vitamin-b-12 and Choline-Deficiency

Topics: Animals; Antibody Formation; Carcinogens; Choline; Choline Deficiency; Diet; DNA; Folic Acid; Folic Acid Deficiency; Humans; Immunity, Cellular; Lipotropic Agents; Liver; Liver Neoplasms; Methionine; Methylation; Neoplasms; Neoplasms, Experimental; Pharmaceutical Preparations; Risk; Tetrahydrofolates; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Antibody Formation; Choline Deficiency; Deoxyuridine; Drug Interactions; Folic Acid; Folic Acid Deficiency; Humans; Hypersensitivity, Delayed; Immunity; Lymphocyte Activation; Lymphocytes; Lymphoid Tissue; Methionine; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Choline Deficiency; Diet; Methionine; Rats; Vitamin B 12

Choline and betaine are nutrients involved in one-carbon metabolism. Choline is essential for neurodevelopment and brain function. We studied the associations between cognitive function and plasma concentrations of free choline and betaine. In a cross-sectional study, 2195 subjects (55 % women), aged 70-74 years, underwent extensive cognitive testing including the Kendrick Object Learning Test (KOLT), Trail Making Test (part A, TMT-A), modified versions of the Digit Symbol Test (m-DST), Block Design (m-BD), Mini-Mental State Examination (m-MMSE) and Controlled Oral Word Association Test (COWAT). Compared with low concentrations, high choline (>8·4 μmol/l) was associated with better test scores in the TMT-A (56·0 v. 61·5, P=0·004), m-DST (10·5 v. 9·8, P=0·005) and m-MMSE (11·5 v. 11·4, P=0·01). A generalised additive regression model showed a positive dose-response relationship between the m-MMSE and choline (P=0·012 from a corresponding linear regression model). Betaine was associated with the KOLT, TMT-A and COWAT, but after adjustments for potential confounders, the associations lost significance. Risk ratios (RR) for poor test performance roughly tripled when low choline was combined with either low plasma vitamin B₁₂ (≤257 pmol/l) concentrations (RR(KOLT)=2·6, 95 % CI 1·1, 6·1; RR(m-MMSE)=2·7, 95 % CI 1·1, 6·6; RR(COWAT)=3·1, 95 % CI 1·4, 7·2) or high methylmalonic acid (MMA) (≥3·95 μmol/l) concentrations (RR(m-BD)=2·8, 95 % CI 1·3, 6·1). Low betaine (≤31·1 μmol/l) combined with high MMA was associated with elevated RR on KOLT (RR(KOLT)=2·5, 95 % CI 1·0, 6·2). Low plasma free choline concentrations are associated with poor cognitive performance. There were significant interactions between low choline or betaine and low vitamin B₁₂ or high MMA on cognitive performance.

Topics: Aged; Aging; Betaine; Biomarkers; Choline; Choline Deficiency; Cognitive Dysfunction; Cohort Studies; Cross-Sectional Studies; Diet; Female; Follow-Up Studies; Geriatric Assessment; Humans; Male; Methylmalonic Acid; Norway; Risk Factors; Statistics as Topic; Vitamin B 12; Vitamin B 12 Deficiency

