Each capsule contains: Vitamin B12 (as methylycobalamin) 250 mcg • Lithium (as lithium orotate) 5 mg • Trimethylglycine (TMG) 200 mg. Other Ingredients: Microcrystalline Cellulose, Magnesium Stearate.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Lithium Synergy. 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
Below is general information about the safety of the known ingredients contained in the product Lithium Synergy. 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 in doses of up to 6 grams daily (698,10631). However, some patients have used up to 20 grams daily with apparent safety (698). Betaine anhydrous is available as an FDA-approved prescription product (Cystadane) (698), and also as a supplement. The European Food Safety Authority states that betaine anhydrous is safe to use in doses up to 6 mg/kg daily, in addition to usual dietary intake (105548). There is insufficient reliable information available about the safety of topical betaine anhydrous.
CHILDREN: LIKELY SAFE
when used orally and appropriately in doses up to 150 mg/kg daily (698).
However, some patients have used up to 20 grams daily with apparent safety (698). Prescription betaine anhydrous (Cystadane) is approved by the US FDA for use in infants and children (698).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when taken orally as a single dose of up to 1500 mg (93328,93329). There is insufficient reliable information available about the safety of betaine hydrochloride when used in multiple doses.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when lithium carbonate or lithium citrate is used orally and appropriately. Lithium carbonate and lithium citrate are FDA-approved drugs and have been used safely in clinical studies (15,97770). Lithium has a narrow therapeutic window and plasma levels must be monitored to avoid toxicity (15). Lithium levels should be drawn 12 hours after the last dose of lithium after steady state concentrations have been attained (approximately 3 days). Toxicity is most common at levels of 1.5 mEq/L, although some patients develop toxicity at levels less than 1 mEq/L (15,97770). There is insufficient reliable information available about the safety of lithium aspartate, lithium orotate, or other forms of supplemental lithium.
CHILDREN: POSSIBLY SAFE
when prescription lithium carbonate or lithium citrate is used orally and appropriately under medical supervision in children 7 years of age and older (15).
There is insufficient reliable information available about the safety of lithium aspartate, lithium orotate, or other forms of supplemental lithium.
PREGNANCY: POSSIBLY UNSAFE
when lithium carbonate and lithium citrate are used orally (15).
Lithium can cause fetal toxicity and increases the risk for cardiac and other abnormalities, including neural tube and urethral defects. However, it does not seem to increase the risk for preterm birth or low birth rate (15,9166,97770,104266). Some research suggests lithium might increase the risk for spontaneous abortion. Based on a meta-analysis of 2 population studies, taking lithium during pregnancy may increase the risk for spontaneous abortion when compared with the general population, but not when compared with patients with affective disorders not taking lithium during pregnancy (104266). This suggests that it may be the presence of affective disorder itself, or the possible associated use of other teratogenic drugs or substances during pregnancy, which may increase the risk for spontaneous abortion.
When the potential benefits to the mother and child outweigh the possible risk to the fetus, prescription lithium may be used with close monitoring by a healthcare professional (15,9166,97770,104266). The safety of lithium supplements during pregnancy is unknown.
LACTATION: LIKELY UNSAFE
when used orally.
Lithium is secreted into breast milk and may cause adverse effects in the nursing infant (15). Prescription lithium may be used in circumstances when the potential maternal benefits outweigh the possible risk to the infant. The infant should be closely monitored for signs of lithium toxicity (97770).
LIKELY SAFE ...when used orally, topically, intravenously, intramuscularly, or intranasally and appropriately. Vitamin B12 is generally considered safe, even in large doses (15,1344,1345,1346,1347,1348,2909,6243,7289,7881)(9414,9416,10126,14392,15765,82832,82949,82860,82864,90386)(111551,111554).
PREGNANCY: LIKELY SAFE
when used orally in amounts that do not exceed the recommended dietary allowance (RDA).
The RDA for vitamin B12 during pregnancy is 2.6 mcg daily (6243). There is insufficient reliable information available about the safety of larger amounts of vitamin B12 during pregnancy.
LACTATION: LIKELY SAFE
when used orally in amounts that do not exceed the recommended dietary allowance (RDA).
The RDA of vitamin B12 during lactation is 2.8 mcg daily (6243). There is insufficient reliable information available about the safety of larger amounts of vitamin B12 while breastfeeding.
Below is general information about the interactions of the known ingredients contained in the product Lithium Synergy. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Betaine hydrochloride increases stomach acidity and could decrease the effects of antacids.
Details
|
Betaine hydrochloride increases stomach acidity and could decrease the effects of H2-blockers.
Details
|
Betaine hydrochloride increases stomach acidity and could decrease the effects of PPIs.
