You can get recommended amounts of choline by eating a variety of foods, including the following:. Some multivitamin-mineral dietary supplements contain choline, often in the form of choline bitartrate, phosphatidylcholine, or lecithin. Dietary supplements that contain only choline are also available. The diets of most people in the United States provide less than the recommended amounts of choline.
Even when choline intakes from both food and dietary supplements are combined, total choline intakes for most people are below recommended amounts. One reason might be that our bodies can make some choline.
Scientists are studying choline to better understand how it affects health. Here are some examples of what this research has shown. Cardiovascular disease Some research shows that getting enough choline might help keep the heart and blood vessels healthy, partly by reducing blood pressure. Other research suggests that higher amounts of choline might increase cardiovascular disease risk.
More research is needed to understand whether getting more choline from the diet and supplements might raise or lower the risk of cardiovascular disease. Neurological disorders Some studies have found a link between higher intakes of choline and higher blood levels of choline and better cognitive function such as verbal and visual memory. More research is needed to understand the relationship between choline intakes and cognitive function as well as to find out whether choline supplements offer any benefit to patients with dementia.
Nonalcoholic fatty liver disease There may be a link between low intakes of choline and the risk of developing nonalcoholic fatty liver disease NAFLD. Sphingomyelin is a type of sphingosine-containing phospholipid sphingolipid that is synthesized by the transfer of a phosphocholine residue from a phosphatidylcholine to a ceramide Figure 3. Sphingomyelin is found in cell membranes and in the fatty sheath that envelops myelinated nerve fibers.
The choline-containing phospholipids , phosphatidylcholine and sphingomyelin, are precursors for the intracellular messenger molecules, diacylglycerol and ceramide. Specifically, sphingomyelinases also known as sphingomyelin phosphodiestarases catalyze the cleavage of sphingomyelin, generating phosphocholine and ceramide. Diacylglycerol is released by the degradation of phosphatidylcholine by phospholipases.
Other choline metabolites known to be cell-signaling molecules include platelet activating factor PAF and sphingophosphocholine. Choline is a precursor for acetylcholine, an important neurotransmitter synthesized by cholinergic neurons and involved in muscle control, circadian rhythm, memory, and many other neuronal functions. Choline acetyltransferase catalyzes the acetylation of choline to acetylcholine, and acetylcholine esterase hydrolyzes acetylcholine to choline and acetate 4.
CDP-choline administration was also found to stimulate the synthesis and release of a family of neurotransmitters derived from tyrosine i. Of note, non-neuronal cells of various tissues and organ systems also synthesize and release acetylcholine, which then binds and stimulates cholinergic receptors on target cells reviewed in 6.
Fat and cholesterol consumed in the diet are transported to the liver by lipoproteins called chylomicrons. In the liver, fat and cholesterol are packaged into lipoproteins called very-low-density lipoproteins VLDL for transport in the bloodstream to extrahepatic tissues.
Without adequate phosphatidylcholine, fat and cholesterol accumulate in the liver see Deficiency. Choline may be oxidized in the liver and kidney to form a metabolite called betaine via a two-step enzymatic reaction. In the mitochondrial inner membrane, flavin adenine dinucleotide FAD -dependent choline oxidase catalyzes the conversion of choline to betaine aldehyde, which is then converted to betaine by betaine aldehyde dehydrogenase in either the mitochondrial matrix or the cytosol 2.
Betaine homocysteine methyltransferase BHMT uses betaine as a methyl donor to convert homocysteine to methionine in one-carbon metabolism Figure 4.
The ubiquitous vitamin B 12 -dependent methionine synthase MS enzyme also catalyzes the re-methylation of homocysteine, using the folate derivative, 5-methyltetrahydrofolate, as a methyl donor see Nutrient interactions. Elevated concentrations of homocysteine in the blood have been associated with increased risk of cardiovascular disease The conversion of choline to betaine is irreversible. Betaine is an osmolyte that regulates cell volume and protect cell integrity against osmotic stress especially in the kidney.
