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Choline (Acetylcholine) |
Exciting break through new product to improve your memory, protect against premature brain aging, and even have a positive effect on mood.
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What is Choline (Acetylcholine): |
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Choline is a natural amine that is classified as an essential nutrient (meaning the body cannot synthesize it and has to have it supplemented through diet) and is grouped with the vitamin B complex. It forms the structural component of many lipid membranes and is also a part of acetylcholine. Acetylcholine, made up of choline and acetic acid, is a major neurotransmitter (transmits signals in the brain via neuronal cells) in the brain. Choline is important for maintaining the structural integrity of cells, signaling to and/or from cell membranes, neurotransmissions involving synthesis of acetylcholine, and is a major source of methyl groups via its metabolites. These methyl groups transfer supplements like vitamin B6, B12 and folic acid, and play an important role in preventing heart diseases.
Acetylcholine on the other hand, plays an important role in the central and peripheral nervous systems. It has excitatory effects in the peripheral nervous system, meaning that it excites the neuronal cells and activates a series of reactions that leads to muscle contraction. While it increases the contraction of skeletal muscles, it concurrently decreases the contraction of cardiac muscles. Acetylcholine also has excitability functions in the central nervous system. Any damage to this cholinergic system leads to neurodegenerative disorders of the brain, like Alzheimer's disease.
Choline is regarded as a water-soluble vitamin, though the debate is still on whether it is a true vitamin or not. It works in close association with folic acid and cobalamine. It is also required for synthesis of the major brain neurotransmitter, acetylcholine. Choline is extremely important for efficient development of brain cognitive functions in newborns. Hence, pregnant and lactating women are advised to take plenty of choline supplements. Choline is also responsible for removing lipids from the liver, thus preventing liver damage. In the process, it also helps lower cholesterol levels in the body.
Acetylcholine forms an important part of central and peripheral nervous systems where it is involved in contraction of skeletal and cardiac muscles. It is also involved in synaptic plasticty like learning, memory and mood. While acetylcholine is synthesized from choline and acetyl CoA via the enzyme choline acetyltransferase, used up acetylcholine that has to be cleared from neuronal synapses in the brain is broken down into inactive choline and acetic acid via the enzyme acetylcholinesterase. Any deficiency in acetylcholine leads to neurodegenerative disorders like Alzheimer's and Parkinson's while deficiency of the acetylcholinesterase enzyme leads to paralysis of muscles (due to over-accumulation of acetylcholine in the brain).
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History of Choline (Acetylcholine): |
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Choline was first discovered by Andreas Strecker in 1864, and was first chemically synthesized in 1866. Acetylcholine was officially identified in 1914 by Henry Hallett Dale. It was the first neurotransmitter to be identified and was confirmed as a neurotransmitter by Otto Loewi. The role of choline in clearing up the lipids and fats in liver was established only in 1935. It was classified as an essential nutrient by the Food and Nutrition Board of the Institute of Medicine, USA, in 1998.
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Benefits of Choline (Acetylcholine): |
Liver damage:
Choline is essential for proper functioning of the liver. Liver is the site of storage of phosphatidylcholine, one of the major fatty acid components of cell wall. Phosphatidylcholine is a major source of choline and hence, efficient synthesis of choline from phosphatidylcholine mobilizes this fat from the liver, thus clearing the liver from fat depositions. Hence, choline prevents development of liver steatosis. Choline is also responsible for preventing liver cirrhosis.
Cognitive functions:
Choline is the raw material for synthesis of the neurotransmitter, acetylcholine. Acetylcholine is involved in many central and peripheral nervous system responses. It is the major brain neurotransmitter and is responsible for learning, short-term memory, and mood. Deficiency of choline, and subsequently acetylcholine, leads to neurodegenerative disorders like dementia, Alzheimer's and Parkinson's diseases.
New cell synthesis:
Choline and acetylcholine are also involved in synthesis of new cells. Choline/acetylcholine are involved in the synthesis of brain synaptic cells, that are involved in transmission of brain signals in the neuronal cells.
Neurotransmitter:
Acetylcholine is major brain neurotransmitter that is responsible for transmission of nerve impulses and signals in the brain leading to varied functions like muscle contraction, learning and memory.
Muscle function:
Acetylcholine plays a very important role in efficient muscle functioning. By acting as a neurotransmitter and transducing signals at synpases in neuronal cells of brain, acetylcholine leads to a series of reactions that ultimately help in inducing skeletal muscle contraction. However, by the same mechanism, acetylcholine reduces contraction of cardiac muscles, thus preventing many cardiac diseases. It is also responsible for prevention of artherosclerosis and thrombosis.
Major source of methyl groups:
Choline is metabolized in the body to its methyl form, betaine. Betaine is an important source of methyl groups for other reactions in the body, like metabolizing homocysteine to methionine. Higher levels of homocysteine in plasma leads to increased risk of cardiovascular diseases, hence, it has to be converted to methionine.
