Amino acids

@article{pmid15465197,

title = {Biochemical signs of impaired cobalamin status during and after radiotherapy for rectal cancer},

author = {Marianne Grønlie Guren and Jørn Schneede and Kjell Magne Tveit and Per Magne Ueland and Ebba Nexø and Svein Dueland},

doi = {10.1016/j.ijrobp.2004.04.018},

issn = {0360-3016},

year  = {2004},

date = {2004-11-01},

journal = {Int J Radiat Oncol Biol Phys},

volume = {60},

number = {3},

pages = {807--813},

abstract = {PURPOSE: The aim of the study was to investigate whether pelvic radiotherapy for rectal cancer had a negative impact on cobalamin status.nnMETHODS AND MATERIALS: Consecutive patients receiving pelvic radiotherapy (50 Gy) for rectal cancer were evaluated prospectively (n = 54). Serum cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), and total homocysteine (tHcy) were measured at start and end of radiotherapy, at follow-up 4-6 weeks and 1 year (n = 23) after radiotherapy.nnRESULTS: Mean serum cobalamin decreased from 306 pmol/L before treatment to 267 pmol/L at the end of radiotherapy (p < 0.001), 247 pmol/L 4-6 weeks after radiotherapy (p < 0.001), and 249 pmol/L 1 year after radiotherapy (p = 0.02). Mean serum MMA was 0.16 micromol/L pretreatment, 0.17 micromol/L at the end of radiotherapy (n.s.), and increased to 0.19 micromol/L after 4-6 weeks (p = 0.007), and to 0.21 micromol/L after 1 year (p < 0.001). There was no change in serum tHcy. Mean serum holoTC was reduced from 111 pmol/L pretreatment to 93 pmol/L 4-6 weeks after radiotherapy (p = 0.002).nnCONCLUSIONS: The data suggest rapid and persistent decrease in cobalamin status after radiotherapy for rectal cancer, as reflected by reduced serum cobalamin combined with increased serum MMA. This observation, though modest, may motivate routine monitoring of cobalamin status at follow-up after radiotherapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15447919,

title = {Phenotypic expression of the methylenetetrahydrofolate reductase 677C-->T polymorphism and flavin cofactor availability in thyroid dysfunction},

author = {Steinar Hustad and Bjørn G Nedrebø and Per Magne Ueland and Jørn Schneede and Stein Emil Vollset and Arve Ulvik and Ernst A Lien},

doi = {10.1093/ajcn/80.4.1050},

issn = {0002-9165},

year  = {2004},

date = {2004-10-01},

journal = {Am J Clin Nutr},

volume = {80},

number = {4},

pages = {1050--1057},

abstract = {BACKGROUND: The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) 677C-->T polymorphism modifies the risk of coronary artery disease and colon cancer and is related to plasma concentrations of total homocysteine (tHcy). Riboflavin status modifies the metabolic effect of the polymorphism, and thyroid hormones increase the synthesis of flavin cofactors.nnOBJECTIVE: The aim of the study was to investigate the phenotypic expression of the MTHFR 677C-->T polymorphism in terms of plasma tHcy concentrations in patients with thyroid dysfunction.nnDESIGN: The study population consisted of 182 patients with hyperthyroidism. We studied plasma tHcy in relation to MTHFR genotype, riboflavin, and folate before and during 6 mo of treatment with antithyroid drugs.nnRESULTS: Before treatment, tHcy was higher in patients with the mutant enzyme than in those with the wild-type enzyme. A genotype effect was observed only at low riboflavin or folate concentrations (P T polymorphism, possibly by modifying the availability of flavin cofactors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15319318,

title = {Screening for serum total homocysteine in newborn children},

author = {Helga Refsum and Anne W Grindflek and Per M Ueland and Ase Fredriksen and Klaus Meyer and Arve Ulvik and Anne B Guttormsen and Ole E Iversen and Jørn Schneede and Bengt F Kase},

