Ingredients | Amount Per Serving |
---|---|
(as thiamine tetrahydrofurfuryl disulfide)
(Thiamine (Form: as thiamine tetrahydrofurfuryl disulfide) )
|
100 mcg |
(Pyridoxine Hydrochloride)
(Vitamin B6 (Form: as Pyridoxine HCl) )
|
20 mg |
(as Manganese Gluconate)
(Manganese (Form: as Manganese Gluconate) )
|
2 mg |
Choline Dihydrogen Citrate
|
200 mg |
(soy ingredient)
|
180 mg |
Phosphatidylethanolamine
(soy ingredient)
|
120 mg |
(Dimethylaminoethanol Bitartrate)
|
100 mg |
Phosphatidylinositol
(soy ingredient)
|
84 mg |
60 mg | |
60 mg | |
20 mg | |
Ginko Biloba Extract
|
10 mg |
Silicon Dioxide (Alt. Name: SiO2), Magnesium Stearate
Below is general information about the effectiveness of the known ingredients contained in the product Omnicholine. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Omnicholine. 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. Deanol has been safely used at doses up to 2 grams daily for up to 4 weeks and doses up to 500 mg daily for up to 3 months (1668,1671,1672,1673,1674,1675,1676,1679,1680,1681). There is insufficient reliable information available about the safety of deanol when used topically.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. Glutamine has been safely used in clinical research in doses up to 40 grams per day or 1 gram/kg daily (2334,2337,2338,2365,5029,5462,7233,7288,7293), (52288,52307,52308,52311,52313,52337,52349,52350,96516,97366). A specific glutamine product (Endari) is approved by the US Food and Drug Administration (FDA) (96520). ...when used intravenously. Glutamine has been safely incorporated into parenteral nutrition in doses up to 600 mg/kg daily in clinical trials (2363,2366,5448,5452,5453,5454,5458,7293,52272,52275), (52283,52289,52304,52306,52316,52341), (52359,52360,52371,52377,52381,52284,52385,52408,96637,96507,96516).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Glutamine has been shown to be safe in clinical research when used in amounts that do not exceed 0.7 grams/kg daily in children 1-18 years old (11364,46657,52321,52323,52363,86095,96517). A specific glutamine product (Endari) is approved by the US Food and Drug Administration for certain patients 5 years of age and older (96520). ...when used intravenously. Glutamine has been safely incorporated into parenteral nutrition in doses up to 0.4 grams/kg daily in clinical research (52338,96508). There is insufficient reliable information available about the safety of glutamine when used in larger amounts in children.
PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods.
There is insufficient reliable information available about the safety of glutamine when used in larger amounts as medicine during pregnancy or lactation.
LIKELY SAFE ...when used orally and appropriately. Oral manganese is safe when used in doses below the tolerable upper intake level (UL) of 11 mg daily for adults 19 years and older (1994,7135). ...when used parenterally and appropriately. Parenteral manganese chloride and manganese sulfate are FDA-approved prescription products.
POSSIBLY UNSAFE ...when used orally in high doses. Doses exceeding 11 mg daily can cause significant adverse effects (7135). ...when used parenterally in moderate or high doses, long-term. Reports of neurotoxicity and Parkinson-like symptoms have been reported with parenteral nutrition manganese doses above 60 mcg daily. It is recommended that adults on long-term parenteral nutrition receive manganese in doses of no more than 55 mcg daily (99302).
LIKELY UNSAFE ...when inhaled in moderate doses, long-term. According to the US Occupational Safety and Health Administration (OSHA), the permissible exposure limit (PEL) for manganese is 5 mg/m3. Exposure to higher amounts of manganese dust or fumes has been associated with central nervous system toxicity, Parkinson-like symptoms, and poor bone health (61296,102516).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Manganese is safe in children when used in daily doses less than the tolerable upper intake level (UL) of 2 mg in children 1-3 years, 3 mg in children 4-8 years, 6 mg in children 9-13 years, and 9 mg in children 14-18 years (7135).
CHILDREN: POSSIBLY UNSAFE
when used orally in excessive doses.
Daily doses greater than the UL are associated with a greater risk of toxicity (7135).
