
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Concomitant intake of phenylalanine may reduce the intestinal absorption of baclofen.
Details
Phenylalanine and baclofen share the same intestinal carrier for absorption; phenylalanine competitively inhibits the absorption of baclofen, reducing its plasma levels (23788).
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Phenylalanine, especially in high doses, can reduce the effectiveness of levodopa.
Details
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Theoretically, concomitant use of L-phenylalanine and non-selective MAOIs might increase the risk of hypertensive crisis.
Details
L-phenylalanine is metabolized to tyrosine (2052,9949). Some evidence suggests that L-phenylalanine, given with the non-selective MAOI pargyline, might prevent the elimination of tyramine, increasing the risk of hypertensive crisis (2021). However, this was not reported in a small number of patients when using L-phenylalanine with the partially selective MAO-B inhibitor, selegiline (2469).
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Theoretically, taking rhodiola with antidiabetes drugs might increase the risk of hypoglycemia.
Details
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Theoretically, taking rhodiola with antihypertensive drugs might increase the risk of hypotension.
Details
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Theoretically, rhodiola might increase levels of drugs metabolized by CYP1A2.
Details
In vitro research shows that rhodiola inhibits CYP1A2. This effect is highly variable and appears to be dependent on the rhodiola product studied (96461). However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of caffeine, a CYP1A2 substrate (96463).
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Theoretically, rhodiola might increase levels of drugs metabolized by CYP2C9.
Details
In vitro research shows that rhodiola inhibits CYP2C9. This effect is highly variable and appears to be dependent on the rhodiola product studied (96461). Also, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours (96463).
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Theoretically, rhodiola might increase levels of drugs metabolized by CYP3A4.
Details
In vitro research shows that rhodiola inhibits CYP3A4 (19497,96461). This effect is highly variable and appears to be dependent on the rhodiola product studied (96461). However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of midazolam, a CYP3A4 substrate (96463).
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Theoretically, rhodiola use might interfere with immunosuppressive therapy.
Details
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Rhodiola might increase the levels and adverse effects of losartan.
Details
A clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours (96463).
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Theoretically, rhodiola might increase levels of P-glycoprotein substrates.
Details
In vitro research shows that rhodiola inhibits P-glycoprotein (19497). Theoretically, using rhodiola with P-glycoprotein substrates might increase drug levels and potentially increase the risk of adverse effects.
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Selenium may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
Clinical research suggests that taking selenium 10 mcg/kg/day can increase bleeding times by increasing prostacyclin production, which inhibits platelet activity (14540). Other clinical research suggests that taking selenium 75 mcg daily, in combination with ascorbic acid 600 mg, alpha-tocopherol 300 mg, and beta-carotene 27 mg, reduces platelet aggregation (74406).
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Theoretically, selenium might prolong the sedating effects of barbiturates.
Details
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Contraceptive drugs might increase levels of selenium, although the clinical significance of this effect is unclear.
Details
Some research suggests that oral contraceptives increase serum selenium levels in women taking oral contraceptives; however, other research shows no change in selenium levels (14544,14545,14546,101343). It is suggested that an increase could be due to increased carrier proteins, indicating a redistribution of selenium rather than a change in total body selenium (14545).
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Gold salts might interfere with selenium activity in tissues.
Details
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Theoretically, selenium supplementation may reduce the effectiveness of immunosuppressant therapy.
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Selenium might reduce the beneficial effects of niacin on high-density lipoprotein (HDL) levels.
Details
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease (7388,11537). It is not known whether this adverse effect is due to a single antioxidant such as selenium, or to the combination. It also is not known whether it will occur in other patient populations.
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Theoretically, selenium might interfere with warfarin activity.
Details
Animal research suggests that selenium can increase warfarin activity. Selenium might interact with warfarin by displacing it from albumin binding sites, reducing its metabolism in the liver, or by decreasing production of vitamin K-dependent clotting factors (14541). Selenium can also prolong bleeding times in humans by increasing prostacyclin production, which inhibits platelet activity (14540).
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Theoretically, tyrosine might decrease the effectiveness of levodopa.