doi = {10.1373/clinchem.2004.036194},

issn = {0009-9147},

year  = {2004},

date = {2004-10-01},

journal = {Clin Chem},

volume = {50},

number = {10},

pages = {1769--1784},

abstract = {BACKGROUND: Newborn screening for total homocysteine (tHcy) in blood may identify babies with vitamin B12 (B12) deficiency or homocystinuria, but data on the causes of increased tHcy in screening samples are sparse.nnMETHODS: Serum concentrations of tHcy, cystathionine, methionine, folate, and B12 and the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism were determined in 4992 capillary blood samples collected as part of the routine screening program in newborn children. Methylmalonic acid (MMA), gender (SRY genotyping), and the frequency of six cystathionine beta-synthase (CBS) mutations were determined in 20-27% of the samples, including all samples with tHcy > 15 micromol/L (n = 127), B12 < 100 pmol/L (n = 159), or methionine > 40 micromol/L (n = 154).nnRESULTS: The median (5th-95th percentile) tHcy concentration was 6.8 (4.2-12.8) micromol/L. B12 status, as determined by serum concentrations of B12, tHcy, and MMA, was moderately better in boys than in girls. tHcy concentrations between 10 and 20 micromol/L were often associated with low B12, whereas tHcy > 20 micromol/L (n = 43) was nearly always explained by increased methionine. tHcy did not differ according to folate concentrations or MTHFR 677C > T genotypes. None of the babies had definite CBS deficiencies, but heterozygosity led to low cystathionine, increased methionine, but normal tHcy concentrations.nnCONCLUSION: Increased tHcy is a common but not specific finding in newborns. The metabolite and vitamin profiles will point to the cause of hyperhomocysteinemia. Screening for tHcy and related factors should be further evaluated in regions with high prevalence of homocystinuria and in babies at high risk of B12 deficiency.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15321804,

title = {Changes in basal and postmethionine load concentrations of total homocysteine and cystathionine after B vitamin intervention},

author = {Øyvind Bleie and Helga Refsum and Per Magne Ueland and Stein Emil Vollset and Anne Berit Guttormsen and Ebba Nexo and Jørn Schneede and Jan Erik Nordrehaug and Ottar Nygård},

doi = {10.1093/ajcn/80.3.641},

issn = {0002-9165},

year  = {2004},

date = {2004-09-01},

journal = {Am J Clin Nutr},

volume = {80},

number = {3},

pages = {641--648},

abstract = {BACKGROUND: Vitamin B-6 is necessary for the metabolism of homocysteine and is often used in combination with folic acid and vitamin B-12 in clinical trials that investigate whether the lowering of plasma total homocysteine (tHcy) can prevent vascular disease.nnOBJECTIVE: We compared the effects of vitamin B-6 with the effects of folic acid and vitamin B-12, as used in the Western Norway B-vitamin Intervention Trial (WENBIT), on basal and postmethionine load (PML) tHcy and cystathionine concentrations.nnDESIGN: Ninety patients with suspected coronary artery disease were randomly assigned to 1 of 4 groups to receive daily oral treatment with 1) 0.8 mg folic acid, 0.4 mg vitamin B-12, and 40 mg vitamin B-6 (group A); 2) 0.8 mg folic acid and 0.4 mg vitamin B-12 (group B); 3) 40 mg vitamin B-6 (group C); or 4) placebo (group D). For the first 2 wk, groups A and B received additional folic acid (5 mg/d). A methionine-loading test was performed at baseline and after 3 mo.nnRESULTS: Treatment with folic acid and vitamin B-12 caused a rapid and significant lowering of basal (31%) and PML tHcy concentrations (22%), with no effect on cystathionine. Vitamin B-6 did not change basal tHcy and had a significant but limited effect on PML tHcy concentrations. However, vitamin B-6 treatment markedly lowered basal and PML cystathionine by 31% and 42%, respectively.nnCONCLUSION: The folic acid and vitamin B-12 combination applied in WENBIT provides rapid, substantial, and long-term tHcy-lowering effects, whereas the effect of vitamin B-6 on tHcy was relatively small and confined to PML tHcy. However, vitamin B-6 treatment caused a marked reduction in plasma cystathionine. Cystathionine could be a useful marker for assessment of the vitamin B-6 effect and should, together with tHcy, be related to clinical outcome in ongoing trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15210385,

title = {Associations between maternal methylenetetrahydrofolate reductase polymorphisms and adverse outcomes of pregnancy: the Hordaland Homocysteine Study},

author = {Eha Nurk and Grethe S Tell and Helga Refsum and Per M Ueland and Stein E Vollset},

