Choline bitartrate

253.25

253.116150

201-763-4

White crystalline powder

2923900090

138.12000

log Kow = -4.99 (est)

White crystalline powder

1.47 g/cm3

148.5 °C

399.3ºC at 760 mmHg

209.4ºC

soluble in alcohol and slightly soluble in water.

Store at RT.

Odorless or faint trimethylamine-like odor

Acid taste

Hygroscopic when exposed to air|Hydroxyl radical reaction rate constant = 2.8X10-11 cu cm/molecule-sec at 25 °C (est)

NONH for all modes of transport

3

36/37/38

26-36

Xi

Stable at room temperature in closed containers under normal storage and handling conditions.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Choline bitartrate used as a nutrient in food for human consumption is generally recognized as safe when used in accordance with good manufacturing practice.|Choline bitartrate used as a nutrient and/or dietary supplement in animal drugs, feeds, and related products is generally recognized as safe when used in accordance with good manufacturing or feeding practice.|Since 1994, dietary supplements have been regulated under the Dietary Supplement Health and Education Act (DSHEA). The DSHEA requires no proof of safety for dietary supplements on the market prior to October 15, 1994. Labeling requirements for such supplements allow warnings and dosage recommendations as well as substantiated "structure or function" claims. All claims must prominently note that they have not been evaluated by the FDA, and they must bear the statement "This product is not intended to diagnose, treat, cure, or prevent any disease".

National Academy of Sciences. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (1998). Available from: http://www.nal.usda.gov/fnic/DRI//DRI_Thiamin/390-422_150.pdf as of February 28, 2008.

Methotrexate may diminish pools of all choline metabolites. Choline supplementation reverses fatty liver caused by methotrexate admin in rats. /Choline/|Repeated admin of choline chloride to female rats incr liver necrosis caused by carbon tetrachloride.|This study was designed to examine the biochemical and embryotoxic interaction of excessive dietary vitamin A and deficiency of methylation pathway constituents, namely absence of folate and choline and a reduction of methionine. Simonsen albino rats were maintained for 36 days on a diet with either normal (4 IU per gram of diet) or excessive retinyl palmitate (RP) (100 or 1000 IU per gram of diet), and normal (2 ug folic acid, 5 mg methionine and 4.2 mg choline bitartrate per gram of diet) or absence of the three dietary factors. CD-1 mouse embryos were exposed to the diet from gestational day 0 to 8, and rat serum from day 8 to 10 during whole embryo culture. The high dose of RP induced 55.4% open anterior neuropores when methylation pathway constituents were included in the diet, but this same retinoid level produced only 12.5% embryos with this defect when these constituents were omitted. Acidic retinoid levels were low in serum (less than 5 ng/mL) via HPLC. Measurements of selected methylation and transsulfuration pathway components did not yield differences in these biochemical intermediates. Thus, dietary folate, choline and methionine facilitate the induction of retinoid-induced neural tube defects.

Oral LD50 for man is estimated to be of the order of 200-400 g. /CHOLINE/

Individuals with trimethylaminuria (fish odor syndrome), renal disease, liver disease, depression, and Parkinson's disease may have increased susceptibility to the adverse effects of choline. /Choline/|Persistent trimethylaminuria in children is caused by autosomal recessively inherited impairment of hepatic trimethylamine (TMA) oxidation due to deficiency of flavin monooxygenase 3 (FMO3) secondary to mutations in the FMO3 gene. Trimethylaminuria or 'fish odor syndrome' is due to excessive excretion into body fluids and breath of TMA derived from the enterobacterial metabolism of dietary precursors. The disorder is present from birth but becomes apparent as foods containing high amounts of choline or of trimethylamine N-oxide (TMAO) from marine (sea or saltwater) fish are introduced into the diet. ... Trimethylaminuria (FMO3 deficiency) in children is rare. ... The dynamics and diagnostic efficacy of choline loading with marine fish meals in six children with trimethylaminuria /were compared/. Loading with a marine fish meal provides a simple and acceptable method for confirmation of diagnosis of suspected trimethylaminuria in children, with the effects being cleared more quickly than with a choline load test. However, oral loading with choline bitartrate allows estimation of residual oxidative capacity in vivo and is a useful adjunct to molecular studies. Patients homozygous for the 'common' P153L mutation in the FMO3 gene showed virtual complete lack of residual TMA N-oxidative capacity, consistent with a nonfunctional or absent FMO3 enzyme, whereas a patient with the M82T mutation showed some residual oxidative capacity. A patient compound heterozygous for two novel mutations, G193E and R483T, showed considerable residual N-oxidative capacity. A further patient, heterozygous for two novel sequence variations in the FMO3 gene, consistently showed malodor and elevated urinary TMA/TMAO ratios under basal conditions but a negative response to both choline and marine fish meal loading. Comparison of the effects of administration of antibiotics (metronidazole, amoxicillin, neomycin) on gut bacterial production of trimethylamine from choline showed they all reduced TMA production to a limited extent, with neomycin being most effective. 'Best-practice' diagnostic and treatment guidelines are summarized.