Details
Tyrosine and levodopa compete for absorption in the proximal duodenum by the large neutral amino acid (LNAA) transport system (2719). Advise patients to separate doses of tyrosine and levodopa by at least 2 hours.
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Theoretically, tyrosine might have additive effects with thyroid hormone medications.
Details
Tyrosine is a precursor to thyroxine and might increase levels of thyroid hormones (7212).
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Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.
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Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.
Details
Research in hypertensive rats shows that vitamin B6 can decrease systolic blood pressure (30859,82959,83093). Similarly, clinical research in patients with hypertension shows that taking high doses of vitamin B6 may reduce systolic and diastolic blood pressure, possibly by reducing plasma levels of epinephrine and norepinephrine (83091).
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Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.
Details
Vitamin B6 (pyridoxine) enhances the metabolism of levodopa, reducing its clinical effects. However, this interaction does not occur when carbidopa is used concurrently with levodopa (Sinemet). Therefore, it is not likely to be a problem in most people (3046).
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High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
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High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
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Below is general information about the adverse effects of the known ingredients contained in the product PreDop Lift. 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 topically, cocoa is generally well tolerated.
Most Common Adverse Effects:
Orally: Borborygmi, constipation, diuresis, gastrointestinal discomfort, headaches, and nausea.
Serious Adverse Effects (Rare):
Orally: Tachycardia.
Cardiovascular ...Some cases of increased heart rate have been reported with oral cocoa use (13161,42132).
Dermatologic ...In some cases, when taken orally, cocoa can cause allergic skin reactions (13161). Topically, cocoa butter has occasionally caused a rash. In animals, it has been shown to block pores and cause acne; however, this has not been found in humans (11).
Gastrointestinal ...In human trials, chocolate consumption was associated with a higher incidence of flatulence, irritable bowel syndrome, upset stomach, gastric upset, borborygmi (a gurgling noise made by fluid or gas in the intestines), bloating, nausea, vomiting, and constipation or obstipation (41986,42221,41921,1374,42220,1373,42099,42097,42156,42123,18229,42169,42111). Chocolate consumption has been implicated as a provoking factor in gastroesophageal reflux disease (GERD) (41974,42005,41946,1374). Unpalatability has been reported (42079,42169). Consumption of chocolate and other sweet foods may lead to increased dental caries (42129,42030).
Genitourinary ...In some cases, when taken orally, cocoa can cause increased urination (13161).
Neurologic/CNS ...In some cases, when taken orally, cocoa can cause shakiness and might trigger migraine and other headaches (13161,42169,92271).
Other ...Due to the high sugar and caloric content of chocolate, there is concern about weight gain in people who consume large amounts of chocolate (17187).
General
...Orally, eleuthero root is generally well tolerated when used short-term.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, gastrointestinal upset, headache, nausea, and urticaria.
Cardiovascular ...Orally, increased blood pressure has been reported in children with hypotension taking eleuthero in one clinical study (74980). Eleuthero has been reported to cause tachycardia, hypertension, and pericardial pain in patients with rheumatic heart disease or atherosclerosis. It is unclear if these effects were caused by eleuthero, or by the cardioglycoside-containing herb, silk vine (Periploca sepium), which is a common adulterant found in eleuthero products (12,797,6500).
Dermatologic ...Orally, eleuthero has been reported to cause rash in some clinical studies (75013,75028).
Gastrointestinal ...Orally, eleuthero has been reported to cause dyspepsia, nausea, diarrhea, and gastrointestinal upset in some patients (74938,75028,91510).
Genitourinary ...Orally, mastalgia and uterine bleeding were reported in 7. 3% of females taking eleuthero 2 grams daily in one clinical study (6500,11099). These adverse effects seem to be more likely with higher doses.
Neurologic/CNS
...Orally, headaches have been reported in 9.
8% of people taking eleuthero in one clinical study (11099).
In one case report, a 53-year-old female developed spontaneous subarachnoid hemorrhage associated with the use of an herbal supplement containing red clover, dong quai, and eleuthero (70419). It is unclear if this event was related to the use of eleuthero, the other ingredients, the combination, or another cause entirely.
Psychiatric ...Orally, nervousness has been reported in 7. 3% of people taking eleuthero in one clinical study (11099). Eleuthero has also been reported to cause slight anxiety, irritability, and melancholy in some patients (6500,11099). These adverse effects seem to be more likely to occur with higher doses.
