Ottar K Nygård

• Medical Doctor at Haukeland University Hospital

Background/Aim Trimethyllysine (TML) is a methylated amino acid, which is linked to epigenetic regulation and can serve as a precursor of trimethylamine-N-oxide (TMAO). TMAO is a microbiota-derived metabolite and a potential risk factor of cardiovascular disease. TML has recently been linked to atherosclerosis, acute myocardial infarction and preva...

Background Malnutrition or risk of malnutrition is present in about one‐third of patients admitted to Western hospitals and is identified by either screening for malnutrition or further nutrition assessment. To date, there are no commonly accepted biomarkers of malnutrition, which could expedite screening efforts, ease diagnosis, and hasten treatme...

Introduction: As substrates for nitric oxide, arginine (Arg) and its metabolites are involved in the regulation of vascular function. Ischemia caused by vascular dysfunction is common in patients with non-obstructive coronary artery disease (NOCAD) and may indicate a subgroup at increased risk of cardiovascular disease (CVD) mortality. Research que...

To improve the interpretation and utilisation of blood lipids, ketones and acylcarnitine concentrations as biomarkers in clinical assessments, more information is needed on their dynamic alterations in response to dietary intake and fasting. The aim of this intervention study was to characterise the changes in serum lipid, ketone and acylcarnitine...

Detailed knowledge regarding the associations between intake of different types of seafood and meat and the risk of type 2 diabetes (T2D), and insight into possible mechanisms are warranted. In this study we aimed to evaluate the associations between intake of different types of seafood and meat and the subsequent risk of T2D using the Norwegian Mo...

Background Risk of malnutrition and malnutrition have been previously associated with increased risk of mortality. It remains unclear, however, whether the severity of malnutrition differentiates in association with all‐cause mortality. The aim was to assess the association between being at risk of malnutrition or being diagnosed with malnutrition...

Elevated plasma concentrations of several one-carbon metabolites are associated with increased CVD risk. Both diet-induced regulation and dietary content of one-carbon metabolites can influence circulating concentrations of these markers. We cross-sectionally analyzed 1928 patients with suspected stable angina pectoris (geometric mean age 61), repr...

Metabolomics has been utilized in epidemiological studies to investigate biomarkers of nutritional status and metabolism in relation to non-communicable diseases. However, little is known about the effect of prandial status on several biomarker concentrations. Therefore, the aim of this intervention study was to investigate the effect of a standard...

Purpose Dietary intake may have pronounced effects on circulating biomarker concentrations. Therefore, the aim was to provide a descriptive overview of serum metabolite concentrations in relation to time since last meal, focusing on amino acids, lipids, one-carbon metabolites, and biomarkers of vitamin status. Methods We used baseline data from th...

Nutritional risk screening, to identify patients at risk of malnutrition, is the first step in the prevention and treatment of malnutrition in hospitalized patients, and should be followed by a thorough nutritional assessment resulting in a diagnosis of malnutrition and subsequent treatment. In 2019, a consensus on criteria has been suggested for t...

The kynurenine pathway is implicated in aging, longevity, and immune regulation, but longitudinal studies and assessment of the cerebrospinal fluid (CSF) are lacking. We investigated tryptophan (Trp) and downstream kynurenine metabolites and their associations with age and change over time in four cohorts using comprehensive, targeted metabolomics....

Background: Trimethylamine N-oxide (TMAO) is an amine oxide generated by gut microbial metabolism. TMAO may contribute to atherothrombosis and systemic inflammation. However, the prognostic value of circulating TMAO for risk stratification is uncertain. Methods: We assessed prospective relationships of plasma TMAO with long-term risk of all-caus...

Protein biomarkers and microheterogeneity have attracted increasing attention in epidemiological and clinical research. Knowledge of within-person reproducibility over time is paramount to determine whether a single measurement accurately reflects an individual’s long-term exposure. Yet, research investigating within-person reproducibility for prot...

[This corrects the article DOI: 10.1016/j.ijcrp.2021.200109.].

Background: Choline is an essential nutrient for humans and is involved in various physiological functions. Through its metabolite betaine, it is closely connected to the one-carbon metabolism and the fat-soluble choline form phosphatidylcholine is essential for very-low-density-lipoprotein synthesis and secretion in the liver connecting choline t...

Background: Choline is an essential nutrient for humans and is involved in various physiological functions. Through its metabolite betaine, it is closely connected to the one-carbon metabolism and the fat-soluble choline form phosphatidylcholine is essential for very-low-density-lipoprotein synthesis and secretion in the liver connecting choline to...

Background Higher systemic concentrations of cardiac troponins and biomarkers of inflammation and endothelial dysfunction as well as obesity are associated with increased risk of cardiovascular disease (CVD) and may share pathophysiological pathways. We sought to explore the association between serum high sensitive cardiac troponin T (hs-cTnT) and...