doi = {10.1016/j.amjmed.2004.01.019},

issn = {0002-9343},

year  = {2004},

date = {2004-07-01},

journal = {Am J Med},

volume = {117},

number = {1},

pages = {26--31},

abstract = {PURPOSE: Methylenetetrahydrofolate reductase (MTHFR) is involved in the metabolism of folate and homocysteine; a polymorphism in the MTHFR gene (677C-->T) has been associated with adverse outcomes of pregnancy. We studied whether two polymorphisms in the MTHFR gene (677C-->T and 1298A-->C) are associated with pregnancy complications, adverse outcomes, and birth defects.nnMETHODS: MTHFR polymorphisms were determined in blood collected in 1992 and 1993 from 5883 women aged 40 to 42 years, and linked with 14,492 pregnancies in the same women recorded in the Medical Birth Registry of Norway from 1967 to 1996.nnRESULTS: The 677TT genotype in mothers was associated with increased risk of placental abruption (odds ratio [OR] = 2.6; 95% confidence interval [CI]: 1.4 to 4.8) compared with the CC variant. The risk of intrauterine growth restriction increased with number of T alleles (P for trend = 0.04). Compared with the 1298AA variant, the CC variant was associated with a reduced risk of very low birth weight infants (OR = 0.4; 95% CI: 0.2 to 0.8). No significant associations were found between MTHFR polymorphisms and birth defects.nnCONCLUSION: The maternal MTHFR 677C-->T polymorphism was a risk factor for placental abruption. The unexpected protective effect of the 1298A-->C polymorphism on very low birth weight needs further study.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15192637,

title = {Birth prevalence of homocystinuria},

author = {Helga Refsum and Ase Fredriksen and Klaus Meyer and Per M Ueland and Bengt Frode Kase},

doi = {10.1016/j.jpeds.2004.03.004},

issn = {0022-3476},

year  = {2004},

date = {2004-06-01},

journal = {J Pediatr},

volume = {144},

number = {6},

pages = {830--832},

abstract = {Serious complications of homocystinuria caused by cystathionine beta-synthase deficiency can be prevented by early intervention. We determined the prevalence of 6 specific mutations in 1133 newborn blood samples. Our results suggest that homocystinuria is more common than previously reported. Newborn screening for homocystinuria through mutation detection should be further considered.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid15113719,

title = {Changes in lifestyle and plasma total homocysteine: the Hordaland Homocysteine Study},

author = {Eha Nurk and Grethe S Tell and Stein E Vollset and Ottar Nygård and Helga Refsum and Roy M Nilsen and Per M Ueland},

doi = {10.1093/ajcn/79.5.812},

issn = {0002-9165},

year  = {2004},

date = {2004-05-01},

journal = {Am J Clin Nutr},

volume = {79},

number = {5},

pages = {812--819},

abstract = {BACKGROUND: Elevated plasma concentrations of total homocysteine (tHcy) are a risk factor for cardiovascular disease. tHcy is a marker of folate and cobalamin deficiencies and is also related to several lifestyle factors.nnOBJECTIVE: We examined whether changes in lifestyle influence tHcy over time.nnDESIGN: A population-based, prospective study was conducted in 7031 subjects from western Norway who constituted 2 age groups (41-42 and 65-67 y) at baseline (1992-1993). The subjects were reinvestigated in 1997-1999 ( follow-up: 6 y).nnRESULTS: During follow-up, median tHcy concentrations decreased 0.10 (25th and 75th percentiles: -1.24, 1.00) micromol/L in the younger subjects and increased 0.39 (25th and 75th percentiles: -0.99, 1.79) micromol/L in the older subjects. Changes in plasma vitamin status and vitamin supplement use were the strongest determinants of changes in tHcy over time. Each unit increase in plasma folate (nmol/L) and vitamin B-12 (pmol/L) was associated with reductions in tHcy concentrations of 0.2 and 0.1 micromol/L, respectively. Among the younger and older age groups, those who started to take vitamin supplements during follow-up had significant reductions in tHcy concentrations of 0.42 (95% CI: -0.65, -0.20) and 0.41 (-0.78, -0.03) micromol/L, respectively. In the younger subjects who quit smoking, tHcy concentrations decreased 0.54 (-0.91, -0.16) micromol/L. Weight changes were inversely related to tHcy. Both baseline history of cardiovascular disease or hypertension and cardiovascular events during follow-up were significantly associated with changes in tHcy.nnCONCLUSIONS: Changes in lifestyle factors over time influence tHcy concentrations. These changes are modest when compared with the strong associations between tHcy and lifestyle factors in cross-sectional studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14752013,

title = {High-level multiplex genotyping of polymorphisms involved in folate or homocysteine metabolism by matrix-assisted laser desorption/ionization mass spectrometry},