General
...Orally, licorice is generally well tolerated when used in amounts commonly found in foods.
It seems to be well tolerated when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes or when used topically, short-term.
Most Common Adverse Effects:
Orally: Headache, nausea, and vomiting.
Topically: Contact dermatitis.
Intravenously: Diarrhea, itching, nausea, and rash.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about acute renal failure, cardiac arrest, cardiac arrhythmias, hypertension, hypokalemia, muscle weakness, paralysis, pseudohyperaldosteronism, and seizure associated with long-term use or large amounts of licorice containing glycyrrhizin.
Cardiovascular
...Orally, excessive licorice ingestion can lead to pseudohyperaldosteronism, which can precipitate cardiovascular complications such as hypertension and hypertensive crisis, ventricular fibrillation or tachycardia, sinus pause, and cardiac arrest.
These effects are due to the licorice constituent glycyrrhizin and usually occur when 20-30 grams or more of licorice product is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,97213) (104563,108574,108576,110305,112234). In one case report, an 89-year-old female taking an herbal medicine containing licorice experienced a fatal arrhythmia secondary to licorice-induced hypokalemia. The patient presented to the hospital with recurrent syncope, weakness, and fatigue for 5 days after taking an herbal medicine containing licorice for 2 months. Upon admission to the hospital, the patient developed seizures, QT prolongation, and ventricular arrhythmia requiring multiple defibrillations. Laboratory tests confirmed hypokalemia and pseudohyperaldosteronism (112234).
However, people with cardiovascular or kidney conditions may be more sensitive, so these adverse events may occur with doses as low as 5 grams of licorice product or glycyrrhizin 100 mg daily (15589,15593,15598,15600,59726). A case report in a 54-year-old male suggests that malnutrition might increase the risk of severe adverse effects with excessive licorice consumption. This patient presented to the emergency room with cardiac arrest and ventricular fibrillation after excessive daily consumption of licorice for about 3 weeks. This caused pseudohyperaldosteronism and then hypokalemia, leading to cardiovascular manifestations. In spite of resuscitative treatment, the patient progressed to kidney failure, refused dialysis, and died shortly thereafter (103791).
Dermatologic
...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912).
There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578). Burning sensation, itching, redness, and scaling were reported rarely in patients applying a combination of licorice, calendula, and snail secretion filtrate to the face. The specific role of licorice is unclear (110322).
In rare cases, the glycyrrhizin constituent of licorice has caused rash and itching when administered intravenously (59712).
Endocrine
...Orally, excessive licorice ingestion can cause a syndrome of apparent mineralocorticoid excess, or pseudohyperaldosteronism, with sodium and water retention, increased urinary potassium loss, hypokalemia, and metabolic alkalosis due to its glycyrrhizin content (781,10619,15591,15592,15593,15594,15595,15596,15597,15598)(15600,16057,16835,25659,25660,25673,25719,26439,59818,59822)(59832,59864,91722,104563,108568,108574,110305,112234).
These metabolic abnormalities can lead to hypertension, edema, EKG changes, fatigue, syncope, arrhythmias, cardiac arrest, headache, lethargy, muscle weakness, dropped head syndrome (DHS), rhabdomyolysis, myoglobinuria, paralysis, encephalopathy, respiratory impairment, hyperparathyroidism, and acute kidney failure (10393,10619,15589,15590,15593,15594,15596,15597,15599)(15600,16057,16835,25660,25673,25719,26439,31562,59709,59716)(59720,59740,59787,59820,59826,59882,59889,59900,91722,97214,100522) (104563,108576,108577). These effects are most likely to occur when 20-30 grams of licorice products containing glycyrrhizin 400 mg or more is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,108574). However, some people may be more sensitive, especially those with hypertension, diabetes, heart problems, or kidney problems (15589,15593,15598,15600,59726,108576,108577) and even low or moderate consumption of licorice may cause hypertensive crisis or hypertension in normotensive individuals (1372,97213). The use of certain medications with licorice may also increase the risk of these adverse effects (108568,108577). One case report determined that the use of large doses of licorice in an elderly female stabilized on fludrocortisone precipitated hypokalemia and hypertension, requiring inpatient treatment (108568). Another case report describes severe hypokalemia necessitating intensive care treatment due to co-ingestion of an oral glycyrrhizin-specific product and hydrochlorothiazide for 1 month (108577). Glycyrrhetinic acid has a long half-life, a large volume of distribution, and extensive enterohepatic recirculation. Therefore, it may take 1-2 weeks before hypokalemia resolves (781,15595,15596,15597,15600). Normalization of the renin-aldosterone axis and blood pressure can take up to several months (781,15595,108568). Treatment typically includes the discontinuation of licorice, oral and intravenous potassium supplementation, and short-term use of aldosterone antagonists, such as spironolactone (108574,108577).