Details
|
Theoretically, taking lithium supplements with ACEIs might increase levels and adverse effects of lithium.
Details
|
Theoretically, taking lithium supplements with anticonvulsants might increase the risk of neurotoxicity.
Details
|
Theoretically, taking lithium supplements with antipsychotic drugs might increase the risk of encephalopathic syndrome.
Details
Encephalopathic syndrome has been reported in multiple patients taking prescription lithium and antipsychotics concomitantly. Symptoms have included weakness and lethargy, fever, confusion, and extrapyramidal symptoms. In some patients, resulting brain damage was irreversible. Although there is no established causal relationship between these symptoms and the combination of lithium and antipsychotic medications, there is a theoretical relationship (97770). It is unclear if this interaction would occur with the smaller doses found in lithium supplements.
|
Theoretically, taking lithium supplements with calcium channel blockers might reduce lithium levels and might also increase the risk of certain adverse effects.
Details
Calcium channel blockers might reduce lithium concentrations. Monitor lithium levels with concurrent use. Calcium channel blockers might also increase the adverse neurological and gastrointestinal adverse effects of lithium (9,15). It is unclear if these interactions would occur with the smaller doses found in lithium supplements.
|
Theoretically, taking lithium supplements with loop diuretics might increase lithium levels and adverse effects.
Details
Thiazide diuretics and loop diuretics might reduce lithium excretion, particularly in sodium-restricted patients (9,15). If lithium is clinically indicated and other treatment options are unavailable or inadequate in patients using diuretics, lithium treatment can be initiated with extreme caution. Serum lithium should be measured frequently and the doses used should be the lowest dose ordinarily tolerated (97770). It is unclear if this interaction would be clinically significant with the smaller doses found in lithium supplements.
|
Theoretically, taking lithium supplements with methyldopa might increase the risk of lithium toxicity.
Details
Concurrent use of methyldopa with lithium increases the risk of lithium toxicity (9). It is unclear if this interaction would be clinically significant with the smaller doses found in lithium supplements.
|
Theoretically, taking lithium supplements with methylxanthines might decrease lithium levels.
Details
|
Theoretically, taking lithium supplements with NSAIDs might increase lithium levels and adverse effects.
Details
|
Theoretically, taking lithium supplements with phenothiazines might decrease the levels and clinical effects of phenothiazines.
Details
|
Theoretically, taking lithium supplements with serotonergic drugs might both mask and increase the risk of serotonin syndrome.
Details
In a case report, a 67-year-old female with depression and bipolar disorder using lithium in combination with selective serotonin reuptake inhibitors (SSRIs) and other medications developed serotonin syndrome with symptoms of deep tendon hyperreflexia, muscle rigidity, tremor, and hyperthermia. However, agitation, one classical symptom of serotonin syndrome, was lacking. This was thought to be due to masking by lithium toxicity (105343). Lithium can increase serotonin levels (9,15), thus, combining serotonergic drugs with lithium might increase the risk of serotonergic side effects including serotonin syndrome and cerebral vasoconstrictive disorders. It is unclear if this interaction would occur with the smaller doses found in lithium supplements.
|
Theoretically, taking lithium supplements with skeletal muscle relaxants might prolong neuromuscular blockade.
Details
|
Below is general information about the adverse effects of the known ingredients contained in the product Lithium Synergy. 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, betaine anhydrous is generally well tolerated.
Most Common Adverse Effects:
Orally: Body odor, diarrhea, elevated cholesterol levels, GI distress, nausea, vomiting.
Serious Adverse Effects (Rare):
Orally: Cerebral edema.
Cardiovascular ...Betaine anhydrous might have adverse effects on the plasma lipid profile. Some studies have reported a 3% to 4% increase in total and low-density lipoprotein (LDL) cholesterol levels with betaine anhydrous 6 grams daily (16452,16455,16456,34904). A meta-analysis of 6 studies in adults, some with obesity and/or prediabetes, shows that taking betaine anhydrous 4-6 grams daily for 6-24 weeks is associated with a mean increase in total cholesterol of 4 mg/dL, with no significant change in LDL cholesterol, high-density lipoprotein (HDL) cholesterol, or triglyceride levels (105814). Another meta-analysis of 12 studies, some in healthy adults and others in adults with various disease states, shows that taking betaine anhydrous 1.5-20 grams daily for 2-52 weeks is associated with a mean increase in total cholesterol of 14 mg/dL, and a mean increase in LDL cholesterol of 10 mg/dL, with no change in triglyceride or HDL cholesterol levels (105813).
Gastrointestinal ...Orally, betaine anhydrous can cause vomiting, nausea, GI distress, and diarrhea (698,10631,34888,34928,111374).
