The Experts below are selected from a list of 345 Experts worldwide ranked by ideXlab platform
Per Magne Ueland - One of the best experts on this subject based on the ideXlab platform.
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epidemiology of 40 blood biomarkers of one carbon metabolism Vitamin Status inflammation and renal and endothelial function among cancer free older adults
Scientific Reports, 2021Co-Authors: Hana Zahed, O Midttun, Per Magne Ueland, Mattias Johansson, Roger L Milne, Graham G GilesAbstract:Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, Vitamin Status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40-80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking Status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was - 0.91 standard-deviations lower in women than men (95%CI - 0.98; - 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p < 0.05) association with time since smoking cessation was observed for 8 markers, including C-reactive protein, kynurenine, choline, and total homocysteine. We conclude that most blood biomarkers show small variations across demographic characteristics. Patterns by smoking Status point to normalization of multiple physiological processes after smoking cessation.
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lifestyle metabolite and genetic determinants of formate concentrations in a cross sectional study in young healthy adults
The American Journal of Clinical Nutrition, 2018Co-Authors: John T Brosnan, Per Magne Ueland, James L Mills, Barry Shane, Ruzong Fan, Chiyang Chiu, Faith Pangilinan, Lawrence C Brody, Margaret E Brosnan, Theerawat PongnopparatAbstract:Background Formate is an important metabolite that serves as a donor of one-carbon groups to the intracellular tetrahydrofolate pool. However, little is known of its circulating concentrations or of their determinants. Objective This study aimed to define formate concentrations and their determinants in a healthy young population. Design Serum formate was measured in 1701 participants from the Trinity Student Study. The participants were men and women, aged 18 to 28 y, enrolled at Trinity College, Dublin. Formate concentrations were compared with other one-carbon metabolites, Vitamin Status, potential formate precursors, genetic polymorphisms, and lifestyle factors. Results Serum formate concentrations ranged from 8.7 to 96.5 µM, with a mean of 25.9 µM. Formate concentrations were significantly higher in women than in men; oral contraceptive use did not further affect them. There was no effect of smoking or of alcohol ingestion, but the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) 677C→T (rs1801133) polymorphism was associated with a significantly decreased formate concentration. Formate was positively associated with potential metabolic precursors (serine, methionine, tryptophan, choline) but not with glycine. Formate concentrations were positively related to serum folate and negatively related to serum Vitamin B-12. Conclusions Formate concentrations were sensitive to the concentrations of metabolic precursors. In view of the increased susceptibility of women with the TT genotype of MTHFR to give birth to infants with neural tube defects as well as the effectiveness of formate supplementation in decreasing the incidence of folate-resistant neural tube defects in susceptible mice, it will be important to understand how this genotype decreases the serum formate concentration. This trial was registered at www.clinicaltrials.gov as NCT03305900.
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Genotype, B-Vitamin Status, and androgens affect spaceflight-induced ophthalmic changes
FASEB Journal, 2016Co-Authors: Sara R. Zwart, Charles R. Gibson, Thomas H. Mader, Martina A. Heer, Jason M. Kinchen, Robert Ploutz-snyder, Steven H Zeisel, Jesse F Gregory, Per Magne Ueland, Scott M SmithAbstract:Ophthalmic changes have occurred in a subset of astronauts on International Space Station missions. Visual deterioration is considered the greatest human health risk of spaceflight. Affected astronauts exhibit higher concentrations of 1-carbon metabolites (e.g., homocysteine) before flight. We hypothesized that genetic variations in 1-carbon metabolism genes contribute to susceptibility to ophthalmic changes in astronauts. We investigated 5 polymorphisms in the methionine synthase reductase (MTRR), methylenetetrahydrofolate reductase (MTHFR), serine hydroxymethyltransferase (SHMT), and cystathionine β-synthase (CBS) genes and their association with ophthalmic changes after flight in 49 astronauts. The number of G alleles of MTRR 66 and C alleles of SHMT1 1420 both contributed to the odds of visual disturbances. Preflight dehydroepiandrosterone was positively associated with cotton wool spots, and serum testosterone response during flight was associated with refractive change. Block regression showed that B-Vitamin Status and genetics were significant predictors of many of the ophthalmic outcomes that we observed. In one example, genetics trended toward improving (P = 0.10) and B-Vitamin Status significantly improved (P < 0.001) the predictive model for refractive change after flight. We document an association between MTRR 66 and SHMT1 1420 polymorphisms and spaceflight-induced vision changes. This line of research could lead to therapeutic options for both space travelers and terrestrial patients.
