| Ingredients | Amount Per Serving |
|---|---|
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(Withania somnifera )
(standardized for 7% Total Withanolides)
|
200 mg |
|
(Bacopa monnieri )
(Standardized for 35% Bacosides)
|
200 mg |
|
(Ginkgo biloba )
(leaf)
(Standardized for 22% Ginkgoflavonglycosides, and 5% total terpene lactones)
|
100 mg |
| 50 mg | |
|
Bronson BioAccelerators
|
23 mg |
|
(root)
|
|
|
Trikatu
|
|
|
Digezyme
|
|
Gelatin, Magnesium Stearate, Silicon Dioxide (Alt. Name: SiO2), Microcrystalline Cellulose
Below is general information about the effectiveness of the known ingredients contained in the product Cogni-PS Plus. 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
Below is general information about the safety of the known ingredients contained in the product Cogni-PS Plus. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Ashwagandha has been used with apparent safety in doses of up to 1250 mg daily for up to 6 months (3710,11301,19271,90649,90652,90653,97292,101816,102682,102683) (102684,102685,102687,103476,105824,109586,109588,109589,109590). ...when used topically. Ashwagandha lotion has been used with apparent safety in concentrations up to 8% for up to 2 months (111538).
PREGNANCY: LIKELY UNSAFE
when used orally.
Ashwagandha has abortifacient effects (12).
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when taken orally and appropriately. Bacillus coagulans spores in doses up to 6 billion colony-forming units (CFUs) daily have been used with apparent safety in clinical studies for up to 3 months (92726,92730,92734,92735,92736,92739,92740,104231,105169)(107611,107612,107614). Lower doses of B. coagulans up to 100 million CFUs daily have been used with apparent safety in clinical studies for up to one year (92738). There is insufficient reliable information available about the safety of non-viable, heat-killed B. coagulans formulations when used orally.
CHILDREN: POSSIBLY SAFE
when taken orally and appropriately.
Bacillus coagulans spores in doses up to 100 million colony-forming units (CFUs) daily have been used with apparent safety in clinical studies in infants of most ages for up to one year (92729,92733,92738) and in doses of one billion CFUs in children aged 6-8 years for 3 months (107615). There is insufficient reliable information available about the safety of Bacillus coagulans in preterm infants with a birth weight under 1000 grams. Cases of bacteremia have occurred rarely in preterm infants given other probiotics (102416,111610,111612,111613,111850,111852,111853). The US Food and Drug Administration (FDA) has issued a warning about cases of serious infections caused by probiotics reported in very preterm or very low birth weight infants under 1000 grams (111610). Similarly, the American Academy of Pediatrics does not support the routine administration of probiotics to these infants due to conflicting data on safety and efficacy (111608).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Bacopa has been used safely in clinical trials at a dose of up to 600 mg daily for up to 12 weeks (10058,10059,17946,97605).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Clinical research suggests bacopa extract might be safe to use at a dose of 225 mg daily for up to 6 months or 320 mg daily for up to 14 weeks in children aged 6-14 years (33304,97603,109625).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Black pepper has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when black pepper oil is applied topically. Black pepper oil is nonirritating to the skin and is generally well tolerated (11). ...when black pepper oil is inhaled through the nose or as a vapor through the mouth, short-term. Black pepper oil as a vapor or as an olfactory stimulant has been used with apparent safety in clinical studies for up to 3 days and 30 days, respectively (29159,29160,29161,90502). There is insufficient reliable information available about the safety of black pepper when used orally in medicinal amounts.
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (11).
CHILDREN: POSSIBLY UNSAFE
when used orally in large amounts.
Fatal cases of pepper aspiration have been reported in some patients (5619,5620). There is insufficient reliable information available about the safety of topical pepper oil when used in children.
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods (11).
PREGNANCY: LIKELY UNSAFE
when used orally in large amounts.
Black pepper might have abortifacient effects (11,19); contraindicated. There is insufficient reliable information available about the safety of topical pepper when used during pregnancy.
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (11).
There is insufficient reliable information available about the safety of black pepper when used in medicinal amounts during breast-feeding.
LIKELY SAFE ...when used orally and appropriately. Ginger has been safely used in multiple clinical trials (721,722,723,5343,7048,7084,7085,7400,7623,11346)(12472,13080,13237,13244,17369,17928,17929,89889,89890,89894)(89895,89898,89899,90102,96252,96253,96259,96260,96669) (101760,101761,101762,103359,107903).
POSSIBLY SAFE ...when used topically and appropriately, short-term (89893,89897).
CHILDREN: LIKELY SAFE
when consumed in the amounts typically found in foods.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Ginger powder has been used with apparent safety at a dose of up to 750 mg daily for 4 days in girls aged 14-18 years (96255).
PREGNANCY: LIKELY SAFE
when consumed in the amounts typically found in foods.
Ginger is considered a first-line nonpharmacological treatment option for nausea in pregnancy by the American College of Obstetrics and Gynecology (ACOG) (111601). However, it should not be used long-term or without medical supervision and close monitoring.
PREGNANCY: POSSIBLY SAFE
when used for medicinal purposes.
Despite some early reports of adverse effects (721,7083) and one observational study suggesting that taking dried ginger and other herbal supplements during the first 20 weeks of pregnancy marginally increased the chance of stillbirth (96254), most research shows that ginger is unlikely to cause harm to the baby. The risk for major malformations in infants of parents who took ginger when pregnant does not appear to be higher than the baseline rate of 1% to 3% (721,1922,5343,11346,13071,13080,96254). Also, other research suggests that ginger intake during various trimesters does not significantly affect the risk of spontaneous abortion, congenital malformations, stillbirth, perinatal death, preterm birth, low birth weight, or low Apgar scores (18211,90103). Ginger use has been associated with an increase in non-severe vaginal bleeding, including spotting, after week 17 of pregnancy (18211).
LACTATION: LIKELY SAFE
when consumed in the amounts typically found in foods.
There is insufficient reliable information available about the safety of ginger when used for medicinal purposes; avoid amounts greater than those found in foods.
