| Ingredients | Amount Per Serving |
|---|---|
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(Acetyl-L-Carnitine HCl)
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500 mg |
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(Ginkgo biloba )
(Leaf)
|
120 mg |
| 100 mg |
Gelatin, Magnesium Stearate (Alt. Name: Mg Stearate), Microcrystalline Cellulose, Silica
Below is general information about the effectiveness of the known ingredients contained in the product Cognitin (Memory Support Formula). Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Cognitin (Memory Support Formula). 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. Acetyl-L-carnitine has been used safely in doses up to 3 grams daily in clinical trials lasting up to 33 months (42,1589,1594,1595,1596,1597,1598,1599,3600,3601) (9105,9791,10076,12743,12745,58375,90755,90756,90759,90761)(90766,90767,90768,95063,95067,111862).
POSSIBLY SAFE ...when used parenterally and appropriately under medical supervision (1591,1592,12743).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Acetyl-L-carnitine has been safely used orally in children for up to 6 weeks (90754).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. Alpha-lipoic acid has been used with apparent safety in doses of up to 2 grams daily for 3 months to 2 years. Lower doses of 600 mg daily have been used with apparent safety for up to 4 years (3540,3541,3542,20479,96449,97630,101867,101869,103327,103333)(103335,104651,104660,113892,113897). ...when used topically and appropriately. A cream containing alpha-lipoic acid 5% has been used with apparent safety in clinical trials lasting up to 12 weeks (12021). ...when given intravenously and appropriately. Intravenous alpha-lipoic acid has been used safely in doses of up to 6000 mg weekly in clinical trials lasting up to 3 weeks (3540,3557,10148,12106).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately.
Alpha-lipoic acid has been used with apparent safety in doses of up to 600 mg daily for 3 months in children aged 10-17 years (103330).
CHILDREN: POSSIBLY UNSAFE
when used orally in amounts over 600 mg daily.
At least five cases of alpha-lipoic acid intoxication have been reported for children aged 14 months to 16 years who consumed alpha-lipoic acid at doses up to 226 mg/kg (approximately 2400 mg). Symptoms of alpha-lipoic acid-induced intoxication included seizures, acidosis, vomiting, and unconsciousness (90444,96227,96234,104653).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term.
Alpha-lipoic acid has been used safely during pregnancy at doses up to 600 mg daily for up to 4 weeks (96222).
LACTATION:
Insufficient reliable information available; avoid using.
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).
Below is general information about the interactions of the known ingredients contained in the product Cognitin (Memory Support Formula). 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, acetyl-L-carnitine might increase the anticoagulant effects of acenocoumarol.
 Details
L-carnitine, the parent compound of acetyl-L-carnitine, might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant that is similar to warfarin, but shorter-acting (9878,12165). There are at least two case reports of INR elevation when L-carnitine was taken with acenocoumarol. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product (12165). It is unclear if such an interaction would also occur with acetyl-L-carnitine.
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Theoretically, acetyl-L-carnitine might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders, when taken with serotonergic drugs.
Details
Animal research shows that acetyl-L-carnitine can increase levels of serotonin in the brain (95065).
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Theoretically, acetyl-L-carnitine might decrease the effectiveness of thyroid hormone replacement.
Details
L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells (12761). Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism (8047). It is unclear if such an interaction would occur with acetyl-L-carnitine.
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Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of warfarin.
Details
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Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of alkylating agents.
Details
The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals (391). However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy. Advise patients to consult their oncologist before using alpha-lipoic acid.
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Theoretically, alpha-lipoic acid may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Details
In vitro, alpha-lipoic acid inhibits platelet aggregation (98682).
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Theoretically, taking alpha-lipoic acid with antidiabetes drugs might increase the risk of hypoglycemia.
Details
Although some small clinical studies have suggested that alpha-lipoic acid can lower blood glucose levels (3545,3874,3875,3876,20490,20493,104650), larger clinical studies in patients with diabetes have shown no clinically meaningful effect (20494,20495,20496,90443,90445,110118). Additionally, co-administration of single doses of alpha-lipoic acid and glyburide or acarbose did not cause detectable drug interactions in healthy volunteers (3870).