CHILDREN: LIKELY UNSAFE
when inhaled at moderate doses, long-term.
Exposure to high amounts of manganese dust has been associated with central nervous system toxicity and Parkinson-like symptoms (61296).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Manganese is safe when used in doses below the tolerable upper intake level (UL) of 11 mg daily during pregnancy or lactation in those aged 19 or older. However, those under 19 years of age should limit doses to less than 9 mg daily (7135).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses.
Doses over the UL are associated with a greater risk of toxicity (7135). Additionally, observational research shows that adults with higher blood manganese levels have greater odds of delivering low birth weight or small for gestational age (SGA) male, but not female, infants (102515).
PREGNANCY AND LACTATION: LIKELY UNSAFE
when inhaled at moderate doses, long-term.
Manganese salts can cross the placenta, and animal research suggests that large amounts of manganese may be teratogenic (61296).
LIKELY SAFE ...when used orally in amounts commonly found in food (94500).
POSSIBLY SAFE ...when used orally or intravenously and appropriately in medicinal amounts under the supervision of a healthcare professional (2410,2411,2413).
POSSIBLY UNSAFE ...when used orally or intravenously in excessive doses. Doses larger than 100 mg/kg should be avoided to prevent severe and potentially lethal cerebral effects (9339).
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (94500).
CHILDREN: POSSIBLY SAFE
when used intravenously and appropriately (9338).
CHILDREN: POSSIBLY UNSAFE
when used intravenously in infants receiving parenteral nutrition.
In infants, blood methionine concentration can increase due to lower enzyme activity and inability to metabolize methionine. High levels of methionine can cause liver toxicity (9338).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food (94500).
There is insufficient reliable information available about the safety of methionine in medical doses during pregnancy and lactation; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. Large doses up to 30 grams per day for 6 weeks (5223) and smaller doses of up to 6 grams daily for up to 24 months have been well tolerated (68839,68843,105728). ...when used subcutaneously and appropriately, short-term. Some research suggests that subcutaneous injections of 0.2 mL to 5 mL of a 5% phosphatidylcholine solution do not cause significant serious adverse effects when doses are administered up to five times and spaced apart by 2-4 weeks (15621,15623,15624,15625). ...when used topically as an emulsion also containing niacinamide for up to 12 weeks (93388).
PREGNANCY: POSSIBLY SAFE
when used orally from 18 weeks of gestation at doses of up to 5 grams daily (93386)
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. A tolerable upper intake level (UL) has not been established for thiamine, and doses up to 50 mg daily have been used without adverse effects (15,6243). ...when used intravenously or intramuscularly and appropriately. Injectable thiamine is an FDA-approved prescription product (15,105445).
CHILDREN: LIKELY SAFE
when used orally and appropriately in dietary amounts.
A tolerable upper intake level (UL) has not been established for healthy individuals (6243).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in dietary amounts of 1.
4 mg daily. A tolerable upper intake level (UL) has not been established for healthy individuals (3094,6243).
LIKELY SAFE ...when used orally and appropriately in doses that do not exceed the tolerable upper intake level (UL) of 100 mg daily for adults (15). ...when used parenterally and appropriately. Injectable vitamin B6 (pyridoxine) is an FDA-approved prescription product (15).
POSSIBLY SAFE ...when used orally and appropriately in doses of 101-200 mg daily (6243,8558).
POSSIBLY UNSAFE ...when used orally in doses at or above 500 mg daily. High doses, especially those exceeding 1000 mg daily or total doses of 1000 grams or more, pose the most risk. However, neuropathy can occur with lower daily or total doses (6243,8195). ...when used intramuscularly in high doses and frequency due to potential for rhabdomyolysis (90795).
CHILDREN: LIKELY SAFE
when used orally and appropriately (3094).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately in amounts exceeding the recommended dietary allowance (5049,8579,107124,107125,107135).
CHILDREN: POSSIBLY UNSAFE
when used orally in excessive doses, long-term (3094).
PREGNANCY: LIKELY SAFE
when used orally and appropriately.