Dietary methyl donors and their genetic determinants are associated with Crohn's disease risk. We investigated whether a methyl-deficient diet (MDD) may affect development and functions of the small intestine in rat pups from dams subjected to the MDD during gestation and lactation. At 1 month before pregnancy, adult females were fed with either a standard food or a diet without vitamin B12, folate and choline. A global wall hypotrophy was observed in the distal small bowel (MDD animals 0·30 mm v. controls 0·58 mm; P< 0·001) with increased crypt apoptosis (3·37 v. 0·4%; P< 0·001), loss of enterocyte differentiation in the villus and a reduction in intestinal alkaline phosphatase production. Cleaved caspase-3 immunostaining (MDD animals 3·37% v. controls 0·4%, P< 0·001) and the Apostain labelling index showed increased crypt apoptosis (3·5 v. 1·4%; P= 0·018). Decreased proliferation was observed in crypts of the proximal small bowel with a reduced number of minichromosome maintenance 6 (MDD animals 52·83% v. controls 83·17%; P= 0·048) and proliferating cell nuclear antigen-positive cells (46·25 v. 59 %; P= 0·05). This lack of enterocyte differentiation in the distal small bowel was associated with an impaired expression of β-catenin and a decreased β-catenin-E-cadherin interaction. The MDD affected the intestinal barrier in the proximal small bowel by decreasing Paneth cell number after immunostaining for lysosyme (MDD animals 8·66% v. controls 21·66%) and by reducing goblet cell number and mucus production after immunostaining for mucin-2 (crypts 8·66 v. 15·33%; villus 7 v. 17%). The MDD has dual effects on the small intestine by producing dramatic effects on enterocyte differentiation and barrier function in rats.

Topics: Alkaline Phosphatase; Animal Feed; Animals; Apoptosis; beta Catenin; Cadherins; Caspase 3; Cell Differentiation; Choline; Choline Deficiency; Enterocytes; Female; Folic Acid; Folic Acid Deficiency; Gene Expression Regulation; Intestine, Small; Muramidase; Paneth Cells; Rats; Rats, Wistar; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Inflammatory bowel diseases (IBD) result from complex interactions between environmental and genetic factors. Low blood levels of vitamin B12 and folate and genetic variants of related target enzymes are associated with IBD risk, in population studies. To investigate the underlying mechanisms, we evaluated the effects of a methyl-deficient diet (MDD, folate, vitamin B12 and choline) in an experimental model of colitis induced by dextran sodium sulphate (DSS), in rat pups from dams subjected to the MDD during gestation and lactation. Four groups were considered (n = 12-16 per group): C DSS(-) (control/DSS(-)), D DSS(-) (deficient/DSS(-)), C DSS(+) (control/DSS(+)) and D DSS(+) (deficient/DSS(+)). Changes in apoptosis, oxidant stress and pro-inflammatory pathways were studied within colonic mucosa. In rat pups, the MDD produced a decreased plasma concentration of vitamin B12 and folate and an increased homocysteine (7.8 ± 0.9 versus 22.6 ± 1.2 μmol/l, P < 0.001). The DSS-induced colitis was dramatically more severe in the D DSS(+) group compared with each other group, with no change in superoxide dismutase and glutathione peroxidase activity, but decreased expression of caspase-3 and Bax, and increased Bcl-2 levels. The mRNA levels of tumour necrosis factor (TNF)-α and protein levels of p38, cytosolic phospolipase A2 and cyclooxygenase 2 were significantly increased in the D DSS(+) pups and were accompanied by a decrease in the protein level of tissue inhibitor of metalloproteinases (TIMP)3, a negative regulator of TNF-α. MDD may cause an overexpression of pro-inflammatory pathways, indicating an aggravating effect of folate and/or vitamin B12 deficiency in experimental IBD. These findings suggest paying attention to vitamin B12 and folate deficits, frequently reported in IBD patients.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Choline Deficiency; Colitis, Ulcerative; Colon; Cyclooxygenase 2; Dextran Sulfate; Diet; Folic Acid; Folic Acid Deficiency; Glutathione Peroxidase; Homocysteine; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phospholipases A2; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; RNA, Messenger; Superoxide Dismutase; Tissue Inhibitor of Metalloproteinase-3; Tumor Necrosis Factor-alpha; Vitamin B 12; Vitamin B 12 Deficiency