Osmotic stress has been associated with a reduced BHMT expression such that the role of betaine in osmoregulation may be temporarily prioritized over its function as a methyl donor 2. Men and women fed intravenously IV with solutions that contained adequate methionine and folate but lacked choline have been found to develop a condition called nonalcoholic fatty liver disease NAFLD and signs of liver damage that resolved when choline was provided The occurrence of NAFLD is usually associated with the co-presentation of metabolic disorders, including obesity , dyslipidemia, insulin resistance , and hypertension , in subjects with metabolic syndrome.
Because phosphatidylcholine is required in the synthesis of very-low-density lipoprotein VLDL particles see Function , choline deficiency results in impaired VLDL secretion and accumulation of fat in the liver steatosis , ultimately leading to liver damage. Abnormally elevated biomarkers of organ dysfunction in the blood, including creatine phosphokinase, aspartate aminotransferase, and alanine aminotransferase, are corrected upon choline repletion. Choline deficiency-induced organ dysfunction has also been associated with increased DNA damage and apoptosis in circulating lymphocytes In the liver, the accumulation of lipids is thought to impair mitochondrial function, thus reducing fatty acid oxidation and increasing the production of reactive oxygen species ROS that trigger lipid peroxidation , DNA damage, and apoptosis.
Further, oxidative stress is thought to be responsible for prompting inflammatory processes that can lead to the progression of NAFLD to NASH and cirrhosis end-stage liver disease These signs of organ dysfunction resolved upon choline reintroduction in the diet.
Because estrogen stimulates the endogenous synthesis of phosphatidylcholine via the phosphatidylethanolamine N-methyltransferase PEMT pathway, premenopausal women may be less likely to develop signs of choline deficiency in response to a low-choline diet compared to postmenopausal women 17, Additional genetic polymorphisms occurring in choline and one-carbon metabolic pathways may alter the dietary requirement for choline and thus increase the likelihood of developing signs of deficiency when choline intake is inadequate Of note, intestinal microbiota-dependent metabolism of dietary phosphatidylcholine might also be involved in the pathogenesis of cardiovascular disease see Safety 23, See Disease Prevention for more information on fatty liver diseases.
Together with several B-vitamins i. SAM is synthesized from the essential amino acid, methionine. Three molecules of SAM are required for the methylation reaction that converts phosphatidylethanolamine into phosphatidylcholine see Figure 2 above.
Homocysteine can be converted back to methionine in a reaction catalyzed by vitamin B 12 -dependent methionine synthase, which requires 5-methyltetrahydrofolate 5-meTHF as a methyl donor. Alternately, betaine a metabolite of choline is used as the methyl donor for the methylation of homocysteine to methionine by the enzyme , betaine-homocysteine methyltransferase BHMT 1. Homocysteine can also be metabolized to cysteine via the vitamin B 6 -dependent transsulfuration pathway see Figure 4 above.
Thus, the human requirement for choline is especially influenced by the relationship between choline and other methyl group donors such as folate and S-adenosylmethionine.
A low intake of folate leads to an increased demand for choline-derived metabolite, betaine. Moreover, the de novo synthesis of phosphatidylcholine is not sufficient to maintain adequate choline nutritional status when dietary intakes of folate and choline are low Conversely, the demand for folate is increased when dietary supply for choline is limited The main criterion for establishing the AI for choline was the prevention of liver damage.
A large body of research indicates that even moderately elevated levels of homocysteine in the blood increase the risk of cardiovascular disease CVD The most common cause of a myocardial infarction or a stroke is the rupture of atherosclerotic plaques in arterial walls causing blood clot formation thrombogenesis. High homocysteine concentrations may promote the development of atherosclerosis atherogenesis and thrombogenesis via mechanisms involving oxidative stress and endothelial dysfunction, inflammation , abnormal blood coagulation , and disordered lipid metabolism reviewed in Once formed from dietary methionine , homocysteine can be catabolized to cysteine via the transsulfuration pathway or re-methylated to methionine see Figure 4 above.