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genotype b Vitamin Status and androgens affect spaceflight induced ophthalmic changes
The FASEB Journal, 2016Co-Authors: Sara R. Zwart, Charles R. Gibson, Thomas H. Mader, Jason M. Kinchen, Steven H Zeisel, Jesse F Gregory, Per Magne Ueland, Robert Ploutzsnyder, Martina Heer, Scott M SmithAbstract:Ophthalmic changes have occurred in a subset of astronauts on International Space Station missions. Visual deterioration is considered the greatest human health risk of spaceflight. Affected astronauts exhibit higher concentrations of 1-carbon metabolites (e.g., homocysteine) before flight. We hypothesized that genetic variations in 1-carbon metabolism genes contribute to susceptibility to ophthalmic changes in astronauts. We investigated 5 polymorphisms in the methionine synthase reductase (MTRR), methylenetetrahydrofolate reductase (MTHFR), serine hydroxymethyltransferase (SHMT), and cystathionine β-synthase (CBS) genes and their association with ophthalmic changes after flight in 49 astronauts. The number of G alleles of MTRR 66 and C alleles of SHMT1 1420 both contributed to the odds of visual disturbances. Preflight dehydroepiandrosterone was positively associated with cotton wool spots, and serum testosterone response during flight was associated with refractive change. Block regression showed that ...
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Vitamins b 2 and b 6 as determinants of kynurenines and related markers of interferon γ mediated immune activation in the community based hordaland health study
British Journal of Nutrition, 2014Co-Authors: Despoina Theofylaktopoulou, Steinar Hustad, Arve Ulvik, O Midttun, Per Magne Ueland, Ottar Nygård, Stein Emil Vollset, Grethe S Tell, Simone EussenAbstract:Vitamins B2 and B6 are cofactors in the kynurenine pathway. Many of the kynurenines are neuroactive compounds with immunomodulatory effects. In the present study, we aimed to investigate plasma concentrations of Vitamins B2 and B6 as determinants of kynurenines and two markers of interferon-g-mediated immune activation (kynurenine:tryptophan ratio (KTR) and neopterin). We measured the concentrations of Vitamins B2 and B6 vitamers, neopterin, tryptophan and six kynurenines (i.e. kynurenine, anthranilic acid, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid) in plasma from 7051 individuals. Dietary intake of Vitamins B2 and B6 was assessed using a validated FFQ. Associations were investigated using partial Spearman’s correlations, generalised additive models, and segmented or multiple linear regression. The B2 vitamer, riboflavin, was positively associated with 3-hydroxyanthranilic acid and xanthurenic acid, with correlation coefficients, as obtained by segmented regression, of 0·20 (95 % CI 0·16, 0·23) and 0·24 (95 % CI 0·19, 0·28), at riboflavin concentrations below the median value (13·0 nmol/l). The Vitamin B6 vitamer, pyridoxal 5 0 -phosphate (PLP), was positively associated with most kynurenines at PLP concentrations ,39·3–47·0 nmol/l, and inversely associated with 3-hydroxykynurenine with the association being more prominent at PLP concentrations ,18·9 nmol/l. Riboflavin and PLP were associated with xanthurenic acid only at relatively low, but normal concentrations of both vitamers. Lastly, PLP was negatively correlated with neopterin and KTR. These results demonstrate the significant and complex determination of kynurenine metabolism by Vitamin Status. Future studies on B-Vitamins and kynurenines in relation to chronic diseases should therefore integrate data on relevant biomarkers related to B-Vitamins Status and tryptophan metabolism.