LIKELY SAFE ...when used orally and appropriately. Standardized ginkgo leaf extracts have been used safely in trials lasting for several weeks up to 6 years (1514,1515,3461,5717,5718,6211,6212,6213,6214,6215)(6216,6222,6223,6224,6225,6490,14383,14499,16634,16635)(16636,16637,17402,17716,17718,87794,87819,87826,87848,87864)(87888,87897,87901,87904,89701,89707,107359,107360). There have been some reports of arrhythmias associated with ginkgo leaf extract. However, it is not yet clear if ginkgo might cause arrhythmia (105253,105254). There is some concern about toxic and carcinogenic effects seen in animals exposed to a ginkgo leaf extract containing 31.2% flavonoids, 15.4% terpenoids, and 10.45 ppm ginkgolic acid, in doses of 100 to 2000 mg/kg five times per week for 2 years (18272). However, the clinical relevance of this data for humans, using typical doses, is unclear. The content of the extract used is not identical to that commonly used in supplement products, and the doses studied are much higher than those typically used by humans. A single dose of 50 mg/kg in rats is estimated to be equivalent to a single dose of about 240 mg in humans (18272).
POSSIBLY SAFE ...when used intravenously, short-term. A standardized ginkgo leaf extract called EGb 761 ONC has been safely administered intravenously for up to 14 days (9871,9872,107360,107452). A Chinese preparation containing ginkgo leaf extract and dipyridamole has been safely administered intravenously for up to 30 days (102881,102882). ...when applied topically, short-term. There was no dermal irritation during a 24-hour patch test using the leaf extract, and no sensitization with repeat applications (112946). When used topically in cosmetics, extracts of ginkgo leaves are reported to be safe, but there is insufficient data to determine the safety of nut and root extracts, and isolated biflavones and terpenoids (112946).
POSSIBLY UNSAFE ...when the roasted seed or crude ginkgo plant is used orally. Consuming more than 10 roasted seeds per day can cause difficulty breathing, weak pulse, seizures, loss of consciousness, and shock (8231,8232). Crude ginkgo plant parts can exceed concentrations of 5 ppm of the toxic ginkgolic acid constituents and can cause severe allergic reactions (5714).
LIKELY UNSAFE ...when the fresh ginkgo seed is used orally. Fresh seeds are toxic and potentially deadly (11296).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
There is concern that ginkgo might have labor-inducing and hormonal effects. There is also concern that the antiplatelet effects of ginkgo could prolong bleeding time if taken around the time of labor and delivery (15052). Theoretically, ginkgo might adversely affect pregnancy outcome; avoid using during pregnancy.
LACTATION:
Insufficient reliable information available; avoid using.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term (87790,89708).
A specific ginkgo dried extract (Ginko T.D., Tolidaru Pharmaceuticals), has been safely used in doses of 80-120 mg daily for 6 weeks in children aged 6-14 years (17112,95669). Another specific combination product containing ginkgo leaf extract and American ginseng extract (AD-FX, CV Technologies, Canada) has also been safely used in children aged 3-17 years for up to 4 weeks (8235).
CHILDREN: LIKELY UNSAFE
when ginkgo seed is used orally.
The fresh seeds have caused seizures and death in children (8231,11296).
POSSIBLY SAFE ...when used orally and appropriately. Phosphatidylserine has been used with apparent safety at dose of up to 300 mg daily for up to 6 months (2255,2437,2438,2439,2440,2441,7118,15539,68855).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term (7117).
Phosphatidylserine has been used with apparent safety in clinical research in doses of 200-300 mg daily for up to 4 months in children aged 4-18 years (7117,89498).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Cogni-PS Plus. 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 ashwagandha with antidiabetes drugs might increase the risk of hypoglycemia.
 Details
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Theoretically, taking ashwagandha with antihypertensive drugs might increase the risk of hypotension.
Details
Animal research suggests that ashwagandha might lower systolic and diastolic blood pressure (19279). Theoretically, ashwagandha might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.
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Theoretically, taking ashwagandha might increase the sedative effects of benzodiazepines.
Details
There is preliminary evidence that ashwagandha might have an additive effect with diazepam (Valium) and clonazepam (Klonopin) (3710). This may also occur with other benzodiazepines.
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Theoretically, taking ashwagandha might increase the sedative effects of CNS depressants.
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Ashwagandha seems to have sedative effects. Theoretically, this may potentiate the effects of barbiturates, other sedatives, and anxiolytics (3710).
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Theoretically, ashwagandha might decrease the levels and clinical effects of CYP1A2 substrates.
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In vitro research shows that ashwagandha extract induces CYP1A2 enzymes (111404).
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Theoretically, ashwagandha might decrease the levels and clinical effects of CYP3A4 substrates.
Details
In vitro research shows that ashwagandha extract induces CYP3A4 enzymes (111404).
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Theoretically, taking ashwagandha with hepatotoxic drugs might increase the risk of liver damage.
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Theoretically, taking ashwagandha might decrease the effects of immunosuppressants.
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Ashwagandha might increase the effects and adverse effects of thyroid hormone.
Details
Concomitant use of ashwagandha with thyroid hormones may cause additive therapeutic and adverse effects. Preliminary clinical research and animal studies suggest that ashwagandha boosts thyroid hormone synthesis and secretion (19281,19282,97292). In one clinical study, ashwagandha increased triiodothyronine (T3) and thyroxine (T4) levels by 41.5% and 19.6%, respectively, and reduced serum TSH levels by 17.4% from baseline in adults with subclinical hypothyroidism (97292).
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Theoretically, taking antibiotics with Bacillus coagulans might decrease the effectiveness of B. coagulans.
Details
B. coagulans preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms. Tell patients to separate administration of antibiotics and B. coagulans preparations by at least two hours.
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Theoretically, concurrent use might decrease the effectiveness of both agents.
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Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels, which could counteract the effects of anticholinergic drugs (17946). Similarly, anticholinergic drugs might counteract the cholinergic effects of bacopa.
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Theoretically, bacopa might increase the effects and adverse effects of cevimeline.
Details
In one case, a 58-year-old female taking cevimeline long-term for Sjogren syndrome experienced hyperhidrosis, malaise, nausea, and tachycardia shortly after taking a single dose of bacopa. Symptoms resolved after two days. Cevimeline is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4, and researchers theorize that bacopa may have inhibited these isoenzymes (109627). However, it is unclear if bacopa causes clinically significant inhibition of either CYP2D6 or CYP3A4.