Deficiency in nutritional determinants of homocysteine (HCY) metabolism, such as vitamin B(12) and folate, during pregnancy is known to influence HCY levels in the progeny, which in turn may exert adverse effects during development, including liver defects. Since short hypoxia has been shown to induce tolerance to subsequent stress in various cells including hepatocytes, and as vitamins B deficiency and hypoxic episodes may simultaneously occur in neonates, we aimed to investigate the influence of brief postnatal hypoxia (100% N(2) for 5 min) on the liver of rat pups born from dams fed a deficient regimen, i.e., depleted in vitamins B(12), B(2), folate, and choline. Four experimental groups were studied: control, hypoxia, deficiency, and hypoxia + deficiency. Although hypoxia transiently stimulated HCY catabolic pathways, it was associated with a progressive increase of hyperhomocysteinemia in deficient pups, with a fall of cystathionine beta-synthase activity at 21 days. At this stage, inducible NO synthase activity was dramatically increased and glutathione reductase decreased, specifically in the group combining hypoxia and deficiency. Also, hypoxia enhanced the deficiency-induced drop of the S-adenosylmethionine/S-adenosylhomocysteine ratio. In parallel, early exposure to the methyl-deficient regimen induced oxidative stress and led to hepatic steatosis, which was found to be more severe in pups additionally exposed to hypoxia. In conclusion, brief neonatal hypoxia may accentuate the long-term adverse effects of impaired HCY metabolism in the liver resulting from an inadequate nutritional regimen during pregnancy, and our data emphasize the importance of early factors on adult disease.

Topics: Animals; Animals, Newborn; Apoptosis; Cell Proliferation; Choline Deficiency; Cystathionine beta-Synthase; Female; Folic Acid; Folic Acid Deficiency; Food, Formulated; Glutathione; Homocysteine; Hypoxia; Liver; Nitric Oxide Synthase Type II; Pregnancy; Rats; Rats, Wistar; Riboflavin; Riboflavin Deficiency; S-Adenosylhomocysteine; S-Adenosylmethionine; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Deficiency

Epidemiological studies report an inverse relationship between intake of the B vitamin folic acid and colon cancer. Folate is important for DNA synthesis and repair. Moreover, the production of S-adenosylmethionine (SAM), essential for normal DNA methylation and gene expression, is dependent on folic acid. Folate deficiency may increase the risk of malignant transformation by perturbing these pathways.. The principal aim of this study was to determine the effects of folate deficiency on DNA stability and DNA methylation in rat colonocytes in vivo. As the metabolic pathways of folate and other dietary methyl donors are closely linked, the effects of methionine and choline deficiency were also evaluated.. Male Hooded-Lister rats were fed a diet deficient in folic acid, or in methionine and choline, or in folate, methionine and choline for 10 weeks. DNA strand breakage and misincorporated uracil were determined in isolated colonocytes using alkaline single cell gel electrophoresis. Global DNA methylation was measured in colonic scrapings. Folate was measured in plasma, erythrocyte and liver samples.. Methyl donor deficiency induced DNA strand breakage in colonocytes isolated from all experimental groups. Uracil levels in colonocyte DNA remained unchanged compared with controls. DNA methylation was unaffected either by folate and/or methionine and choline depletion. Rats fed a folate-deficient diet had less folate in plasma, red blood cells and liver than controls.. Folate and methyl deficiency in vivo primarily affects DNA stability in isolated colonocytes of rats, without affecting overall DNA methylation.

Topics: Animals; Choline Deficiency; Colon; Colonic Neoplasms; Comet Assay; DNA; DNA Damage; DNA Methylation; Folic Acid; Folic Acid Deficiency; Liver; Male; Methionine; Rats; S-Adenosylmethionine; Vitamin B 12

The development of certain human cancers has been linked with inadequate intake of folates. The effects of folate deficiency in vivo on DNA stability (strand breakage, misincorporated uracil and oxidative base damage) in lymphocytes isolated from rats fed a diet deficient in folic acid was determined. Because the metabolic pathways of folate and other methyl donors are closely coupled, the effects of methionine and choline deficiency alone or in combination with folate deficiency were determined. Feeding male Hooded Lister rats a folate-free diet for 10 weeks created a moderate folate deficiency (25-50% (approx.) decrease in plasma, red blood cell and hepatic folate concentrations (P < 0.05) and a 20% rise in plasma homocysteine (P < 0.05)). Lymphocyte DNA strand breakage was increased successively in all groups after 4 weeks and 8 weeks on the diet (50-100% (approx.) after 8 weeks). Only low folate specifically and progressively induced uracil misincorporation throughout the study (100% (approx.) after 8 weeks). Neither folate deficiency nor choline/methionine deficiency altered oxidative DNA base damage. In summary, moderate folate deficiency in vivo is associated with a decrease in DNA stability, measured as increased DNA strand breakage and misincorporated uracil.

