Publications by authors named "Per Magne Ueland"

196 Publications

Investigating novel biomarkers of immune activation and modulation in the context of sedentary behaviour: a multicentre prospective ischemic stroke cohort study.

BMC Neurol 2021 Aug 16;21(1):318. Epub 2021 Aug 16.

Department of Geriatric Medicine, Oslo University Hospital, Ullevaal, Oslo, Norway.

Background: Sedentary behaviour is associated with disease, but the molecular mechanisms are not understood. Valid biomarkers with predictive and explanatory properties are required. Therefore, we have investigated traditional and novel biomarkers of inflammation and immune modulation and their association to objectively measured sedentary behaviour in an ischemic stroke population.

Methods: Patients admitted to hospital with acute ischemic stroke were included in the multicentre Norwegian Cognitive Impairment After Stroke (Nor-COAST) study (n = 815). For this sub-study (n = 257), sedentary behaviour was registered 3 months after stroke using position transition data from the body-worn sensor, ActivPal®. Blood samples were analysed for high sensitive C-reactive protein (hsCRP), the cytokines interleukin-6 (IL-6) and 10 (IL-10), neopterin, tryptophan (Trp), kynurenine (kyn), kynurenic acid (KA), and three B6 vitamers, pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and pyridoxic acid (PA). The kynurenine/tryptophan ratio (KTR) and the pyridoxic acid ratio index (PAr = PA: PL + PLP) were calculated.

Results: Of the 815 patients included in the main study, 700 attended the three-month follow-up, and 257 fulfilled the inclusion criteria for this study. Sedentary time was significantly associated with levels of hsCRP, IL-6, neopterin, PAr-index, and KA adjusted for age, sex, waist circumference, and creatinine. In a fully adjusted model including all the significant biomarkers except hsCRP (because of missing values), sedentary time was independently positively associated with the PAr-index and negatively with KA. We did not find an association between sedentary behaviour, IL-10, and KTR.

Conclusions: The PAr-index is known to capture several modes of inflammation and has previously shown predictive abilities for future stroke. This novel result indicates that the PAr-index could be a useful biomarker in future studies on sedentary behaviour and disease progression. KA is an important modulator of inflammation, and this finding opens new and exciting pathways to understand the hazards of sedentary behaviour.

Trial Registration: The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted 08/01/2016.
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http://dx.doi.org/10.1186/s12883-021-02343-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365944PMC
August 2021

Baked cod consumption delayed the development of kidney and liver dysfunction and affected plasma amino acid concentrations, but did not affect blood pressure, blood glucose or liver triacylglycerol concentrations in obese fa/fa Zucker rats.

Nutr Res 2021 08 12;92:72-83. Epub 2021 Jun 12.

Dietary Protein Research Group, Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway. Electronic address:

Obesity is associated with changes in amino acid metabolism, and studies show that ingestion of fish proteins influence amino acid composition in plasma and urine, in addition to affecting risk factors for metabolic syndrome. Since the majority of fish proteins consumed by humans are as fish fillet, it is of interest to investigate if cod fillet intake affects amino acid composition and metabolic disorders. We hypothesized that a modified AIN-93G diet containing cod fillet would affect amino acid compositions in plasma and urine in obese rats, and also affect risk factors for metabolic syndrome when compared to rats fed a regular AIN-93G diet with casein as the protein source. Obese Zucker fa/fa rats, a rat model of metabolic syndrome, received diets containing 25% protein from lyophilized baked cod fillet and 75% protein from casein (Baked cod diet), or a Control diet with casein for four weeks. The Baked cod diet affected the amino acid composition in plasma, with e.g., lower glycine, histidine, homoarginine, homocysteine, methionine, proline and tyrosine concentrations, but did not affect amino acid concentrations in urine. The concentrations of markers for kidney and liver dysfunction were lower in the Baked cod group, however blood pressure development, fasting and postprandial glucose, and hepatic triacylglycerol concentrations were similar to the Control group. To conclude, substituting 25% of dietary protein with baked cod fillet affected concentrations of some amino acids in plasma and delayed development of kidney and liver dysfunction, but did not affect blood pressure, glucose concentration or fatty liver.
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http://dx.doi.org/10.1016/j.nutres.2021.05.009DOI Listing
August 2021

Circulating tryptophan metabolites and risk of colon cancer: Results from case-control and prospective cohort studies.

Int J Cancer 2021 Nov 12;149(9):1659-1669. Epub 2021 Jul 12.

International Agency for Research on Cancer, Lyon, France.

Dysregulation of tryptophan metabolism has been linked to colorectal tumorigenesis; however, epidemiological studies investigating tryptophan metabolites in relation to colorectal cancer risk are limited. We studied associations of plasma tryptophan, serotonin and kynurenine with colon cancer risk in two studies with cancer patients and controls, and in one prospective cohort: ColoCare Study (110 patients/153 controls), the Colorectal Cancer Study of Austria (CORSA; 46 patients/390 controls) and the European Prospective Investigation into Cancer and Nutrition (EPIC; 456 matched case-control pairs). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for colon cancer risk. Tryptophan was inversely associated with colon cancer risk in ColoCare (OR per 1-SD = 0.44; 95% CI, 0.31-0.64) and EPIC (OR per 1-SD = 0.86; 95% CI, 0.74-0.99). Comparing detectable vs nondetectable levels, serotonin was positively associated with colon cancer in CORSA (OR = 6.39; 95% CI, 3.61-11.3) and EPIC (OR = 2.03; 95% CI, 1.20-3.40). Kynurenine was inversely associated with colon cancer in ColoCare (OR per 1-SD = 0.74; 95% CI, 0.55-0.98), positively associated in CORSA (OR per 1-SD = 1.79; 95% CI, 1.27-2.52), while no association was observed in EPIC. The kynurenine-to-tryptophan ratio was positively associated with colon cancer in ColoCare (OR per 1-SD = 1.38; 95% CI, 1.03-1.84) and CORSA (OR per 1-SD = 1.44; 95% CI, 1.06-1.96), but not in EPIC. These results suggest that higher plasma tryptophan may be associated with lower colon cancer risk, while increased serotonin may be associated with a higher risk of colon cancer. The kynurenine-to-tryptophan ratio may also reflect altered tryptophan catabolism during colon cancer development.
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http://dx.doi.org/10.1002/ijc.33725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429124PMC
November 2021

Pre-diagnostic circulating concentrations of fat-soluble vitamins and risk of glioma in three cohort studies.