O Midttun - One of the best experts on this subject based on the ideXlab platform.
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epidemiology of 40 blood biomarkers of one carbon metabolism Vitamin Status inflammation and renal and endothelial function among cancer free older adults
Scientific Reports, 2021Co-Authors: Hana Zahed, O Midttun, Per Magne Ueland, Mattias Johansson, Roger L Milne, Graham G GilesAbstract:Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, Vitamin Status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40-80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking Status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was - 0.91 standard-deviations lower in women than men (95%CI - 0.98; - 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p < 0.05) association with time since smoking cessation was observed for 8 markers, including C-reactive protein, kynurenine, choline, and total homocysteine. We conclude that most blood biomarkers show small variations across demographic characteristics. Patterns by smoking Status point to normalization of multiple physiological processes after smoking cessation.
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circulating concentrations of biomarkers and metabolites related to Vitamin Status one carbon and the kynurenine pathways in us nordic asian and australian populations
The American Journal of Clinical Nutrition, 2017Co-Authors: O Midttun, Arve Ulvik, Despoina Theofylaktopoulou, Klaus Meyer, Adrian Mccann, Anouar Fanidi, David C Muller, Wei Zheng, Xiaoou ShuAbstract:Background: Circulating concentrations of biomarkers that are related to Vitamin Status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also ...
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circulating concentrations of biomarkers and metabolites related to Vitamin Status one carbon and the kynurenine pathways in us nordic asian and australian populations
The American Journal of Clinical Nutrition, 2017Co-Authors: O Midttun, Arve Ulvik, Despoina Theofylaktopoulou, Klaus Meyer, Adrian Mccann, Anouar Fanidi, David C Muller, Wei Zheng, Xiaoou ShuAbstract:Background: Circulating concentrations of biomarkers that are related to Vitamin Status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies.Objective: We robustly and comprehensively assessed differences in biomarkers that are related to Vitamin Status across geographic regions.Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to Vitamin Status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory.Results: Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, Vitamin B-12, all-trans retinol, 25-hydroxyVitamin D, and α-tocopherol as well as combined Vitamin scores that were based on these nutrients showed that the general B-Vitamin concentration was highest in the United States and that the B Vitamins and lipid soluble Vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B Vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-Vitamin concentration in the United States appears to be driven mainly by multiVitamin-supplement users.Conclusions: The observed differences likely reflect the variation in intake of Vitamins and, in particular, the widespread multiVitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.
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Multianalyte Quantification of Vitamin B6 and B2 Species in the Nanomolar Range in Human Plasma by Liquid Chromatography–Tandem Mass
2014Co-Authors: O Midttun, Steinar Hustad, Einar Solheim, Jørn Schneede, Per M. UelAbstract:cular disease, cognitive disorders, and pregnancy com-plications, exists at a point of metabolic convergence of several B Vitamins, including Vitamins B6 and B2 (ribo-flavin). Measurement of the various forms of these Vitamins may be useful for the study of hyperhomocys-teinemia as well as for the assessment of Vitamin Status. Methods: Plasma (60 L) was deproteinized by mixing with an equal volume of 50 g/L trichloroacetic acid that contained d2-pyridoxal 5-phosphate, d3-pyridoxal, and d8-riboflavin as internal standards. Pyridoxal (PL), pyr-idoxal 5-phosphate (PLP), pyridoxine (PN), pyridoxine 5-phosphate, pyridoxamine (PM), pyridoxamine 5-phosphate, 4-pyridoxic acid (PA), riboflavin, flavin mononucleotide (FMN), and FAD were separated on a C8 reversed-phase column, which was developed wit
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Vitamins b 2 and b 6 as determinants of kynurenines and related markers of interferon γ mediated immune activation in the community based hordaland health study
