Choline
Choline/Nutrient Depletion:
Choline deficiencyCholine deficiency: A case report on a 56 year-old man who presented to the hospital with deteriorating speech, balance, and writing for nine months described that he demonstrated, upon examination, titubation, slurred speech, horizontal nystagmus, cerebellar ataxia in the arms, and ataxia of the gait (106). The patient was given choline chloride 1g four times daily by mouth and showed dramatic improvement, evidenced by his ability to walk without a cane and hop on either foot alone, reduced time taken to perform tasks such as drawing helices, and 50% improvement on finger dexterity tests. The patient was stabilized on 5g of choline chloride daily, but all symptoms resumed within two days of discontinuing choline treatment. Graves' disease: Reduced total choline has been observed in the acute thyrotoxic phase of Graves' disease (138). Hepatic abnormalities: The effects of a choline-deficient diet on liver function have been reviewed (139; 140; 141; 142). A choline-deficient diet in healthy male volunteers resulted in decreased plasma choline and phosphatidylcholine concentrations and plasma and erythrocyte phosphatidylcholine concentrations (37). Alanine aminotransferase (ALT) activity increased (a marker of liver injury) and serum cholesterol decreased in the choline-deficient group. It has been observed that certain individuals fed a low-choline diet may develop hepatosteatosis, liver and muscle damage, and lymphocyte apoptosis and that this risk may be associated with a single-nucleotide polymorphism in a gene involved in choline metabolism (143). In healthy men and postmenopausal women (N=57) fed a choline-deficient diet, the majority (77% and 80%, respectively) developed fatty liver or muscle damage, whereas only 44% of premenopausal women developed such signs (144). Choline deficiency has been shown to induce lymphocyte DNA damage and apoptosis, particularly in individuals who developed liver or muscle dysfunction (145). In patients receiving TPN, plasma free choline concentrations significantly decreased; these decreases were associated with increased liver density, hepatic steatosis, and decreased serum ALT and serum aspartate aminotransferase (AST) levels (94). Lectin supplementation in this population was shown to reverse such indices of liver failure (146). In a rat study, choline deficiency altered protein kinase C-mediated signal transduction within the liver, contributing to hepatic carcinogenesis in the studied animals (147). Malnourishment: Malnourishment has been shown to result in low plasma choline levels, and a diet further restricted following a lipid-restricted diet during TPN therapy further decreased lipid plasma levels (148). Dextro-amphetamineDextro-amphetamine: According to human evidence, administration of dextroamphetamine decreased brain choline:phosphocholine+creatine (Cho:Cr) ratios in healthy subjects, but not in patients with bipolar disorder who were taking lithium or valproate at the time of the study (149). DiethanolamineDiethanolamine: According to a review, diethanolamine (DEA) is a chemical used widely in a number of industries and is present in many consumer products (150). According to this review, the available data suggest that DEA may induce mouse liver tumors by a nongenotoxic mode of action that involves its ability to cause choline deficiency. FolateFolate: According to secondary sources, choline and folate may be metabolically connected, since they have been shown to share methylation pathways. According to human evidence, however, folate depletion did not result in a subsequent functional choline deficiency, as measured by serum transaminase and lipid concentrations, despite decreases in plasma choline levels (151). Upon folate repletion, decreases in choline returned to baseline levels. GlucoseGlucose: Choline has been associated with decreasing blood glucose concentrations in patients with severe hepatitis (83).