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Theoretically, the antioxidant effects of alpha-lipoic acid might alter the effectiveness of antitumor antibiotics.
Details
The use of antioxidants like alpha-lipoic acid during chemotherapy is controversial. There are concerns that antioxidants could reduce the activity of antitumor antibiotic drugs, which work by generating free radicals (391). However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as alpha-lipoic acid have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using alpha-lipoic acid.
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Theoretically, alpha-lipoic acid might decrease the effects of thyroid hormone drugs.
Details
Animal research suggests that co-administration of thyroxine with alpha-lipoic acid reduces conversion into the active T3 form (8946).
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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.
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 (244,578,579,8581,13002,13135,13179,13194,14456,87868). 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.
Details
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.
Details
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Theoretically, ginkgo might decrease levels of drugs metabolized by CYP2C19.
Details
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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Below is general information about the adverse effects of the known ingredients contained in the product Cognitin (Memory Support Formula). 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, acetyl-L-carnitine is generally well tolerated.
Most Common Adverse Effects:
Orally: Agitation, dry mouth, headache, insomnia, and reduced appetite. A metabolite of acetyl-L-carnitine has been reported to cause a fishy odor of the urine, breath, and sweat.
Cardiovascular ...Orally, one patient in a pharmacokinetic study reported high blood pressure 8 hoursafter taking acetyl-L-carnitine 500 mg; however, it is unclear if this was due to acetyl-L-carnitine or another factor (95061).
Dermatologic ...Orally, a combination of acetyl-L-carnitine and alpha-lipoic acid may cause rash (90441).
Gastrointestinal ...Orally, acetyl-L-carnitine may cause nausea, vomiting, diarrhea, constipation, hiccups, abdominal distension and gastrointestinal upset or pain. However, gastrointestinal symptoms do not usually occur more often in patients receiving acetyl-L-carnitine than in patients receiving placebo (1596,1599,12743,13007,58922,90755,95063,95067,111889,111894). Acetyl-L-carnitine may also cause dry mouth and anorexia (58342). When taken orally, a combination of acetyl-L-carnitine and alpha-lipoic acid may cause diarrhea, constipation, and dyspepsia (90441).
Neurologic/CNS ...Orally, acetyl-L-carnitine may cause headache and insomnia (90760,90767,95063). In one clinical trial, two patients with antiretroviral toxic neuropathy reported paresthesia, pain, and neuropathy after taking acetyl-L-carnitine 1000 mg daily (58342). A case of mania has been reported for a patient with bipolar I disorder currently in remission. The patient presented with symptoms after taking multiple supplements for the past 4 weeks including acetyl-L-carnitine 1000 mg twice daily. The symptoms appeared 3 days after beginning to take acetyl-L-carnitine and worsened over the next week. The patient had increased speech rate and volume and reported increased energy levels and racing thoughts. The patient's parent reported irritability and an increase in loud behaviors at home, similar to a previous episode of mania. The patient was advised to discontinue acetyl-L-carnitine, and the manic symptoms disappeared 3 days later (95062).
Psychiatric ...Orally, acetyl-L-carnitine may cause agitation (restlessness and motor overactivity) (1596,1599,12743,13007). Side effects reported in people with Alzheimer disease include psychiatric disturbances such as depression, mania, confusion and aggression, but it is not clear whether these are due to acetyl-L-carnitine or the condition itself (1594,1595,1596,1597,1598,1599,9105,10391).
Other ...One of the metabolites of acetyl-L-carnitine can cause the urine, breath, and sweat to have a fishy odor (12756). Also, foul smelling urine has been reported following oral use of a combination of acetyl-L-carnitine and alpha-lipoic acid (90441).
General
...Alpha-lipoic acid appears to be generally well tolerated when used orally, intravenously, or topically.
Most Common Adverse Effects:
Orally: Headache, heartburn, nausea, and vomiting.
Topically: Irritation and rash.
Intravenously: Nausea and vomiting.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about insulin autoimmune syndrome (IAS).
Cardiovascular ...Orally, hypotension has been reported rarely in a clinical trial (104650).