Choline admin significantly incr ... milk choline content during the first mo of lactation in cows ... Human milk contains 1.5 to 2 mM choline moiety per liter ... Plasma choline concn varies in response to diet and can rise as much as twofold after a 2-egg meal. Fasting plasma choline concn vary from 7 to 20 uM, with most subjects having concn of 10 uM. Individuals who have starved for up to 7 days have diminished plasma choline, but levels never drop below 50% of normal. Plasma phosphatidylcholine concn also decr in choline deficiency, but these values are also influenced by factors that change plasma lipoprotein levels. Fasting plasma phosphatidylcholine concn are approx 1 to 1.5 mM. /Choline/

Some clinical improvement with choline treatment has also been reported in huntington's chorea...in gilles de la tourette's disease, in friedreich's ataxia, & in presenile dementia ... /Choline/|A nutrient and/or dietary supplement food additive|/EXPL THER/ Eight lithium-treated patients with DSM-IV bipolar disorder, rapid cycling type were randomly assigned to 50 mg/kg/day of choline bitartrate or placebo for 12 weeks. Brain purine, choline and lithium levels were assessed using 1H- and 7Li-MRS. Patients received four to six MRS scans, at baseline and weeks 2, 3, 5, 8, 10 and 12 of treatment (n = 40 scans). Patients were assessed using the Clinical Global Impression Scale (CGIS), the Young Mania Rating Scale (YRMS) and the Hamilton Depression Rating Scale (HDRS) at each MRS scan. ... There were no significant differences in change-from-baseline measures of CGIS, YMRS, and HDRS, brain choline/creatine ratios, and brain lithium levels over a 12-week assessment period between the choline and placebo groups or within each group. However, the choline treatment group showed a significant decrease in purine metabolite ratios from baseline (purine/n-acetyl aspartate: coef = -0.08, z = -2.17, df = 22, p = 0.030; purine/choline: coef = -0.12, z = -1.97, df = 22, p = 0.049) compared to the placebo group, controlling for brain lithium level changes. Brain lithium level change was not a significant predictor of purine ratios. ... The current study reports that oral choline supplementation resulted in a significant decrease in brain purine levels over a 12-week treatment period in lithium-treated patients with DSM-IV bipolar disorder, rapid-cycling type, which may be related to the anti-manic effects of adjuvant choline. This result is consistent with mitochondrial dysfunction in bipolar disorder inadequately meeting the demand for increased ATP production as exogenous oral choline administration increases membrane phospholipid synthesis.|/EXPL THER/ ... Choline bitartrate was given openly to 6 consecutive lithium-treated outpatients with rapid-cycling bipolar disorder. Five patients also underwent brain proton magnetic resonance spectroscopy. Five of 6 rapid-cycling patients had a substantial reduction in manic symptoms, and 4 patients had a marked reduction in all mood symptoms during choline therapy. The patients who responded to choline all exhibited a substantial rise in the basal ganglia concentration of choline-containing compounds. Choline was well tolerated in all cases. Choline, in the presence of lithium, was a safe and effective treatment for 4 of 6 rapid-cycling patients in our series. A hypothesis is suggested to explain both lithium refractoriness in patients with bipolar disorder and the action of choline in mania, which involves the interaction between phosphatidylinositol and phosphatidylcholine second-messenger systems.|For more Therapeutic Uses (Complete) data for CHOLINE BITARTRATE (6 total), please visit the HSDB record page.

