Jörn Schneede

Umeå University | UMU · Department of Pharmacology and Clinical Neuroscience

Background The choline oxidation pathway and metabolites involved have been linked to diseases including cardiovascular disease, type 2 diabetes and cancer. A healthy Nordic diet is a recently defined dietary pattern associated with decreased risk for these diseases. Our aim was to explore associations between adherence to a healthy Nordic diet and...

Plasma total homocysteine (tHcy) is a risk marker, and smoking is an established risk factor for cardiovascular disease. It is unclear if the effect of smoked tobacco on homocysteine is mediated by nicotine or other combustion products in smoked tobacco. Snus (moist smokeless tobacco) is high nicotine-containing tobacco, and little is known about t...

Objective Smoking has previously been associated with inflammatory bowel disease (IBD), but no study has reported on cotinine, an objective, biochemical measure of tobacco use. We aimed at testing the hypothesis that cotinine levels among healthy subjects are associated with an increased risk of developing IBD in later life. Design We analysed pla...

Background: Autism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to...

Pancreatic cancer (PC) has an exceptionally low survival rate and primary prevention strategies are limited. Folate plays an important role in one‐carbon metabolism and has been associated with the risk of several cancers, but not consistently with PC risk. We aimed to investigate the association between dietary folate intake and PC risk, using the...

Disturbances in one-carbon metabolism, intracellular reactions involved in nucleotide synthesis and methylation, likely increase the risk of colorectal cancer (CRC). However, results have been inconsistent. To explore whether this inconsistency could be explained by intertumoral heterogeneity, we evaluated a comprehensive panel of one-carbon metabo...

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Supplementary tables A-I. (XLSX)

PurposeTo assess whether comprehensive medication reviews conducted by clinical pharmacists as part of a healthcare team reduce drug-related hospital readmission rates among people with dementia or cognitive impairment. Methods This randomized controlled trial was carried out between January 9, 2012, and December 2, 2014. Patients aged ≥65 years wi...

Background: Higher plasma concentrations of the vitamin B-6 marker pyridoxal 5′-phosphate (PLP) have been associated with reduced colorectal cancer (CRC) risk. Inflammatory processes, including vitamin B-6 catabolism, could explain such findings. Objective: We investigated 3 biomarkers of vitamin B-6 status in relation to CRC risk. Design: This was...

The role of one-carbon metabolism (1CM), particularly folate, in colorectal cancer (CRC) development has been extensively studied, but with inconclusive results. Given the complexity of 1CM, the conventional approach, investigating components individually, may be insufficient. We used a machine learning-based Bayesian network approach to study, sim...

Purpose Drug treatment associated problems are common and are the cause of a large proportion of hospitalizations in old people. People with dementia are especially at risk of drug-related problems. The objectives of this study were to assess the occurrence and character of drug-related problems that lead to acute hospital admissions among old peop...

Background: Pyridoxal 5’-phospate (PLP) is the most commonly used marker of circulating vitamin B6 status. In prospective case-control studies, individuals with higher plasma concentrations of PLP had a 30-50% decreased risk of colorectal cancer (CRC). This may partly be explained by decreased PLP due to inflammatory activity in persons at an incre...

Background: Colorectal cancer (CRC) is a heterogeneous disease caused by a number of distinct pathways defined by genetic and epigenetic events. These molecular subtypes differ in prognosis and treatment options, and recent studies also imply differences in etiology. One-carbon metabolism has been extensively studied in relation to incident CRC ris...

Background: Despite extensive study, the role of folate in colorectal cancer remains unclear. Research has therefore begun to address the role of other elements of the folate-methionine metabolic cycles. This study investigated factors other than folate involved in one-carbon metabolism, i.e. choline, betaine, dimethylglycine, sarcosine, and methi...

Cobalamin and folate are especially important for women of childbearing age due to their ubiquitous role in fetal growth and development. Population-based data on cobalamin and folate status are lacking from Nepal, where diets are mostly vegetarian. The objectives of the study were to investigate cobalamin and folate intake and status, and to explo...