Sci Rep 2021 04 29;11(1):9318. Epub 2021 Apr 29.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Few prospective studies have evaluated the relation between fat-soluble vitamins and glioma risk. Using three cohorts-UK Biobank (UKB), Nurses' Health Study (NHS), and Health Professionals Follow-Up Study (HPFS), we investigated associations of pre-diagnostic concentrations of fat-soluble vitamins D, A, and E with incident glioma. In 346,785 participants (444 cases) in UKB, associations with vitamin D (25-hydroxyvitamin D [25(OH)D]) were evaluated by Cox proportional hazards regression. In NHS (52 cases, 104 controls) and HPFS (32 cases, 64 controls), associations with 25(OH)D, vitamin A (retinol), and vitamin E (α- and γ-tocopherol) were assessed using conditional logistic regression. Our results suggested plasma concentrations of 25(OH)D and retinol were not associated with glioma risk. Comparing the highest to lowest tertile, the multivariable hazard ratio (MVHR) for 25(OH)D was 0.87 (95% confidence interval [CI] 0.68-1.11) in UKB and the multivariable risk ratio (MVRR) was 0.97 (95% CI 0.51-1.85) in NHS and HPFS. In NHS and HPFS, the MVRR for the same comparison for retinol was 1.16 (95% CI 0.56-2.38). Nonsignificant associations were observed for α-tocopherol (MVRR = 0.61, 95% CI 0.29-1.32) and γ-tocopherol (MVRR  = 1.30, 95% CI 0.63-2.69) that became stronger in 4-year lagged analyses. Further investigation is warranted on a potential association between α- and γ-tocopherol and glioma risk.
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http://dx.doi.org/10.1038/s41598-021-88485-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084971PMC
April 2021

Serum tyrosine is associated with better cognition in Lewy body dementia.

Brain Res 2021 08 16;1765:147481. Epub 2021 Apr 16.

Department of Internal Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.

Amino acids' neuroactivity, and roles in excitotoxity and oxidative stress are linked to dementia. We aimed to investigate whether circulating amino acid concentrations were associated with cognitive decline in patients with mild Alzheimer's disease (AD) and Lewy body dementia (LBD). Baseline serum amino acid concentrations were measured in 89 patients with AD and 65 with LBD (13 with Parkinson's disease dementia and 52 with dementia with Lewy bodies). The Mini-Mental State Examination (MMSE) was administered at baseline and annually for five years. Associations between baseline amino acid concentrations and longitudinal MMSE score were assessed using a linear-mixed effects model stratified by diagnosis with adjustment for multiple comparisons. The results of the study indicated that serum tyrosine was positively associated with MMSE performance during the five-year follow-up period in patients with LBD (q-value = 0.012), but not AD. In conclusion, higher baseline serum concentrations of tyrosine, the precursor amino acid in dopamine and norepinephrine synthesis, was associated with better cognitive performance in patients with LBD, but not AD, throughout the 5-year follow-up period.
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http://dx.doi.org/10.1016/j.brainres.2021.147481DOI Listing
August 2021

A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Am J Clin Nutr 2021 07;114(1):338-347

Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.

Background: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health.

Objectives: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics.

Medthods: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP.

Results: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers.

Conclusions: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors.
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http://dx.doi.org/10.1093/ajcn/nqab045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246608PMC
July 2021

The Kynurenine Pathway Is Upregulated by Methyl-deficient Diet and Changes Are Averted by Probiotics.

Mol Nutr Food Res 2021 05 24;65(9):e2100078. Epub 2021 Mar 24.

Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, Building 57, Homburg/Saar, D-66421, Germany.

Scope: Probiotics exert immunomodulatory effects and may influence tryptophan metabolism in the host. Deficiency of nutrients related to C1 metabolism might stimulate inflammation by enhancing the kynurenine pathway. This study used Sprague Dawley rats to investigate whether a methyl-deficient diet (MDD) may influence tryptophan/kynurenine pathways and cytokines and whether probiotics can mitigate these effects.

Methods And Results: Rats are fed a control or MDD diet. Animals on the MDD diet received vehicle, probiotics (L. helveticus R0052 and B. longum R0175), choline, or probiotics + choline for 10 weeks (n = 10 per group). Concentrations of plasma kynurenine metabolites and the methylation and inflammatory markers in plasma and liver are measured.

Results: MDD animals (vs controls) show upregulation of plasma kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyxanthranilic acid, quinolinic acid, nicotinic acid, and nicotinamide (all p < 0.05). In the MDD rats, the probiotics (vs vehicle) cause lower anthranilic acid and a trend towards lower kynurenic acid and picolinic acid. Compared to probiotics alone, probiotics + choline is associated with a reduced enrichment of the bacterial strains in cecum. The interventions have no effect on inflammatory markers.

Conclusions: Probiotics counterbalance the effect of MDD diet and downregulate downstream metabolites of the kynurenine pathway.
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http://dx.doi.org/10.1002/mnfr.202100078DOI Listing
May 2021

Vegan Diet and Bone Health-Results from the Cross-Sectional RBVD Study.

