Choline is an essential nutrient that is the foundation of the phosphatidylcholine (PC) and of the sphingomyelin that are the primary structural phospholipids of all cell membranes, and it is also the precursor of the acetylcholine (the neurotransmitter of the cholinergic neurons) and of the betaine (the methyl group donor that is essential for the methylation cycle). The phosphatidylcholine is the most abundant phospholipid in the eukaryotic cell membrane — it accounts for approximately 40-50% of the total phospholipids in most cell membranes, and it is particularly abundant in the lung surfactant (where it is the primary component of the surfactant that prevents the alveolar collapse during the breathing) and in the circulating lipoproteins (where it is essential for the packaging and the transport of the dietary fats in the form of the VLDL particles). Without adequate choline, the phosphatidylcholine synthesis is impaired, the cell membrane integrity is compromised, and the liver cannot package and export the fat as VLDL — producing the fatty liver, the elevated blood triglycerides, and the increased risk of the cardiovascular disease that are the hallmark of the choline deficiency. The dietary sources of choline include the egg yolks, the liver, the meat, the fish, the poultry, the soybeans, and the wheat germ, and the estimated requirement for the adult is 425-550mg daily.
Phosphatidylcholine and the Cell Membrane Integrity
Phosphatidylcholine (PC) is the primary structural component of all eukaryotic cell membranes — it forms the lipid bilayer that is the fundamental structure of the cell membrane, and it is the platform on which the membrane proteins (receptors, channels, transporters, enzymes) are embedded and function. The PC bilayer is not merely a passive barrier — it is a dynamic, fluid structure that regulates the membrane protein function, the membrane trafficking, the signal transduction, and the cell-cell communication. The PC is synthesised by the CDP-choline pathway (also called the Kennedy pathway) — the pathway that uses the choline that is taken up from the blood by the choline transporter, converts it to the CDP-choline intermediate using the CTP and the energy of the ATP, and then attaches the CDP-choline to the diacylglycerol (DAG) to form the phosphatidylcholine. This synthesis pathway is the primary route for the PC synthesis in all cells, and it is the pathway that is impaired in the choline deficiency — when choline is not available, the PC synthesis is reduced, the cell membrane integrity is compromised, and the cell function is impaired.
The clinical importance of the choline for the cell membrane integrity is underscored by the observation that the choline deficiency produces the fatty liver (because the liver cannot synthesise enough PC to package the fat as VLDL), the muscle damage (because the sarcolemma of the muscle cells requires the PC for its integrity), and the cognitive decline (because the neuronal membranes require the PC for their integrity and for the function of the neurotransmitter receptors and the synaptic vesicle fusion proteins). These are the most sensitive indicators of the choline deficiency, and they are the markers that are used to define the estimated average requirement (EAR) and the recommended dietary allowance (RDA) for choline.
Choline and the Brain Function
Choline is also the precursor of the acetylcholine — the neurotransmitter that is synthesised by the cholinergic neurons of the basal forebrain, of the medial septal nucleus, and of the other cholinergic nuclei of the brain. The acetylcholine is the primary neurotransmitter of the parasympathetic nervous system (where it regulates the heart rate, the GI motility, and the glandular secretion), of the neuromuscular junction (where it activates the skeletal muscle contraction), and of the central nervous system (where it is involved in the memory formation, in the attention, and in the cognitive function). The cholinergic neurons of the basal forebrain (the nucleus basalis of Meynert) are particularly important for the cognitive function — they project to the hippocampus and to the cortical regions and provide the cholinergic input that is essential for the memory formation and for the cortical plasticity. The degeneration of these cholinergic neurons in the Alzheimer disease is one of the most important pathological findings in this condition, and it is the basis for the use of the acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) in the treatment of the Alzheimer disease.
Practical Application
For general choline supplementation, the evidence-based approach is to supplement with 250-500mg of choline daily (as the choline bitartrate, the choline citrate, or the alpha-GPC form — the alpha-GPC is the most bioavailable form for the brain, because it crosses the blood-brain barrier and is used directly for the acetylcholine synthesis). The AI of choline is 550mg daily for men and 425mg daily for women, and it is easily obtained from the egg yolks (approximately 150mg per egg yolk), from the liver (approximately 300mg per 100g), and from the meat, fish, and poultry. The supplementation of choline is particularly important for the vegans, for the people with the liver disease, for the pregnant women (who have a higher choline requirement because of the foetal brain development), and for the people with the genetic polymorphisms that increase the choline requirement (particularly the MTHFR polymorphisms, which affect the methylation cycle and which increase the demand for the betaine as a methyl donor). For comprehensive liver and brain support, choline pairs well with the inositol (which is the precursor of the other major phospholipids, including the phosphatidylinositol), with the folate and the B12 (which are required for the methylation cycle and for the synthesis of the phosphatidylcholine), and with the DMAE (which is a precursor of the acetylcholine and which is used in the nootropic formulations for the memory enhancement).
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