author = {Klaus Meyer and Ase Fredriksen and Per Magne Ueland},

doi = {10.1373/clinchem.2003.026799},

issn = {0009-9147},

year  = {2004},

date = {2004-02-01},

journal = {Clin Chem},

volume = {50},

number = {2},

pages = {391--402},

abstract = {BACKGROUND: Increased plasma total homocysteine (tHcy), a risk factor for cardiovascular disease, is related to genetic, environmental, and nutritional factors, in particular folate status. Future large epidemiologic studies of the genetic basis of hyperhomocysteinemia will require high-throughput assays for polymorphisms of genes related to folate and Hcy metabolism.nnMETHOD: We developed a high-level multiplex genotyping method based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the detection of 12 polymorphisms in 8 genes involved in folate or Hcy metabolism. The assay includes methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C, methionine synthase (MTR) 2756A>G, methionine synthase reductase (MTRR) 66A>G, cystathionine beta-synthase (CBS) 844ins68 and 699C>T, transcobalamin II (TCII) 776C>G and 67A>G, reduced folate carrier-1 (RFC1) 80G>A, paraoxonase-1 (PON1) 575A>G and 163T>A, and betaine homocysteine methyltransferase (BHMT) 742G>A.nnRESULTS: The failure rate of the assay was < or = 1.7% and was attributable to unsuccessful DNA purification, nanoliter dispensing, and spectrum calibration. Most errors were related to identification of heterozygotes as homozygotes. The mean error rate was 0.26%, and error rates differed for the various single-nucleotide polymorphisms. Identification of CBS 844ins68 was carried out by a semiquantitative approach. The throughput of the MALDI-TOF MS assay was 1152 genotypes within 20 min.nnCONCLUSIONS: This high-level multiplex method is able to genotype 12 polymorphisms involved in folate or Hcy metabolism. The method is rapid and reproducible and could facilitate large-scale studies of the genetic basis of hyperhomocysteinemia and associated pathologies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14699020,

title = {Betaine as a determinant of postmethionine load total plasma homocysteine before and after B-vitamin supplementation},

author = {Pål I Holm and Øyvind Bleie and Per M Ueland and Ernst A Lien and Helga Refsum and Jan E Nordrehaug and Ottar Nygård},

doi = {10.1161/01.ATV.0000114569.54976.31},

issn = {1524-4636},

year  = {2004},

date = {2004-02-01},

journal = {Arterioscler Thromb Vasc Biol},

volume = {24},

number = {2},

pages = {301--307},

abstract = {OBJECTIVE: Betaine is a substrate in the betaine-homocysteine methyltransferase reaction, converting homocysteine to methionine. There are only sparse data on plasma betaine as a determinant of the plasma total homocysteine (tHcy) concentration.nnMETHODS AND RESULTS: Ninety patients undergoing coronary angiography were randomized into 4 groups administered oral: (1) folic acid (0.8 mg), vitamin B12 (0.4 mg), and vitamin B6 (40 mg); (2) folic acid and vitamin B12; (3) vitamin B6 alone; or (4) placebo. Nonfasting blood samples were collected at baseline and 3, 14, and 28 days and 3, 6, and 12 months after treatment start. A 4-hour methionine-loading test (0.1 g/kg) was performed at baseline and after 3 months. At baseline, median (interquartile range) plasma betaine was 36.9 micromol/L (range: 30.3 to 46.8) and was increased by 15% after methionine loading. The postmethionine load (PML) increase in tHcy was inversely related to plasma betaine (beta=-0.29, P=0.02) and even more strongly to PML betaine (beta=-0.47, P<0.001). After 3 months of intervention, the relation between the PML increase in tHcy and PML betaine was weakened (beta=-0.33, P=0.007).nnCONCLUSIONS: Plasma betaine is a strong determinant of the PML increase in tHcy in subjects not supplemented with B-vitamins.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14739552,

title = {Hematological parameters and cobalamin status in infants born to smoking mothers},

author = {Anne-Lise Bjørke Monsen and Stein Emil Vollset and Helga Refsum and Trond Markestad and Per Magne Ueland},

doi = {10.1159/000076362},

issn = {0006-3126},

year  = {2004},

date = {2004-01-01},

journal = {Biol Neonate},

volume = {85},

number = {4},

pages = {249--255},

abstract = {Hematological parameters, serum cobalamin and folate levels, and the concentrations of the functional markers plasma methylmalonic acid and total homocysteine were determined in 173 newborns and 46 infants at 6 weeks to see whether maternal smoking influences the hematological parameters and the vitamin status of the newborn. At birth, there was a strong inverse correlation between the number of cigarettes smoked per day during pregnancy and red blood cell count (r = -0.56, p = 0.001) and hemoglobin level (r = -0.52, p = 0.003) in the newborns. Neonates born to smoking mothers had lower red blood cell counts and lower hemoglobin and serum cobalamin levels as compared with infants born to nonsmoking mothers. At 6 weeks, maternal smoking significantly predicted the methylmalonic acid and total homocysteine levels, suggesting an influence from smoking on the cobalamin function in these infants.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14709635,

