Choline
Choline
Also known as: Choline bitartrate, Choline citrate, CDP-choline (Citicoline), Alpha-GPC, Phosphatidylcholine, Lecithin
Choline is an essential nutrient critical for brain function, liver health, and fetal development. It was officially recognized as essential by the Institute of Medicine in 1998.
Introduction
Choline is an essential nutrient that was only officially classified as required by the Institute of Medicine in 1998. Although the body can synthesize small amounts, dietary intake is necessary to maintain health, making it conditionally essential.
Choline serves multiple critical functions: it is a structural component of cell membranes, a precursor for the neurotransmitter acetylcholine, and a methyl donor for epigenetic regulation and homocysteine metabolism. It is also essential for lipid transport from the liver.
Perhaps most importantly, choline is critical during pregnancy and early childhood for proper brain development. It contributes to neural tube closure, hippocampal development, and lifelong cognitive function. Despite its importance, most pregnant women consume inadequate choline.
Choline deficiency causes non-alcoholic fatty liver disease (NAFLD), muscle damage, and cognitive dysfunction. While overt deficiency is uncommon, suboptimal intake is widespread, with only about 10% of Americans meeting the AI.
Beyond its essential functions, choline has been studied for cognitive enhancement (particularly CDP-choline and Alpha-GPC), athletic performance, and liver protection. The evidence varies by form and application.
Main Benefits
Critical for fetal brain development; adequate intake reduces risk of neural tube defects and supports cognitive development.
Prevents and treats non-alcoholic fatty liver disease (NAFLD); required for exporting fat from the liver via VLDL.
Precursor for acetylcholine, essential for memory, learning, muscle control, and nervous system function.
Supports cardiovascular health as methyl donor for homocysteine metabolism; works with folate and B12.
CDP-choline and Alpha-GPC forms may enhance cognitive function and support recovery from stroke/TBI.
Mechanism of Action
Choline operates through several distinct biochemical pathways:
Cell Membrane Structure: Choline is phosphorylated to form phosphocholine, which combines with diacylglycerol to create phosphatidylcholine (PC), a major component of cell membranes. PC maintains membrane fluidity and integrity.
Neurotransmitter Synthesis: Choline is the rate-limiting precursor for acetylcholine synthesis via the enzyme choline acetyltransferase. Acetylcholine is critical for:
- Memory formation and retrieval
- Muscle contraction
- Parasympathetic nervous system function
- REM sleep regulation
Lipid Transport: Phosphatidylcholine is essential for assembling very-low-density lipoproteins (VLDL) in the liver. Without adequate choline, triglycerides accumulate in the liver, causing fatty liver disease.
One-Carbon Metabolism: Choline (as betaine, via oxidation) serves as a methyl donor in the methionine cycle. This is critical for:
- DNA methylation (epigenetic regulation)
- Homocysteine reduction to methionine
- Synthesis of creatine and other methylated compounds
Sphingomyelin Synthesis: Choline contributes to sphingomyelin formation, important for nerve myelination and cell signaling.
Natural Sources
Choline is found in many foods, with eggs and liver being the richest sources. Most people do not consume adequate choline.
Examples:
Beef liver
Eggs (especially yolks)
Beef
Chicken
Fish (cod, salmon)
Soybeans and tofu
Wheat germ
Broccoli
Beans (kidney, navy)
Milk and yogurt
Rich sources (liver, eggs) are not universally consumed; vegetarians/vegans may struggle to get adequate amounts; most diets fall short of AI.
Deficiency Symptoms
Choline deficiency causes fatty liver, muscle damage, and neurological impairment. Suboptimal intake is common.
Common Symptoms:
Fatty liver (hepatosteatosis)
Elevated liver enzymes (ALT, AST)
Muscle damage and myalgia
Cognitive impairment
Neural tube defects (in pregnancy)
Only ~10% of Americans meet AI; suboptimal intake widespread; overt deficiency less common but underdiagnosed.
NAFLD affects ~25% of population; pregnancy deficiency affects fetal brain development; significant public health impact.
Recommended Daily Intake
AI: men 550 mg/day, women 425 mg/day. Higher during pregnancy (450 mg) and lactation (550 mg). Upper Limit (UL) is 3,500 mg/day.