Nutrients 2021 Feb 21;13(2). Epub 2021 Feb 21.

Department of Food Safety, German Federal Institute for Risk Assessment, 10589 Berlin, Germany.

Scientific evidence suggests that a vegan diet might be associated with impaired bone health. Therefore, a cross-sectional study ( = 36 vegans, = 36 omnivores) was used to investigate the associations of veganism with calcaneal quantitative ultrasound (QUS) measurements, along with the investigation of differences in the concentrations of nutrition- and bone-related biomarkers between vegans and omnivores. This study revealed lower levels in the QUS parameters in vegans compared to omnivores, e.g., broadband ultrasound attenuation (vegans: 111.8 ± 10.7 dB/MHz, omnivores: 118.0 ± 10.8 dB/MHz, = 0.02). Vegans had lower levels of vitamin A, B2, lysine, zinc, selenoprotein P, n-3 fatty acids, urinary iodine, and calcium levels, while the concentrations of vitamin K1, folate, and glutamine were higher in vegans compared to omnivores. Applying a reduced rank regression, 12 out of the 28 biomarkers were identified to contribute most to bone health, i.e., lysine, urinary iodine, thyroid-stimulating hormone, selenoprotein P, vitamin A, leucine, α-klotho, n-3 fatty acids, urinary calcium/magnesium, vitamin B6, and FGF23. All QUS parameters increased across the tertiles of the pattern score. The study provides evidence of lower bone health in vegans compared to omnivores, additionally revealing a combination of nutrition-related biomarkers, which may contribute to bone health. Further studies are needed to confirm these findings.
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http://dx.doi.org/10.3390/nu13020685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924854PMC
February 2021

Untargeted Metabolomics Reveals Major Differences in the Plasma Metabolome between Colorectal Cancer and Colorectal Adenomas.

Metabolites 2021 Feb 19;11(2). Epub 2021 Feb 19.

Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria.

Sporadic colorectal cancer is characterized by a multistep progression from normal epithelium to precancerous low-risk and high-risk adenomas to invasive cancer. Yet, the underlying molecular mechanisms of colorectal carcinogenesis are not completely understood. Within the "Metabolomic profiles throughout the continuum of colorectal cancer" (MetaboCCC) consortium we analyzed data generated by untargeted, mass spectrometry-based metabolomics using plasma from 88 colorectal cancer patients, 200 patients with high-risk adenomas and 200 patients with low-risk adenomas recruited within the "Colorectal Cancer Study of Austria" (CORSA). Univariate logistic regression models comparing colorectal cancer to adenomas resulted in 442 statistically significant molecular features. Metabolites discriminating colorectal cancer patients from those with adenomas in our dataset included acylcarnitines, caffeine, amino acids, glycerophospholipids, fatty acids, bilirubin, bile acids and bacterial metabolites of tryptophan. The data obtained discovers metabolite profiles reflecting metabolic differences between colorectal cancer and colorectal adenomas and delineates a potentially underlying biological interpretation.
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http://dx.doi.org/10.3390/metabo11020119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922413PMC
February 2021

Targeted Plasma Metabolic Profiles and Risk of Recurrence in Stage II and III Colorectal Cancer Patients: Results from an International Cohort Consortium.

Metabolites 2021 Feb 24;11(3). Epub 2021 Feb 24.

Huntsman Cancer Institute Salt Lake City, Salt Lake City, UT 84112, USA.

The identification of patients at high-risk for colorectal cancer (CRC) recurrence remains an unmet clinical need. The aim of this study was to investigate associations of metabolites with risk of recurrence in stage II/III CRC patients. A targeted metabolomics assay (128 metabolites measured) was performed on pre-surgery collected EDTA plasma samples from n = 440 newly diagnosed stage II/III CRC patients. Patients have been recruited from four prospective cohort studies as part of an international consortium: Metabolomic profiles throughout the continuum of CRC (MetaboCCC). Cox proportional hazard models were computed to investigate associations of metabolites with recurrence, adjusted for age, sex, tumor stage, tumor site, body mass index, and cohort; false discovery rate (FDR) was used to account for multiple testing. Sixty-nine patients (15%) had a recurrence after a median follow-up time of 20 months. We identified 13 metabolites that were nominally associated with a reduced risk of recurrence. None of the associations were statistically significant after controlling for multiple testing. Pathway topology analyses did not reveal statistically significant associations between recurrence and alterations in metabolic pathways (e.g., sphingolipid metabolism = 0.04; p = 1.00). To conclude, we did not observe statistically significant associations between metabolites and CRC recurrence using a well-established metabolomics assay. The observed results require follow-up in larger studies.
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http://dx.doi.org/10.3390/metabo11030129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996362PMC
February 2021

Effect of high intake of cod or salmon on serum total neopterin concentration: a randomised clinical trial.

Eur J Nutr 2021 Sep 12;60(6):3237-3248. Epub 2021 Feb 12.

Department of Clinical Medicine, University of Bergen, Haukeland University Hospital, 5021, Bergen, Norway.

Purpose: Primarily, to investigate the effect of high intake of cod (lean fish) or salmon (fatty fish) on serum concentration of total neopterin, a marker of cellular immune activation that is associated with cardiovascular disease. Second, to investigate effects of high cod/salmon intake on antioxidant vitamins and elements essential for activity of antioxidant enzymes.

Methods: In this randomised clinical trial, 63 participants with overweight/obesity consumed 750 g/week of either Atlantic cod (N = 22) or Atlantic salmon (N = 22) or were instructed to continue their normal eating habits but avoid fish intake (Control group, N = 19) for 8 weeks. Food intake was recorded, and fasting serum were collected at baseline and endpoint.