title = {Facts and recommendations about total homocysteine determinations: an expert opinion},

author = {Helga Refsum and A David Smith and Per M Ueland and Ebba Nexo and Robert Clarke and Joseph McPartlin and Carole Johnston and Frode Engbaek and Jørn Schneede and Catherine McPartlin and John M Scott},

doi = {10.1373/clinchem.2003.021634},

issn = {0009-9147},

year  = {2004},

date = {2004-01-01},

journal = {Clin Chem},

volume = {50},

number = {1},

pages = {3--32},

abstract = {BACKGROUND: Measurement of plasma total homocysteine has become common as new methods have been introduced. A wide range of disorders are associated with increased concentrations of total homocysteine. The purpose of this review is to provide an international expert opinion on the practical aspects of total homocysteine determinations in clinical practice and in the research setting and on the relevance of total homocysteine measurements as diagnostic or screening tests in several target populations.nnMETHODS: Published data available on Medline were used as the basis for the recommendations. Drafts of the recommendations were critically discussed at meetings over a period of 3 years.nnOUTCOME: This review is divided into two sections: (a) determination of homocysteine (methods and their performance, sample collection and handling, biological determinants, reference intervals, within-person variability, and methionine loading test); and (b) risk assessment and disease diagnosis (homocystinuria, folate and cobalamin deficiencies, cardiovascular disease, renal failure, psychiatric disorders and cognitive impairment, pregnancy complications and birth defects, and screening of elderly and newborns). Each of these subsections concludes with a separate series of recommendations to assist the clinician and the research scientist in making informed decisions. The review concludes with a list of unresolved questions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14695861,

title = {Vitamin B12 and folate deficiency in later life},

author = {Robert Clarke and J Grimley Evans and J Schneede and E Nexo and C Bates and A Fletcher and A Prentice and C Johnston and P M Ueland and H Refsum and P Sherliker and J Birks and G Whitlock and E Breeze and J M Scott},

doi = {10.1093/ageing/afg109},

issn = {0002-0729},

year  = {2004},

date = {2004-01-01},

journal = {Age Ageing},

volume = {33},

number = {1},

pages = {34--41},

abstract = {OBJECTIVES: to examine the prevalence of vitamin B12 deficiency and folate deficiency in later life in representative samples of the elderly population in the United Kingdom.nnDESIGN: a population-based cross-sectional analysis of 3,511 people aged 65 years or older from three studies was used to estimate the age-specific prevalence of vitamin B12 deficiency and of folate deficiency. Vitamin B12 deficiency is conventionally diagnosed if serum vitamin B12 < 150 pmol/l ('low vitamin B12'). We defined 'metabolically significant vitamin B12 deficiency' as vitamin B12 < 200 pmol/l and blood total homocysteine >20 micro mol/l. Folate deficiency, which usually refers to serum folate <5 nmol/l, was defined as 'metabolically significant' if serum folate was <7 nmol/l and homocysteine >20 micro mol/l.nnRESULTS: the prevalence of vitamin B12 deficiency, whether defined as low vitamin B12 or metabolically significant vitamin B12 deficiency increased with age in all three studies, from about 1 in 20 among people aged 65-74 years to 1 in 10 or even greater among people aged 75 years or greater. The prevalence of folate deficiency also increased with age, and was similar to that for vitamin B12 deficiencies, but only about 10% of people with low vitamin B12 levels also had low folate levels.nnCONCLUSION: the high prevalence of vitamin B12 and folate deficiency observed in older people indicates a particular need for vigilance for deficiency of these vitamins. Reliable detection and treatment of vitamin deficiency could reduce the risk of deficiency-related disability in old age.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14633879,

title = {Cobalamin status and its biochemical markers methylmalonic acid and homocysteine in different age groups from 4 days to 19 years},

author = {Anne-Lise Bjørke Monsen and Helga Refsum and Trond Markestad and Per Magne Ueland},