Buchman AL, Amen ME, Sohel M, et al. Choline deficiency causes reversible hepatic abnormalities in patients receiving parenteral nutrition: proof of a human choline requirement: a placebo-controlled trial. JPEN J Parenter Enteral Nutr. 2001;25(5):260-8.
Buchman AL, Dubin MD, Moukarzel AA, et al. Choline deficiency: a cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology. 1995; 22(5):1399-403.
Buchman AL., Sohel M, Brown M, et al. Verbal and visual memory improve after choline supplementation in long-term total parenteral nutrition: a pilot study. JPEN J Parenter Enteral Nutr. 2001; 25(1):30-5.
Cansev M, Wurtman RJ, Sakamoto T, Ulus IH. Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses. Alzheimers Dement. 2008;4(1 Suppl 1):S153-68.
Chawla RK, Wolf DC, Kutner MH, Bonkovsky HL. Choline may be an essential nutrient in malnourished children with cirrhosis. Gastroenterology. 1989;97(6):1514-20.
Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington, DC:National Academy Press. (1998). pp 390-422.
Hasselmo ME. Neuromodulation and cortical function: Modeling the physiological basis of behavior. Behav Brain Res. 1995;67(1):1-27.
Liu Y, Sun HL, Li DL, et al. Choline produces antiarrhythmic actions in animal models by cardiac M3 receptors: improvement of intracellular Ca2+ handling as a common mechanism. Can J Physiol Pharmacol. 2008;86(12):860-5.
Micronutrient Research for Optimum Health, Linus Pauling Institute.
Shronts EP. Essential nature of choline with implications for total parenteral nutrition. J Am Diet Assoc. 1997;97(6):639-46.
Wurtman RJ. Synapse formation and cognitive brain development: effect of docosahexaenoic acid and other dietary constituents. Metabolism. 2008;57 Suppl 2:S6-10.
Yang B, Lin H, Xu C, et al. Choline produces cytoprotective effects against ischemic myocardial injuries: evidence for the role of cardiac m3 subtype muscarinic acetylcholine receptors. Cell Physiol Biochem. 2005;16(4-6):163-74.
Zeisel SH. Choline: an essential nutrient for humans. Nutrition. 2000;16:669-71.
Zeisel SH. (1999). Shils I, Olson JA, Shike M, Ross AC, (eds). Choline and phosphatidylcholine.. Modern Nutrition in Health and Disease, 9th ed. Baltimore:Williams & Wilkins. pp 513-523.
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Sources and Forms of Choline (Acetylcholine): |
Choline/Acetylcholine are found naturally in a variety of foods. Milk, peanuts, eggs and the liver are especially highly rich in choline/acetylcholine. Foods rich in lecithin, like soy and egg yolk, are also rich in choline/acetylcholine. Chemically, lecithin is phosphatidylcholine, which, apart from being a component of cell wall, also acts a source of choline/acetylcholine. Some foods like lettuce, cabbage and cauliflower contain choline/acetylcholine in trace amounts. On average, a person gets about 1 g/day of choline from their diet. Wheat germ is also highly rich in choline/acetylcholine. Bananas, oranges, grapefruit, broccoli, spinach, yellow corn and peas, though not very rich sources of choline/acetylcholine, still have much higher concentrations than many other fruits and vegetables.
USDA Database for Choline content of common foods.
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Recommended Dosage of Choline (Acetylcholine): |
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There are many choline supplements in the market like phosphatidylcholine (lecithin), choline chloride and choline bitartarate. Lecithin is the most commonly found natural source of choline in foods. Lecithin supplements are more popular than other forms of choline supplements. Moreover, there are no human studies involving choline chloride and choline bitartarate. The recommended dietary allowance of choline for men is 550 mg/day and for women is 400-425 mg/day of choline. The recommended dietary allowance for children below one year of age is 125-150 mg/day while children of 1-13 years of age require 200-375 mg/day. Pregnant and lactating women require much higher amounts of choline, about 550 mg/day.
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Safety and Side Effects of Choline (Acetylcholine): |
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Generally, there are no severe side-effects observed with excess choline/acetylcholine intake. Administration of very high doses of choline, (more than 10 g/day) can lead to nausea and vomiting. It may also result in increased body temperature and sweating. Appetite may also be reduced in rare cases. Lecithin has the ability to increase synthesis of acetylcholine. Increased concentrations of acetylcholine will lead to increase synaptic neurotransmission resulting in excitation and hyperactivity.
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Frequently Asked Questions on Choline (Acetylcholine): |
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How important is choline in diet? How serious is choline deficiency?