Oral LD50 for man is estimated to be of the order of 200-400 g. /CHOLINE/

Choline is absorbed from diet as such or as lecithin. Latter is hydrolyzed by intestinal mucosa to glycerophosphoryl choline, which either passes to liver to liberate choline or to peripheral tissues via intestinal lymphatics. /Choline/|Choline are absorbed via the portal circulation ... The liver takes up the majority of choline and stores it in the form of phosphatidylcholine and sphingomyelin. Kidney and brain also accumulate choline ... Some free choline is excreted with urine ... A specific carrier is needed for the transport of free choline across the blood-brain barrier, and the capacity is especially high in neonates. /Choline/|Free choline is transported across the blood-brain barrier at a rate that is proportional to serum choline level ... In advanced age ... brain choline uptake /is decr/ ... /Choline/|During pregnancy, large amt of choline are delivered to the fetus across the placenta and this depletes maternal stores. Choline concn in amniotic fluid is 10-fold greater than that in maternal blood. At birth, humans and other mammals have plasma choline concn that are much higher than those in adults ... In rats, the liver choline concn in late pregnancy decr to less than one-third that of nonpregnant females ... /Choline/|For more Absorption, Distribution and Excretion (Complete) data for CHOLINE BITARTRATE (8 total), please visit the HSDB record page.

Free choline is not fully absorbed, especially after large doses, and intestinal bacteria metabolize choline to trimethylamine. /Choline/|/The/ ability to form choline /de novo via the methylation of phosphatidylethanolamine using S-adenosylmethionine as the methyl donor, mostly in the liver,/ means that some of the demand for choline can ... be met using methyl groups derived from 1-carbon metabolism (via methyl-folate and methionine). Several vitamins (folate, vitamin B12, vitamin B6, and riboflavin) and the amino acid methionine interact with choline in 1-carbon metabolism ... Methionine, methyl-tetrahydrofolate (THF), and choline can be fungible sources of methyl groups. /Choline/|Before choline can be absorbed in the gut, some is metabolized by bacteria to form betaine and methylamines (which are not methyl donors) ... Although some free choline is excreted with urine, most is oxidized in the kidney to form betaine ... /Choline/|Acetylcholine is one of the most important neurotransmitters used by neurons in the memory centers of the brain (hippocampus and septum). Choline accelerates the synth and release of acetylcholine in nerve cells. Choline used by brain neurons is largely derived from membrane lecithin /(phosphatidylcholine)/, or from dietary intake of choline and lecithin ... Choline derived from lecithin may be especially important when extracellular choline is in short supply, as might be expected to occur in advanced age because of decr brain choline uptake ... /Choline/|For more Metabolism/Metabolites (Complete) data for CHOLINE BITARTRATE (6 total), please visit the HSDB record page.