Chewing tobacco flavored with licorice has also been associated with toxicity. Chewing licorice-flavored tobacco, drinking licorice tea, or ingesting large amounts of black licorice flavored jelly beans or lozenges has been associated with hypertension and suppressed renin and aldosterone levels (12671,12837,97214,97215,97217,108574). One case report suggests that taking a combination product containing about 100 mg of licorice and other ingredients (Jintan, Morishita Jintan Co.) for many decades may be associated with hypoaldosteronism, even up to 5 months after discontinuation of the product (100522). In another case report, licorice ingestion led to hyperprolactinemia in a female (59901). Licorice-associated hypercalcemia has also been noted in a case report (59766).
Gastrointestinal ...Nausea and vomiting have been reported rarely following oral use of deglycyrrhizinated licorice (25694,59871). Intravenously, the glycyrrhizin constituent of licorice has rarely caused gastric discomfort, diarrhea, or nausea (59712,59915).
Immunologic ...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912). There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578).
Musculoskeletal ...In a case report, excessive glycyrrhizin-containing licorice consumption led to water retention and was thought to trigger neuropathy and carpal tunnel syndrome (59791).
Neurologic/CNS ...Orally, licorice containing larger amounts of glycyrrhizin may cause headaches. A healthy woman taking glycyrrhizin 380 mg daily for 2 weeks experienced a headache (59892). Intravenously, the glycyrrhizin constituent of licorice has rarely caused headaches or fatigue (59721). In a case report, licorice candy ingestion was associated with posterior reversible encephalopathy syndrome accompanied by a tonic-clonic seizure (97218).
Ocular/Otic ...Orally, consuming glycyrrhizin-containing licorice 114-909 grams has been associated with transient visual loss (59714).
Pulmonary/Respiratory ...Orally, large amounts of licorice might lead to pulmonary edema. In one case report, a 64-year old male consumed 1020 grams of black licorice (Hershey Twizzlers) containing glycyrrhizin 3.6 grams over 3 days, which resulted in pulmonary edema secondary to pseudohyperaldosteronism (31561). Intravenously, the glycyrrhizin constituent of licorice has caused cold or flu-like symptoms, although these events are not common (59712,59721).
General
...Orally, L-phenylalanine and D-phenylalanine are generally well tolerated when used in typical doses.
Most Common Adverse Effects:
Orally: Anxiety, constipation, headache, heartburn, insomnia, nausea, and sedation.
Topically: Burning, erythema, and itching.
Cardiovascular ...One patient in a small case series developed extrasystoles after 10 days of treatment with DL-phenylalanine, but this resolved on the 12th day of treatment without discontinuing phenylalanine (68825).
Dermatologic ...Topically, erythema, itching, and burning have been reported in some patients using an undecylenoyl phenylalanine 2% cream for treatment of age spots (92704).
Gastrointestinal ...Orally, constipation, heartburn, and nausea has been reported in some patients taking phenylalanine (2463,68827,68829,68830).
Neurologic/CNS
...Orally, headaches, which are typically transient and do not require treatment or dosage reduction, have been reported during the first 10 days of treatment with L-, D-, and DL-phenylalanine (68795,68825,68827,68829).
Transient vertigo has also been reported with D- and DL-phenylalanine (68795).
In patients with Parkinson disease, taking DL-phenylalanine, especially in high doses, interferes with levodopa transport into the brain, causing increased rigidity, tremor, and occurrence of the on-off phenomenon. Akinesia has been reported more rarely (3291,3292,3293,3294,68828). In patients with schizophrenia, taking a single dose of L-phenylalanine 100 mg/kg has been associated with worsening of medication-induced tardive dyskinesia (2457).
