Choline deficiency

Choline was isolated from ox bile in 1849 by Strecker. During 1900 to 1920, observations led to interest in the vasodepressor properties of the esters of choline, and in the 1920s it was shown that acetylcholine was presumably the "vagus-substance." The nutritional importance of choline was recognized in the 1930s, when it was found that choline would prevent fatty infiltration of the Hver in rats. Subsequent observations showed that choline deficiency could produce cirrhosis (1) or hemorrhagic kidneys (2) in experimental animals under various conditions. 

Chemiluminescence has been used to demonstrate increased free-radical activity after induction of caerulein pancreatitis, with levels peaking at about 20 min and decreasing rapidly to control values thereafter (Gough et al., 1990). Electron spin resonance has been used to demonstrate increased hydroxyl radical activity in choline-deficient diet pancreatitis in the mouse (Nonaka etal., 1989a). 

Neuschwander-Tetri et al., 1992) and pancreatitis induced by a choline-deficient methionine-supplemented diet is less severe when mice are treated with a new synthetic ascorbic-acid derivative (CV 3611) (Nonaka et al., 1991). 

Yoshiji, H., Nakae, D., Mizumoto, Y., Horiguchi, K., Tamura, K., Denda, A., Tsujii, T. and Konishi, Y. (1992). Inhibitory effect of dietary iron deficiency on inductions of putative preneoplastic lesions as well as 8-hydroxydeoxyguanosine in DNA and lipid peroxidation in the livers of rats caused by exposure to a choline-deficient L-amino acid defined diet. Carcinogenesis 13, 1227-1233. 

Hepatic steatosis usually is a result of excessive administration of carbohydrates and/or lipids, but deficiencies of carnitine, choline, and essential fatty acids also may contribute. Hepatic steatosis can be minimized or reversed by avoiding overfeeding, especially from dextrose and lipids.35,38 Carnitine is an important amine that transports long-chain triglycerides into the mitochondria for oxidation, but carnitine deficiency in adults is extremely rare and is mostly a problem in premature infants and patients receiving chronic dialysis. Choline is an essential amine required for synthesis of cell membrane components such as phospholipids. Although a true choline deficiency is rare, preliminary studies of choline supplementation to adult patients PN caused reversal of steatosis. 

Sasaki FI, Yanai M, Meguro K, Sekizawa K, Ikarashi Y, Maruyama Y, Yamamoto M, Matsuzaki Y, Takishima T. (1991). Nicotine improves cognitive disturbance in rodents fed with a choline-deficient diet. Pharmacol Biochem Behav. 138(4) 921-25. 

A minor pathway to synthesize PC, which is mainly active in liver cells, utilizes the enzyme phosphatidylethanolamine-A-methyltransferase (PEMT), which converts phosphatidylethanolamine (PE) to PC by the subsequent transfer of three methyl groups from S-adenosylmethionine (Vance et al, 1997). The PEMT pathway, which links PE synthesis to PC, was found to be critical for PC homeostasis in the Uver dining choline deficiency (Walkey et al, 1997). 

Vitamin 6 2 deficiency is known to manifest as dementia along with other neurological sequelae, as subacute combined degeneration (SCD). A study done on choline-deficient mice fed with vitamin B12 showed... 

Orotic acid added to rat diet also provokes an. excessive biosynthesis of porphyrins in liver, erythrocytes and bone marrow. Administration of adenine monophosphate (AMP) counteracted this effect of orotic acid intoxication [165]. Haemorrhagic renal necrosis in rats, caused by choline deficiency, can be relieved by orotic acid [166], Simultaneous supplementation of the diet with adenine does not influence the protective effect of orotic acid. It has been suggested that orotic acid may lower the body requirement for choline through a metabolic interaction—orotic acid may stimulate the cytidine phosphate choline pathway of lecthin biosynthesis [166]. 

In mice, diethanolamine alters choline homeostasis in a manner resembling choline deficiency. Stott et al. (2000) showed that diethanolamine induced choline deficiency and depleted several choline-containing compounds in B6C3Fi mice, while Lehman-McKeeman Gamsky (1999, 2000) found that diethanolamine inhibited the uptake of choline into mammalian cells. 