Dermatologic ...Orally, skin rash and itching have been reported after use of alpha-lipoic acid (16391,20490,21674,96233,104650). Topically, alpha-lipoic acid can cause local irritation, including burning, stinging, mild rash, or contact dermatitis (12021,30836,111701). In one case, an 86-year-old female developed allergic contact dermatitis with severe itching and oozing after applying alpha-lipoic acid 5% cream to her lower extremities. The patient had a positive skin patch test for alpha-lipoic acid, confirming the causative agent (111701). In another case, a 47-year-old female developed contact dermatitis characterized by a pruritic rash and labial adhesions hours after applying a 5% vulvar serum containing lipoic acid 0.9 grams, vitamin E, vitamin C, hyaluronic acid, and retinol palmitate to the vulva to treat vulvar lichen sclerosis. Testing confirmed that the causative agent was alpha-lipoic acid (111704). Intravenously, local allergic reactions have occurred at the injection site (1547).
Endocrine ...Orally, at least 50 published cases of insulin autoimmune syndrome (IAS) thought to be associated with use of alpha-lipoic acid have been reported (16392,104656,104657,104658,104659,107893,112941). Most reported cases have been associated with alpha-lipoic acid supplements or enriched foods; IAS has not been reported with intake of alpha-lipoic acid in food. IAS has been linked to compounds, such as alpha-lipoic acid, that contain sulfhydryl groups, but it is unclear if taking alpha-lipoic acid with other drugs known to trigger IAS increases the risk (107893,112941). IAS is characterized by very high serum insulin levels and high titers of autoantibodies against endogenous insulin. Sulfhydryl groups interact with disulfide bonds of insulin, increasing its immunogenicity (112941). Symptoms include severe spontaneous hypoglycemic episodes, as well as hunger and neuroglycopenic symptoms such as blurred vision, weakness, confusion, dizziness, sweating, and palpitations (104656,104657,107893,112941). Time to onset of IAS ranges from 1 week to 4 months (107893). Most cases of IAS have been reported in Japan and have occurred in individuals with the human leucocyte antigen (HLA)-DRB1*04:06 allele (16392,104656,107893). For patients of European decent, cases of IAS have mainly occurred in individuals with the HLA-DRB1*04:03 allele (104656,104658,104659,107893). This suggests that either of these alleles might produce a genetic predisposition to alpha-lipoic acid-associated IAS. Reported doses of alpha-lipoic acid have ranged from 200-800 mg daily, most commonly 600 mg daily (104656,104658,104659,107893). IAS-related hypoglycemic episodes have been treated with oral or intravenous glucose or sucrose, as well as prednisone. Episodes decline following discontinuation of alpha-lipoic acid, and insulin values normalize within 3-9 months (104656,104658,104659,107893).
Gastrointestinal ...Orally, heartburn, nausea, and vomiting have been reported after use of alpha-lipoic acid (3557,12106,16391,20475,30844,96225,101868,103327,103328,103333)(103335,104650,104654,104655). Higher doses (1200-1800 mg daily) seem to cause more severe effects than lower doses (600 mg daily) (3557,20475,30844,96225). Alpha-lipoic acid may also cause a burning sensation from the throat to the stomach, abdominal discomfort, or bitter taste when used orally (20478,20490,21664,96225). Intravenously, alpha-lipoic acid can cause gastrointestinal upset, including nausea and vomiting. Adverse effects are more common in patients receiving higher intravenous doses (3557) and may be more common in the elderly (96225).
Genitourinary ...Orally, alpha-lipoic acid may cause urinary disorders (20479). Oral alpha-lipoic acid has also been associated with a change in urine odor (96225,103327).
Neurologic/CNS
...Orally, alpha-lipoic acid may cause headache (21664,103328,104655) or dizziness (104650).
Intravenously, paresthesias have been reported to worsen temporarily at the beginning of therapy. Also, intravenous alpha-lipoic acid can cause headache. Adverse effects are more common in patients receiving higher intravenous doses (3557).
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).
Increases in blood pressure were commonly reported with ginkgo in a safety database analysis; however, information on the magnitude of the increase was limited, and reports included both oral and intravenous administration (115628).
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 (87858,115628).
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 (87839,115628), 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 may cause tinnitus is some patients (8543,115628).
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.