Acute vasodilator testing is recommended in patients with pulmonary arterial hypertension to identify individuals who may benefit from long-term treatment with oral calcium channel blockers. The aim of this study was to investigate the use of vardenafil in acute vasoreactivity testing compared to adenosine. A total of 20 patients eligible for right...

The aims of this study were to investigate trends in the prevalence of potentially inappropriate drug use among old people living in geriatric care units in the county of Västerbotten between 2007 and 2013 using six national quality indicators and to assess the impact of medication reviews on those quality indicators. Data were collected concerning...

There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 367993 women age 35 to 70...

Importance Colorectal cancer is a major health burden. Screening is recommended in many countries.Objective To estimate the effectiveness of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality in a population-based trial.Design, Setting, and Participants Randomized clinical trial of 100 210 individuals aged 50 to 64 yea...

Background: A diet rich in folate is associated with a reduced colorectal cancer risk, whereas the role of circulating levels is less clear. The aim of this study was to relate prediagnostic plasma folate, vitamin B12, and homocysteine concentrations to the risk of colorectal cancer. Methods: This was a prospective case–control study of 331 cases a...

Background Patients suffering from critical limb ischemia (CLI) have poor wound healing in the ankle and foot areas. Secondary wound infections are frequent and often treated with prolonged courses of antibiotics. Purpose This study set out to investigate to what extent the unbound fraction of 4 g of cloxacillin i.v. reaches its target organ in poo...

Background: Data on early biochemical and hematological responses to cobalamin therapy in vitamin B12-deficient patients are scarce. Therefore, we investigated whether cobalamin injections would include prompt biochemical and hematological responses in vitamin B12-deficient patients. Subjects and methods: Seven female patients (mean age: 69.4 ye...

Background: Micronutrient deficiencies can affect cognitive function. Many young children in low- and middle-income countries have inadequate cobalamin (vitamin B-12) status. Objective: The objective was to measure the association of plasma concentrations of folate, cobalamin, total homocysteine, and methylmalonic acid with cognitive performance...

Different lifestyle patterns across Europe may influence plasma concentrations of B-vitamins and one-carbon metabolites and their relation to chronic disease. Comparison of published data on one-carbon metabolites in Western European regions is difficult due to differences in sampling procedures and analytical methods between studies. The present s...

Total plasma homocysteine (tHcy) has been suggested as a risk factor of dementia. Our aim was to investigate potential differences in tHcy status in relation to the prescription of vitamin B(12) and dementia diagnosis. We examined whether vitamin B(12) prescriptions, a family history of dementia, or the need for home care service might be associate...

Purpose: To evaluate the pharmacokinetic parameters of a single oral dose of vardenafil in patients with pulmonary hypertension (PH). Methods: Sixteen patients with PH received vardenafil in single oral doses (20, 10 or 5 mg), and repeated blood sampling for up to 9 h was performed. Vardenafil plasma concentration was determined using liquid chr...

Poor micronutrient status is associated with diarrheal illness, but it is not known whether low folate and/or cobalamin status are independent risk factors for diarrhea. We measured the association between plasma folate and cobalamin and subsequent diarrheal morbidity in a prospective cohort study of 2296 children aged 6-30 mo in New Delhi, India....

Two polymorphic variants in the gene coding for transcobalamin II (TCN2), TCN2 776C- > G and TCN2 67A- > G, may alter serum holotranscobalamin (holoTC), which in turn may affect cellular uptake of cobalamin (Cbl) and thereby Cbl status indicators. We studied the effects of TCN2 776C- > G and TCN2 67A- > G on blood concentrations of holoTC, Cbl, met...

Efficient one-carbon metabolism, which requires adequate supply of methyl group donors and B-vitamins, may protect against colorectal carcinogenesis. However, plasma folate and vitamins B2 and B12 have inconsistently been associated with colorectal cancer risk, and there have been no previous studies relating plasma concentrations of methionine, ch...

The observed effect of zinc supplementation on diarrheal morbidity varies between trials and there is a need to identify subgroups most likely to benefit from improved zinc nutriture. In a randomized, double-blind trial in 2296 children in New Delhi, India, we assessed whether baseline cobalamin or folate status modified the effect of zinc suppleme...