A special sustained-release product providing vitamin B6 (pyridoxine) 75 mg daily is FDA-approved for use in pregnancy. Vitamin B6 (pyridoxine) is also considered a first-line treatment for nausea and vomiting in pregnancy by the American College of Obstetrics and Gynecology (111601). However, it should not be used long-term or without medical supervision and close monitoring.
PREGNANCY: POSSIBLY UNSAFE
when used orally in excessive doses.
There is some concern that high-dose maternal vitamin B6 (pyridoxine) can cause neonatal seizures (4609,6397,8197).
LACTATION: LIKELY SAFE
when used orally in doses not exceeding the recommended dietary allowance (RDA) (3094).
The RDA in lactating women is 2 mg daily. There is insufficient reliable information available about the safety of vitamin B6 when used in higher doses in breast-feeding women.
Below is general information about the interactions of the known ingredients contained in the product Omnicholine. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Deanol is thought to increase acetylcholine levels (1669). Theoretically, concurrent use of anticholinergic drugs and deanol might decrease the effectiveness of the anticholinergic agent.
Details
Some anticholinergic drugs include atropine, benztropine (Cogentin), biperiden (Akineton), procyclidine (Kemadrin), trihexyphenidyl (Artane), and others.
|
Deanol is thought to increase acetylcholine levels (1669). Theoretically, concurrent use of deanol with cholinergic drugs might have additive effects and increase the risk of cholinergic side effects.
Details
Some cholinergic drugs include bethanechol (Urecholine), donepezil (Aricept), echothiophate (Phospholine Iodide), edrophonium (Enlon, Reversol, Tensilon), neostigmine (Prostigmin), physostigmine (Antilirium), pyridostigmine (Mestinon, Regonol), succinylcholine (Anectine, Quelicin), and tacrine (Cognex).
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Theoretically, glutamine might antagonize the effects of anticonvulsant medications.
Details
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Theoretically, concomitant use of inositol nicotinate with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
Details
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Theoretically, inositol nicotinate might increase blood glucose levels and may diminish the effects of antidiabetes drugs.
Details
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Theoretically, concomitant use of inositol nicotinate and statins might increase the risk of myopathy and rhabdomyolysis.
Details
Inositol nicotinate is metabolized to niacin in the body (496). Some case reports have raised concerns that niacin might increase the risk of myopathy and rhabdomyolysis when combined with statins (14508,25918) However, a significantly increased risk of myopathy has not been demonstrated in clinical trials (7388,11689,12033,14509).
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Theoretically, concomitant use of inositol nicotinate and transdermal nicotine might increase the risk of flushing and dizziness.
Details
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Theoretically, the risk for manganese toxicity might increase when taken with antipsychotic drugs.
Details
Hallucinations and behavioral changes have been reported in a patient with liver disease who was taking haloperidol and manganese. Researchers speculate that taking manganese along with haloperidol, phenothiazine-derivatives, or other antipsychotic medications might increase the risk of manganese toxicity in some patients (61493).
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Theoretically, manganese might reduce the absorption of quinolone antibiotics.
Details
Manganese is a multivalent cation. Interactions resulting in reduced quinolone absorption have been reported between quinolones and other multivalent cations, such as calcium and iron (488).
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Theoretically, manganese might reduce the absorption of tetracycline antibiotics.
Details
Manganese is a multivalent cation. Interactions resulting in reduced tetracycline absorption have been reported between tetracyclines and other multivalent cations, such as calcium and iron (488).
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Trimethoprim might increase blood levels of thiamine.
Details
In vitro, animal, and clinical research suggest that trimethoprim inhibits intestinal thiamine transporter ThTR-2, hepatic transporter OCT1, and renal transporters OCT2, MATE1, and MATE2, resulting in paradoxically increased thiamine plasma concentrations (111678).
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Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.
Details
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Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.
Details
Research in hypertensive rats shows that vitamin B6 can decrease systolic blood pressure (30859,82959,83093). Similarly, clinical research in patients with hypertension shows that taking high doses of vitamin B6 may reduce systolic and diastolic blood pressure, possibly by reducing plasma levels of epinephrine and norepinephrine (83091).
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Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.