Psychiatric ...Orally, L-phenylalanine has been associated with anxiety, insomnia, and, more rarely, hypomania (68827,68829). DL-phenylalanine has been associated with fatigue and sedation (9951).
General
...Orally, rhodiola seems to be well tolerated.
Most Common Adverse Effects:
Orally: Dizziness, increased or decreased production of saliva.
Gastrointestinal ...Orally, rhodiola extract may cause dry mouth or excessive saliva production (16410,16411).
Neurologic/CNS ...Orally, rhodiola extract can cause dizziness (16410).
General
...Orally, selenium is generally well-tolerated when used in doses that do not exceed the tolerable upper intake level (UL) of 400 mcg daily.
Intravenously, selenium is generally well-tolerated.
Most Common Adverse Effects:
Orally: Gastric discomfort, headache, and rash. Excessive amounts can cause alopecia, dermatitis, fatigue, nail changes, nausea and vomiting, and weight loss.
Serious Adverse Effects (Rare):
Orally: Excessive ingestion has led to cases of multi-organ failure and death.
Dermatologic ...Excess selenium can produce selenosis in humans, affecting liver, skin, nails, and hair (74304,74326,74397,74495,90360) as well as dermatitis (74304). Results from the Nutritional Prevention of Cancer Trial conducted among individuals at high risk of nonmelanoma skin cancer demonstrate that selenium supplementation is ineffective at preventing basal cell carcinoma and that it increases the risk of squamous cell carcinoma and total nonmelanoma skin cancer (10687). Mild skin rash has been reported in patients taking up to 200 mcg of selenium daily for up to 12 months (97943).
Endocrine
...Multiple clinical studies have found an association between increased intake of selenium, either in the diet or as a supplement, and the risk for type 2 diabetes (97091,99661).
One meta-analysis shows that a selenium plasma level of 90 mcg/L or 140 mcg/L is associated with a 50% or 260% increased risk for developing type 2 diabetes, respectively, when compared with plasma levels below 90 mcg/L. Additionally, consuming selenium in amounts exceeding the recommended dietary allowance (RDA) is associated with an increased risk of developing diabetes when compared with consuming less than the RDA daily. Also, taking selenium 200 mcg daily as a supplement is associated with an 11% increased risk for diabetes when compared with a placebo supplement (99661).
Hypothyroidism, secondary to iodine deficiency, has been reported as a result of selenium intravenous administration (14563,14565). One large human clinical trial suggested a possible increased risk of type 2 diabetes mellitus in the selenium group (16707).
Gastrointestinal ...In human research, nausea, vomiting, and liver dysfunction has been reported as a result of high selenium exposure (74439,74376). Mild gastric discomfort has been reported in patients taking up to 200 mcg of selenium daily for up to 12 months (97943).
Genitourinary ...The effect of selenium supplementation on semen parameters is unclear. In human research, selenium supplementation may reduce sperm motility (9729); however, follow-up research reported no effect on sperm motility or any other semen quality parameter (74441).
Neurologic/CNS ...Chronic exposure to organic and inorganic selenium may cause neurotoxicity, particularly motor neuron degeneration, leading to an increased risk of amyotrophic lateral sclerosis (ALS) (74304). Mild headache has been reported in patients taking up to 200 mcg of selenium daily for up to 12 months (97943).
General
...Orally, tyrosine seems to be well tolerated.
No serious adverse effects have been documented; however, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Fatigue, headache, heartburn, and nausea.
Gastrointestinal ...Orally, tyrosine can cause nausea and heartburn when taken at a dose of 150 mg/kg (7211). Taking tyrosine 4 grams daily in combination with 5-hydroxytryptophan 800 mg and carbidopa 100 mg can cause diarrhea, nausea, and vomiting. These effects can be mitigated by lowering the dosage (918).
Musculoskeletal ...Orally, larger doses of tyrosine (150 mg/kg) can cause arthralgia, but this is uncommon (7211).