British Journal of Nutrition, 2014Co-Authors: Despoina Theofylaktopoulou, Steinar Hustad, Arve Ulvik, O Midttun, Per Magne Ueland, Ottar Nygård, Stein Emil Vollset, Grethe S Tell, Simone EussenAbstract:Vitamins B2 and B6 are cofactors in the kynurenine pathway. Many of the kynurenines are neuroactive compounds with immunomodulatory effects. In the present study, we aimed to investigate plasma concentrations of Vitamins B2 and B6 as determinants of kynurenines and two markers of interferon-g-mediated immune activation (kynurenine:tryptophan ratio (KTR) and neopterin). We measured the concentrations of Vitamins B2 and B6 vitamers, neopterin, tryptophan and six kynurenines (i.e. kynurenine, anthranilic acid, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid) in plasma from 7051 individuals. Dietary intake of Vitamins B2 and B6 was assessed using a validated FFQ. Associations were investigated using partial Spearman’s correlations, generalised additive models, and segmented or multiple linear regression. The B2 vitamer, riboflavin, was positively associated with 3-hydroxyanthranilic acid and xanthurenic acid, with correlation coefficients, as obtained by segmented regression, of 0·20 (95 % CI 0·16, 0·23) and 0·24 (95 % CI 0·19, 0·28), at riboflavin concentrations below the median value (13·0 nmol/l). The Vitamin B6 vitamer, pyridoxal 5 0 -phosphate (PLP), was positively associated with most kynurenines at PLP concentrations ,39·3–47·0 nmol/l, and inversely associated with 3-hydroxykynurenine with the association being more prominent at PLP concentrations ,18·9 nmol/l. Riboflavin and PLP were associated with xanthurenic acid only at relatively low, but normal concentrations of both vitamers. Lastly, PLP was negatively correlated with neopterin and KTR. These results demonstrate the significant and complex determination of kynurenine metabolism by Vitamin Status. Future studies on B-Vitamins and kynurenines in relation to chronic diseases should therefore integrate data on relevant biomarkers related to B-Vitamins Status and tryptophan metabolism.
Jacob Selhub - One of the best experts on this subject based on the ideXlab platform.
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b Vitamins and the aging brain
Nutrition Reviews, 2010Co-Authors: Jacob Selhub, Aron M Troen, Irwin H RosenbergAbstract:Deficiencies of the Vitamins folate, B12, and B6 are associated with neurological and psychological dysfunction and with congenital defects. In the elderly, cognitive impairment and incident dementia may be related to the high prevalence of inadequate B Vitamin Status and to elevations of plasma homocysteine. Plausible mechanisms include homocysteine neurotoxicity, vasotoxicity, and impaired S-adenosylmethionine-dependent methylation reactions vital to central nervous system function. In light of this, it is imperative to find safe ways of improving Vitamin B Status in the elderly without exposing some individuals to undue risk.
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plasma b Vitamins homocysteine and their relation with bone loss and hip fracture in elderly men and women
The Journal of Clinical Endocrinology and Metabolism, 2008Co-Authors: Robert R Mclean, Jacob Selhub, Paul F Jacques, Lisa Fredman, Katherine L Tucker, Elizabeth J Samelson, Douglas P Kiel, Adrienne L Cupples, Marian T HannanAbstract:Context: Elevated homocysteine is a strong risk factor for osteoporotic fractures among elders, yet it may be a marker for low B-Vitamin Status. Objective: Our objective was to examine the associations of plasma concentrations of folate, Vitamin B12, Vitamin B6, and homocysteine with bone loss and hip fracture risk in elderly men and women. Design: This was a longitudinal follow-up study of the Framingham Osteoporosis Study. Setting: Community dwelling residents of Framingham, MA, were included in the study. Participants: A total of 1002 men and women (mean age 75 yr) was included in the study. Main Outcome Measures: Baseline (1987–1989) blood samples were used to categorize participants into plasma B-Vitamin (normal, low, deficient) and homocysteine (normal, high) groups. Femoral neck bone mineral density (BMD) measured at baseline and 4-yr follow-up was used to calculate annual percent BMD change. Incident hip fracture was assessed from baseline through 2003. Results: Multivariable-adjusted mean bone lo...