Details
Vitamin B6 (pyridoxine) enhances the metabolism of levodopa, reducing its clinical effects. However, this interaction does not occur when carbidopa is used concurrently with levodopa (Sinemet). Therefore, it is not likely to be a problem in most people (3046).
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High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
Details
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High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
Details
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Below is general information about the adverse effects of the known ingredients contained in the product Omnicholine. 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 ...Deanol is well-tolerated in most patients (1668,1671,1672,1673,1674,1675,1676,1679,1680,1681). However, deanol has been reported to cause constipation, diarrhea, urticaria, headache, drowsiness, insomnia, overstimulation, lucid dreams, confusion, motor retardation, depression, hypomania, and an increase in schizophrenia symptoms (1674,1680,1684,1685,1686,2706).
Cardiovascular ...Orally, small elevations in blood pressure have been reported in some patients taking deanol up to 1800 mg daily. These effects improved after deanol discontinuation (1680).
Gastrointestinal ...Orally, deanol has been reported to cause diarrhea, abdominal cramps, abdominal pain, nausea, and vomiting (1674,1680).
Musculoskeletal ...Orally, deanol up to 1800 mg daily has been reported to cause motor retardation in a small number of patients. This effect improved after deanol discontinuation (1680).
Neurologic/CNS ...Orally, deanol has been reported to cause drowsiness, apathy, and confusion (1674,1680). In one case report, a physician promoted the use of deanol to induce lucid dreams, which may be considered an undesirable outcome for some patients (1686).
Psychiatric ...Orally, taking deanol at doses greater than 1000 mg daily has been reported to cause mood changes, including depression and hypomania, in patients with psychiatric conditions (1685). Deanol 1500 mg daily has been reported to increase schizophrenic symptoms in patients with chronic schizophrenia (1674).
General
...Orally and intravenously, glutamine is generally well tolerated.
Most Common Adverse Effects:
Orally: Belching, bloating, constipation, cough, diarrhea, flatulence, gastrointestinal pain, headache, musculoskeletal pain, nausea, and vomiting.
Endocrine ...One case of hot flashes has been reported in a patient taking glutamine 5-15 grams orally twice daily for up to 1 year (96520).
Gastrointestinal ...Orally, glutamine has been associated with belching, bloating, constipation, flatulence, nausea, vomiting, diarrhea, and gastrointestinal (GI) pain. Nausea, vomiting, constipation, diarrhea, and GI pain have been reported in clinical trials using high-dose glutamine 10-30 grams (0.3 grams/kg) in two divided doses daily to treat sickle cell disease (99414). One case of dyspepsia and one case of abdominal pain have been reported in patients taking glutamine 5-15 grams twice daily orally for up to 1 year (96520). In a small trial of healthy males, taking a single dose of about 60 grams (0.9 grams/kg of fat free body mass [FFM]) was associated with a 50% to 79% incidence of GI discomfort, nausea, and belching, compared with a 7% to 28% incidence with a lower dose of about 20 grams (0.3 gram/kg FFM). Flatulence, bloating, lower GI pain, and urge to regurgitate occurred at similar rates regardless of dose, and there were no cases of heartburn, vomiting, or diarrhea/constipation (105013). It is possible that certain GI side effects occur only after multiple doses of glutamine.
Musculoskeletal ...Orally, glutamine 30 grams daily has been associated with cases of musculoskeletal pain and non-cardiac chest pain in clinical trials for patients with sickle cell disease (99414).
Neurologic/CNS ...Orally, glutamine has been associated with dizziness and headache. A single case of dizziness has been reported in a patient treated with oral glutamine 0.5 grams/kg. However, the symptom resolved after reducing the dose to 0.25 grams/kg (91356). Mania and hypomania have been reported in 2 patients with bipolar disorder taking commercially purchased glutamine up to 4 grams daily (7291). Glutamine is metabolized to glutamate and ammonia, both of which might have neurological effects in people with neurological and psychiatric diseases or in people predisposed to hepatic encephalopathy (7293).
Oncologic ...There is some concern that glutamine might be used by rapidly growing tumors and possibly stimulate tumor growth. Although tumors may utilize glutamine and other amino acids, preliminary research shows that glutamine supplementation does not increase tumor growth (5469,7233,7738). In fact, there is preliminary evidence that glutamine might actually reduce tumor growth (5469).
