Usage
Choline dihydrogen citrate is primarily used to prevent or treat choline deficiency. Choline is an essential nutrient required for various bodily functions, including liver function, brain development, nerve function, and lipid metabolism. It’s crucial during pregnancy and breastfeeding for proper fetal development.
While choline is available from dietary sources, supplementation with choline dihydrogen citrate may be necessary in cases of deficiency or increased need.
It’s classified as an essential nutrient and a cholinergic compound due to its role in acetylcholine synthesis.
Choline’s mechanism of action involves acting as a precursor for the neurotransmitter acetylcholine, a key component of cell membranes (phosphatidylcholine and sphingomyelin), and a methyl donor involved in various metabolic processes.
Alternate Names
- Choline citrate
- (2-Hydroxyethyl)trimethylammonium 2-hydroxypropane-1,2,3-tricarboxylate
There are no widely recognized brand names specifically for choline dihydrogen citrate. It’s usually found as an ingredient in multivitamin supplements or as a generic supplement.
How It Works
Pharmacodynamics: Choline is crucial for several physiological processes:
- Neurotransmission: It acts as a precursor for acetylcholine, a neurotransmitter vital for muscle control, memory, and other brain functions.
- Cell Membrane Integrity: Choline is a key component of phosphatidylcholine and sphingomyelin, essential phospholipids that maintain the structural integrity and fluidity of cell membranes.
- Lipid Metabolism: It facilitates lipid transport and prevents fat accumulation in the liver.
- Methylation: Choline acts as a methyl donor through its metabolite, betaine, participating in various metabolic reactions.
Pharmacokinetics:
- Absorption: Choline dihydrogen citrate is readily absorbed in the gastrointestinal tract.
- Distribution: Distributed throughout the body, with higher concentrations in the liver, brain, and kidneys.
- Metabolism: Metabolized in the liver to betaine, trimethylamine N-oxide (TMAO), and other metabolites.
- Elimination: Excreted primarily through the kidneys.
Mode of Action:
- Acetylcholine Synthesis: Choline is transported into presynaptic nerve terminals where it’s acetylated by choline acetyltransferase to form acetylcholine.
- Membrane Synthesis: Choline is incorporated into phosphatidylcholine and sphingomyelin, the major phospholipids in cell membranes, influencing membrane fluidity and signal transduction.
- Methyl Donor: Betaine, a metabolite of choline, acts as a methyl donor in various metabolic processes, including homocysteine remethylation.
Receptor Binding/Enzyme Inhibition: Choline’s primary action is as a substrate for choline acetyltransferase, the enzyme responsible for acetylcholine synthesis. It doesn’t directly bind to receptors or inhibit enzymes other than indirectly through the actions of acetylcholine.
Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Adequate Intake (AI): 550 mg/day for men, 425 mg/day for women.
- Supplementation: 1-3 grams/day, usually divided into multiple doses. Maximum daily intake should not exceed 3.5 grams to avoid potential side effects.
Children:
- AI varies by age group:
- 0-6 months: 125 mg/day
- 7-12 months: 150 mg/day
- 1-3 years: 200 mg/day
- 4-8 years: 250 mg/day
- 9-13 years: 375 mg/day
- 14-18 years: 400 mg/day (girls), 550 mg/day (boys)
Special Cases:
- Elderly Patients: No specific dosage adjustments are generally recommended, but individual needs may vary.
- Patients with Renal Impairment: Caution is advised. Dose adjustments may be necessary.
- Patients with Hepatic Dysfunction: Caution is advised. Dose adjustments may be necessary.
- Patients with Comorbid Conditions: Individualized assessment is required.
Clinical Use Cases
Choline dihydrogen citrate is not typically used in acute clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its role is primarily in nutritional support and preventing or treating choline deficiency.
Dosage Adjustments
Dose modifications should be based on individual patient factors such as renal or hepatic function, other medical conditions, and response to therapy. Monitoring choline levels may be useful in some cases.