Results: Serum total neopterin concentration was reduced in the Cod group (median change - 2.65 (25th, 75th percentiles - 3.68, - 0.45) nmol/l, P = 0.018) but not in the Salmon group (median change 0.00 (25th, 75th percentiles - 4.15, 3.05) nmol/l, P = 0.59) when compared with the Control group after 8 weeks. The estimated daily intake of selenium, iron, magnesium and zinc were similar between all groups. Increased serum concentration of selenium was observed only after cod intake when compared to the Control group (P = 0.017). Changes in serum concentrations of copper, iron, magnesium, all-trans retinol, α-tocopherol and γ-tocopherol were similar between the groups.

Conclusion: A high intake of cod, but not of salmon, lowered serum total neopterin concentration when compared to the Control group.

Clinical Trial Registration: This trial was registered at clinicaltrials.gov as NCT02350595.
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http://dx.doi.org/10.1007/s00394-021-02497-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354862PMC
September 2021

Microheterogeneity and preanalytical stability of protein biomarkers of inflammation and renal function.

Talanta 2021 Feb 14;223(Pt 1):121774. Epub 2020 Oct 14.

Bevital AS, Jonas Lies veg 87, Laboratory building, 5021, Bergen, Norway.

Protein biomarker microheterogeneity has attracted increasing attention in epidemiological and clinical research studies. Knowledge concerning the preanalytical stability of proteins is paramount to assess the biological significance of their proteoforms. We investigated the stability of the inflammatory markers C-reactive protein (CRP), serum amyloid A (SAA), and calprotectin (S100A8/9), and the renal function marker, cystatin C (CnC). In total 16 proteoforms were quantified by immuno-MALDI-TOF MS in EDTA plasma and serum samples from 15 healthy volunteers. Prior to analysis blood samples were stored at either room temperature from 1 h up to 8 days, or underwent up to 9 consecutive freeze/thaw cycles. Pearson's correlation coefficient and t-test, intra-class correlation coefficient (ICC), and Autoregressive Integrated Moving-Average (ARIMA) models were used to investigate the stability of proteoform concentrations and distributions in blood. Plasma and serum concentrations of CRP and SAA proteoforms were highly stable during room temperature exposure and repeated freeze/thaw cycles, demonstrating excellent reproducibility (ICC > 0.75), no serial dependency in ARIMA models, and stable distribution of proteoforms. Stability analyses for proteoforms of S100A8/9 and CnC identified only minor preanalytical changes in concentrations and distributions, and none of the proteoforms were produced during prolonged exposure to room temperature or repeated freezing/thawing. The four proteins and their proteoforms are stable during sub-optimal sample handling, and represent robust biomarker candidates for future biobank studies aimed at investigating the microheterogeneity of SAA, S100A8/9, and CnC in relation to inflammation, renal dysfunction and various clinical outcomes.
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http://dx.doi.org/10.1016/j.talanta.2020.121774DOI Listing
February 2021

Effects of high intake of cod or salmon on gut microbiota profile, faecal output and serum concentrations of lipids and bile acids in overweight adults: a randomised clinical trial.

Eur J Nutr 2021 Jun 27;60(4):2231-2248. Epub 2020 Oct 27.

Dietary Protein Research Group, Department of Clinical Medicine, Haukeland University Hospital, University of Bergen, 5021, Bergen, Norway.

Purpose: To explore whether high intake of cod or salmon would affect gut microbiota profile, faecal output and serum concentrations of lipids and bile acids.

Methods: Seventy-six adults with overweight/obesity with no reported gastrointestinal disease were randomly assigned to consume 750 g/week of either cod or salmon, or to avoid fish intake (Control group) for 8 weeks. Fifteen participants from each group were randomly selected for 72 h faeces collection at baseline and end point for gut microbiota profile analyses using 54 bacterial DNA probes. Food intake was registered, and fasting serum and morning urine were collected at baseline and end point.

Results: Sixty-five participants were included in serum and urine analyses, and gut microbiota profile was analysed for 33 participants. Principal component analysis of gut microbiota showed an almost complete separation of the Salmon group from the Control group, with lower counts for bacteria in the Bacteroidetes phylum and the Clostridiales order of the Firmicutes phyla, and higher counts for bacteria in the Selenomonadales order of the Firmicutes phylum. The Cod group showed greater similarity to the Salmon group than to the Control group. Intake of fibres, proteins, fats and carbohydrates, faecal daily mass and output of fat, cholesterol and total bile acids, and serum concentrations of cholesterol, triacylglycerols, non-esterified fatty acids and total bile acids were not altered in the experimental groups.

Conclusion: A high intake of cod or salmon fillet modulated gut microbiota but did not affect faecal output or serum concentrations of lipids and total bile acids.

Clinical Trial Registration: This trial was registered at clinicaltrials.gov as NCT02350595.
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http://dx.doi.org/10.1007/s00394-020-02417-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137623PMC
June 2021

Acinar adipose tissue infiltration in salivary gland biopsy is associated with kynurenines-Interferon-γ pathway inflammation biomarkers.

Clin Exp Rheumatol 2020 Jul-Aug;38 Suppl 126(4):27-33. Epub 2020 Oct 22.

Hospital Universitário Cassiano Antônio de Moraes, Departamento de Clínica Médica, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Brazil.

Objectives: Assess if kynurenines metabolites are biomarkers of damage at labial salivary gland biopsy (LSGB).

Methods: This is a cross-sectional study including 99 patients with primary Sjögren's syndrome (AECG 2002 or ACR/EULAR 2017). Kynurenines were measured in plasma using liquid chromatography-tandem mass spectrometry.