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Theoretically, concurrent use of bacopa with other cholinergic drugs might have additive effects.
Details
Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels (17946). Theoretically, this could result in additive cholinergic effects when used with cholinergic drugs.
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Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.
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Theoretically, bacopa might increase the levels and adverse effects of CYP2C19 substrates.
Details
In vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C19 enzymes (97606). It is not known whether this is clinically significant.
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Theoretically, bacopa might increase the levels and adverse effects of CYP2C9 substrates.
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Theoretically, bacopa might increase the levels and adverse effects of CYP3A4 substrates.
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Theoretically, bacopa might have additive effects when used with thyroid hormone.
Details
Animal research suggests that bacopa increases thyroxine (T4) levels in mice by about 40% (33286).
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Theoretically, black pepper might increase the effects and side effects of amoxicillin.
Details
Animal research shows that taking piperine, a constituent of black pepper, with amoxicillin increases plasma levels of amoxicillin (29269). This has not been reported in humans.
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Theoretically, black pepper might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.
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In vitro research shows that piperine, a constituent of black pepper, seems to inhibit platelet aggregation (29206). This has not been reported in humans.
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Theoretically, black pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Details
Animal research shows that piperine, a constituent of black pepper, can reduce blood glucose levels (29225). Monitor blood glucose levels closely. Dose adjustments might be necessary.
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Theoretically, black pepper might increase blood levels of atorvastatin.
Details
Animal research shows that taking piperine, a constituent of black pepper, 35 mg/kg can increase the maximum serum concentration of atorvastatin three-fold (104188). This has not been reported in humans.
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Theoretically, black pepper might increase blood levels of carbamazepine, potentially increasing the effects and side effects of carbamazepine.
Details
One clinical study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that taking a single 20 mg dose of purified piperine, a constituent of black pepper, increases carbamazepine levels. Piperine may increase carbamazepine absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or inhibiting cytochrome P450 3A4 (CYP3A4) in the gut wall. Absorption was significantly increased by 7-10 mcg/mL/hour. The time to eliminate carbamazepine was also increased by 4-8 hours. Although carbamazepine levels were increased, this did not appear to increase side effects (16833). In vitro research also shows that piperine can increase carbamazepine levels by 11% in a time-dependent manner (103819).
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Theoretically, black pepper might increase the effects and side effects of cyclosporine.
Details
In vitro research shows that piperine, a constituent of black pepper, increases the bioavailability of cyclosporine (29282). This has not been reported in humans.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP1A1.
Details
In vitro research suggests that piperine, a constituent of black pepper, inhibits CYP1A1 (29213). This has not been reported in humans.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP2B1.
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In vitro research suggests that piperine, a constituent of black pepper, inhibits CYP2B1 (29332). This has not been reported in humans.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.
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Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
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Theoretically, black pepper might increase blood levels of lithium due to its diuretic effects. The dose of lithium might need to be reduced.
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Black pepper is thought to have diuretic properties (11).
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Black pepper might increase blood levels of nevirapine.
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Clinical research shows that piperine, a constituent of black pepper, increases the plasma concentration of nevirapine. However, no adverse effects were observed in this study (29209).
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Theoretically, black pepper might increase levels of P-glycoprotein substrates.
Details
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Theoretically, black pepper might increase the sedative effects of pentobarbital.
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Animal research shows that piperine, a constituent of black pepper, increases pentobarbital-induced sleeping time (29214).
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Black pepper might increase blood levels of phenytoin.
Details
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption, slow elimination, and increase levels of phenytoin (537,14442). Taking a single dose of black pepper 1 gram along with phenytoin seems to double the serum concentration of phenytoin (14375). Consuming a soup with black pepper providing piperine 44 mg/200 mL of soup along with phenytoin also seems to increase phenytoin levels when compared with consuming the same soup without black pepper (14442).
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Black pepper might increase blood levels of propranolol.
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Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of propranolol (538).
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Black pepper might increase blood levels of rifampin.
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Black pepper might increase blood levels of theophylline.
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Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of theophylline (538).
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Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Details
Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation (7622,12634,20321,20322,20323,96257). However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials (96257). Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.
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Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.
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Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension.
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Some animal and in vitro research suggests that ginger has hypotensive and calcium channel-blocking effects (12633). Another animal study shows that concomitant administration of ginger and the calcium channel blocker amlodipine leads to greater reductions in blood pressure when compared with amlodipine alone (107901).
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Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.
Details
In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time (20401).
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Theoretically, ginger might increase the levels of CYP1A2 substrates.
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In vitro research shows that ginger inhibits CYP1A2 activity (111544). However, this interaction has not been reported in humans.
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Theoretically, ginger might increase the levels of CYP2B6 substrates.
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In vitro research shows that ginger inhibits CYP2B6 activity (111544). However, this interaction has not been reported in humans.
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Theoretically, ginger might increase the levels of CYP2C9 substrates.
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In vitro research shows that ginger inhibits CYP2C9 activity (111544). However, this interaction has not been reported in humans.
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Ginger might increase or decrease the levels of CYP3A4 substrates.
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In vitro research and some case reports suggest that ginger inhibits CYP3A4 activity (111544,111644). Three case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are CYP3A4 substrates (imatinib, dabrafenib, and crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644).
Conversely, other in vitro research suggests that ginger induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates (111404). However, this interaction has not been reported in humans. |
Theoretically, ginger might increase levels of losartan and the risk of hypotension.
Details
In animal research, ginger increased the levels and hypotensive effects of a single dose of losartan (102459). It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.
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Theoretically, ginger might increase levels of metronidazole.
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In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced (20350).
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Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.
Details
Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone (20324).
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Ginger might increase the absorption and blood levels of P-glycoprotein (P-gp) substrates.
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In vitro research and case reports suggest that ginger inhibits drug efflux by P-gp, potentially increasing absorption and serum levels of P-gp substrates (111544,111644). Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are P-gp substrates (trametinib, crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644).
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Ginger might increase the risk of bleeding with phenprocoumon.