To investigate the contribution of genetic polymorphisms of vitamin K epoxide reductase complex subunit 1 gene VKORC1-1639G>A, cytochrome P450 2C9 gene (CYP2C9), EPHXI, and clinical factors to warfarin sensitivity in southwest Chinese Han patients with mechanical heart valve prostheses. A total of 127 patients with mechanical heart valve prostheses...

Measurement of methylmalonic acid (MMA) in serum or plasma is useful for diagnosing cobalamin deficiency. We developed a method for quantifying MMA in plasma based on hydrophilic interaction liquid chromatography (HILIC) and single-stage negative electrospray ionization (ESI) mass spectrometry. We deproteinized plasma samples (200 microL) with 800...

Deficiencies of cobalamin (vitamin B12) or folate are common conditions that predispose for anemia and chronic diseases. An elevated concentration of methylmalonic acid in plasma/serum is an indicator of cobalamin deficiency, whereas an increased concentration of total homocysteine in plasma occurs with deficiency of both cobalamin and folate. The...

Population-based data on the prevalence of cobalamin and folate deficiency in India are lacking. The objective was to measure the prevalence of cobalamin and folate deficiency among children aged 6-30 mo residing in a low-to-middle income community in North India. Children aged 6-30 mo (n = 2482) were identified through a community survey in a low-...

Elevated total homocysteine (tHcy) concentrations have been associated with cognitive impairment, but it is unclear whether low vitamin B-12 or folate status is responsible for cognitive decline. We examined the associations of cognitive decline with vitamin B-12 and folate status in a longitudinal cohort study performed from 1993 to 2003 in Oxford...

Several polymorphisms of genes involved in one-carbon metabolism have been identified. The reported metabolic phenotypes are often based on small studies providing inconsistent results. This large-scale study of 10,601 population-based samples was carried out to investigate the association between a panel of biochemical parameters and genetics vari...

Compromised cobalamin status during pregnancy may put both mother and child at risk of deficiency during lactation and subsequent development. We investigated whether changes in cobalamin status during pregnancy are associated with impaired status in the mother and the cord. Plasma cobalamin, methylmalonic acid (MMA), and holotranscobalamin (holoTC...

Vitamin B-6 exists in different forms; one of those forms, pyridoxal 5'-phosphate (PLP), serves a cofactor in many enzyme reactions, including the transsulfuration pathway, in which homocysteine is converted to cystathionine and then to cysteine. Data on the relations between indexes of vitamin B-6 status and transsulfuration metabolites in plasma...

Vitamin deficiencies are often part of malnutrition, which predisposes to acute lower respiratory tract infections. The objective was to measure the association between cobalamin and folate status and subsequent respiratory morbidity. A prospective cohort study was conducted in 2482 children aged 6-30 mo nested in a zinc supplementation trial. We m...

Mildly cobalamin-deficient elderly were supplemented with 1000 microg cobalamin (group C, n=34), 1000 microg cobalamin with 400 microg folic acid (group CF, n=31) or a placebo (n=30) for 6 months. Participants provided one single blood sample 3, 5 or 7 months after cessation of supplementation to monitor early changes in plasma concentrations of co...

Impaired vitamin B(12) function and decreased vitamin B(12) status have been associated with neurological and cognitive impairment. Current assays analyze total vitamin B(12) concentration, only a small percentage of which is metabolically active. Concentrations of this active component, carried on holotranscobalamin (holoTC), may be of greater rel...

Folates are carriers of one-carbon units and are metabolized by 5,10-methylenetetrahydrofolate reductase (MTHFR) and other enzymes that use riboflavin, cobalamin, or vitamin B6 as cofactors. These B vitamins are essential for the remethylation and transsulfuration of homocysteine, which is an important intermediate in one-carbon metabolism. We stud...

Betaine is formed from the essential nutrient choline or is supplied from the diet. It serves as a substrate in the betaine-homocysteine methyltransferase reaction and thereby provides methyl groups for the homocysteine-methionine cycle, which is regulated by enzymes dependent on folate, vitamin B12, riboflavin (vitamin B2), or vitamin B6. We inves...