Results: 95.9% were females, 51±12 years. Most had focal lymphocytic sialadenitis with focus score ≥1 (73.7%, n=73/99). The majority had mild to severe acinar atrophy (70.4%, n=57/81) and adipose infiltration (51.2%, n=39/80). Individuals with adipose infiltration were older (53.49±12.33 vs. 47.51±11.29 years, p=0.016), showed higher frequency of glandular dysfunction and higher kynurenines levels. Schirmer's test ≤ 5 mm/5min was found in 69.2% of individuals with adipose infiltration compared to 41% without (p=0.012) and unstimulated whole salivary flow (UWSF) was found in 87.2% compared to 70% without adipose infiltration (p=0.063). Additionally, individuals with adipose infiltration showed higher kynurenines metabolites compared with those without: quinolinic acid (503.35±193.30 vs. 427.35±285.76 nmol/L, p=0.029), kynurenine (1.99±0.6, 54 vs. 1.61±0.46 μmol/L, p=0.006), kynurenine/tryptophan ratio (KTR) (0.030±0.09 vs. 0.025±0.01, p=0.031) and anthranilic acid (03±4.96 vs. 16.46±5.24 nmol/L, p=0.022).

Conclusions: Kynurenines are biomarkers of greater adipose infiltration in LSGB and glandular dysfunction suggesting that activation of interferon-γ pathway is involved in the salivary and lacrimal glands damage.
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October 2020

Elevated plasma cotinine is associated with an increased risk of developing IBD, especially among users of combusted tobacco.

PLoS One 2020 2;15(7):e0235536. Epub 2020 Jul 2.

Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.

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 plasma cotinine and evaluated corresponding lifestyle questionnaires that included tobacco habits in subjects (n = 96) who later developed late-onset IBD (70 ulcerative colitis (UC) and 26 Crohn's disease (CD)) and in sex and age-matched controls (n = 191).

Results: Patients who later developed IBD had significantly higher plasma cotinine levels compared to controls. In multivariable analysis, higher log-cotinine was associated with a higher risk of developing IBD (OR 1.34 (95% CI 1.01-1.63)). After stratifying for time to diagnosis, the association was only significant in subjects with shorter time (< 5.1 years) to diagnosis (OR 1.45 (1.09-1.92)). The findings were similar for UC- and CD-cases, but did not reach statistical significance in CD-cases. Although plasma cotinine concentrations were higher in snuff users compared to combusted tobacco users, no increase in the risk of IBD and lower risk of developing IBD among subjects with shorter time (< 5.1 years) to diagnosis was seen among snuff users.

Conclusions: Cotinine, a biomarker of tobacco use, is associated with increased risk of developing late-onset IBD in general, and UC in particular. No increased risk among snuff users indicates that other components in combusted tobacco than nicotine may be involved in the pathogenesis of IBD among smokers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235536PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332008PMC
September 2020

Metabolomics profiling of visceral and abdominal subcutaneous adipose tissue in colorectal cancer patients: results from the ColoCare study.

Cancer Causes Control 2020 Aug 19;31(8):723-735. Epub 2020 May 19.

Huntsman Cancer Institute, Salt Lake City, UT, USA.

Purpose: Underlying mechanisms of the relationship between body fatness and colorectal cancer remain unclear. This study investigated associations of circulating metabolites with visceral (VFA), abdominal subcutaneous (SFA), and total fat area (TFA) in colorectal cancer patients.

Methods: Pre-surgery plasma samples from 212 patients (stage I-IV) from the ColoCare Study were used to perform targeted metabolomics. VFA, SFA, and TFA were quantified by computed tomography scans. Partial correlation and linear regression analyses of VFA, SFA, and TFA with metabolites were computed and corrected for multiple testing. Cox proportional hazards were used to assess 2-year survival.

Results: In patients with metastatic tumors, SFA and TFA were statistically significantly inversely associated with 16 glycerophospholipids (SFA: p range 0.017-0.049; TFA: p range 0.029-0.048), while VFA was not. Doubling of ten of the aforementioned glycerophospholipids was associated with increased risk of death in patients with metastatic tumors, but not in patients with non-metastatic tumors (p range: 0.00044-0.049). Doubling of PC ae C34:0 was associated with ninefold increased risk of death in metastatic tumors (Hazard Ratio [HR], 9.05; 95% confidence interval [CI] 2.17-37.80); an inverse association was observed in non-metastatic tumors (HR 0.17; 95% CI 0.04-0.87; p = 0.00044).

Conclusion: These data provide initial evidence that glycerophospholipids in metastatic colorectal cancer are uniquely associated with subcutaneous adiposity, and may impact overall survival.
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http://dx.doi.org/10.1007/s10552-020-01312-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425810PMC
August 2020

Effect of Cod Residual Protein Supplementation on Markers of Glucose Regulation in Lean Adults: A Randomized Double-Blind Study.

Nutrients 2020 May 16;12(5). Epub 2020 May 16.

Dietary Protein Research Group, Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway.

Large quantities of protein-rich cod residuals, which are currently discarded, could be utilized for human consumption. Although fish fillet intake is related to beneficial health effects, little is known about the potential health effects of consuming cod residual protein powder. Fifty lean adults were randomized to consume capsules with 8.1 g/day of cod residual protein (Cod-RP) or placebo capsules (Control group) for eight weeks, in this randomized, double-blind study. The intervention was completed by 40 participants. Fasting glucose and insulin concentrations were unaffected by Cod-RP supplementation, whereas plasma concentrations of α-hydroxybutyrate, β-hydroxybutyrate and acetoacetate all were decreased compared with the Control group. Trimethylamine N-oxide concentration in plasma and urine were increased in the Cod-RP group compared with the Control group. To conclude, the reduction in these potential early markers of impaired glucose metabolism following Cod-RP supplementation may indicate beneficial glucoregulatory effects of cod residual proteins. Trimethylamine N-oxide appears to be an appropriate biomarker of cod residual protein intake in lean adults.
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http://dx.doi.org/10.3390/nu12051445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285039PMC
May 2020

Relationship of Cerebrospinal Fluid Vitamin B12 Status Markers With Parkinson's Disease Progression.