It is known that deprivation of choline in the diet of rodents predisposes to the appearance of hepatocellular carcinomas (Zeisel, 1996). Diethanolamine-induced choline deficiency thus provides a mechanism for the tumorigenesis noted in mice but not in rats. 

Diethanolamine is metabolized by biosynthetic routes common to endogenous alkanolamines (ethanolamine and choline) and incorporated into phospholipids. It is excreted predominantly unchanged with a half-life of approximately one week in urine. In the absence of sodium nitrite, no conversion to TV-nitrosodiethanolamine is observed. Diethanolamine competitively inhibits the cellular uptake of choline in vitro and hepatic changes in choline homeostasis, consistent with choline deficiency, are observed in vivo. 

Pomfret, E.A., daCosta, K.A. Zeisel, S.H. (1990) Effects of choline deficiency and methotrexate treatment upon rat liver. J. Nutr. Biochem., 1, 533-541... 

Choline deficiency developed in a 41-year-old woman with advanced cervical cancer who underwent prolonged parenteral nutrition (915). Her liver function tests became abnormal and she became jaundiced and complained of nausea and vomiting. The serum choline concentration was 5.77 mmol/1 and there was histological evidence of hepatic steatosis. There was steady improvement with oral choline supplementation, 3 g/ day, and with oral glutamine 15 g/day. There was a 45% improvement in serum choline concentration over baseline. 

Intravenous fat emulsions contain choline, but not in sufficient amounts to prevent choline deficiency (915,916). 

Hager L. Choline deficiency and TPN associated liver dysfunction a case report. Nutrition 1998 14(l) 60-2. 

M.I.R. (1985) Interactions of Barbiturates and a Choline Deficient Diet in Promotion of Liver Carcinogenesis. This Volume. 

A choline deficient (CD) diet has been shown to exert a strong promoting effect on the emergence of foci of enzyme altered hepatocytes and on the induction of hepatomas in rats initiated with a carcinogen. 

Polychlorinated (brominated) Choline-deficient diet biphenyl(s)... 

We have been investigating a few selected aspects of the mechanism of liver tumor promotion by a diet devoid of choline, a choline deficient (CD) diet. The diet is an effective promoter of the emergence of early presumptive preneoplastic foci of Y-glutamyltranspeptidase (GGT)-positive hepatocytes as well as of the progression of GGT-positive foci to hepatomas (3 4). A CD diet with a high fat content (14%) exerted a stronger promoting action than a CD diet with a low fat content (5%) (5). 

Barbiturates, Choline-Deficient Diet, and Liver Cancer 329... 

Figure 1. Conjugated diene absorption in rat liver 2 days after feeding choline-deficient (CD), choline-supplemented (CS), choline-deficient with corn oil (CDCO) or choline-supplemented with corn oil (CS-CO) diets. The. difference spectrum (inset) is obtained by subtracting the mean values of the control spectra from the mean values of the experimental spectra.

DEHP effects on the peroxisomal system of the liver appeared to be increased in rats kept on a choline deficient diet (Perera et al. 1986). This conclusion was based on an increase in the conjugated dienes in the microsomes of choline-deficient animals exposed to 500 mg/kg DEHP for 4 weeks. Conjugated dienes are indicators of free radical oxygen modification of cellular lipids. 

Perera MI, Katyal SL, Shinozuka H. 1986. Suppression of choline-deficient diet-induced hepatocyte membrane lipid peroxidation in rats by the peroxisome proliferators 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio(N-beta-hydroxyethyl)acetamide and di(2-ethylhcxyl)phthalate. Cancer Res 46 3304-3308. 

Apoptosis is induced by choline deficiency in fetal brain and in PC 12 cells. Brain Res. 

In many animals, dietary deprivation of choline leads to liver dysfunction and growth retardation, and some patients maintained on choline-free total parenteral nutrition develop liver damage that resolves when choline is provided, suggesting that endogenous synthesis may be inadequate to meet requirements (Zeisel, 2000). There is inadequate information to permit the setting of reference intakes, but the Acceptable Intake for adults is 550 mg (for men) or 425 mg (for women) per day (Institute of Medicine, 1998). In experimental animals choline deficiency is exacerbated by deficiency of methionine, folic acid, or vitamin B12, which impairs the capacity for de novo synthesis. 

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