Folate and choline are involved in alternate pathways that catalyze the re-methylation of homocysteine see Nutrient interactions. Specifically, choline is the precursor of betaine, which provides a methyl group for the conversion of homocysteine to methionine via the enzyme, betaine-homocysteine methyltransferase BHMT. While the amount of homocysteine in the blood is regulated by several nutrients, including folate and choline, conditions that cause damage to the liver like nonalcoholic steatohepatitis NASH may also affect homocysteine metabolism Because both folate - and choline-dependent metabolic pathways catalyze the re- methylation of homocysteine , dietary intakes of both nutrients need to be considered when the association between homocysteine concentrations and cardiovascular disease is assessed.
Yet, despite its relevance, the relationship of betaine and choline to homocysteine metabolism has been only lightly investigated in humans, essentially because the choline content of foods could not be accurately measured until recently.
Yet, in a cross-sectional analysis of a large cohort of 16, women ages, years , lower betaine doses in the range of dietary intakes were not found to be correlated with homocysteine concentrations This study also showed that levels of choline intake were inversely associated with homocysteine concentrations in the blood.
Also, in a recent analysis of the Health Professionals Follow-up Study HPFS that enrolled 44, men for a period of 24 years, the risk of peripheral artery disease was positively correlated with homocysteine concentrations but neither with betaine nor choline levels of intake While further research is indicated, convincing evidence that increased dietary intake of choline or betaine could benefit cardiovascular health through lowering homocysteine concentrations in the blood is presently lacking.
A study had found that elevated blood homocysteine concentrations in patients who experienced a vascular occlusion were associated with higher urinary excretion of betaine, rather than with reduced intake of choline or betaine or diminished activity of BHMT In a recent prospective study , high urinary betaine excretion was also associated with increased risk of heart failure in nondiabetic subjects who have been hospitalized for acute coronary syndrome In the same study, both top and bottom quintiles of plasma betaine concentrations were associated with an increased risk of secondary acute myocardial infarction.
The findings of another prospective study the Hordaland Health Study that followed 7, healthy adults ages, years and years suggested that high choline and low betaine plasma concentrations were associated with an unfavorable cardiovascular risk profile Indeed, plasma choline was positively associated with a number of cardiovascular risk factors, such as BMI , percentage body fat, waist circumference, and serum triglycerides , and inversely associated with HDL -cholesterol.
On the contrary, plasma betaine was positively correlated to HDL-cholesterol and inversely associated with the above-mentioned risk factors as well as with systolic and diastolic blood pressure.
More recent studies now suggest that the blood concentration of trimethylamine N-oxide TMAO , generated from trimethylamine-containing nutrients like dietary choline, rather than that of choline, might influence the risk of cardiovascular events see Safety.
While a choline-deficient diet results in organ dysfunction and nonalcoholic fatty liver disease NAFLD see Deficiency ; 16 , it is not known whether suboptimal dietary choline intakes in healthy subjects may contribute to an increased risk for NAFLD. Another cross-sectional study of individuals with NAFLD or nonalcoholic steatohepatitis NASH also reported that disease severity was inversely correlated with dietary choline intakes in postmenopausal women, but not in premenopausal women, men, or children In animal models, dietary choline deficiency has been associated with an increased incidence of spontaneous liver cancer hepatocellular carcinoma and increased sensitivity to carcinogenic chemicals 9.
A number of mechanisms have been proposed to contribute to the cancer-promoting effects of choline deficiency: 1 enhanced liver cell regeneration and tissue sensitivity to chemical insults; 2 altered expression of numerous genes regulating cell proliferation , differentiation , DNA repair, and apoptosis due to improper DNA methylation ; 3 increased likelihood of DNA damage caused by mitochondrial dysfunction-induced oxidative stress ; and 4 activated protein kinase C-mediated cell-signaling cascade, eventually leading to an increase in liver cell apoptosis 2.
Yet, it is not known whether choline deficiency can increase the susceptibility to cancer in humans 2. It is known that folate is critical for normal embryonic development, and maternal supplementation with folic acid decreases the incidence of neural tube defects NTDs NTDs include various malformations, such as lesions of the brain e.
These defects occur between the 21 st and 28 th days after conception, a time when many women do not realize that they are pregnant While the protective effect of folate against NTD is well established, only a few studies have investigated the role of other methyl group donors, including choline and betaine, in the occurrence of NTDs.