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relation between homocysteine and b Vitamin Status indicators and bone mineral density in older americans
Bone, 2005Co-Authors: Martha Savaria Morris, P. F. Jacques, Jacob SelhubAbstract:Abstract Recent studies have found a connection between hyperhomocysteinemia and hip fracture. If this association is causal, it could be mediated through detrimental effects of low B-Vitamin Status on bone mineral density (BMD). Studies have linked homocysteine (Hcy) and the established Hcy determinants folate and Vitamin B12, to BMD, but results have been inconsistent. Furthermore, only one study considered the specific marker of tissue Vitamin B12 Status, methylmalonic acid (MMA), and none have considered red blood cell (RBC) folate. To further explore associations between Hcy and B-Vitamin Status indicators and bone health, we used data collected on older (i.e., aged >55 years) men and women who underwent DEXA scans of the hip as participants in phase 2 of the third U.S. National Health and Nutrition Examination Survey ( n = 1550). We used BMD at the total hip as a continuous outcome variable in some analyses. In others, we used osteoporosis defined on a sex- and race/ethnicity-specific basis according to World Health Organization (WHO) guidelines. After adjusting for demographic factors, body mass index, and other osteoporosis risk factors, BMD decreased and osteoporosis increased significantly with increasing serum MMA quartile category ( P
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homocysteine versus the Vitamins folate b6 and b12 as predictors of cognitive function and decline in older high functioning adults macarthur studies of successful aging
The American Journal of Medicine, 2005Co-Authors: Deborah M Kado, Jacob Selhub, Aron M Troen, Mei Hua Huang, Arun S Karlamangla, John W Rowe, Teresa E SeemanAbstract:Background Elevated plasma total homocysteine concentration may be a risk factor for cognitive decline and Alzheimer disease, but data from prospective studies are limited. Further, high homocysteine levels are associated with low Vitamin Status, and it is unknown whether it is homocysteine toxicity or Vitamin insufficiency that is responsible for the observed cognitive dysfunction. Methods We performed cross-sectional and longitudinal analyses of a cohort of 499 high-functioning community-dwelling persons aged 70 to 79 years to determine the effect of homocysteine and related Vitamin plasma concentrations on cognitive function and cognitive decline. Nonfasting plasma concentrations of homocysteine, folate, Vitamin B 6 , and Vitamin B 12 were measured at baseline. Summary measures of cognitive function were created from tests of multiple cognitive domains administered at baseline and again after 7 years. Results In cross-sectional analyses investigating each variable separately, subjects with elevated homocysteine levels, or low levels of folate or Vitamin B 6 , demonstrated worse baseline cognitive function. In longitudinal analyses, after adjusting for multiple covariates, including homocysteine, those in the bottom quartile of folate had a 1.6-fold increased risk (95% confidence interval: 1.01 to 2.31; P =0.04) of being in the worst quartile of 7-year cognitive decline. Low folate levels largely accounted for a trend towards greater cognitive decline with elevated homocysteine level. Conclusion In high-functioning older adults, low folate levels appear to be a risk factor for cognitive decline. The risk of developing cognitive decline might be reduced through dietary folate intake.