Other ...Orally, glutamine has been associated with cough when a powdered formulation is used. It is unclear if this was due to accidental inhalation. One case of a burning sensation and one case of hypersplenism has been reported in a patient taking glutamine 5-15 grams twice daily orally for up to 1 year (96520).
General
...Orally, inositol nicotinate is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, flushing, heartburn, liver enzyme elevation, nausea, vomiting.
Cardiovascular ...Orally, inositol nicotinate is converted to niacin and is therefore likely to cause similar side effects as niacin (496). A prostaglandin-mediated flushing reaction is a common adverse effect of oral niacin. A large pooled analysis of clinical studies shows that up to 70% of people may experience flushing with oral niacin (96211). Although flushing can occur with doses of niacin as low as 30 mg daily, it is more common with the larger doses of 500-2000 mg used for treatment of dyslipidemia (4889,26089,93341,93345). Inositol nicotinate is often promoted as a "no-flush" niacin; however, this benefit has not been demonstrated in clinical trials.
Dermatologic ...Orally, inositol nicotinate is converted to niacin and is therefore likely to cause similar side effects as niacin, including pruritus (496).
Endocrine ...Orally, inositol nicotinate is converted to niacin and is therefore likely to cause similar side effects as niacin (496). Niacin can impair glucose tolerance in a dose-dependent manner. Dosages of niacin 3-5 grams daily appear to increase blood glucose in patients with or without diabetes, while dosages of 1.5 grams or less have minimal effects (12033). Because inositol nicotinate is converted to niacin, it may also impair glucose tolerance (496).
Gastrointestinal ...Orally, inositol nicotinate is converted to niacin and is therefore likely to cause similar side effects as niacin, including gastrointestinal complaints such as nausea, vomiting, bloating, heartburn, diarrhea, and constipation (496). These adverse effects from niacin may be reduced by taking it with meals or antacids, and usually disappear within two weeks of continued therapy (4851,11690,26094).
Hematologic ...Orally, inositol nicotinate is converted to niacin and is therefore likely to cause similar side effects as niacin, including hyperuricemia (496).
Hepatic ...Orally, inositol nicotinate is converted to niacin and is therefore likely to cause similar side effects as niacin (496). Niacin is associated with elevated liver function tests and jaundice, especially with doses of 3 grams daily or more, and when doses are rapidly increased (4458,4863,6243,11690). Because inositol nicotinate is converted to niacin, it may also cause hepatotoxicity (496)
General
...Orally and parenterally, manganese is generally well tolerated when used in appropriate doses.
High doses might be unsafe.
Serious Adverse Effects (Rare):
All routes of administration: Neurotoxicity, including Parkinson-like extrapyramidal symptoms, when used in high doses.
Cardiovascular ...Chronic occupational exposure to manganese dust or fumes can cause orthostatic hypotension, and heart rate and rhythm disturbances (61363).
Endocrine ...Chronic occupational exposure to manganese dust or fumes can cause elevations in thyrotropin-releasing hormone (TRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels (61378).
Hepatic ...Manganese intoxication may cause cirrhosis and hepatic steatosis. In one case, a 13-year-old female with manganese intoxication developed severe, life-threatening neurological symptoms, with liver biopsy indicating incomplete cirrhosis and microvesicular steatosis. Chelation therapy and multiple rounds of therapeutic plasma exchange were required before symptoms resolved. The source of manganese exposure was not identified, and it is not clear if the impaired liver function contributed to the manganese accumulation or if elevated manganese exposure led to the liver damage.
Musculoskeletal ...Chronic occupational exposure to manganese dust or fumes has been associated with lower bone quality in females, but not males, suggesting that prolonged manganese exposure might increase the risk of osteoporosis in females (102516). A meta-analysis of 11 observational studies in adults also suggests that increased environmental exposure to airborne manganese sources is associated with lower motor function scores (108537).
Neurologic/CNS
...Orally, there is concern that higher doses of manganese might increase the risk of neurotoxicity, including Parkinson-like extrapyramidal symptoms (7135,10665,10666).
