Phosphatidylcholine and sphingomyelin, two important components of cell membranes in vitro, are precursors to choline [3]. Through its metabolite betaine, which is involved in the S-adenosylmethionine synthesis pathway, choline serves as the primary source of methyl groups as well [4].

Use oral gavage to provide choline bitartrate (300 mg/kg as opposed to 5 g/kg). Mice on choline restriction (300 mg/kg) had significant hepatic steatosis, inflammation, and cell damage in addition to a robust ketosis and weight loss. Moderate ketosis and the build-up of liver fat can be minimized when choline levels are adequate [4].

Absorption, Distribution and Excretion
Choline can be absorbed directly from the diet or bound to lecithin. Lecithin is hydrolyzed in the intestinal mucosa to glycerophosphate choline, which either enters the liver to release choline or is transported to peripheral tissues via the intestinal lymphatic system. /Choline/ Choline is absorbed through the portal venous circulation… The liver absorbs most choline and stores it in the form of phosphatidylcholine and sphingomyelin. Choline also accumulates in the kidneys and brain… Some free choline is excreted in urine… Free choline requires specific carriers to cross the blood-brain barrier, and newborns have a particularly strong transport capacity. Choline The rate at which free choline crosses the blood-brain barrier is proportional to serum choline levels… With age… the brain's uptake of choline decreases… Choline During pregnancy, a large amount of choline is transported to the fetus through the placenta, which depletes the mother's choline stores. The concentration of choline in amniotic fluid is 10 times the concentration of choline in the mother's blood. Humans and other mammals have much higher plasma choline concentrations at birth than adults… In late pregnancy, liver choline concentrations in rats drop to less than one-third of those in non-pregnant females… /choline/
For more complete data on the absorption, distribution, and excretion of tartrate choline (8 types), please visit the HSDB records page.

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Metabolism/Metabolites
Free choline is not completely absorbed, especially after high doses, as intestinal bacteria metabolize it into trimethylamine. Choline
The human body can synthesize choline de novo, primarily in the liver, through the methylation of phosphatidylethanolamine using S-adenosylmethionine as a methyl donor. This means that some choline needs can be met by methyl groups produced through one-carbon metabolism (via methylfolate and methionine). Many vitamins (folate, vitamin B12, vitamin B6, and riboflavin) and the amino acid methionine interact with choline in one-carbon metabolism…Methionine, methyltetrahydrofolate (THF), and choline can serve as alternative sources of methyl groups. Choline
Before being absorbed by the intestines, some choline is metabolized by bacteria into betaine and methylamine (methylamine is not a methyl donor)... Although some free choline is excreted in urine, most is oxidized in the kidneys to form betaine... Choline
Acetylcholine is one of the most important neurotransmitters used by neurons in the brain's memory centers (hippocampus and septum). Choline accelerates the synthesis and release of acetylcholine in nerve cells. The choline used by brain neurons mainly comes from membrane lecithin (phosphatidylcholine), or from dietary choline and lecithin... When extracellular choline supply is insufficient, lecithin-derived choline may be particularly important, for example, in the elderly due to reduced brain choline uptake... /Choline/
For more complete data on the metabolism/metabolites of tartratecholine (6 types), please visit the HSDB record page.

Interactions
Methotrexate may reduce the pool of all choline metabolites. Choline supplementation reverses methotrexate-induced fatty liver in rats. /Choline/
Repeated injections of choline chloride into female rats exacerbate carbon tetrachloride-induced liver necrosis.
This study aimed to investigate the biochemical and embryotoxic interactions between dietary vitamin A excess and deficiencies in methylation pathway components (i.e., folic acid and choline deficiency, and methionine reduction). Simonson albino rats were fed for 36 days with diets containing normal (4 IU/g) or excessive (100 or 1000 IU/g) retinyl palmitate (RP), and diets containing normal (2 μg folic acid, 5 mg methionine, and 4.2 mg choline tartrate) or deficient in these three dietary components. During whole embryo culture, CD-1 mouse embryos were exposed to the specific diet from day 0 to day 8 of gestation and to rat serum from day 8 to day 10. When the diet contained components of the methylation pathway, high-dose retinol induced anterior neural tube defects in 55.4% of embryos; conversely, when the diet did not contain these components, the same dose of retinol resulted in this defect in only 12.5% of embryos. High-performance liquid chromatography (HPLC) revealed low serum levels of acidic retinol (below 5 ng/mL). Determination of selected methylation and transsulfurization pathway components did not reveal differences in these biochemical intermediates. Therefore, dietary folic acid, choline, and methionine promote retinol-induced neural tube defects.

[1]. An introduction to the nutrition and metabolism of choline. Cent Nerv Syst Agents Med Chem. 2012 Jun;12(2):100-13.

[2]. Choline metabolism provides novel insights into nonalcoholic fatty liver disease and its progression. Curr Opin Gastroenterol. 2012 Mar;28(2):159-65.

[3]. Development of a chemically defined platform fed-batch culture media for monoclonal antibody-producing CHO cell lines with optimized choline content. Cytotechnology. 2018 Jun;70(3):939-948.

[4]. Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet. PLoS One. 2013 Aug 29;8(8):e74806.