Topics: Animals; Choline Deficiency; Comet Assay; DNA; DNA Damage; Erythrocytes; Folic Acid; Folic Acid Deficiency; Liver; Lymphocytes; Male; Methionine; Rats; Uracil; Vitamin B 12

Choline-deficiency causes liver cells to die by apoptosis, and it has not been clear whether the effects of choline-deficiency are mediated by methyl-deficiency or by lack of choline moieties. SV40 immortalized CWSV-1 hepatocytes were cultivated in media that were choline-sufficient, choline-deficient, choline-deficient with methyl-donors (betaine or methionine), or choline-deficient with extra folate/vitamin B12. Choline-deficient CWSV-1 hepatocytes were not methyl-deficient as they had increased intracellular S-adenosylmethionine concentrations (132% of control; P < 0.01). Despite increased phosphatidylcholine synthesis via sequential methylation of phosphatidylethanol-amine, choline-deficient hepatocytes had significantly decreased (P < 0.01) intracellular concentrations of choline (20% of control), phosphocholine (6% of control), glycerophosphocholine (15% of control), and phosphatidylcholine (55% of control). Methyl-supplementation in choline-deficiency enhanced intracellular methyl-group availability, but did not correct choline-deficiency induced abnormalities in either choline metabolite or phospholipid content in hepatocytes. Methyl-supplemented, choline-deficient cells died by apoptosis. In a rat study, 2 weeks of a choline deficient diet supplemented with betaine did not prevent the occurrence of fatty liver and the increased DNA strand breakage induced by choline-deficiency. Though dietary supplementation with betaine restored hepatic betaine concentration and increased hepatic S-adenosylmethionine/S-adenosylhomocysteine ratio, it did not correct depleted choline (15% of control), phosphocholine (6% control), or phosphatidylcholine (48% of control) concentrations in deficient livers. These data show that decreased intracellular choline and/or choline metabolite concentrations, and not methyl deficiency, are associated with apoptotic death of hepatocytes.

Topics: Animals; Apoptosis; Betaine; Cell Line; Choline Deficiency; Culture Media; Folic Acid; Liver; Male; Methylation; Rats; Rats, Inbred F344; Vitamin B 12

The effect of vitamin B12 on learning disturbance was tested in rats. Rats were fed a choline-enriched, choline-deficient, and choline-deficient diet with vitamin B12. Concentrations of acetylcholine in the brain were significantly lower in rats fed a choline-deficient diet than rats fed a choline-enriched diet. Passive avoidance learning shows that rats on a choline-deficient diet showed significantly impaired learning compared to rats on a choline-enriched diet. However, there was no significant difference of acetylcholine in the brain or in the passive avoidance learning between rats fed a choline-enriched and a choline-deficient with vitamin B12 diet. We, therefore, suggest that vitamin B12 potentiates learning in an acetylcholine-deprived brain.