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effect of l dopa on plasma homocysteine in pd patients relationship to b Vitamin Status
Neurology, 2003Co-Authors: Joshua W Miller, Jacob Selhub, M R Nadeau, C A Thomas, R G Feldman, Philip A WolfAbstract:To the Editor: We read with interest the article by Miller et al. describing the effect of l-dopa on plasma homocysteine in Parkinson disease (PD).1 We welcome the attention that this important metabolic phenomenon now receives, as we think that l-dopa–induced hyperhomocystenemia in PD is indicative of a broader metabolic alteration of the trans- methyl pathway with potential clinical consequences that extend beyond vascular disease and dementia. As reported by the authors,1 the increase in homocysteine is due to l-dopa O - methylation, a reaction catalyzed by catechol- O -methyltransferase (COMT). This reaction consumes the methyl donor S-adenosylmethionine, the principal methyl-group donor in the brain, and leads to increased production of (demethylated) S- adenosylhomocysteine, and, ultimately, homocysteine. Increased O -methylation, however, cannot only lead to hyperhomocystenemia, but can also cause a depletion of S- adenosylmethionine, inducing a state of relative hypomethylation. In addition to COMT- dependent O -methylation of catecholamines, S-adenosylmethionine is the methylating agent in vital metabolic reactions, including the synthesis of phosphatidylcholine and creatine, the methylation of phospholipids and of proteins, including N- and carboxyl- methylation of proteins, essential for the proper function of receptors configuration and permeability of ion channels.2 Of immediate clinical relevance is the fact that S- adenosylmethionine depletion has been associated with depression, common in patients with Parkinson …
Jaason Haapakoski - One of the best experts on this subject based on the ideXlab platform.
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α tocopherol and β carotene supplements and lung cancer incidence in the alpha tocopherol beta carotene cancer prevention study effects of base line characteristics and study compliance
Journal of the National Cancer Institute, 1996Co-Authors: Demetrius Albanes, Olli P Heinonen, Philip R Taylor, Jarmo Virtamo, Brenda K Edwards, Matti Rautalahti, Anne M Hartman, Juni Palmgren, Laurence S Freedman, Jaason HaapakoskiAbstract:BACKGROUND: Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of Vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of Vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and Vitamin A. PURPOSE: We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum Vitamin Status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. METHODS: A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. RESULTS: No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). CONCLUSIONS: Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. IMPLICATIONS: While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.
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α tocopherol and β carotene supplements and lung cancer incidence in the alpha tocopherol beta carotene cancer prevention study effects of base line characteristics and study compliance
Journal of the National Cancer Institute, 1996Co-Authors: Demetrius Albanes, Olli P Heinonen, Philip R Taylor, Jarmo Virtamo, Brenda K Edwards, Matti Rautalahti, Anne M Hartman, Juni Palmgren, Laurence S Freedman, Jaason HaapakoskiAbstract:Background: Experimental and epidemiologic investigations suggest that α-tocopherol (the most prevalent chemical form of Vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and β-carotene (a plant pigment and major precursor of Vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received β-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of β-carotene and Vitamin A. Purpose: We examined the effects of α-tocopherol and β-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum Vitamin Status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. Methods: A total of 29 133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive α-tocopherol (50 mg), β-carotene (20 mg), α-tocopherol and β-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of α-tocopherol and β-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. Results: No overall effect was observed for lung cancer from α-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P =.86, logrank test). β-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P =.02, logrank test). The β-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (≥11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). Conclusions: Supplementation with α-tocopherol or β-carotene does not prevent lung cancer in older men who smoke. β-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. Implications: While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose β-carotene supplementation.
Steinar Hustad - One of the best experts on this subject based on the ideXlab platform.