Side Effects
Common Side Effects:
- Gastrointestinal upset (nausea, vomiting, diarrhea)
- Fishy body odor
Rare but Serious Side Effects:
- Hypotension
- Liver toxicity (with very high doses)
Long-Term Effects:
Limited data available. Monitoring is recommended with prolonged use.
Adverse Drug Reactions (ADR):
Severe gastrointestinal distress or signs of liver dysfunction (jaundice, abdominal pain) require immediate medical attention.
Contraindications
- Hypersensitivity to choline or any component of the formulation.
- Trimethylaminuria (fish odor syndrome)
Drug Interactions
- Medications metabolized by the liver (CYP450 enzymes): Potential for altered metabolism. Consult drug interaction resources for specific interactions.
Pregnancy and Breastfeeding
- Pregnancy: Adequate choline intake is crucial for fetal development. AI is 450 mg/day. Supplementation may be necessary if dietary intake is insufficient.
- Breastfeeding: AI is 550 mg/day. Supplementation may be necessary if dietary intake is insufficient.
Drug Profile Summary
- Mechanism of Action: Precursor for acetylcholine, component of cell membranes, methyl donor.
- Side Effects: Gastrointestinal upset, fishy body odor, rarely hypotension or liver toxicity.
- Contraindications: Hypersensitivity, trimethylaminuria.
- Drug Interactions: Potential interactions with drugs metabolized by the liver.
- Pregnancy & Breastfeeding: Essential nutrient; supplementation may be needed.
- Dosage: AI varies with age and sex; supplementation typically 1-3 grams/day.
- Monitoring Parameters: Choline levels (if clinically indicated), liver function tests (with high doses or prolonged use).
Popular Combinations
Choline is often included in multivitamin formulations and prenatal vitamins. There are no specific drug combinations routinely recommended for use with choline dihydrogen citrate itself.
Precautions
- Assess choline status through dietary recall and consider supplementation in individuals at risk of deficiency.
- Monitor for side effects, particularly gastrointestinal issues and fishy body odor.
- Exercise caution in patients with liver or kidney disease.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Choline Dihydrogen Citrate?
A: The adequate intake for adults is 550 mg/day for men and 425 mg/day for women. Therapeutic doses range from 1-3 grams/day, divided into multiple doses, but not exceeding 3.5 grams/day.
Q2: What are the main functions of choline?
A: Choline supports neurotransmission (acetylcholine synthesis), cell membrane integrity (phospholipid synthesis), lipid metabolism, and methylation reactions.
Q3: Is choline safe during pregnancy and breastfeeding?
A: Yes, adequate choline intake is essential during these periods. AIs are 450 mg/day during pregnancy and 550 mg/day while breastfeeding.
Q4: What are the common side effects of choline supplementation?
A: Common side effects include gastrointestinal issues (nausea, vomiting, diarrhea) and a fishy body odor.
Q5: Are there any contraindications for choline supplementation?
A: Contraindications include hypersensitivity to choline and trimethylaminuria.
Q6: How does choline work at the cellular level?
A: Choline is transported into cells and used for acetylcholine synthesis, phospholipid synthesis for cell membranes, and methylation reactions via its metabolite, betaine.
Q7: Does choline interact with any medications?
A: Potential interactions exist with drugs metabolized by the liver. Consult drug interaction resources.
Q8: What foods are rich in choline?
A: Good dietary sources of choline include beef liver, eggs, chicken, fish, milk, and cruciferous vegetables like broccoli and Brussels sprouts.
Q9: How is choline deficiency diagnosed?
A: Choline deficiency is typically diagnosed based on symptoms, dietary assessment, and potentially serum choline levels.
Q10: What is the role of choline in brain health?
A: Choline is essential for brain development and function, particularly in the synthesis of acetylcholine, a neurotransmitter involved in memory, learning, and muscle control.