Two functional single nucleotide polymorphisms, 677C > T and 1298A > C have been described for the methylenetetrahydrofolate (MTHFR) gene. Both are associated with reduced enzyme activity in vitro. For the 677T, but not the 1298C allele, significantly lower serum folate and higher plasma total homocysteine (tHcy) have been reported. We genotyped 10...

The association between body size at birth and risk of later cardiovascular disease is thought to be a consequence of metabolic changes that accompany slow growth in utero. The metabolism of methionine and homocysteine has been investigated in relation to cardiovascular risk and has also been assigned an important role in organogenesis and normal f...

BACKGROUND: Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive. OBJECTIVE: The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone o...

Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive. The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with f...

low vitamin B12 concentrations are common in older people, but the clinical relevance of biochemical evidence of vitamin B12 deficiency in the absence of anaemia is uncertain. to examine associations of cognitive impairment, depression and neuropathy with blood measurements of vitamin B12 and folate status in older people. cross-sectional study in...

Cobalamin deficiency is prevalent in vegetarians and has been associated with increased risk of osteoporosis. To examine the association between cobalamin status and bone mineral density in adolescents formerly fed a macrobiotic diet and in their counterparts. In this cross-sectional study bone mineral density (BMD) and bone mineral content (BMC) w...

Homocysteine, a risk factor of cardiovascular disease, cognitive disorders, and pregnancy complications, exists at a point of metabolic convergence of several B vitamins, including vitamins B(6) and B(2) (riboflavin). Measurement of the various forms of these vitamins may be useful for the study of hyperhomocysteinemia as well as for the assessment...

New developments in diagnostic markers and a better understanding of the limitations of traditional diagnostic strategies have allowed diagnosis of earlier stages and atypical forms of cobalamin deficiency. Still, there are no generally accepted guidelines for the definition, diagnosis, treatment, and follow-up of cobalamin deficiency. The new tren...

Supplementation with high doses of oral cobalamin is as effective as cobalamin administered by intramuscular injection to correct plasma markers of vitamin B(12) deficiency, but the effects of lower oral doses of cobalamin on such markers are uncertain. We conducted a randomized, parallel-group, double-blind, dose-finding trial to determine the low...

A commercially available holotranscobalamin (holo-TC) radioimmunoassay (RIA) (Axis-Shield, Dundee, Scotland) was evaluated in four laboratories and compared with a holoTC ELISA run in one laboratory. The performance of the holoTC RIA assay was comparable in three of the four participating laboratories. The results from these three laboratories, inv...

Background Supplementation with high doses of oral cobalamin is as effective as cobalamin administered by intramuscular injection to correct plasma markers of vitamin B12 deficiency, but the effects of lower oral doses of cobalamin on such markers are uncertain. Methods We conducted a randomized, parallel-group, double-blind, dose-finding trial to...

The aim of the study was to investigate whether pelvic radiotherapy for rectal cancer had a negative impact on cobalamin status. 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) wer...

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. The...

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. We compared the effects of vitamin B-6 with the effects of folic acid and vitamin B-12, as used in th...

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. Serum concentrations of tHcy, cystathionine, methionine, folate, and B12 and the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism...

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...

The flavoenzyme methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which serves as a me thyl group donor in the conversion of homocysteine to methionine. In rats, experimental riboflavin deficiency is associated with low MTHFR activity and reduced levels of 5-methylte...

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. 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 fol...

To investigate plasma total homocysteine levels and its relation to B-vitamins and smoking in Graves' disease before and after antithyroid therapy. A longitudinal study taking place at four hospitals in Norway. Plasma total homocysteine, serum folate, serum cobalamin and riboflavin, flavin mononucleotide and flavin adenine dinucleotide in plasma we...

To study the total number of combined analyses of methylmalonic acid (MMA) and total plasma homocysteine (tHcy) carried out during February 1998 at the Central Laboratory of Haukeland University Hospital. Laboratory data and requester comments of 2917 subjects in whom MMA was requested during February 1998, were retrieved from the laboratory inform...

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. We assessed the prevalence of vitamin B-12 and folate def...

Assessment of functional vitamin B(12) status in a subset of the respondents in the British National Diet and Nutrition Survey of people aged 65 y and over. National Diet and Nutrition Survey: a British nationwide cross-sectional sample of people aged 65 y and over, living either in the community or in institutions such as nursing homes, during one...