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Multianalyte Quantification of Vitamin B6 and B2 Species in the Nanomolar Range in Human Plasma by Liquid Chromatography–Tandem Mass
2014Co-Authors: O Midttun, Steinar Hustad, Einar Solheim, Jørn Schneede, Per M. UelAbstract:cular disease, cognitive disorders, and pregnancy com-plications, exists at a point of metabolic convergence of several B Vitamins, including Vitamins B6 and B2 (ribo-flavin). Measurement of the various forms of these Vitamins may be useful for the study of hyperhomocys-teinemia as well as for the assessment of Vitamin Status. Methods: Plasma (60 L) was deproteinized by mixing with an equal volume of 50 g/L trichloroacetic acid that contained d2-pyridoxal 5-phosphate, d3-pyridoxal, and d8-riboflavin as internal standards. Pyridoxal (PL), pyr-idoxal 5-phosphate (PLP), pyridoxine (PN), pyridoxine 5-phosphate, pyridoxamine (PM), pyridoxamine 5-phosphate, 4-pyridoxic acid (PA), riboflavin, flavin mononucleotide (FMN), and FAD were separated on a C8 reversed-phase column, which was developed wit
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Vitamins b 2 and b 6 as determinants of kynurenines and related markers of interferon γ mediated immune activation in the community based hordaland health study
British Journal of Nutrition, 2014Co-Authors: Despoina Theofylaktopoulou, Steinar Hustad, Arve Ulvik, O Midttun, Per Magne Ueland, Ottar Nygård, Stein Emil Vollset, Grethe S Tell, Simone EussenAbstract:Vitamins B2 and B6 are cofactors in the kynurenine pathway. Many of the kynurenines are neuroactive compounds with immunomodulatory effects. In the present study, we aimed to investigate plasma concentrations of Vitamins B2 and B6 as determinants of kynurenines and two markers of interferon-g-mediated immune activation (kynurenine:tryptophan ratio (KTR) and neopterin). We measured the concentrations of Vitamins B2 and B6 vitamers, neopterin, tryptophan and six kynurenines (i.e. kynurenine, anthranilic acid, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthurenic acid) in plasma from 7051 individuals. Dietary intake of Vitamins B2 and B6 was assessed using a validated FFQ. Associations were investigated using partial Spearman’s correlations, generalised additive models, and segmented or multiple linear regression. The B2 vitamer, riboflavin, was positively associated with 3-hydroxyanthranilic acid and xanthurenic acid, with correlation coefficients, as obtained by segmented regression, of 0·20 (95 % CI 0·16, 0·23) and 0·24 (95 % CI 0·19, 0·28), at riboflavin concentrations below the median value (13·0 nmol/l). The Vitamin B6 vitamer, pyridoxal 5 0 -phosphate (PLP), was positively associated with most kynurenines at PLP concentrations ,39·3–47·0 nmol/l, and inversely associated with 3-hydroxykynurenine with the association being more prominent at PLP concentrations ,18·9 nmol/l. Riboflavin and PLP were associated with xanthurenic acid only at relatively low, but normal concentrations of both vitamers. Lastly, PLP was negatively correlated with neopterin and KTR. These results demonstrate the significant and complex determination of kynurenine metabolism by Vitamin Status. Future studies on B-Vitamins and kynurenines in relation to chronic diseases should therefore integrate data on relevant biomarkers related to B-Vitamins Status and tryptophan metabolism.
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Kinetic modeling of storage effects on biomarkers related to B Vitamin Status and one-carbon metabolism
Clinical Chemistry, 2012Co-Authors: Steinar Hustad, Arve Ulvik, Puck M. Van De Kant, Randi Gislefoss, O Midttun, Simone Eussen, Lars Mørkrid, Per Magne UelandAbstract:BACKGROUND: Biomarkers and metabolites related to B Vitamin function and one-carbon metabolism have been studied as predictors of chronic diseases in studies based on samples stored in biobanks. For most biomarkers, stability data are lacking or fragmentary.\n\nMETHODS: Degradation and accumulation kinetics of 32 biomarkers were determined at 23 °C in serum and plasma (EDTA, heparin, and citrate) collected from 16 individuals and stored for up to 8 days. In frozen serum (-25 °C), stability was studied cross-sectionally in 650 archival samples stored for up to 29 years. Concentration vs time curves were fitted to monoexponential, biexponential, linear, and nonlinear models.\n\nRESULTS: For many biomarkers, stability was highest in EDTA plasma. Storage effects were similar at room temperature and at -25 °C; notable exceptions were methionine, which could be recovered as methionine sulfoxide, and cystathionine, which decreased in frozen samples. Cobalamin, betaine, dimethylglycine, sarcosine, total homocysteine, total cysteine, tryptophan, asymetric and symmetric dimethyl argenine, creatinine, and methylmalonic acid were essentially stable under all conditions. Most B Vitamins (folate and Vitamins B2 and B6) were unstable; choline increased markedly, and some amino acids also increased, particularly in serum. The kynurenines showed variable stability. For many biomarkers, degradation (folate and flavin mononucleotide) or accumulation (pyridoxal, riboflavin, choline, amino acids) kinetics at room temperature were non-first order.\n\nCONCLUSIONS: Data on stability and deterioration kinetics for individual biomarkers are required to optimize procedures for handling serum and plasma, and for addressing preanalytical bias in epidemiological and clinical studies.