Neurologic/CNS ...Orally, larger doses of tyrosine (150 mg/kg) can cause headache and fatigue (7211). Taking a combination of tyrosine 4 grams, 5-hydroxytryptophan 800 mg, and carbidopa 100 mg can cause drowsiness and agitation. These effects can be mitigated by lowering the dosage (918).
General
...Orally or by injection, vitamin B6 is well tolerated in doses less than 100 mg daily.
Most Common Adverse Effects:
Orally or by injection: Abdominal pain, allergic reactions, headache, heartburn, loss of appetite, nausea, somnolence, vomiting.
Serious Adverse Effects (Rare):
Orally or by injection: Sensory neuropathy (high doses).
Dermatologic ...Orally, vitamin B6 (pyridoxine) has been linked to reports of skin and other allergic reactions and photosensitivity (8195,9479,90375). High-dose vitamin B6 (80 mg daily as pyridoxine) and vitamin B12 (20 mcg daily) have been associated with cases of rosacea fulminans characterized by intense erythema with nodules, papules, and pustules. Symptoms may persist for up to 4 months after the supplement is stopped, and may require treatment with systemic corticosteroids and topical therapy (10998).
Gastrointestinal ...Orally or by injection, vitamin B6 (pyridoxine) can cause nausea, vomiting, heartburn, abdominal pain, mild diarrhea, and loss of appetite (8195,9479,16306,83064,83103,107124,107127,107135). In a clinical trial, one patient experienced infectious gastroenteritis that was deemed possibly related to taking vitamin B6 (pyridoxine) orally up to 20 mg/kg daily (90796). One small case-control study has raised concern that long-term dietary vitamin B6 intake in amounts ranging from 3.56-6.59 mg daily can increase the risk of ulcerative colitis (3350).
Hematologic ...Orally or by injection, vitamin B6 (pyridoxine) can cause decreased serum folic acid concentrations (8195,9479). One case of persistent bleeding of unknown origin has been reported in a clinical trial for a patient who used vitamin B6 (pyridoxine) 100 mg twice daily on days 16 to 35 of the menstrual cycle (83103). It is unclear if this effect was due to vitamin B6 intake.
Musculoskeletal ...Orally or by injection, vitamin B6 (pyridoxine) can cause breast soreness or enlargement (8195).
Neurologic/CNS ...Orally or by injection, vitamin B6 (pyridoxine) can cause headache, paresthesia, and somnolence (8195,9479,16306). Vitamin B6 (pyridoxine) can also cause sensory neuropathy, which is related to daily dose and duration of intake. Doses exceeding 1000 mg daily or total doses of 1000 grams or more pose the most risk, although neuropathy can occur with lower daily or total doses as well (8195). The mechanism of the neurotoxicity is unknown, but is thought to occur when the liver's capacity to phosphorylate pyridoxine via the active coenzyme pyridoxal phosphate is exceeded (8204). Some researchers recommend taking vitamin B6 as pyridoxal phosphate to avoid pyridoxine neuropathy, but its safety is unknown (8204). Vitamin B6 (pyridoxine) neuropathy is characterized by numbness and impairment of the sense of position and vibration of the distal limbs, and a gradual progressive sensory ataxia (8196,10439). The syndrome is usually reversible with discontinuation of pyridoxine at the first appearance of neurologic symptoms. Residual symptoms have been reported in patients taking more than 2 grams daily for extended periods (8195,8196). Tell patients daily doses of 100 mg or less are unlikely to cause problems (3094).
Oncologic ...In females, population research has found that a median intake of vitamin B6 1. 63 mg daily is associated with a 3.6-fold increased risk of rectal cancer when compared with a median intake of 1.05 mg daily (83024). A post-hoc subgroup analysis of results from clinical research in adults with a history of recent stroke or ischemic attack suggests that taking folic acid, vitamin B12, and vitamin B6 does not increase cancer risk overall, although it was associated with an increased risk of cancer in patients who also had diabetes (90378). Also, in patients with nasopharyngeal carcinoma, population research has found that consuming at least 8.6 mg daily of supplemental vitamin B6 during treatment was associated with a lower overall survival rate over 5 years, as well as a reduced progression-free survival, when compared with non-users and those with intakes of up to 8.6 mg daily (107134).