However, more recent studies failed to find an inverse relationship between maternal choline intake and risk of NTDs 46, Finally, a more recent study, including 71 NTD-affected pregnancies, pregnancies with non NTD malformations, 98 normal pregnancies in women with prior NTD-affected pregnancies, and normal pregnancies, found no associations between maternal blood concentrations of choline during pregnancy, choline- and folate-related genetic variants, and risk of NTDs However, it is important to note that circulating choline concentrations do not accurately reflect dietary intake of choline.
More research is needed to determine whether supplemental choline could add to the protective effect currently being achieved by periconceptual folic acid supplementation. Choline supplementation of the mothers of unborn rats, as well as rat pups during the first month of life, led to improved performance in spatial memory tests months after choline supplementation had been discontinued A review by McCann et al.
Because of the importance of DNA methylation in normal brain development, neuronal functions, and cognitive processes 53 , methyl donor nutrients like choline are essential for optimal brain functioning. However, clinical evidence to determine whether findings in rodent studies are applicable to humans is currently limited. Recently, the analysis of the Seychelles Child Development Nutrition Cohort study reported a lack of an association between plasma concentrations of choline and its related metabolites and cognitive abilities in five-year-old children.
Only plasma betaine concentrations were found to be positively correlated with preschool language test scores Project Viva is an ongoing prospective study that has examined the relationship between daily intakes of methyl donor nutrients in 1, women during pregnancy and child cognition at three and seven years postpartum. Another report of the study indicated that upper vs. Cognitive function, including the domains of memory, speed, and executive function , decline gradually with increasing age.
Am J Hum Genet ; Early second trimester maternal plasma choline and betaine are related to measures of early cognitive development in term infants. PLoS One ;7:e Choline and risk of neural tube defects in a folate-fortified population. Epidemiology ; Maternal choline concentrations during pregnancy and choline-related genetic variants as risk factors for neural tube defects.
Importance of choline as essential nutrient and its role in prevention of various toxicities. Prague Med Rep ; The addition of choline to parenteral nutrition.
Gastroenterology ;S Verbal and visual memory improve after choline supplementation in long-term total parenteral nutrition: a pilot study. Low plasma free choline is prevalent in patients receiving long term parenteral nutrition and is associated with hepatic aminotransferase abnormalities. Clin Nutr ; Whole-blood-free choline and choline metabolites in infants who require chronic parenteral nutrition therapy. J Pediatr Gastroenterol Nutr ; Dietary phosphatidylcholine and risk of all-cause and cardiovascular-specific mortality among US women and men.
Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med ; Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease.
Atherosclerosis ; BMC Cardiovasc Disord ; Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women. Eur J Clin Nutr ; Lecithin for dementia and cognitive impairment.
Plasma free choline, betaine and cognitive performance: the Hordaland Health Study. Br J Nutr ; The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. Improved human visuomotor performance and pupil constriction after choline supplementation in a placebo-controlled double-blind study. Sci Rep ; Non-alcoholic fatty liver disease, diet and gut microbiota.
Excli j ; Non-alcoholic fatty liver disease: need for a balanced nutritional source. Choline deficiency: a cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology ; Sex and menopausal status influence human dietary requirements for the nutrient choline. Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. J Biol Chem ; Higher dietary choline intake is associated with lower risk of nonalcoholic fatty liver in normal-weight Chinese women.
J Nutr ; Choline intake in a large cohort of patients with nonalcoholic fatty liver disease. Choline deficiency causes reversible hepatic abnormalities in patients receiving parenteral nutrition: proof of a human choline requirement: a placebo-controlled trial.
Disclaimer This fact sheet by the Office of Dietary Supplements ODS provides information that should not take the place of medical advice. Health Information. About ODS. The richest food sources of choline are egg yolks, followed by: meat and fish whole grains vegetables and fruit fats and oils. Does choline interact with other nutrients?
What happens if I have too little choline? What happens if I have too much choline? When should I pay extra attention to my choline intake? References European Food Safety Authority. Scientific opinion on Dietary Reference Values for choline.
0コメント