One severe case of irreversible Parkinson disease possibly related to taking manganese 100 mg daily for 2-4 years has been reported (96418). In another case, a 13-year-old female with manganese intoxication (diagnosed from blood manganese levels and cranial MRI evidence) developed severe neurological symptoms including loss of consciousness, decorticate posture, clonus, increased reflexes in the extremities, isochoric pupils, and no painful stimulus response. Liver biopsy also showed incomplete cirrhosis and microvesicular steatosis. The patient was intubated, and chelation therapy and multiple rounds of therapeutic plasma exchange were required before symptoms resolved. The source of the child's manganese exposure was not identified (112137). Individuals with impaired manganese excretion can also experience these effects even with very low manganese intake. Manganese accumulation due to chronic liver disease seems to cause Parkinson-like extrapyramidal symptoms, encephalopathy, and psychosis (1992,7135). One review recommends stopping supplementation if aminotransferase or alkaline phosphatase levels rise beyond twice normal (99302).
Chronic occupational exposure to manganese dust or fumes can also cause extrapyramidal reactions (1990,7135). In 1837, Couper observed that exposure to manganese dust particles produces a neurological syndrome characterized by muscle weakness, tremor, bent posture, whispered speech, and excess salivation (61264). Additionally, observational research in children has found that elevated manganese levels detected in the hair and fingernails due to environmental exposure may be associated with impaired neurocognitive function or development (108535). A meta-analysis of 11 observational studies in adults also suggests that increased environmental exposure to airborne manganese sources is associated with lower cognitive function scores (108537).
Intravenously, manganese might increase the risk of neurotoxicity when administered at high doses or for an extended duration. Cases of Parkinson-like symptoms have been reported in patients receiving parenteral nutrition containing more than 60 mcg of manganese daily. Moderate MRI intensity uptake for manganese in the globus pallidus and basal ganglion areas of the brain has been shown in patients receiving parenteral manganese (96416,99302).
Psychiatric ...Chronic occupational exposure to manganese dust or fumes can cause mood disturbance and dementia (1990,7135). A case report describes a man who presented with confusion, psychosis, dystonic limb movements, and cognitive impairment after chronic industrial manganese exposure (99415). Symptoms of manganese toxicity from inhalational exposure develop slowly with initial fatigue and personality changes, progressing to hallucinations, delusions, hyperexcitability, Parkinson-like symptoms, dystonia, and dementia (99415). Additionally, observational research has found that chronic environmental exposure to manganese sources such as mining operations and various industrial processes may be associated with a greater risk for developing symptoms of depression (108536).
Pulmonary/Respiratory ...Chronic occupational exposure to manganese dust or fumes can cause acute chemical pneumonitis, pulmonary edema, or acute tracheobronchitis (61495).
General
...Orally, methionine is well tolerated when used in amounts commonly found in foods.
Intravenously, methionine is generally well tolerated.
Most Common Adverse Effects:
All ROAs: Dizziness, drowsiness, hypotension, irritability, and vomiting. Methionine may also cause headache, increased homocysteine levels, increased urinary calcium excretion, and leukocytosis.
Serious Adverse Effects (Rare):
All ROAs: Cerebral edema, hepatic encephalopathy. In infants, intravenous methionine has been linked to liver toxicity.
Cardiovascular ...Orally or intravenously, methionine can cause hypotension (9339,9340). High-dose methionine (75-100 mg/kg daily) may increase plasma concentrations of homocysteine, which is a risk factor for vascular disease (63112,63114,63115). However, a study of patients with type 2 diabetes and a history of cardiovascular disease (CVD) showed that methionine loading did not increase homocysteine concentrations, and that a cause-effect relationship between increased intake of methionine and endothelial dysfunction has not been clearly established (63110).
Gastrointestinal ...Orally or intravenously, methionine can cause vomiting (9339,9340).
Genitourinary ...Orally or intravenously, methionine may increase urinary calcium excretion (9340,63112,94095).
Hematologic ...Orally or intravenously, methionine may cause leukocytosis when used at a dose of 8-13. 9 grams daily for 4-5 days (9340).