Several mechanisms are suggested for the cancer-promoting effect of a choline-devoid diet. These incl incr cell proliferation related to regeneration after parenchymal cell death occurs in the choline deficient liver, hypomethylation of DNA (alters expression of genes), reactive oxygen species leakage from mitochondria with incr lipid peroxidation in liver, activation of protein kinase C signaling due to accumulation of diacylglycerol in liver, mutation of the fragile histidine triad (FHIT) gene, which is a tumor suppressor gene, and defective cell-suicide (apoptosis) mechanisms. Loss of phposphatidylethanolamine N-methyl-transferase (PEMT) function may also contribute to malignant transformation of hepatocytes. /Choline/|Acetylcholine is one of the most important neurotransmitters used by neurons in the memory centers of the brain (hippocampus and septum). Choline accelerates the synth and release of acetylcholine in nerve cells. /Choline/|... Choline deficiency in cell culture causes apoptosis or programmed cell death. This appears to be due to abnormalities in cell membrane phosphatidylcholine content and an incr in ceramide, a precursor, as well as a metabolite of sphingomyelin. Ceramide accumulation, which is caused by choline deficiency, appears to activate a caspase, a type of enzyme that mediates apoptosis. /Choline/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ /In a/ study involved a double-blind, crossover protocol, 9 g/day (wk 1) and 12 g/day (wk 2) given as a chloride or bitartrate, /choline caused/ mild cholinergic toxicity: lacrimation, blurred vision, anorexia, and diarrhea. /Chloride or bitartrate/ /From table/|/SIGNS AND SYMPTOMS/ At 7.5 g of choline daily, nausea, diarrhea and a small decr in blood pressure were reported in some patients. The upper limit (UL) for adults is 3.5 g daily. Individuals that may be at incr risk of side effects with choline intakes at the UL include those with trimethylaminuria, liver disease, renal disease, depression and Parkinson's disease. /Choline/|/SIGNS AND SYMPTOMS/ There are some reports of depression or incr symptoms of depression in those using high doses of choline bitartrate.|/SIGNS AND SYMPTOMS/ High doses of choline have been associated with excessive cholinergic stimulation, such as vomiting, salivation, sweating, and gastrointestinal effects. In addition, fishy body odor results from the excretion of trimethylamine, a choline metabolite from bacterial action. /Choline/|For more Human Toxicity Excerpts (Complete) data for CHOLINE BITARTRATE (7 total), please visit the HSDB record page.

AVAILABLE GENERICALLY: TABLETS 250 MG...|Grade: FCC

QUALITATIVELY CHOLINE HAS THE SAME PHARMACOLOGICAL ACTIONS AS DOES ACETYLCHOLINE, BUT IT IS FAR LESS ACTIVE. /CHOLINE/|SINCE HUMAN BREAST MILK CONTAINS 7 MG CHOLINE/100 KCAL, COMMITTEE ON NUTRITION OF AMERICAN ACADEMY OF PEDIATRICS (1976) RECOMMENDS THE FORTIFICATION OF INFANT FORMULAS TO THIS LEVEL. /CHOLINE/|CHOLINE IS NOT AT PRESENT AN OFFICIAL DRUG. HOWEVER, PREPN OF CHOLINE BITARTRATE...AVAILABLE.|... The dominating industrial process /for choline/ is reacting ethylene oxide with trimethylamine and water, or an acid if one of its salts is desired, in a batch or continuous manufacturing process.

MICROCHEMICAL TEST FOR CHOLINE. /CHOLINE/|Analyte: choline bitartrate; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: choline bitartrate; matrix: chemical purity; procedure: dissolution in water; add glacial acetic acid; potentiometric titration with silver nitrate|Analyte: choline bitartrate; matrix: pharmaceutical preparation (capsule, tablet), food (bovine liver, cereal, egg yolk, infant formula, meat-based pet food, soybean); procedure: capillary zone electrophoresis with indirect ultraviolet detection at 214 nm; limit of detection: 50 ug/g|For more Analytic Laboratory Methods (Complete) data for CHOLINE BITARTRATE (10 total), please visit the HSDB record page.

Analyte: choline bitartrate; matrix: blood (plasma); procedure: high-performance liquid chromatography with ultraviolet detection at 254 nm; limit of quantitation: 1 nmole/mL|Analyte: choline bitartrate; matrix: blood (plasma, red blood cell); procedure: high-performance liquid chromatography with electrochemical detection; limit of detection: 10 nM|Analyte: choline bitartrate; matrix: blood (plasma); procedure: high-performance liquid chromatography with electrochemical detection; limit of quantitation: 3.58 uM|Analyte: choline bitartrate; matrix: cerebrospinal fluid, dialysate, tissue (brain); procedure: high-performance liquid chromatography with electrochemical detection; limit of detection: 10 fmole|For more Clinical Laboratory Methods (Complete) data for CHOLINE BITARTRATE (12 total), please visit the HSDB record page.