Neurologic/CNS ...When used orally to treat homocystinuria due to cystathionine beta-synthase deficiency, elevated plasma methionine concentrations can occur following use of betaine anhydrous, which might lead to cerebral edema (698,111374).
Other ...Orally, betaine anhydrous can cause body odor (698,10631).
General ...Orally, betaine hydrochloride is generally well tolerated when taken as a single dose.
Gastrointestinal ...Theoretically, the hydrochloric acid produced from betaine hydrochloride might irritate gastric or duodenal ulcers or impede ulcer healing. It might also cause heartburn.
General
...Orally, prescription forms of lithium are generally well tolerated when used as prescribed.
Plasma levels must be monitored to avoid toxicity. It is unclear how the lower doses of lithium found in supplements may alter the occurrence and likelihood of these adverse effects.
Most Common Adverse Effects:
Orally: Edema, fatigue, fine tremor, gastrointestinal symptoms, lethargy, muscle weakness, polydipsia, polyuria, skin conditions, vertigo, and weight gain.
Cardiovascular ...Orally, lithium has been reported to cause bradyarrhythmia. A case of symptomatic bradycardia due to sinoatrial node dysfunction is reported in a patient with bipolar disorder who took lithium orotate 20 mg daily for 5 years, despite a serum lithium level in the therapeutic range (111327). Deep vein thrombosis is also reported in 2 patients with bipolar disorder who experienced toxic serum levels of lithium (111329). It is unclear if these effects are a concern with the smaller doses found in lithium supplements.
Dermatologic ...Orally, lithium can cause or exacerbate skin disorders such as hair loss, acne, psoriasis, and rash (9,15,97770). A case of Stevens-Johnson syndrome is also reported in a patient with bipolar disorder who took lithium carbonate at an unknown dose for 17 days (111317).
Endocrine ...Orally, chronic use of lithium has been reported to cause various endocrine disorders. Case reports associate chronic lithium use with hypothyroidism, hyperthyroidism, goiter, hyperparathyroidism, and diabetes insipidus (9,15,104267,104269,104270,104271,111320). In one case report, a 68-year-old male with schizophrenia developed severe hypothyroidism resulting in myxedema coma after taking oral lithium carbonate. He recovered after discontinuation of lithium and administration of levothyroxine. At least two other cases of lithium-associated myxedema coma have been reported (97740). At least 4 cases of lithium-associated hyperparathyroidism have been reported in females aged 53-68 years that had taken lithium for 24 years or more. These patients presented with hypernatremia, hypercalcemia, elevated serum creatinine, thyroid or parathyroid abnormalities, and nephrogenic diabetes insipidus (104269,105344). It is unclear if these effects are a concern with the smaller doses found in lithium supplements.
Gastrointestinal ...Orally, lithium can cause gastrointestinal symptoms. These adverse effects often improve with continued use (9). It is unclear if this effect would occur with the smaller doses found in lithium supplements.
Musculoskeletal ...Orally, lithium can cause muscle weakness. This adverse effect often improves with continued use (9). It is unclear if this effect would occur with the smaller doses found in lithium supplements.
Neurologic/CNS ...Orally, lithium can cause vertigo, muscle weakness, lethargy, fatigue, and a dazed feeling. These adverse effects often improve with continued use. Fine tremor can occur and may persist with continued use. Chronic use of lithium can cause mild cognitive and memory impairment, particularly in the presence of dehydration or hyponatremia (9,15,97745). These long-term neurological adverse effects of lithium are potentially due to accumulation in the central nervous system even when blood levels appear within the therapeutic range (97745). Lithium-associated hyperparathyroidism-induced hypercalcemia has resulted in hallucinations, confusion, insomnia, and agitation (105344). A case of delirium and transient difficulty with word finding is reported in a patient with bipolar disorder treated with lithium 250-500 mg twice daily and 9 sessions of electroconvulsive therapy (111316). A case of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is also reported in a patient with bipolar disorder who had a toxic lithium level of 1.94 mEq/L (111318). It is unclear if these effects would occur with the smaller doses found in lithium supplements.
Psychiatric ...Abrupt discontinuation of lithium resulting in a rapid reduction in serum lithium levels can precipitate recurrence of bipolar symptoms (9165). Lithium should be tapered gradually over at least 14 days (9165).
Renal ...Orally, lithium can cause polyuria, polydipsia, and edema (9). Chronic lithium use has been reported to cause central or nephrogenic diabetes insipidus, hypocalciuric hypercalcemia, and nephrotic syndrome (104269,104271,111314,111319). Long-term lithium use is estimated to increase the odds of chronic kidney disease (CKD) by at least 2-fold and may contribute to CKD progression (111315,111324). It is unclear if these effects would occur with the smaller doses found in lithium supplements.