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Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea (12880).
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Ginger might increase the risk of bleeding with warfarin.
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Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation (7622,12634,20321,20322,20323). In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin (12880). In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen (20349). A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months (20348). However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin (12881,15176). Until more is known, monitor INRs closely in patients taking large amounts of ginger.
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Theoretically, ginkgo might decrease the levels and clinical effects of alprazolam.
Details
In clinical research, ginkgo extract (Ginkgold) 120 mg twice daily seems to decrease alprazolam levels by about 17%. However, ginkgo does not appear to decrease the elimination half-life of alprazolam. This suggests that ginkgo is more likely to decrease absorption of alprazolam rather than induce hepatic metabolism of alprazolam (11029).
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Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin. Theoretically, ginkgo might increase the risk of bleeding if used with other anticoagulant or antiplatelet drugs.
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Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation (6048,9760). Several case reports have documented serious bleeding events in patients taking ginkgo (244,578,579,8581,13002,13135,13179,13194,14456,87868). However, population and clinical studies have produced mixed results. Some evidence shows that short-term use of ginkgo leaf does not significantly reduce platelet aggregation and blood clotting (87732). A study in healthy males who took a specific ginkgo leaf extract (EGb 761) 160 mg twice daily for 7 days found no change in prothrombin time (12114). An analysis of a large medical record database suggests that ginkgo increases the risk of a bleeding adverse event by 38% when taken concurrently with warfarin (91326). It has been suggested that ginkgo has to be taken for at least 2-3 weeks to have a significant effect on platelet aggregation (14811). However, a meta-analysis of 18 studies using standardized ginkgo extracts, 80-480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT (17179). In addition, a single dose of ginkgo plus clopidogrel (14811) or ticlopidine does not seem to significantly increase bleeding time or platelet aggregation (17111,87846). Also, taking ginkgo leaf extract daily for 8 days in conjunction with rivaroxaban does not affect anti-factor Xa activity; however, this study did not evaluate bleeding time (109526).
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Theoretically, ginkgo might reduce the effectiveness of anticonvulsants.
Details
Ginkgo seeds contain ginkgotoxin. Large amounts of ginkgotoxin can cause neurotoxicity and seizure. Ginkgotoxin is present in much larger amounts in ginkgo seeds than leaves (8232). Ginkgo leaf extract contains trace amounts of ginkgotoxin. The amount of ginkgotoxin in ginkgo leaf and leaf extract seems unlikely to cause toxicity (11296). However, there are anecdotal reports of seizure occurring after use of ginkgo leaf both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy (7030,7090).
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Theoretically, taking ginkgo with antidiabetes drugs might alter the response to antidiabetes drugs.
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Ginkgo leaf extract seems to alter insulin secretion and metabolism, and might affect blood glucose levels in people with type 2 diabetes (5719,14448,103574). The effect of ginkgo seems to differ depending on the insulin and treatment status of the patient. In diet-controlled diabetes patients with hyperinsulinemia, taking ginkgo does not seem to significantly affect insulin or blood glucose levels. In patients with hyperinsulinemia who are treated with oral hypoglycemic agents, taking ginkgo seems to decrease insulin levels and increase blood glucose following an oral glucose tolerance test. Researchers speculate that this could be due to ginkgo-enhanced hepatic metabolism of insulin. In patients with pancreatic exhaustion, taking ginkgo seems to stimulate pancreatic beta-cells, resulting in increased insulin and C-peptide levels, but with no significant change in blood glucose levels in response to an oral glucose tolerance test (14448).
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Theoretically, ginkgo might decrease the levels and clinical effects of atorvastatin.
Details
In humans, intake of ginkgo extract appears to increase atorvastatin clearance, reducing the area under the curve of atorvastatin by 10% to 14% and the maximum concentration by 29%. However, this interaction does not appear to affect cholesterol synthesis and absorption (89706). Further, a model in rats with hyperlipidemia suggests that administering ginkgo extract does not impact blood levels of atorvastatin and leads to lower total cholesterol, low-density lipoprotein cholesterol, and triglycerides when compared with rats given atorvastatin alone (111331).
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Theoretically, ginkgo might increase levels of drugs metabolized by CYP1A2.
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Theoretically, ginkgo might decrease levels of drugs metabolized by CYP2C19.
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Some clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce CYP2C19 enzymes and potentially decrease levels of drugs metabolized by these enzymes (13108). However, other clinical research shows that taking ginkgo 120 mg twice daily for 12 days has no effect on levels of drugs metabolized by CYP2C19 (87824).
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Theoretically, ginkgo might increase levels of drugs metabolized by CYP2C9.
Details
In vitro, a specific standardized extract of ginkgo leaf (EGb 761) inhibits CYP2C9 activity (11026,12061,14337). The terpenoid (ginkgolides) and flavonoid (quercetin, kaempferol, etc.) constituents seem to be responsible for this effect. Most ginkgo extracts contain some amount of these constituents. Therefore, other ginkgo leaf extracts might also inhibit the CYP2C9 enzyme. However, clinical research suggests that ginkgo might not have a significant effect on CYP2C9 in humans. Ginkgo does not seem to significantly affect the pharmacokinetics of CYP2C9 substrates diclofenac or tolbutamide.
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Theoretically, ginkgo might decrease levels of drugs metabolized by CYP3A4.
Details
There is conflicting evidence about whether ginkgo induces or inhibits CYP3A4 (1303,6423,6450,11026,87800,87805,111330). Ginkgo does not appear to affect hepatic CYP3A4 (11029). However, it is not known if ginkgo affects intestinal CYP3A4. Preliminary clinical research suggests that taking ginkgo does not significantly affect levels of donepezil, lopinavir, or ritonavir, which are all CYP3A4 substrates (11027,87800,93578). Other clinical research also suggests ginkgo does not significantly affect CYP3A4 activity (10847). However, there are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4) (16821,25464).
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Theoretically, ginkgo might decrease the levels and clinical effects of efavirenz.