Topics: Acetylcholine; Animals; Body Weight; Brain Chemistry; Choline; Choline Deficiency; Cognition; Diet; Male; Motor Activity; Organ Size; Rats; Rats, Wistar; Vitamin B 12

Total cobalamin and methylcobalamin levels were determined in tissues of male F344 rats fed a complete, amino acid-defined diet or a diet deficient in methionine, choline and/or cyanocobalamin. Total cobalamin levels in rats fed the complete diet were (picograms/milligram tissue +/- SEM): liver, 67 +/- 13; kidneys, 738 +/- 133; spleen, 23 +/- 2; and adrenals, 268 +/- 36. Corresponding methylcobalamin levels were: liver, 1.6 +/- 0.5; kidneys, 107.6 +/- 22.2; spleen, 0.3 +/- 0.1; and adrenals, 26.9 +/- 5.3; these values represent 2.4, 14.5, 1.4 and 9.7%, respectively, of the total cobalamin levels. Total cobalamin levels of all tissues studied were altered by cobalamin deprivation alone or in conjunction with methionine and/or choline deprivation. Methylcobalamin levels were more resistant to dietary alteration. Regardless of the presence or absence of methionine and cobalamin in the diet, choline deprivation always decreased the proportion of methylcobalamin in the liver. Kidney levels of methylcobalamin, like those of total cobalamin, were decreased by removal of cobalamin from the complete or the methyl-deficient diets. The results demonstrate that cobalamin, methionine and choline exert quite different effects on tissue levels of the cobalamins in rats.

Topics: Adrenal Glands; Amino Acids; Animals; Choline Deficiency; Diet; Kidney; Liver; Male; Methionine; Rats; Rats, Inbred F344; Spleen; Tissue Distribution; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Cholesterol; Choline; Choline Deficiency; Diet; Drug Synergism; Lipotropic Agents; Liver; Male; Methionine; Methotrexate; Phospholipids; Rats; Triglycerides; Vitamin B 12

Topics: Ammonia-Lyases; Animals; Carcinoma, Hepatocellular; Choline; Choline Deficiency; Diet; Histidine Ammonia-Lyase; Hydro-Lyases; Liver; Liver Neoplasms; Male; Methionine; Neoplasm Transplantation; Neoplasms, Experimental; Rats; Time Factors; Urocanate Hydratase; Vitamin B 12

Topics: Animals; Carcinoma, Hepatocellular; Choline Deficiency; Fatty Liver; Folic Acid; Homocystine; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Methionine; Methylation; Neoplasms, Experimental; Nutrition Disorders; Rats; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Amino Acids; Animal Nutritional Physiological Phenomena; Animals; Arginine; Betaine; Body Weight; Chickens; Choline; Choline Deficiency; Creatine; Cystine; Deficiency Diseases; Depression, Chemical; Folic Acid; Folic Acid Deficiency; Glycine; Glycine max; Guanidines; Lipid Metabolism; Liver; Male; Methionine; Muscles; Ornithine; Stimulation, Chemical; Urea; Vitamin B 12; Vitamin B 12 Deficiency; Zea mays

Topics: Animal Nutritional Physiological Phenomena; Animals; Biotin; Bird Diseases; Birds; Choline Deficiency; Eggs; Female; Folic Acid; Inositol; Methionine; Nutritional Requirements; Ovulation; Vitamin B 12

Topics: Acute Disease; Animals; Blood Urea Nitrogen; Body Weight; Chlortetracycline; Cholesterol; Choline Deficiency; Cystine; Diet; Feces; Germ-Free Life; Hematocrit; Kidney Diseases; Lipid Metabolism; Liver; Male; Neomycin; Rats; Stimulation, Chemical; Vitamin B 12

Topics: Amino Acids; Animals; Body Weight; Choline; Choline Deficiency; Diet; FIGLU Test; Folic Acid; Growth; Hematocrit; Hemoglobins; Kidney; Lipid Metabolism; Liver; Male; Methionine; Organ Size; Rats; Vitamin B 12; Vitamin B Deficiency

Topics: Animals; Choline; Choline Deficiency; Deficiency Diseases; Kidney Diseases; Liver Diseases; Methionine; Rats; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Choline; Choline Deficiency; Diet; Fats; Fatty Acids; Kidney; Liver Diseases; Nutrition Assessment; Protein Deficiency; Rats; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Choline; Choline Deficiency; Corrinoids; Diet; Kidney; Methionine; Rats; Vitamin B 12