Mov Disord 2020 08 14;35(8):1466-1471. Epub 2020 May 14.

Department of Pathology and Laboratory Medicine, UC Davis, Sacramento, California, USA.

Background: Using blood specimens from untreated early Parkinson's disease (PD) patients from the DATATOP trial, we found that subjects in the low serum vitamin B12 tertile experienced greater annualized change in ambulatory capacity score, whereas those with moderately elevated (>15 μmol/L) total homocysteine had greater annualized declines in the Mini-Mental State Exam.

Methods: In this this study we sought to determine whether levels of cerebrospinal fluid (CSF) B12 markers were also associated with progression of PD.

Results: The annualized change in the UPDRS "walking" item, a component of the ambulatory capacity score, was worse in the low B12 tertile. No association with change in the Mini-Mental State Exam was seen for those 7% with the highest baseline CSF total homocysteine.

Conclusions: In these untreated early-PD subjects, low CSF B12 predicted greater worsening of the UPDRS "walking" item, whereas CSF total homocysteine was not associated with progression of cognitive impairment. These findings extend and partially support our findings in serum. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496300PMC
August 2020

Circulating unmetabolized folic acid and 5-methyltetrahydrofolate and risk of breast cancer: a nested case-control study.

Eur J Clin Nutr 2020 09 21;74(9):1306-1315. Epub 2020 Apr 21.

Departments of Population Health and Environmental Medicine, New York University School of Medicine, 650 First Avenue, New York, NY, 10016, USA.

Background/objectives: Folates found in natural foods are thought to protect against cancer. However, folic acid (FA), a synthetic form of folate used in supplements and fortified foods, may increase breast cancer risk if present in unmetabolized form (UMFA) in the circulation. This study examined the associations of serum UMFA and 5-methyltetrahydrofolate (5-mTHF), the predominant form of circulating folate, with breast cancer risk.

Subjects/methods: We conducted a nested case-control study in a prospective cohort. In total, 553 cases of invasive breast cancer, diagnosed before mandatory FA fortification of grain in the US in 1998, were individually-matched to 1059 controls. Serum UMFA and 5-mTHF were measured using liquid chromatography-tandem mass spectrometry in stored serum samples, and 5-mTHF was corrected for storage degradation.

Results: Serum UMFA was not associated with breast cancer risk: the percentage of women with detectable levels of UMFA was similar in cases and controls (18% and 20%, respectively; p = 0.46). Two tag-SNPs in the promoter region of the FA-metabolizing gene were also not associated with risk. There was a marginally significant inverse association of 5-mTHF with breast cancer risk (odds ratio for the highest vs. lowest quintile = 0.69, 95% CI = 0.49 to 0.97; p = 0.08).

Conclusions: Circulating UMFA was not associated with breast cancer risk. These results apply to countries without mandatory FA food fortification. Studies are needed in countries with mandatory fortification, where levels of UMFA are much higher than in our study.
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http://dx.doi.org/10.1038/s41430-020-0615-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508257PMC
September 2020

Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers.

Mol Autism 2020 01 16;11(1). Epub 2020 Jan 16.

Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.

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 occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis.

Methods: Serum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation.

Results: We found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase: 1.70, 95% CI 1.22-2.37, FDR adjusted P = 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring.

Conclusions: Our findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.
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http://dx.doi.org/10.1186/s13229-020-0315-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964211PMC
January 2020

One-carbon metabolites, B vitamins and associations with systemic inflammation and angiogenesis biomarkers among colorectal cancer patients: results from the ColoCare Study.

Br J Nutr 2020 05 5;123(10):1187-1200. Epub 2020 Feb 5.

Division of Cancer Control and Population Sciences, Huntsman Cancer Institute, Salt Lake City, UT, USA.

B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5'-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r -0·33, Plinear < 0·0001), serum amyloid A (SAA) (r -0·23, Plinear = 0·003), IL-6 (r -0·39, Plinear < 0·0001), IL-8 (r -0·20, Plinear = 0·02) and TNFα (r -0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r -0·14), SAA (r -0·14) and TNFα (r -0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.
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http://dx.doi.org/10.1017/S0007114520000422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425811PMC
May 2020

Metabolic analysis of amino acids and vitamin B6 pathways in lymphoma survivors with cancer related chronic fatigue.

PLoS One 2020 10;15(1):e0227384. Epub 2020 Jan 10.

Department of Oncology, National Advisory Unit on Late Effects after Cancer Treatment, Oslo University Hospital, Oslo, Norway.

Chronic cancer-related fatigue (CF) is a common and distressing condition in a subset of cancer survivors and common also after successful treatment of malignant lymphoma. The etiology and pathogenesis of CF is unknown, and lack of biomarkers hampers development of diagnostic tests and successful therapy. Recent studies on the changes of amino acid levels and other metabolites in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have pointed to possible central defects in energy metabolism. Here we report a comprehensive analysis of serum concentrations of amino acids, including metabolites of tryptophan, the kynurenine pathway and vitamin B6 in a well characterized national Norwegian cohort of lymphoma survivors after high-dose therapy and autologous stem cell transplantation. Among the 20 standard amino acids in humans, only tryptophan levels were significantly lower in both males and females with CF compared to non-fatigued survivors, a strikingly different pattern than seen in CFS/ME. Markers of tryptophan degradation by the kynurenine pathway (kynurenine/tryptophan ratio) and activation of vitamin B6 catabolism (pyridoxic acid/(pyridoxal + pyridoxal 5'-phosphate), PAr index) differed in survivors with or without CF and correlated with known markers of immune activation and inflammation, such as neopterin, C-reactive protein and Interleukin-6. Among personal traits and clinical findings assessed simultaneously in participating survivors, higher neuroticism score, obesity and higher PAr index were significantly associated with increased risk of CF. Collectively, these data point to low grade immune activation and inflammation as a basis for CF in lymphoma survivors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227384PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953873PMC
April 2020

Plasma kynurenines and prognosis in patients with heart failure.