doi = {10.1373/clinchem.2003.019869},

issn = {0009-9147},

year  = {2003},

date = {2003-12-01},

journal = {Clin Chem},

volume = {49},

number = {12},

pages = {2067--2075},

abstract = {BACKGROUND: Recent data indicate that cobalamin and folate status, including the metabolic markers methylmalonic acid (MMA) and total homocysteine (tHcy), undergo marked changes during childhood, particularly during the first year.nnMETHODS: Serum cobalamin, serum and whole-blood folate, and plasma MMA and tHcy were determined in a cross-sectional study of 700 children, ages 4 days to 19 years.nnRESULTS: During the first 6 months, serum cobalamin was lower than and plasma MMA, tHcy, and serum folate were higher than the concentrations detected in the other age groups. In infants 6 weeks to 6 months of age, median MMA and tHcy concentrations were >0.78 and >75 micro mol/L, respectively. In older children (>6 months), serum cobalamin peaked at 3-7 years and then decreased, median plasma MMA remained low (<0.26 micro mol/L), median plasma tHcy was low (<6 micro mol/L) and increased from the age of 7 years on, and serum folate gradually decreased. Plasma MMA was inversely associated with cobalamin (r = -0.4) in both age groups, but across the whole range of cobalamin concentrations, MMA was markedly higher in infants (< or =6 months) than in older children. Plasma tHcy showed a strong negative correlation to cobalamin (r = -0.52) but not to serum folate in infants < or =6 months. In older children, tHcy showed the expected association with both cobalamin (r = -0.48) and folate (r = -0.51).nnCONCLUSIONS: In infants 6 weeks to 6 months, concentrations of the metabolic markers MMA and tHcy were higher than in the other age groups and strongly correlated to cobalamin, whereas in older children, both makers showed correlations to cobalamin and folate concentrations documented in adults. Whether this metabolic profile in infants is explained by impaired cobalamin status, which in turn may have long-term effects on psychomotor development, remains to be addressed in intervention studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14656020,

title = {Hyperhomocysteinemia and B-vitamin deficiencies in infants and children},

author = {Per Magne Ueland and Anne Lise Bjørke Monsen},

doi = {10.1515/CCLM.2003.218},

issn = {1434-6621},

year  = {2003},

date = {2003-11-01},

journal = {Clin Chem Lab Med},

volume = {41},

number = {11},

pages = {1418--1426},

abstract = {Measurement of total homocysteine (tHcy) in healthy and diseased children has documented the utility of this marker in pediatric research and diagnostics. This article focuses on novel data obtained in infants, children and adolescents, with emphasis on cobalamin status in infants. In children, determinants of plasma tHcy are similar to those established in adults, and include age, gender, nutrition, B-vitamin status, and some drugs interfering with B-vitamin function. In infants (age < 1 year), tHcy is moderately elevated and related to serum cobalamin, whereas in older children and throughout childhood, plasma tHcy is low (about 60% of adult levels), and folate status becomes a strong tHcy determinant. As in adults, hyperhomocysteinemia in childhood is a risk factor for stroke, and folate-responsive hyperhomocysteinemia has been detected in children with renal failure. tHcy seems to be a sensitive indicator of folate deficiency in children on a poor diet, in HIV-infected children, and in children treated with anti-folate drugs. In children at increased risk of cobalamin deficiency, which includes children born to vegetarian mothers or children in developing countries on a poor diet, tHcy and methylmalonic acid are responsive indicators of a deficiency state. In newborns and infants born to mothers with an adequate nutrition, there are consistent observations of low cobalamin, elevated tHcy and methylmalonic acid, and reduction of both metabolites by cobalamin supplementation. These data have raised the question whether cobalamin deficiency may be widespread and undetected in babies born to non-vegetarian women on a Westernized diet.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid14535973,

title = {Homocysteine and its relation to B-vitamins in Graves' disease before and after treatment: effect modification by smoking},

author = {B G Nedrebø and S Hustad and J Schneede and P M Ueland and S E Vollset and P I Holm and S Aanderud and E A Lien},