Choline is now regarded as an essential nutrient and has to be supplemented in the diet, since our body cannot synthesize it. Choline/acetylcholine are involved in a variety of neuronal functions in the brain - from learning and memory to proper muscular functioning. They also work to prevent many cardiovascular diseases as well as to maintain a healthy, "fat-free" liver. Deficiency of choline in humans leads to a "fatty liver" loaded with fatty acids and cholesterol. Choline is also responsible for forming very low density lipoproteins that transport fat from liver to the tissues. In absence of choline, very low density lipoproteins are not formed and fat accumulates in the liver. Thus choline is important for maintaining a healthy liver and a healthy heart.
Zeisel SH. Choline: an essential nutrient for humans. Nutr. 2000;16:669-71.
Zeisel SH, Blusztajn JK. Choline and human nutrition. Ann Rev Nutr. 1994;14:269-96.
Is choline effective in the treatment or cure of cardiovascular diseases?
Homocysteine concentrations in the blood are directly proportional to risk of cardiovascular diseases. The methyl form of choline, betaine, acts a methyl group donor that helps in converting homocysteine to methionine. Preliminary studies have shown that administration of 1.7-6.0 g/day of betaine led to a decrease in homocysteine concentrations and reduced cardiac disease susceptibility.
Gerhard GT, Duell PB. Homocysteine and atherosclerosis. Curr Opin Lipid. 1999;10:417-28.
Lundberg P, et al. 1H NMR determination of urinary betaine in patients with premature vascular disease and mild hyperhomocysteinemia. Clin Chem. 1995;41:275-83.
Olthof MR, Brink EJ, Katan MB. Verhoef P. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr. 2005;82(1):111-17.
What role does choline play in liver cancer?
Choline deficiency leads to accumulation of fat and cholesterol in the liver, leading to liver steatosis and liver cirrhosis. This leads to increased sensitivity of liver to carcinogenic substances, especially during its daily program of cleaning up bodily toxins, which increases its risk of cancer.
Zeisel SH. Choline: an essential nutrient for humans. Nutr. 2000;16:669-71.
Zeisel SH. (1999). Shils I, Olson JA, Shike M, Ross AC, (eds). Choline and phosphatidylcholine.. Modern Nutrition in Health and Disease, 9th ed. Baltimore:Williams & Wilkins. pp 513-523.
How important is acetylcholine in preventing/treating neurodegenerative disorders like Alzheimer's disease?
Acetylcholine is essential for normal brain neuronal functioning. Deficiency of acetylcholine has been implicated in Alzheimer's disease. However, preliminary studies with lecithin administration to treat dementia in Alzheimer's patients did not yield any positive results.
Higgins JP, Flicker L. Lecithin for dementia and cognitive impairment. Cochrane Database of Systematic Reviews. 2000;2:CD001015.
Whitehouse PJ. The cholinergic deficit in Alzheimer's disease. J Clin Psych. 1998;59(suppl 13):19-22.
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Additional Research on Choline (Acetylcholine): |
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Choline / Acetylcholine and Liver Cancer
Fintelmann V, Lindner H. Diagnostic value of serum cholinesterase in liver diseases. Minerva Med. 1972 Oct 27;63(76):4148-9.
Shinozuka H, Katyal SL, Perera MI. Choline deficiency and chemical carcinogenesis. Adv Exp Med Biol. 1986;206:253-67.
THERET C. Experimental hepatic cancers. Selective modifications brought about by adrenaline and acetylcholine on the action of DAB and 2-AAF. Rev Int Hepatol. 1961;11:641-719.
Wang Y, Wang T, Shi X, Wan D, Zhang P, He X, Gao P, Yang S, Gu J, Xu G. Analysis of acetylcholine, choline and butyrobetaine in human liver tissues by hydrophilic interaction liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2008 Aug 5;47(4-5):870-5.
Choline / Acetylcholine and Brain Function
Krishnaswamy A, Cooper E. An activity-dependent retrograde signal induces the expression of the high-affinity choline transporter in cholinergic neurons. Neuron. 2009 Jan 29;61(2):272-86.
Moore SJ, Cooper DC, Spruston N. Plasticity of burst firing induced by synergistic activation of metabotropic glutamate and acetylcholine receptors. Neuron. 2009 Jan 29;61(2):287-300.
Nicolussi EM, Huck S, Lassmann H, Bradl M. The cholinergic anti-inflammatory system limits T cell infiltration into the neurodegenerative CNS, but can not counteract complex CNS inflammation. Neurobiol Dis. 2009 Mar 31.
Segovia G, Arco AD, Mora F. Environmental enrichment, prefrontal cortex, stress, and aging of the brain. J Neural Transm. 2009 Apr 3.
Choline / Acetylcholine and Cardiovasular Disease
Chen HI, Kao SL, Tsai MH, Shiao MS, Jen CJ. Exercise training modulates the effects of lipoproteins on acetylcholine-induced endothelial calcium signaling in rat aortas. Exp Biol Med (Maywood). 2009 Mar;234(3):323-31.
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