PLoS One 2020 10;15(1):e0227365. Epub 2020 Jan 10.

Department of Clinical Science, University of Bergen, Bergen, Norway.

Background: Metabolites of the kynurenine pathway (mKP) relate to important aspects of heart failure pathophysiology, such as inflammation, energy-homeostasis, apoptosis, and oxidative stress. We aimed to investigate whether mKP predict mortality in patients with heart failure.

Methods: The study included 202 patients with heart failure (73.8% with coronary artery disease (CAD)), propensity score matched to 384 controls without heart disease, and 807 controls with CAD (71%). All underwent coronary angiography and ventriculography at baseline. Plasma mKP, pyridoxal 5'phosphate (PLP) and CRP were measured at baseline. Case-control differences were assessed by logistic regression and survival by Cox regression, adjusted for age, gender, smoking, diabetes, ejection fraction, PLP, eGFR and CRP. Effect measures are reported per standard deviation increments.

Results: Higher plasma levels of kynurenine, 3- hydroxykynurenine (HK), quinolinic acid (QA), the kynurenine-tryptophan-ratio (KTR) and the ratio of HK to xanthurenic acid (HK/XA) were detected in heart failure compared to both control groups. The mortality rate per 1000 person-years was 55.5 in patients with heart failure, 14.6 in controls without heart disease and 22.2 in CAD controls. QA [HR 1.80, p = 0.013], HK [HR 1.77, p = 0.005], HK/XA [HR 1.67, p < 0.001] and KTR [HR 1.55, p = 0.009] were associated with increased mortality in patients with heart failure, while XA [HR 0.68-0.80, p = 0.013-0.037] were associated with lower mortality in all groups. HK and HK/XA had weak associations with increased mortality in CAD-controls.

Conclusion: Elevated plasma levels of mKP and metabolite ratios are associated with increased mortality, independent of CAD, in patients with heart failure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227365PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953806PMC
April 2020

Short-term treatment with a peroxisome proliferator-activated receptor α agonist influences plasma one-carbon metabolites and B-vitamin status in rats.

PLoS One 2019 5;14(12):e0226069. Epub 2019 Dec 5.

Department of Clinical Science, University of Bergen, Bergen, Norway.

Introduction: Peroxisome proliferator-activated receptors (PPARs) have been suggested to be involved in the regulation of one-carbon metabolism. Previously we have reported effects on plasma concentrations of metabolites along these pathways as well as markers of B-vitamin status in rats following treatment with a pan-PPAR agonist. Here we aimed to investigate the effect on these metabolites after specific activation of the PPARα and PPARγ subtypes.

Methods: For a period of 12 days, Male Wistar rats (n = 20) were randomly allocated to receive treatment with the PPARα agonist WY-14.643 (n = 6), the PPARγ agonist rosiglitazone (n = 6) or placebo (n = 8). The animals were sacrificed under fasting conditions, and plasma concentration of metabolites were determined. Group differences were assessed by one-way ANOVA, and planned comparisons were performed for both active treatment groups towards the control group.

Results: Treatment with a PPARα agonist was associated with increased plasma concentrations of most biomarkers, with the most pronounced differences observed for betaine, dimethylglycine, glycine, nicotinamide, methylnicotinamide, pyridoxal and methylmalonic acid. Lower levels were observed for flavin mononucleotide. Fewer associations were observed after treatment with a PPARγ agonist, and the most notable was increased plasma serine.

Conclusion: Treatment with a PPARα agonist influenced plasma concentration of one-carbon metabolites and markers of B-vitamin status. This confirms previous findings, suggesting specific involvement of PPARα in the regulation of these metabolic pathways as well as the status of closely related B-vitamins.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226069PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894826PMC
March 2020

The Associations Between Cognitive Prognosis and Kynurenines Are Modified by the Apolipoprotein ε4 Allele Variant in Patients With Dementia.

Int J Tryptophan Res 2019 15;12:1178646919885637. Epub 2019 Nov 15.

Department of Clinical Science, University of Bergen, Bergen, Norway.

Background: The apolipoprotein E ε4 gene variant (APOEε4) confers considerable risk for dementia and affects neuroinflammation, brain metabolism, and synaptic function. The kynurenine pathway (KP) gives rise to neuroactive metabolites, which have inflammatory, redox, and excitotoxic effects in the brain.

Aim: To assess whether the presence of at least one APOEε4 allele modifies the association between kynurenines and the cognitive prognosis.

Methods: A total of 152 patients with sera for metabolite measurements and APOE genotype were included from the Dementia of Western Norway. The participants had mild Alzheimer disease and Lewy body dementia. Apolipoprotein E ε4 gene variant allele status was classified as one or more ε4 versus any other. Mini-Mental State Examination (MMSE) was measured at baseline and for 5 consecutive years. Mann-Whitney tests and linear mixed-effects models were used for statistical analysis.

Results: There were no significant differences in serum concentrations of tryptophan and kynurenine according to the presence or absence of APOEε4. High serum concentrations of kynurenic acid, quinolinic acid, and picolinic acid, and a higher kynurenine-to-tryptophan ratio, were all associated with more cognitive decline in patients without APOEε4 compared to those with the APOEε4 allele (-value of the interactions < .05).