Vitamin B(6) has attracted renewed interest because of its role in homocysteine metabolism and its possible relation to cardiovascular risk. We examined the plasma B(6) vitamers, pyridoxal 5'-phosphate (PLP), pyridoxal (PL), pyridoxine (PN), and 4-pyridoxic acid (4-PA) before and after vitamin B(6) supplementation. Patients (n = 90; age range, 38-8...

There is currently no consensus on how to define, diagnose and treat vitamin B12 deficiency. This is partly due to insufficient and non-uniform study design. It is essential to come to a harmonization of rational study designs. In order to evaluate new tests for the diagnosis of vitamin B12 deficiency, it is important that independent and unequivoc...

We examined the effect of oral vitamin B(12) treatment on fluctuations in plasma total cobalamin and its binding proteins transcobalamin (TC) and haptocorrin (HC). Patients (n = 88; age range, 38-80 years) undergoing coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial) were allocated to daily oral tre...

Vitamin B(2) exists in blood as riboflavin and its cofactors, flavin mononucleotide (FMN) and FAD. The erythrocyte glutathione reductase activation coefficient (EGRAC) has traditionally been used to assess vitamin B(2) status in humans. We investigated the relationships of EGRAC and plasma and erythrocyte concentrations of riboflavin, FMN, and FAD...

The aim of this study was to investigate homocysteine and methylmalonic acid levels as markers of functional cobalamin and folate status in pregnant Nepali women. Cross-sectional study. Patan Hospital, Kathmandu, Nepal. A sub-sample (n=382) of all pregnant women (n=2856) coming for their first antenatal visit in a 12 month period, 1994-1995. The se...

In India, most people adhere to a vegetarian diet, which may lead to cobalamin deficiency. The objective was to examine indicators of cobalamin status in Asian Indians. The study population included 204 men and women aged 27-55 y from Pune, Maharashtra, India, categorized into 4 groups: patients with cardiovascular disease (CVD) and diabetes, patie...

The enzyme methylenetetrahydrofolate reductase (MTHFR) directs folate species either to DNA synthesis or to homocysteine (Hcy) remethylation. The common MTHFR C677T polymorphism affects the activity of the enzyme and hence folate distribution. Under conditions of impaired folate status, the homozygous TT genotype has been regarded as harmful becaus...

Early detection of cobalamin deficiency is clinically important, and there is evidence that such deficiency occurs more frequently than previously anticipated. However, serum cobalamin and other commonly used tests have limited ability to diagnose a deficiency state. We investigated the ability of hematological variables, serum cobalamin, plasma to...

Lack of cobalamin may lead to neurologic disorders, which have been reported in strict vegetarians. The objective of this study was to investigate whether cognitive functioning is affected in adolescents (aged 10-16 y) with marginal cobalamin status as a result of being fed a macrobiotic diet up to an average age of 6 y. Data on dietary intake, psy...

Plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease. tHcy concentrations are partly determined by folate, cobalamin, and vitamin B(6) status, and methylenetetrahydrofolate reductase (MTHFR) and other flavoenzymes are important for the biotransformation of these vitamins. This motivates the investigation of the possible rela...

This article gives an overview over common physiological, lifestyle, and pathological conditions that may modulate the homocysteine status. The interplay of several environmental factors, including age, gender, nutrition, smoking, and coffee consumption and physical activity with commonly used drugs and prevalent diseases are described. In most cas...

The aim of this study was to investigate the importance of nutritional deficiencies and infections in the development of anaemia in pregnant Nepali women. Case-control study. Setting: Patan Hospital, Kathmandu, Nepal. A sub-sample (n=479) of all pregnant women (n=2856) coming for their first antenatal visit in a 12 month period, 1994-1995. Women wh...

The concentration of total homocysteine in plasma is influenced by a diversity of genetic and acquired factors, and by interactions between such factors. The most prevalent genetic cause of hyperhomocysteinemia is the C677T polymorphism of the methylenetetrahydrofolate reductase gene, which predisposes to hyperhomocysteinemia under conditions of im...