Choline is a fundamental component of lecithin and is found in many animal and plant organs. It plays a crucial role as a precursor to acetylcholine, a methyl donor in various metabolic processes, and an important component of lipid metabolism. Mechanism of Action Currently, it is believed that a choline-deficient diet may promote cancer development through multiple mechanisms. These mechanisms include: increased cell proliferation related to parenchymal cell regeneration after death in the choline-deficient liver; DNA hypomethylation (altering gene expression); increased hepatic lipid peroxidation due to mitochondrial reactive oxygen species leakage; activation of the protein kinase C signaling pathway due to diacylglycerol accumulation in the liver; mutations in the tumor suppressor gene—fragile histidine triad (FHIT); and defects in apoptosis mechanisms. Loss of function of phosphatidylethanolamine N-methyltransferase (PEMT) may also lead to malignant transformation of hepatocytes. Choline: Acetylcholine is one of the most important neurotransmitters in neurons of the brain's memory centers (hippocampus and septum). Choline accelerates the synthesis and release of acetylcholine in nerve cells. Choline deficiency leads to apoptosis or programmed cell death. This appears to be due to abnormal levels of phosphatidylcholine in cell membranes and increased levels of ceramides (precursors and metabolites of sphingomyelin). Ceramide accumulation caused by choline deficiency appears to activate caspase (an enzyme mediating apoptosis). /choline/

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Therapeutic Uses
Choline therapy has been reported to improve clinical symptoms of Huntington's disease, Tourette syndrome, Friedreich ataxia, and Alzheimer's disease…/choline/
A nutrient and/or dietary supplement/food additive
/EXPL THER/ Eight patients with DSM-IV rapid-cycle bipolar disorder receiving lithium therapy were randomly assigned to receive 50 mg/kg/day of choline tartrate or placebo for 12 weeks. Brain levels of purines, choline, and lithium were assessed using 1H- and 7Li-MRS. Patients underwent 4 to 6 MRS scans (n = 40 scans) at baseline and at weeks 2, 3, 5, 8, 10, and 12 of treatment. At each MRS scan, patients were assessed using the Clinical Global Impression Scale (CGIS), Young's Mania Rating Scale (YRMS), and Hamilton Depression Rating Scale (HDRS). …During the 12-week assessment period, there were no significant differences in baseline changes in CGIS, YRMS, and HDRS, brain choline/creatine ratio, and brain lithium levels between the choline and placebo groups, or within each group. However, after controlling for changes in brain lithium levels, the purine metabolite ratios in the choline treatment group were significantly lower than baseline compared to the placebo group (purine/N-acetylaspartate: coefficient = -0.08, z = -2.17, df = 22, p = 0.030; purine/choline: coefficient = -0.12, z = -1.97, df = 22, p = 0.049). Changes in brain lithium levels were not a significant predictor of purine ratios. …This study reports that in patients with DSM-IV rapid-cycle bipolar disorder receiving lithium treatment, oral choline supplementation significantly reduced brain purine levels over a 12-week treatment period, which may be related to the antimanic effect of choline. This result is consistent with the inability of mitochondrial dysfunction in bipolar disorder to adequately meet the increased demand for ATP production, as exogenous oral choline can increase the synthesis of membrane phospholipids.
/EXPL THER/…… Choline tartrate was administered openly to six consecutive outpatients with rapid-cycle bipolar disorder (RCD) who were receiving lithium therapy. Five of these patients also underwent proton magnetic resonance spectroscopy (BMRI). Five of the six RCD patients experienced significant reductions in manic symptoms, and four patients experienced significant reductions in all mood symptoms during choline therapy. All patients who responded to choline showed significantly increased concentrations of choline-containing compounds in their basal ganglia. All patients tolerated choline well. In the presence of lithium, choline was a safe and effective treatment for four of the six RCD patients in our study. We propose a hypothesis to explain the treatment-resistant nature of bipolar disorder to lithium and the role of choline in mania, involving the interaction between the phosphatidylinositol and phosphatidylcholine second messenger systems.
For more complete data on the therapeutic uses of choline tartrate (6 types), please visit the HSDB record page.

C9H19NO7

253.2497

253.116

87-67-2

Choline chloride;67-48-1;Choline theophyllinate;4499-40-5

6900

White to off-white solid powder

1.47 g/cm3

399.3ºC at 760 mmHg

151-153°C

209.4ºC

4

7

4

17

193

2

C[N+](C)(C)CCO.[C@@H]([C@H](C(=O)[O-])O)(C(=O)O)O

QWJSAWXRUVVRLH-LREBCSMRSA-M

InChI=1S/C5H14NO.C4H6O6/c1-6(2,3)4-5-7;5-1(3(7)8)2(6)4(9)10/h7H,4-5H2,1-3H3;1-2,5-6H,(H,7,8)(H,9,10)/q+1;/p-1/t;1-,2-/m.1/s1

2-hydroxyethyl(trimethyl)azanium;(2R,3R)-2,3,4-trihydroxy-4-oxobutanoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~120 mg/mL (~473.84 mM)
DMSO : ~55 mg/mL (~217.18 mM)

Solubility in Formulation 1: ≥ 2.75 mg/mL (10.86 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.75 mg/mL (10.86 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.75 mg/mL (10.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (394.87 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)