Details
There are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. In one case, an HIV-positive male experienced over a 50% decrease in efavirenz levels over the course of 14 months while taking ginkgo extract. HIV-1 RNA copies also increased substantially, from less than 50 to more than 1500. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4) (16821). In another case report, a patient stable on antiviral therapy including efavirenz for 10 years, had an increase in viral load from <50 copies/mL to 1350 copies/mL after 2 months of taking a combination of supplements including ginkgo. After stopping ginkgo, the viral load was again controlled with the same antiviral therapy regimen (25464).
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Theoretically, ginkgo might increase the risk of bleeding when used with ibuprofen.
Details
Ginkgo might have antiplatelet effects and has been associated with several case reports of spontaneous bleeding. In one case, a 71-year-old male had taken a specific ginkgo extract (Gingium, Biocur) 40 mg twice daily for 2.5 years. About 4 weeks after starting ibuprofen 600 mg daily he experienced a fatal intracerebral hemorrhage (13179). However, the antiplatelet effects of ginkgo have been questioned. A meta-analysis and other studies have not found a significant antiplatelet effect with standardized ginkgo extracts, 80 mg to 480 mg taken daily for up to 32 weeks (17179).
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Theoretically, taking ginkgo with oral, but not intravenous, nifedipine might increase levels and adverse effects of nifedipine.
Details
Animal research and some clinical evidence suggests that taking ginkgo leaf extract orally in combination with oral nifedipine might increase nifedipine levels and cause increased side effects, such as headaches, dizziness, and hot flushes (87764,87765). However, taking ginkgo orally does not seem to affect the pharmacokinetics of intravenous nifedipine (87765).
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Theoretically, taking ginkgo with omeprazole might decrease the levels and clinical effects of omeprazole.
Details
Clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce cytochrome P450 (CYP) 2C19 enzymes and decrease levels of omeprazole by about 27% to 42% (13108).
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Theoretically, taking ginkgo with P-glycoprotein substrates might increase the levels and adverse effects of these substrates.
Details
A small clinical study in healthy volunteers shows that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of the P-glycoprotein substrate, talinolol, by 36% in healthy male individuals. However, single doses of ginkgo do not have the same effect (87830).
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Theoretically, taking ginkgo with risperidone might increase the levels and adverse effects of risperidone.
Details
A single case of priapism has been reported for a 26-year-old male with schizophrenia who used risperidone 3 mg daily along with ginkgo extract 160 mg daily (87796). Risperidone is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4. CYP3A4 activity might be affected by ginkgo. Theoretically, ginkgo may inhibit the metabolism of risperidone and increase the risk of adverse effects.
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Theoretically, ginkgo might decrease the levels and clinical effects of rosiglitazone.
Details
Animal research shows that ginkgo leaf extract orally 100 or 200 mg/kg daily for 10 days alters the pharmacodynamics of rosiglitazone in a dose-dependent manner. The 100 mg/kg and 200 mg/kg doses reduce the area under the concentration time curve (AUC) of rosiglitazone by 39% and 52%, respectively, and the half-life by 28% and 39%, respectively. It is hypothesized that these changes may be due to induction of cytochrome P450 2C8 by ginkgo (109525).
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Theoretically, taking ginkgo with drugs that lower the seizure threshold might increase the risk for convulsions.
Details
Ginkgo seeds contain ginkgotoxin. Large amounts of ginkgotoxin can cause neurotoxicity and seizure. Ginkgotoxin is present in much larger amounts in ginkgo seeds than leaves (8232). Ginkgo leaf extract contains trace amounts of ginkgotoxin. The amount of ginkgotoxin in ginkgo leaf and leaf extract seems unlikely to cause toxicity (11296). However, there are anecdotal reports of seizure occurring after use of ginkgo leaf both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy (7030,7090,14281).
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Theoretically, ginkgo might decrease the levels and clinical effects of simvastatin.
Details
Clinical research shows that taking ginkgo extract can reduce the area under the curve and maximum concentration of simvastatin by 32% to 39%. However, ginkgo extract does not seem to affect the cholesterol-lowering ability of simvastatin (89704).
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Theoretically, ginkgo might increase the levels and clinical effects of sofosbuvir.
Details
Animal research in rats shows that giving a ginkgo extract 25 mg/kg orally daily for 14 days increases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 11%, increases the half-life by 60%, and increases the plasma concentration at 4 hours by 38%. This interaction appears to be related to the inhibition of intestinal P-glycoprotein by ginkgo (109524).
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Theoretically, ginkgo might increase the blood levels of tacrolimus.
Details
In vitro evidence suggests that certain biflavonoids in ginkgo leaves (i.e. amentoflavone, ginkgetin, bilobetin) may inhibit the metabolism of tacrolimus by up to 50%. This interaction appears to be time-dependent and due to inhibition of cytochrome P450 (CYP) 3A4 by these bioflavonoids. In rats given tacrolimus 1 mg/kg orally, amentoflavone was shown to increase the area under the concentration time curve (AUC) of tacrolimus by 3.8-fold (111330).
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Taking ginkgo with talinolol seems to increase blood levels of talinolol.
Details
There is some evidence that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of talinolol by 36% in healthy male individuals. However, single doses of ginkgo do not seem to affect talinolol pharmacokinetics (87830).
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Theoretically, ginkgo might increase the levels and clinical effects of trazodone.
Details
In a case report, an Alzheimer patient taking trazodone 20 mg twice daily and ginkgo leaf extract 80 mg twice daily for four doses became comatose. The coma was reversed by administration of flumazenil (Romazicon). Coma might have been induced by excessive GABA-ergic activity. Ginkgo flavonoids are thought to have GABA-ergic activity and act directly on benzodiazepine receptors. Ginkgo might also increase metabolism of trazodone to active GABA-ergic metabolites, possibly by inducing cytochrome P450 3A4 (CYP3A4) metabolism (6423).
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Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin.
Details
Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation (6048,9760). Several case reports have documented serious bleeding events in patients taking ginkgo (244,576,578,579,8581,13002,13135,13179,13194,14456,87868). Information from a medical database suggests that when taken concurrently with warfarin, ginkgo increases the risk of a bleeding adverse event by 38% (91326). There is also some evidence that ginkgo leaf extract can inhibit cytochrome P450 2C9, an enzyme that metabolizes warfarin. This could result in increased warfarin levels (12061). However, population and clinical research has produced mixed results. Clinical research in healthy people suggests that ginkgo has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin (12881,15176,87727,87889). A meta-analysis of 18 studies using standardized ginkgo extracts, 80 mg to 480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT (17179). There is also some preliminary clinical research that suggests ginkgo might not significantly increase the effects of warfarin in patients that have a stable INR (11905).