Hepatic ...A single dose of 8 grams of methionine has reportedly caused hepatic encephalopathy in patients with cirrhosis (9340). Long-term use of methionine-containing parenteral nutrition solution has been linked to liver toxicity in infants (9338).
Neurologic/CNS
...Orally or intravenously, methionine can cause dizziness, drowsiness, headache, and irritability (9339,9340,94095).
A case of cerebral edema ultimately leading to death has been reported in a patient receiving methionine 100 mg/kg orally. The post-load plasma concentrations of methionine were substantially higher in this patient than those previously reported in humans receiving this usual oral loading dose, leading the authors to postulate that an overdose of methionine may have been administered erroneously. This can occur when plasma methionine levels rise above 3000 mcmol/L (9339). Another case of progressive cerebral edema associated with high methionine levels and betaine (N,N,N-trimethylglycine) therapy in a patient with cystathionine beta-synthase (CBS) deficiency has been reported (63119). The authors stated that the cerebral edema was most likely precipitated by the betaine therapy, but that the exact mechanism is uncertain.
Oncologic ...Although one case-control study of incident, histologically-confirmed gastric cancer has indicated that a diet rich in methionine, salt, and nitrite is associated with an increased risk of gastric cancer (2409), a large observational study that adjusted for multiple factors, including sodium intake, has found no association between high dietary intake of methionine and gastric cancer (108041).
General ...Phosphatidylcholine is generally well tolerated when used orally, subcutaneously, or topically. Orally, bloating, diarrhea, altered taste, nausea, vomiting, sweating, and itching have been reported with phosphatidylcholine (5229,63244,68843,93389,93390,105728). Ingesting large amounts of around 30 grams daily is associated with a higher incidence of gastrointestinal upset and diarrhea (5223). Subcutaneously, pain, burning, itching, tenderness to touch, bruising, edema, nodules, hematoma, and erythema at the injection site have been reported with phosphatidylcholine (1562,15623,15624,15625,15626,15627,15628). High subcutaneous doses exceeding 1.2 grams of phosphatidylcholine can cause nausea and abdominal pain in some people (15624). Injecting phosphatidylcholine directly into a lipoma can result in a significant inflammatory response and undesirable fibrotic tissues changes (15622).
Dermatologic ...When taken orally, phosphatidylcholine may increase sweating (5229) and itching (63244). When given subcutaneously, phosphatidylcholine can cause pain, burning, itching, tenderness to touch, bruising, edema, and erythema at the injection site. The pain, itching and erythema usually resolve within 2 days of treatment; however localized tenderness can last longer (15623,15624,15626,15627,15628). Edema and bruising usually resolve within 10 days of treatment (15621,15623,15625). Some people can also develop nodules or hematoma at the injection site. This usually resolves within 30 days (15627).
Gastrointestinal ...Ingesting large amounts of phosphatidylcholine (30 grams per day) can cause gastrointestinal upset and diarrhea (5223). However, bloating, diarrhea, altered taste, nausea, and vomiting have been reported with smaller doses (63244,68843,93389,93390,105728). Although moderate subcutaneous doses do not usually cause systemic side effects, high doses exceeding 1.2 grams of phosphatidylcholine can cause nausea and abdominal pain in some people (15624).
Musculoskeletal ...Injecting phosphatidylcholine directly into a lipoma can result in a significant inflammatory response and undesirable fibrotic tissue changes (15622).
General
...Orally and parenterally, thiamine is generally well tolerated.
Serious Adverse Effects (Rare):
Parenterally: Hypersensitivity reactions including angioedema and anaphylaxis.
Immunologic
...Orally, thiamine might rarely cause dermatitis and other allergic reactions.
Parenterally, thiamine can cause anaphylactoid and hypersensitivity reactions, but this is also rare (<0.1%). Reported symptoms and events include feelings of warmth, tingling, pruritus, urticaria, tightness of the throat, cyanosis, respiratory distress, gastrointestinal bleeding, pulmonary edema, angioedema, hypotension, and death (15,35585,105445).