Other ...Orally, chronic use of lithium has been reported to cause an irreversible reduction in taste and smell in a patient with bipolar disorder who took 400-1000 mg/day for 4 months (111313). Chronic use of lithium 1200 mg/day has also been reported to cause dysphagia in a 17-year-old patient with bipolar disorder; however, the patient's serum lithium level was in the toxic range and the adverse effect resolved once the level normalized (111328). It is unclear if these effects would occur with the smaller doses found in lithium supplements.
General
...Orally, intramuscularly, and topically, vitamin B12 is generally well-tolerated.
Most Common Adverse Effects:
Intramuscular: Injection site reactions.
Serious Adverse Effects (Rare):
Intramuscularly: Severe hypokalemia has been rarely linked with correction of megaloblastic anemia with vitamin B12.
Cardiovascular ...In human clinical research, an intravenous loading dose of folic acid, vitamin B6, and vitamin B12, followed by daily oral administration after coronary stenting, increased restenosis rates (12150). Hypertension following intravenous administration of hydroxocobalamin has been reported in human research (82870,82864).
Dermatologic ...Orally or intramuscularly, vitamin B12 can cause allergic reaction such as rash, pruritus, erythema, and urticaria. Theoretically, allergic reactions might be caused by the cobalt within the vitamin B12 molecule (82864,90373,90381,103974). In one case report, oral methylcobalamin resulted in contact dermatitis in a 59-year-old Japanese woman with a cobalt allergy (103974). Vitamin B12 (intramuscular or oral) has also been associated with at least 19 cases of acneiform eruptions which resolved upon discontinuation of vitamin B12 (90365,90369,90388). High-dose vitamin B12 (20 mcg daily) and vitamin B6 (80 mg daily) have been associated with cases of rosacea fulminans characterized by intense erythema with nodules, papules, and pustules. Symptoms may last up to four months after the supplement is stopped and can be treated with systemic corticosteroids and topical therapy (10998,82870,82871).
Gastrointestinal ...Intravenously, vitamin B12 (hydroxocobalamin) 2. 5-10 grams can cause nausea and dysphagia (82864).
Genitourinary ...Intravenously, vitamin B12 (hydroxocobalamin) 5-15 grams has been associated with chromaturia in clinical research (82870,82871).
Hematologic ...According to case report data, the correction of megaloblastic anemia with vitamin B12 may result in fatal hypokalemia (82914).
Musculoskeletal ...According to case report data, correction of megaloblastic anemia with vitamin B12 has precipitated gout in susceptible individuals (82879).
Neurologic/CNS ...Treatment with vitamin B12 has been rarely associated with involuntary movements in infants with vitamin B12 deficiency (90370,90385,90397). In some cases these adverse reactions were misdiagnosed as seizures or infantile tremor syndrome (90370,90385). These adverse reactions presented 2-5 days after treatment with vitamin B12 and resolved once vitamin B12 was discontinued (90370,90385,90397).
Oncologic ...Although some epidemiological research disagrees (9454), most research has found that elevated plasma levels of vitamin B12 are associated with an increased risk of various types of cancer, including lung and prostate cancers and solid tumors (50411,102383,107743). One study found, when compared with blood levels of vitamin B12 less than 1000 ng/mL, plasma vitamin B12 levels of at least 1000 ng/mL was strongly associated with the occurrence of solid cancer (107743). It is unclear if increased intake of vitamin B12, either through the diet or supplementation, directly affects the risk of cancer. It is possible that having cancer increases the risk of vitamin B12 elevation. However, one observational study has found that the highest quintile of dietary intake of vitamin B12 is associated with a 75% increased incidence of developing esophageal cancer when compared with the lowest quintile in never drinkers, but not drinkers (107147).
Renal ...There is a case report of oxalate nephropathy in a 54-year-old male which was determined to be related to the use of intravenous hydroxocobalamin as treatment for cyanide poisoning. Intermittent hemodialysis was started 5 days after admission, along with a low-oxalate diet, oral calcium acetate, and pyridoxine 5 mg/kg daily (107148). A review of the use of intravenous hydroxocobalamin for suspected cyanide poisoning in 21 intensive care units in France between 2011 and 2017 resulted in a 60% increased odds of acute kidney injury and a 77% increased odds of severe acute kidney injury in the first week. However, biopsies were not conducted and a direct link with use of hydroxocobalamin could not be made (107139).
Other ...Several studies have found that higher vitamin B12 levels may be associated with increased mortality or decreased survival rates in hospitalized elderly patients (82889,82812,82857,82895). Human research has also found a positive correlation between vitamin B12 status and all-cause mortality in Pima Indians with diabetes (82863).