doi = {10.1046/j.1365-2796.2003.01222.x},

issn = {0954-6820},

year  = {2003},

date = {2003-11-01},

journal = {J Intern Med},

volume = {254},

number = {5},

pages = {504--512},

abstract = {OBJECTIVES: To investigate plasma total homocysteine levels and its relation to B-vitamins and smoking in Graves' disease before and after antithyroid therapy.nnDESIGN: A longitudinal study taking place at four hospitals in Norway.nnMETHODS AND SUBJECTS: Plasma total homocysteine, serum folate, serum cobalamin and riboflavin, flavin mononucleotide and flavin adenine dinucleotide in plasma were investigated in 182 patients with hyperthyroidism before treatment. The same parameters were reinvestigated in 112 of these patients after attaining euthyroid state.nnRESULTS: In hyperthyroidism, plasma total homocysteine was low, and inversely related to folate, cobalamin and riboflavin, and positively related to serum creatinine and age. Following antithyroid therapy, total homocysteine increased and the concentration of folate, cobalamin, riboflavin, flavin mononucleotide and flavin adenine dinucleotide decreased significantly. The most pronounced reduction (35%) was observed for flavin mononucleotide. In the hyperthyroid state, smokers had lower levels of folate and flavin mononucleotide than non-smokers. After restoration of euthyroidism, both folate and riboflavin were significantly lower in smokers than non-smokers. Plasma total homocysteine increased according to decreasing quartiles of B-vitamins. For riboflavin, this relation was confined to smokers.nnCONCLUSION: Plasma total homocysteine changes according to thyroid status. These changes may be partly attributable to altered folate, cobalamin but also riboflavin status, particularly in smokers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12816766,

title = {Homocysteine and methylmalonic acid in diagnosis and risk assessment from infancy to adolescence},

author = {Anne Lise Bjørke Monsen and Per Magne Ueland},

doi = {10.1093/ajcn/78.1.7},

issn = {0002-9165},

year  = {2003},

date = {2003-07-01},

journal = {Am J Clin Nutr},

volume = {78},

number = {1},

pages = {7--21},

abstract = {The concentration of total homocysteine (tHcy) in serum and plasma is elevated in both folate and cobalamin deficiencies, whereas methylmalonic acid (MMA) in serum, plasma, or urine is a specific marker of cobalamin function. The combined measurement of both metabolites is useful for the diagnosis and follow-up of these deficiency states. In addition, tHcy is elevated under various pathologic states (eg, renal failure), and hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, cognitive dysfunction, and adverse pregnancy outcomes. The diagnostic utility of tHcy and MMA concentrations as markers of folate and cobalamin deficiencies in healthy and diseased children has been documented. This article briefly summarizes the biochemical background of tHcy and MMA and the associations of tHcy and MMA with various disease states and focuses on novel data obtained in infants, children, and adolescents, with emphasis on cobalamin status in infants. The utility of tHcy and MMA as indicators of cobalamin and folate deficiencies in adults can be extended to infants and older children. Furthermore, as in adults, tHcy is related to unhealthy lifestyle factors and is a risk factor for vascular disease. High MMA concentrations in newborns, occasionally denoted as benign methylmalonic aciduria, may reflect impaired cobalamin function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12796225,

title = {Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study},

author = {Ingvar Bjelland and Grethe S Tell and Stein Emil Vollset and Helga Refsum and Per Magne Ueland},

doi = {10.1001/archpsyc.60.6.618},

issn = {0003-990X},

year  = {2003},

date = {2003-06-01},

journal = {Arch Gen Psychiatry},

volume = {60},

number = {6},

pages = {618--626},

abstract = {BACKGROUND: An association between depression and folate status has been demonstrated in clinical studies, whereas data are sparse on the relationship between depression and other components of 1-carbon metabolism such as vitamin B12, homocysteine, and the methylenetetrahydrofolate reductase 677C-->T polymorphism. The relationship between anxiety and these components is less well known. This study examined the associations between folate, total homocysteine, vitamin B12, and the methylenetetrahydrofolate reductase 677C-->T polymorphism, and anxiety and depression in a large population-based study.nnMETHODS: Anxiety and depression, measured by the Hospital Anxiety and Depression Scale, were assessed in 5948 subjects aged 46 to 49 years (mean, 47.4 years) and 70 to 74 years (mean, 71.9 years) from the Hordaland Homocysteine Study cohort. By means of logistic regression models, anxiety and depression scores were examined in relation to the factors listed above.nnRESULTS: Overall, hyperhomocysteinemia (plasma total homocysteine level > or =15.0 micro mol/L [> or =2.02 mg/dL]) (odds ratio, 1.90; 95% confidence interval, 1.11-3.25) and T/T methylenetetrahydrofolate reductase genotype (odds ratio, 1.69; 95% confidence interval, 1.09-2.62), but not low plasma folate or vitamin B12 levels, were significantly related to depression without comorbid anxiety disorder. Plasma folate level was inversely associated with depression only in the subgroup of middle-aged women. None of the investigated parameters showed a significant relationship to anxiety.nnCONCLUSION: Our results provide further evidence of a role of impaired 1-carbon metabolism in depression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12765985,