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Theoretically, phosphatidylserine might decrease the effectiveness anticholinergic drugs.
Details
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Theoretically, phosphatidylserine might have additive effects with cholinergic drugs.
Details
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Below is general information about the adverse effects of the known ingredients contained in the product Cogni-PS Plus. 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, ashwagandha seems to be well-tolerated.
Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Diarrhea, gastrointestinal upset, nausea, and vomiting. However, these adverse effects do not commonly occur with typical doses.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about acute hepatitis, acute liver failure, hepatic encephalopathy, the need for liver transplantation, and death due to liver failure with ashwagandha treatment.
Dermatologic ...Orally, dermatitis has been reported in three of 42 patients in a clinical trial (19276).
Endocrine ...A case report describes a 73-year-old female who had taken an ashwagandha root extract (unspecified dose) for 2 years to treat hypothyroidism which had been previously managed with levothyroxine. The patient was diagnosed with hyperthyroidism after presenting with supraventricular tachycardia, chest pain, tremor, dizziness, fatigue, irritability, hair thinning, and low thyroid stimulating hormone (TSH) levels. Hyperthyroidism resolved after discontinuing ashwagandha (108745). Additionally, an otherwise healthy adult who was taking ashwagandha extract orally for 2 months experienced clinical and laboratory-confirmed thyrotoxicosis. Thyrotoxicosis resolved 50 days after discontinuing ashwagandha, without other treatment (114111).
Gastrointestinal ...Orally, large doses may cause gastrointestinal upset, diarrhea, and vomiting secondary to irritation of the mucous and serous membranes (3710). When taken orally, nausea and abdominal pain (19276,110490,113609) and gastritis and flatulence (90651) have been reported.
Genitourinary ...In one case report, a 28-year-old male with a decrease in libido who was taking ashwagandha 5 grams daily over 10 days subsequently experienced burning, itching, and skin and mucous membrane discoloration of the penis, as well as an oval, dusky, eroded plaque (3 cm) with erythema on the glans penis and prepuce (32537).
Hepatic ...Orally, ashwagandha in doses of 154 mg to 20 grams daily has played a role in several case reports of cholestatic, hepatocellular, and mixed liver injuries. In most of these cases, other causes of liver injury were excluded, and liver failure did not occur. Symptoms included jaundice, pruritus, malaise, fatigue, lethargy, weight loss, nausea, diarrhea, abdominal pain and distension, stool discoloration, and dark urine. Symptom onset was typically 5-180 days from first intake, although in some cases onset occurred after more than 12 months of use (102686,107372,110490,110491,111533,111535,112111,113610,114113). Laboratory findings include elevated aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, serum bilirubin, and international normalized ratio (INR) (112111,113610,114113). In most cases, liver enzymes normalized within 1-5 months after discontinuation of ashwagandha (102686,107372,110491,111535,112111,114113). However, treatment with corticosteroids, lactulose, ornithine, ursodeoxycholic acid, and plasmapheresis, among other interventions, was required in one case (111533). Rarely, use of oral ashwagandha has been reported to cause hepatic encephalopathy, liver failure requiring liver transplantation, and acute-on-chronic liver failure resulting in death (110490,113610).
Neurologic/CNS ...Orally, ashwagandha has been reported to cause drowsiness (110492,113609). Headache, neck pain, and blurry vision have been reported in a 47-year-old female taking ashwagandha, cannabis, and venlafaxine. Imaging over the course of multiple years and hospital admissions indicated numerous instances of intracranial hemorrhage and multifocal stenosis of intracranial arteries, likely secondary to reversible cerebral vasoconstriction syndrome (RCVS) (112113). It is unclear whether the RCVS and subsequent intracranial hemorrhages were precipitated by ashwagandha, cannabis, or venlafaxine.
General
...Orally, Bacillus coagulans is well tolerated.
Serious Adverse Effects (Rare):
Orally: There is concern that probiotics may cause infections in some people.
Immunologic ...Since many probiotic preparations contain live and active microorganisms, there is some concern that they might cause pathogenic infection in some patients. Bacteremia and sepsis have been reported in patients with indwelling or central venous catheters or patients who are severely ill and/or immunocompromised, including preterm infants, that were using probiotic products (4380,8561,13008,13070,90298,102416,103444,105138,105140,105141)(107543,107597,107599,111610,111612,111613,111850,111852,111853). However, reports of pathogenic colonization in relatively healthy patients with intact immune systems who do not have indwelling or central venous catheters are extremely rare (4380,4389,4390,4391,4393,4398,105139,107543,107545,107546,107547).
General
...Orally, bacopa is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, diarrhea, dry mouth, headache, nausea.
Cardiovascular ...Orally, bacopa has been reported to cause palpitations (10058).
Gastrointestinal ...Orally, bacopa has been reported to cause abdominal cramps, abdominal pain, bloating, decreased appetite, diarrhea, dry mouth, excessive thirst, flatulence, indigestion, nausea, and increased stool frequency. Rates of adverse gastrointestinal events have ranged from 12% to 30% (10058,17946,33295,97605,109623,111520).
Musculoskeletal ...Orally, bacopa has been reported to cause arthralgia, muscle fatigue, and myopathy (10058,109623,111522). In one case, a 21-year-old male experienced progressive proximal weakness, muscle atrophy, weight loss, dark urine, and elevated serum markers of myopathy, with muscle biopsy showing immune-mediated necrotizing myopathy, after taking a supplement containing bacopa for 5 years (111522).
Neurologic/CNS ...Orally, bacopa has been reported to cause drowsiness, headache, insomnia, and vivid dreams (10058,10059,17946,109623).
Other ...Orally, bacopa has been reported to cause flu like symptoms and fatigue (10058,97605,111520).
General
...Orally, black pepper seems to be well tolerated when used in the amounts found in food or when taken as a medicine as a single dose.