Aims Trimethyllysine (TML) is involved in carnitine synthesis, serves as a precursor of trimethylamine N-oxide (TMAO) and is associated with cardiovascular events in patients with established coronary heart disease (CHD). We prospectively examined circulating TML as a predictor of all-cause and cardiovascular mortality in community-dwelling adults...

Background Low-carbohydrate diets are suggested to exert metabolic benefits by reducing circulating triacylglycerol (TG) concentrations, possibly by enhancing mitochondrial activity. Objective We aimed to elucidate mechanisms by which dietary carbohydrate and fat differentially affect hepatic and circulating TG, and how these mechanisms relate to...

Background: Choline is an essential nutrient involved in a wide range of physiological functions. It occurs in water- and lipid-soluble forms in the body and diet. Foods with a known high choline content are eggs, beef, chicken, milk, fish, and selected plant foods. An adequate intake has been set in the US and Europe, however, not yet in the Nordi...

Background: Red and processed meat intake have been associated with increased risk of morbidity and mortality, and a restricted intake is encouraged in patients with cardiovascular disease. However, evidence on the association between total meat intake and clinical outcomes in this patient group is lacking. Objectives: To investigate the associatio...

Objective Discovery of specific markers that reflect altered hepatic fatty acid oxidation could help to detect an individual's risk of fatty liver, type 2 diabetes and cardiovascular disease at an early stage. Lipid and protein metabolism are intimately linked, but our understanding of this crosstalk remains limited. Methods In male Wistar rats, w...

Elucidation of mechanisms that govern lipid storage, oxidative stress and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter 1 (ASC-1), shows st...

Purpose We hypothesized that biomarkers and dietary factors related to cardiovascular disease risk were associated with serum retinol and evaluated these potential associations in patients with suspected coronary artery disease (CAD). Methods We used cross-sectional data from 4116 patients hospitalised for suspected CAD. Dietary data were obtained...

Plasma concentrations of trimethylamine N-oxide (TMAO) have been linked to cardiovascular disease (CVD) risk and mortality. TMAO is formed through the bacterial conversion of trimethylamine which is obtained either directly from food, generated from dietary precursors (e.g. choline) or derived from endogenous trimethyllysine (TML) production. In a...

Introduction Peroxisome Proliferator-Activated Receptor α (PPARα) is a known regulator of lipid and energy metabolism. In animal experiments of PPARα activation, we have reported on altered plasma concentration of metabolites related to one-carbon metabolism and B-vitamin status. Several of these metabolites, e.g. homocysteine and dimethylglycine,...

Background: Non-alcoholic fatty liver disease is often associated with obesity, insulin resistance, dyslipidemia, and the metabolic syndrome in addition to mitochondrial dysfunction and nicotinamide adenine dinucleotide (NAD+) deficiency. The aim of this study was to investigate how inhibition of mitochondrial fatty acid oxidation using the compou...

Objectives Oxidised cholesterol metabolites are linked to increased production of the active vitamin A (Vit-A) form and monocyte/macrophage activation, which may be reflected by neopterin, a marker of both interferon-γ–mediated immune activation and coronary artery disease risk. We examined the influence of serum lipid parameters and Vit-A on the r...

Background/aim Plasma total homocysteine (tHcy) is elevated in patients with persistent vs. paroxysmal atrial fibrillation (AF), and has been related to increased risk of new-onset AF. Homocysteine is degraded to cystathionine (Cysta) and cysteine (Cys). All three metabolites have been linked to potential proarrhythmic traits such as inflammation a...

Objective The role of vitamin K in the regulation of vascular calcification is established. However, the association of dietary vitamins K1 and K2 with risk of coronary heart disease (CHD) is inconclusive. Design Prospective cohort study. Setting We followed participants in the community-based Hordaland Health Study from 1997 - 1999 through 2009...

Background The carnitine precursor trimethyllysine (TML) is associated with progression of atherosclerosis, possibly through a relationship with trimethylamine‐N‐oxide (TMAO). Riboflavin is a cofactor in TMAO synthesis. We examined prospective relationships of circulating TML and TMAO with acute myocardial infarction (AMI) and potential effect modi...

Higher concentrations of cardiac troponin T are associated with coronary artery disease (CAD) and adverse cardiovascular prognosis. The relation with incident atrial fibrillation (AF) is less explored. We studied this association among 3568 patients evaluated with coronary angiography for stable angina pectoris without previous history of AF. The p...

[This corrects the article DOI: 10.1371/journal.pone.0227365.].

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...

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...

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 lea...

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 dietar...