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quantitative profiling of biomarkers related to b Vitamin Status tryptophan metabolism and inflammation in human plasma by liquid chromatography tandem mass spectrometry
Rapid Communications in Mass Spectrometry, 2009Co-Authors: O Midttun, Steinar Hustad, Per Magne UelandAbstract:Vitamins B2 and B6 serve as cofactors in enzymatic reactions involved in tryptophan and homocysteine metabolism. Plasma concentrations of these Vitamins and amino acids are related to smoking and inflammation, and correlate with other markers of immune activation. Large-scale studies of these relations have been hampered by lack of suitable analytical methods. The assay described includes riboflavin, five Vitamin B6 forms (pyridoxal 5′-phosphate, pyridoxal, 4-pyridoxic acid, pyridoxine and pyridoxamine), tryptophan and six tryptophan metabolites (kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid and 3-hydroxyanthranilic acid), cystathionine, neopterin and cotinine. Trichloroacetic acid containing 13 isotope-labelled internal standards was added to 60 µL of plasma, the mixture was centrifuged, and the resulting supernatant used for analysis. The analytes were separated within 5 min on a stable-bond C8 column by a gradient-type mobile phase containing acetonitrile, heptafluorobutyric acid and high concentration (650 mmol/L) of acetic acid, and detected using electrospray ionization tandem mass spectrometry (ESI-MS/MS). The mobile phase ensured sufficient separation and high ionization efficiency of all analytes. Recoveries were 75–123% and within-day and between-day coefficients of variance (CVs) were 2.5–9.5% and 5.4–16.9%, respectively. Limits of detection ranged from 0.05 to 7 nmol/L. The method enables quantification of endogenous plasma concentrations of 16 analytes related to B-Vitamin Status and inflammation, and may prove useful in large-scale epidemiological studies. Copyright © 2009 John Wiley & Sons, Ltd.
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quantitative profiling of biomarkers related to b Vitamin Status tryptophan metabolism and inflammation in human plasma by liquid chromatography tandem mass spectrometry
Rapid Communications in Mass Spectrometry, 2009Co-Authors: O Midttun, Steinar Hustad, Per Magne UelandAbstract:Vitamins B2 and B6 serve as cofactors in enzymatic reactions involved in tryptophan and homocysteine metabolism. Plasma concentrations of these Vitamins and amino acids are related to smoking and inflammation, and correlate with other markers of immune activation. Large-scale studies of these relations have been hampered by lack of suitable analytical methods. The assay described includes riboflavin, five Vitamin B6 forms (pyridoxal 5'-phosphate, pyridoxal, 4-pyridoxic acid, pyridoxine and pyridoxamine), tryptophan and six tryptophan metabolites (kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid and 3-hydroxyanthranilic acid), cystathionine, neopterin and cotinine. Trichloroacetic acid containing 13 isotope-labelled internal standards was added to 60 microL of plasma, the mixture was centrifuged, and the resulting supernatant used for analysis. The analytes were separated within 5 min on a stable-bond C8 column by a gradient-type mobile phase containing acetonitrile, heptafluorobutyric acid and high concentration (650 mmol/L) of acetic acid, and detected using electrospray ionization tandem mass spectrometry (ESI-MS/MS). The mobile phase ensured sufficient separation and high ionization efficiency of all analytes. Recoveries were 75-123% and within-day and between-day coefficients of variance (CVs) were 2.5-9.5% and 5.4-16.9%, respectively. Limits of detection ranged from 0.05 to 7 nmol/L. The method enables quantification of endogenous plasma concentrations of 16 analytes related to B-Vitamin Status and inflammation, and may prove useful in large-scale epidemiological studies.