title = {Plasma total cysteine, mortality, and cardiovascular disease hospitalizations: the Hordaland Homocysteine Study},

author = {Lina El-Khairy and Stein E Vollset and Helga Refsum and Per M Ueland},

doi = {10.1373/49.6.895},

issn = {0009-9147},

year  = {2003},

date = {2003-06-01},

journal = {Clin Chem},

volume = {49},

number = {6 Pt 1},

pages = {895--900},

abstract = {BACKGROUND: We have previously reported a positive association between tHcy and mortality and cardiovascular disease (CVD) hospitalizations in the Hordaland Homocysteine Study cohort. Using the same data set, we assessed the relationship between plasma total cysteine (tCys) and mortality from all causes and from cardiovascular and noncardiovascular conditions, and the association between tCys and the risk of hospitalizations from CVD.nnMETHODS: We measured plasma tCys in blood samples from 12,595 men and women 40-42 years of age and from 4766 men and women 65-67 years of age, collected as part of the Hordaland Homocysteine Study in the year 1992-1993. Follow-up data on mortality were collected through 1999. Data on CVD hospitalizations were collected from hospital records up to May 31, 1998.nnRESULTS: After a follow-up time of 6.6-7.6 years, there were a total of 610 deaths, of which 243 were cardiovascular deaths and 367 were noncardiovascular deaths. There was no association between tCys and all-cause, cardiovascular, or noncardiovascular mortality. When we used tCys values <247.6 micromol/L (lowest quartile) as the reference category, the adjusted mortality ratio (MR) for all-cause mortality at tCys concentrations of 247.6-270.79, 270.8-295.79, and > or =295.8 micromol/L (highest quartile) were 1.0, 0.9, and 1.0, respectively. The adjusted MRs for cardiovascular mortality were 1.0, 1.1, and 1.1, respectively. There were no associations between tCys and 1275 CVD hospitalizations, except that tCys was significantly associated with hospitalizations from coronary artery bypass grafting.nnCONCLUSION: Plasma tCys is not associated with mortality or CVD hospitalizations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid12716678,

title = {Screening for vitamin B-12 and folate deficiency in older persons},

author = {Robert Clarke and Helga Refsum and Jacqueline Birks and John Grimley Evans and Carole Johnston and Paul Sherliker and Per M Ueland and Joern Schneede and Joseph McPartlin and Ebba Nexo and John M Scott},

doi = {10.1093/ajcn/77.5.1241},

issn = {0002-9165},

year  = {2003},

date = {2003-05-01},

journal = {Am J Clin Nutr},

volume = {77},

number = {5},

pages = {1241--1247},

abstract = {BACKGROUND: Vitamin B-12 deficiency is usually accompanied by elevated concentrations of serum total homocysteine (tHcy) and methylmalonic acid (MMA). Folate deficiency also results in elevated tHcy. Measurement of these metabolites can be used to screen for functional vitamin B-12 or folate deficiency.nnOBJECTIVE: We assessed the prevalence of vitamin B-12 and folate deficiency in a population-based study (n = 1562) of older persons living in Oxford City, United Kingdom.nnDESIGN: We postulated that, as vitamin B-12 or folate concentrations declined from adequate to impaired levels, tHcy (or MMA) concentrations would increase. Individuals were classified as being at high risk of vitamin B-12 deficiency if they had low vitamin B-12 (< 150 pmol/L) or borderline vitamin B-12 (150-200 pmol/L) accompanied by elevated MMA (> 0.35 micromol/L) or tHcy (> 15.0 micromol/L). Individuals were classified as being at high risk of folate deficiency if they had low folate (< 5 nmol/L) or borderline folate (5-7 nmol/L) accompanied by elevated tHcy (> 15 micromol/L).nnRESULTS: Cutoffs of 15.0 micro mol/L for tHcy and 0.35 micro mol/L for MMA identified persons with normal or elevated concentrations. Among persons aged 65-74 and >or= 75 y, respectively, approximately 10% and 20% were at high risk of vitamin B-12 deficiency. About 10% and 20%, respectively, were also at high risk of folate deficiency. About 10% of persons with vitamin B-12 deficiency also had folate deficiency.nnCONCLUSION: Use of tHcy or MMA among older persons with borderline vitamin concentrations may identify those at high risk of vitamin B-12 deficiency who should be considered for treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}