Topically and as aromatherapy, black pepper oil seems to be well tolerated.
Most Common Adverse Effects:
Orally: Burning aftertaste, dyspepsia, and reduced taste perception.
Inhalation: Cough.
Serious Adverse Effects (Rare):
Orally: Allergic reaction in sensitive individuals.
Gastrointestinal ...Orally, black pepper can cause a burning aftertaste (5619) and dyspepsia (38061). Single and repeated application of piperine, the active constituent in black pepper, to the tongue and oral cavity can decrease taste perception (29267). By intragastric route, black pepper 1.5 grams has been reported to cause gastrointestinal microbleeds (29164). It is not clear if such an effect would occur with oral administration.
Immunologic ...In one case report, a 17-month-old male developed hives, red eyes, facial swelling, and a severe cough following consumption of a sauce containing multiple ingredients. Allergen skin tests were positive to both black pepper and cayenne, which were found in the sauce (93947).
Ocular/Otic ...Topically, ground black pepper can cause redness of the eyes and swelling of the eyelids (5619).
Pulmonary/Respiratory ...When inhaled through the nose as an olfactory stimulant, black pepper oil has been reported to cause cough in one clinical trial (29162).
General
...Orally, ginger is generally well tolerated.
However, higher doses of 5 grams per day increase the risk of side effects and reduce tolerability. Topically, ginger seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, burping, diarrhea, heartburn, and a pepper-like irritant effect in the mouth and throat. However, some of these mild symptoms may be reduced by ingesting encapsulated ginger in place of powdered ginger.
Topically: Dermatitis in sensitive individuals.
Cardiovascular ...Orally, use of ginger resulted in mild arrhythmia in one patient in a clinical trial (16306).
Dermatologic
...Orally, ginger can cause hives (17933), as well as bruising and flushing (20316) or rash (20316).
Topically, ginger can cause dermatitis in sensitive individuals (12635,46902).
Gastrointestinal
...Orally, common side effects of ginger include nausea (17933,22602,89898,101761), belching (10380,103359), dry mouth (103359), dry retching (10380), vomiting (10380), burning sensation (10380), oral numbness (22602), abdominal discomfort (5343,89898,96253), heartburn (5343,7624,12472,16306,20316,51845,89894,89895,89898,89899)(101760,101761,101762,111543), diarrhea (5343,101760), constipation (89898,101760,101761), or a transient burning or "chilly hot" sensation of the tongue and throat (52076).
Orally, Number Ten, a specific product composed of rhubarb, ginger, astragalus, red sage, and turmeric, can increase the incidence of loose stools (20346).
Four cases of small bowel obstruction due to ginger bolus have been reported following the ingestion of raw ginger without sufficient mastication (chewing). In each case, the bolus was removed by enterotomy. Ginger is composed of cellulose and therefore is resistant to digestion. It can absorb water, which may cause it to swell and become lodged in narrow areas of the digestive tract (52115).
Genitourinary ...In one clinical trial, some patients reported increased menstrual bleeding while taking a specific ginger extract (Zintoma, Goldaru) 250 mg four times daily orally for 3 days (17931). An "intense" urge to urinate after 30 minutes was reported in two of eight patients given 0.5-1 gram of ginger (7624). However, this effect has not been corroborated elsewhere. Dysuria, flank pain, perineal pain, and urinary stream interruption have been reported in a 43-year-old male who drank ginger tea, containing 2-3 teaspoons of dry ginger, daily over 15 years. The adverse effects persisted for 4 years and were not associated with increases in urinary frequency or urgency. Upon discontinuing ginger, the patient's symptoms began to improve within one week and completely resolved after eight weeks, with no relapses six months later (107902).
Immunologic ...In one case report, a 59-year-old Japanese female with multiple allergic sensitivities developed pruritus and then anaphylactic shock after taking an oral ginger-containing herbal supplement for motion sickness (Keimei Gashinsan, Keimeido). The patient had used this supplement previously for over 20 years with no allergic reaction. The authors theorized the development of a cross-reactivity to ginger after the use of an oral supplement containing zedoary and turmeric, which are also in the Zingiberaceae family (102463).
Neurologic/CNS ...Orally, ginger may cause sedation, drowsiness, or dizziness (16306,17933,51845).
General
...Orally, ginkgo leaf extract is generally well tolerated when used for up to 6 years.
However, the seed and crude plant contain toxic constituents and should be avoided.
Intravenously, ginkgo leaf extract seems to be well tolerated when used for up to 30 days.
Topically, no adverse effects have been reported with ginkgo as a single ingredient. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Dizziness, gastrointestinal symptoms, headache.
Serious Adverse Effects (Rare):
Orally: Arrhythmia, bleeding, Stevens-Johnson syndrome.
Cardiovascular
...Cardiac arrhythmias suspected to be related to ginkgo have been reported.
Internationally, there are at least 162 reports from 18 countries, with 34% of cases considered serious, involving five deaths and four life-threatening events. Additionally, a report from Canada found that 10 out of 15 cases of arrhythmia were considered serious. Ginkgo was the only suspect ingredient in 57% of all international reports, with symptoms generally presenting within days of initiation. The most common symptoms included palpitations, tachycardia, bradycardia, syncope, and loss of consciousness. Most cases were reported to be related to oral use of ginkgo leaf products; however, some cases were associated with oral use of the seed, and others with intravenous or intramuscular use of the leaf. Documented discontinuation of ginkgo led to recovery in approximately 84% of cases where ginkgo was the sole suspect. Despite these findings, ginkgo cannot be confirmed as the causal agent. It is possible that these reports are confounded by underlying co-morbidities. Of the reported cases, the main reason for ginkgo use was tinnitus, a symptom commonly associated with pre-existing arrhythmias (105253,105254). Despite this large number of reports, only three cases of cardiac arrhythmia have been published in the literature (105253,105254). In one case, frequent nocturnal episodes of paroxysmal atrial fibrillation were reported for a 35-year-old female taking ginkgo extract 240 mg daily orally for 2 months. Arrythmias ceased following discontinuation of ginkgo (87884).