In one case report, a 46-year-old female presented with systemic allergic dermatitis after applying a specific product (Inzitan, containing lidocaine, dexamethasone, cyanocobalamin and thiamine) topically by iontophoresis; the allergic reaction was attributed to thiamine (91170).
General
...Orally or by injection, vitamin B6 is well tolerated in doses less than 100 mg daily.
Most Common Adverse Effects:
Orally or by injection: Abdominal pain, allergic reactions, headache, heartburn, loss of appetite, nausea, somnolence, vomiting.
Serious Adverse Effects (Rare):
Orally or by injection: Sensory neuropathy (high doses).
Dermatologic ...Orally, vitamin B6 (pyridoxine) has been linked to reports of skin and other allergic reactions and photosensitivity (8195,9479,90375). High-dose vitamin B6 (80 mg daily as pyridoxine) and vitamin B12 (20 mcg daily) have been associated with cases of rosacea fulminans characterized by intense erythema with nodules, papules, and pustules. Symptoms may persist for up to 4 months after the supplement is stopped, and may require treatment with systemic corticosteroids and topical therapy (10998).
Gastrointestinal ...Orally or by injection, vitamin B6 (pyridoxine) can cause nausea, vomiting, heartburn, abdominal pain, mild diarrhea, and loss of appetite (8195,9479,16306,83064,83103,107124,107127,107135). In a clinical trial, one patient experienced infectious gastroenteritis that was deemed possibly related to taking vitamin B6 (pyridoxine) orally up to 20 mg/kg daily (90796). One small case-control study has raised concern that long-term dietary vitamin B6 intake in amounts ranging from 3.56-6.59 mg daily can increase the risk of ulcerative colitis (3350).
Hematologic ...Orally or by injection, vitamin B6 (pyridoxine) can cause decreased serum folic acid concentrations (8195,9479). One case of persistent bleeding of unknown origin has been reported in a clinical trial for a patient who used vitamin B6 (pyridoxine) 100 mg twice daily on days 16 to 35 of the menstrual cycle (83103). It is unclear if this effect was due to vitamin B6 intake.
Musculoskeletal ...Orally or by injection, vitamin B6 (pyridoxine) can cause breast soreness or enlargement (8195).
Neurologic/CNS ...Orally or by injection, vitamin B6 (pyridoxine) can cause headache, paresthesia, and somnolence (8195,9479,16306). Vitamin B6 (pyridoxine) can also cause sensory neuropathy, which is related to daily dose and duration of intake. Doses exceeding 1000 mg daily or total doses of 1000 grams or more pose the most risk, although neuropathy can occur with lower daily or total doses as well (8195). The mechanism of the neurotoxicity is unknown, but is thought to occur when the liver's capacity to phosphorylate pyridoxine via the active coenzyme pyridoxal phosphate is exceeded (8204). Some researchers recommend taking vitamin B6 as pyridoxal phosphate to avoid pyridoxine neuropathy, but its safety is unknown (8204). Vitamin B6 (pyridoxine) neuropathy is characterized by numbness and impairment of the sense of position and vibration of the distal limbs, and a gradual progressive sensory ataxia (8196,10439). The syndrome is usually reversible with discontinuation of pyridoxine at the first appearance of neurologic symptoms. Residual symptoms have been reported in patients taking more than 2 grams daily for extended periods (8195,8196). Tell patients daily doses of 100 mg or less are unlikely to cause problems (3094).
Oncologic ...In females, population research has found that a median intake of vitamin B6 1. 63 mg daily is associated with a 3.6-fold increased risk of rectal cancer when compared with a median intake of 1.05 mg daily (83024). A post-hoc subgroup analysis of results from clinical research in adults with a history of recent stroke or ischemic attack suggests that taking folic acid, vitamin B12, and vitamin B6 does not increase cancer risk overall, although it was associated with an increased risk of cancer in patients who also had diabetes (90378). Also, in patients with nasopharyngeal carcinoma, population research has found that consuming at least 8.6 mg daily of supplemental vitamin B6 during treatment was associated with a lower overall survival rate over 5 years, as well as a reduced progression-free survival, when compared with non-users and those with intakes of up to 8.6 mg daily (107134).