Reference Values:
| Adult men | 550 mg/day (AI) |
| Adult women | 425 mg/day (AI) |
| Pregnancy | 450 mg/day (AI) |
| Lactation | 550 mg/day (AI) |
| Upper Limit (UL) | 3,500 mg/day |
Sources for RDI/AI:
- https://ods.od.nih.gov/factsheets/Choline-HealthProfessional/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3729018/
Most prenatal vitamins contain inadequate choline. Pregnant women should prioritize choline-rich foods or consider supplementation.
Effectiveness for Specific Focuses
Precursor for acetylcholine; critical for fetal brain development; CDP-choline/Alpha-GPC have nootropic evidence.
Critical for pregnancy; reduces neural tube defect risk; supports fetal brain development; most pregnant women deficient.
Essential for liver fat export; prevents/treats NAFLD; supports liver health.
Methyl donor for homocysteine metabolism; may support cardiovascular health through methylation pathways.
May enhance muscle performance and delay fatigue; limited athletic research; Alpha-GPC may boost growth hormone.
Safety Information
Potential Side Effects
Fishy body odor at high doses (from trimethylamine)
Nausea and diarrhea
Low blood pressure (rare)
Contraindications
Trimethylaminuria (fish odor syndrome)
Overdose Information
UL established at 3,500 mg/day; doses above this may cause fishy odor, nausea, and hypotension; generally well-tolerated below UL.
Fishy body odor, nausea, vomiting, diarrhea, sweating, and hypotension at very high doses.
Documented Overdose Symptoms:
Fishy body odor
Gastrointestinal distress
Hypotension
Toxicity Thresholds: UL: 3,500 mg/day for adults based on risk of hypotension.
Generally safe below UL. Fishy odor from bacterial conversion to trimethylamine is the main side effect.
Interactions
Drug Interactions:
Methotrexate (increases choline requirement)
Anticholinergic medications (oppose acetylcholine effects)
Cholinergic medications (additive effects)
Anticholinergics oppose choline's effects; methotrexate increases requirement; generally compatible with most medications.
Other Supplement Interactions:
Folate and B12 - synergistic in methylation pathways
Betaine - alternative methyl donor
Synergistic with folate and B12; safe combinations with most supplements.
Some people are "fishy odor" responders due to gut bacteria converting choline to trimethylamine. Taking with meals may reduce this effect. Very important for pregnant women to ensure adequate intake.
Forms and Bioavailability
Choline salts (bitartrate, citrate) are common. CDP-choline and Alpha-GPC are specialized nootropic forms with better brain penetration.
Choline Bitartrate
Common, inexpensive form; good bioavailability; tart taste.
Well-absorbed; cost-effective; approximately 41% choline by weight.
Most economical choice. Good for general supplementation and liver health.
CDP-Choline (Citicoline)
Choline bound to cytidine; crosses blood-brain barrier efficiently; also provides cytidine for phospholipid synthesis.
Superior brain penetration; well-studied for cognitive enhancement; also provides cytidine for membrane repair.
Preferred for cognitive benefits. More expensive but better evidence for brain health than basic choline salts.
Alpha-GPC
Glycerylphosphorylcholine; crosses blood-brain barrier; appears in blood quickly after oral administration.
Excellent bioavailability; rapidly increases plasma choline; may stimulate growth hormone release.
Popular in nootropic and athletic communities. Good evidence for cognitive enhancement. More expensive than basic forms.
Phosphatidylcholine (Lecithin)
Phospholipid form found in cell membranes; provides choline but also other phospholipids.
Lower choline content (~13%); additional phospholipid benefits; variable absorption.
Provides additional phospholipids but less concentrated choline source. Often derived from soy or sunflower.
Warnings & Suitability
Did You Know...?
Choline was the last nutrient to be officially declared essential by the Institute of Medicine - this happened in 1998, decades after other vitamins were identified.
Two large eggs provide about 250-300 mg of choline, covering more than half the daily requirement for most people.
The human brain is approximately 60% fat, and phosphatidylcholine is one of the most abundant phospholipids in brain tissue.
Choline was named after the Greek word "chole" meaning bile, because it was first isolated from bile in 1862.
General Scientific Sources
Tags
Content Verification
Last Medical Review: 2/13/2026
Reviewed by: Editorial Team