In one clinical trial, the rate of ischemic stroke and transient ischemic attacks was significantly higher in patients taking ginkgo extract orally when compared with placebo (16635). It is unclear if these events were due to ginkgo, other factors, or a combination.
Dermatologic ...Topically, ginkgo fruit pulp can cause contact dermatitis, with intense itching, edema, papules, and pustules which take 7-10 days to resolve after stopping contact (112946).
Gastrointestinal
...Orally, ginkgo extract may cause mild gastrointestinal discomfort or pain (3965,8543,17112,87818,87858), nausea and vomiting (8543,17112,87728,87844,87858), diarrhea (87844), dry mouth (17112), and constipation (5719,87787).
However, post-market surveillance suggests that the incidence of these events is relatively low, occurring in less than 2% of patients (88007).
Fresh ginkgo seeds can cause stomach ache, nausea, vomiting, or diarrhea. Ingesting roasted seeds in amounts larger than the normal food amounts of 8-10 seeds per day, or long-term, can also cause these same adverse reactions (8231,8232).
Genitourinary ...Orally, ginkgo extract has been reported to cause blood in the urine in one patient (87858).
Hematologic
...Spontaneous bleeding is one of the most concerning potential side effects associated with ginkgo.
There are several published case reports linking ginkgo to episodes of minor to severe bleeding; however, not all case reports clearly establish ginkgo as the cause of bleeding. In most cases, other bleeding risk factors were also present including taking other medications or natural medicines, old age, liver cirrhosis, recent surgery, and other conditions. In most cases, bleeding occurred after several weeks or months of taking ginkgo (13135). Large-scale clinical trials and a meta-analysis evaluating standardized ginkgo leaf extracts show that the incidence of bleeding in patients taking ginkgo is not significantly higher than in those taking placebo (16634,16635,17179,17402).
There are several case reports of intracerebral bleeding. Some of these cases resulted in permanent neurological damage and one case resulted in death (244,578,8581,13135,13179,14456,87868,87977).
There are at least 4 cases of ocular bleeding including spontaneous hyphema (bleeding from the iris into the anterior part of the eye) and retrobulbar hemorrhage associated with ginkgo use (579,10450,13135).
There are also cases of surgical and post-surgical complications in patients using ginkgo. Retrobulbar hemorrhage (bleeding behind the eye) during cataract surgery has been associated with ginkgo use (10450). Excessive postoperative bleeding requiring transfusion has also occurred following laparoscopic surgery in a patient who had been taking ginkgo leaf extract (887). There have also been two cases of excessive bleeding during surgery and post-surgical hematoma in patients undergoing rhytidoplasty and blepharoplasty (13002). In another case, an elderly patient taking ginkgo experienced excessive postoperative bleeding following total hip arthroplasty (13194). In another case, use of ginkgo following liver transplantation surgery was associated with subphrenic hematoma requiring evacuation by laparotomy. The patient also subsequently experienced vitreous hemorrhage (14315). In another case, an elderly patient who had taken ginkgo chronically experienced excessive post-operative bleeding following an ambulatory surgical procedure (14453).
In another case, an elderly man experienced nose bleeds and ecchymosis following use of ginkgo. One case of diffuse alveolar hemorrhage in a female taking ginkgo and ginseng for over one year has been reported (95670). These instances of bleeding stopped when ginkgo was discontinued, and recurred when the patient started taking ginkgo again (13135).
Persistent bleeding has also occurred following dental surgery (87862) and laparoscopic cholecystectomy (88000). Nosebleed has also been reported as an adverse effect in a clinical trial (87813).
Immunologic ...Orally, ginkgo leaf extract can cause allergic skin reactions in some patients (14449,15578,112946). In one case, a patient developed acute generalized exanthematous pustulosis 48 hours after taking a single-ingredient ginkgo product. The rash resolved within 10 days after discontinuing ginkgo (14449). In another case, progressive erythema of the face, neck, trunk, and extremities occurred after two 60 mg oral doses of ginkgo extract (112946). There is also a case of Stevens-Johnson syndrome following a second administration of a preparation containing ginkgo leaf extract, choline, vitamin B6, and vitamin B12 (208). In another case, systemic edema and severe arthralgia was reported after contact with a ginkgo tree nut and manifested as multifocal lymphadenopathy associated with an allergic reaction on PET/CT scan imaging (95672).
Musculoskeletal ...Edema has been reported for three patients treated with ginkgo extract 40 mg orally three times daily (87818).
Neurologic/CNS ...Orally, ginkgo extract may cause headache (6220,8543,87818), dizziness (5719,87818), increased desire to sleep (87839), and sedation (10893) in some patients. In addition, although ginkgo leaf and ginkgo leaf extract contain only small amounts of ginkgotoxin, there are anecdotal reports of seizure occurring after use of ginkgo leaf preparations both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy (7030,7090,11296,14281).
Ocular/Otic
...Orally, ginkgo extract may cause tinnitus is some patients, although the incidence is rare (8543).
Topically, eye drops containing ginkgo extract and hyaluronic acid may cause stinging sensations in some people (87829).
Psychiatric ...Orally, ginkgo has been associated with a single case of mood dysregulation. A 50-year-old female with schizophrenia developed irritability, difficulty controlling anger, and agitation after one week of taking ginkgo 80 mg twice daily. The mood changes resolved within 2-3 days of discontinuation. When ginkgo was re-trialed at a later date, the same symptoms reappeared, and again dissipated after discontinuation of the ginkgo product. The relationship between ginkgo and mood dysregulation was considered to be "probable" based on the Naranjo adverse drug reaction probability scale (96763); however, the exact mechanism by which ginkgo may have affected mood regulation is unknown.
General
...Orally, phosphatidylserine is generally well tolerated.
Most Common Adverse Effects:
Orally: Flatulence, gastrointestinal upset, headache, insomnia, and nausea.
Gastrointestinal ...Orally, phosphatidylserine can cause gastrointestinal upset such as flatulence or nausea. Gastrointestinal upset can occur at doses of 200-300 mg/day (7116,7121,15539,68862,90711).
Neurologic/CNS ...Orally, phosphatidylserine can cause insomnia. Insomnia is more likely to occur with a higher dose of 600 mg (7121,68844). Headache has also been reported (90711).