Conclusions: Kynurenic acid, quinolinic acid, picolinic acid, and the kynurenine-to-tryptophan ratio were associated with a significant increase in cognitive decline when the APOEε4 variant was absent, whereas there was a relatively less decline when the APOEε4 variant was present.
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http://dx.doi.org/10.1177/1178646919885637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859685PMC
November 2019

Five salmon dinners per week were not sufficient to prevent the reduction in serum vitamin D in autumn at 60° north latitude: a randomised trial.

Br J Nutr 2020 02 25;123(4):419-427. Epub 2019 Nov 25.

Dietary Protein Research Group, Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway.

Low serum concentrations of several vitamins have been linked to increased risk of diseases including insulin resistance and type 2 diabetes (T2D). Fish is a good source of several vitamins, and the prevalence of T2D is low in populations with high fish intake. The aim of the present study was to investigate the effects of high fish intake on vitamins in serum from adults in autumn in South-Western Norway at 60° north latitude. In this randomised clinical trial, sixty-three healthy participants with overweight/obesity consumed 750 g/week of either cod (n 22) or salmon (n 22) as five weekly dinners or were instructed to continue their normal eating habits but avoid fish intake (Control group, n 19) for 8 weeks. The estimated vitamin D intake was significantly increased in the Salmon group when compared with the Cod group (P = 6·3 × 10-4) and with the Control group (P = 3·5 × 10-6), with no differences between groups for estimated intake of vitamins A, B1, B2, B3, B6, B9, C and E. Serum 25-hydroxyvitamin D3 concentration was decreased in all groups after 8 weeks; however, the reduction in the Salmon group was significantly smaller compared with the Cod group (P = 0·013) and the Control group (P = 0·0060). Cod and salmon intake did not affect serum concentrations of the other measured vitamins. The findings suggest that 750 g/week of salmon was not sufficient to prevent a decrease in serum 25-hydroxyvitamin D3 in autumn in South-Western Norway in adults with overweight/obesity.
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http://dx.doi.org/10.1017/S0007114519002964DOI Listing
February 2020

Plasma Cotinine Cutoff for Distinguishing Smokers From Nonsmokers Among Persons Living With HIV.

J Acquir Immune Defic Syndr 2019 12;82(5):e54-e56

Viro-immunology Research Unit, Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Copenhagen.

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http://dx.doi.org/10.1097/QAI.0000000000002189DOI Listing
December 2019

Dietary choline is related to increased risk of acute myocardial infarction in patients with stable angina pectoris.

Biochimie 2020 Jun 7;173:68-75. Epub 2019 Nov 7.

Centre for Nutrition, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.

High plasma choline has been associated with the metabolic syndrome and risk of chronic diseases, including cardiovascular disease. However, dietary choline is not correlated with choline plasma concentrations, and there are few studies and contradictory evidence regarding dietary choline and cardiovascular events. In addition, a recommended dietary allowance for choline has not been established and remains a point of contention. This study assessed the association between dietary choline, including choline forms, and risk of incident acute myocardial infarction (AMI) in patients with suspected stable angina pectoris (SAP). In total 1981 patients (80% men, median age 62) from the Western Norway B Vitamin Intervention Trial were included in this analysis. Information on dietary choline was obtained using a 169-item food frequency questionnaire. The Cardiovascular Disease in Norway project provided data on AMI. Risk associations were estimated using Cox-regression analysis using energy-adjusted choline intake. Median (25th, 75th percentile) total energy-adjusted choline intake was 288 (255, 326) mg/d. During a median (25th, 75th percentile) follow-up of 7.5 (6.3, 8.8) years, 312 (15.7%) patients experienced at least one AMI. Increased intakes of energy-adjusted choline (HR [95% CI] per 50 mg increase 1.11 [1.03, 1.20]), phosphatidylcholine (HR per 50 mg increase 1.24 [1.08, 1.42]) and sphingomyelin (HR per 5 mg increase 1.16 [1.02, 1.31]) were associated with higher AMI risk. In conclusion, higher dietary intakes of total choline, phosphatidylcholine and sphingomyelin were associated with increased risk of AMI in patients with SAP. Future studies are necessary to explore underlying mechanisms for this observation.
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http://dx.doi.org/10.1016/j.biochi.2019.11.001DOI Listing
June 2020

Encephalitis and aseptic meningitis: short-term and long-term outcome, quality of life and neuropsychological functioning.

Sci Rep 2019 11 6;9(1):16158. Epub 2019 Nov 6.

Department of Physical Medicine and Rehabilitation, Oslo University Hospital Ullevål, Oslo, Norway.

For those surviving encephalitis, the influence on daily life of patients and their relatives may be substantial. In contrast, the prognosis after aseptic meningitis (ASM) is considered good. In this prospective study in patients with encephalitis (n = 20) and ASM (n = 46), we show that both groups experienced reduced Health Related Quality of Life (HRQoL) at two months after discharge, and that workability was reduced in 37% of the patients with ASM. However, 12 months after discharge no neuropsychological deficits were detected in the ASM group, whereas patients with encephalitis had lower scores on tests of fine motor and psychomotor skills as well as on learning and memory. We also found that for patients with encephalitis, neopterin, as a marker of Th1 cell induced macrophage activation, and a putatively neurotoxic ratio of the kynurenine pathway (KP) measured during the acute phase was associated with lower HRQoL. Our data show that not only encephalitis, but also ASM has substantial short-term influence on HRQoL and workability. For patients with encephalitis we suggest a link between immune activation and activation of the KP during the acute phase with impaired HRQoL.
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http://dx.doi.org/10.1038/s41598-019-52570-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834582PMC
November 2019
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