Background Metabolites involved in one-carbon metabolism (OCM) may predict cognitive prognosis in dementia. The link between OCM, apolipoprotein E (APOE), and DNA methylation creates a biologically plausible mechanism of interaction. Aim To assess OCM metabolites as predictors of 5-year cognitive prognosis in patients with mild dementia, and in su...

Background The ESC 0/3-h and High-STEACS study algorithms using high-sensitive troponin assays have proven effective in ruling out NSTEMI, but the safety of out-of-hospital follow-up of ruled out patients is disputable. Clinical risk scores may help to identify patients who develop major adverse cardiac events (MACE) defined as NSTEMI, death or cor...

Dysregulation of the tryptophan (Trp)-NAD+ pathway has been related to several pathological conditions, and the metabolites in this pathway are known to influence mitochondrial respiration and redox status. The aim of this project was to investigate if stimulation of beta-oxidation and mitochondrial proliferation by the mitochondrial-targeted compo...

Background: Vitamin B-6 status is routinely measured as pyridoxal 5'-phosphate (PLP) in plasma. Low concentrations of PLP are associated with rheumatic, cardiovascular, and neoplastic diseases. We have previously shown that vitamin B-6 status affects the kynurenine (Kyn) pathway of tryptophan (Trp) catabolism. Objective: This study aimed to comp...

A fatty acid analogue, 2-(tridec-12-yn-1-ylthio)acetic acid (1-triple TTA), was previously shown to have hypolipidemic effects in rats by targeting mitochondrial activity predominantly in liver. This study aimed to determine if 1-triple TTA could influence carbohydrate metabolism. Male Wistar rats were treated for three weeks with oral supplementat...

Objectives: The main aim of the Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain (WESTCOR-study) (Clinical Trials number NCT02620202) is to improve diagnostic pathways for patients presenting to the Emergency department (ED) with acute chest pain. Design: The WESTCOR-study is a two center, cr...

Aims: Distinct ceramide lipids have been shown to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular death. As phospholipids have also been linked with CVD risk, we investigated whether the combination of ceramides with phosphatidylcholines (PCs) would be synergistic in the prediction of CVD events in patients with...

Dietary fatty acids (FAs) affect certain metabolic routes, including pathways controlled by the peroxisome proliferator-activated receptors (PPARs), but tissue-specific effects are not well-defined. Thus, the aim was to compare the metabolic response in hepatic, adipose, and cardiac tissues after treatment with specific PPAR agonists. Male Wistar r...

PurposeFish is a source of various nutrients beneficial for bone health, but few studies have investigated the association between bone mineral density (BMD) and fish consumption. Thus, the aim was to investigate the relationship between total fish intake and BMD and between both lean and fatty fish intake and BMD. Method These cross-sectional anal...

Background: Elevated circulating cystathionine levels are related to atherosclerotic cardiovascular disease, a leading cause of death globally. Objective: We investigated whether plasma cystathionine was associated with mortality in patients with suspected or established coronary heart disease (CHD). Methods: Data from 2 independent cohorts of...

Background and aim: Hypertensive pregnancy disorders are associated with subsequent cardiovascular disease (CVD), but the extent to which this association is explained by shared risk factors is unknown. We aimed to evaluate whether hypertensive pregnancy disorder in first pregnancy is associated with increased subsequent risk of maternal CVD after...

Background Replacing dietary saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFA) reduces the plasma low-density lipoprotein (LDL) cholesterol and subsequently the risk of cardiovascular disease. However, beyond changes in LDL cholesterol, we lack a complete understanding of the physiologic alterations that occur when improving diet...

OBJECTIVE Altered plasma amino acid levels have been implicated as markers of risk for incident type 2 diabetes; however, amino acids are also related to established diabetes risk factors. Therefore, potential confounding for and the impact from competing risks require evaluation. RESEARCH DESIGN AND METHODS We prospectively followed 2,519 individ...

Background Age-related loss of muscle mass and function is common in older adults, and studies investigating if dietary proteins may protect and possibly build lean body mass are needed. We assessed the feasibility of conducting a nutritional intervention study in older nursing home residents to investigate the effects of fish protein supplementati...

Figure S1. A surface plot depicting increase in risk of AMI by quintiles of log‐transformed Hcy‐thiolactone/creatinine and pyridoxic acid. The prevalence of AMI events in patients without vitamin B6 supplementation was analyzed (n = 1411). Figure S2. Kaplan‐Meier analysis of AMI events according to tertiles of Hcy‐thiolactone/creatinine ratios.

Introduction: Tryptophan, its downstream metabolites in the kynurenine pathway and neopterin have been associated with inflammation and dementia. We aimed to study the associations between plasma levels of these metabolites and cognitive function in community-dwelling, older adults. Methods: This cross-sectional study included 2174 participants...

Plasma concentrations of metabolites along the choline oxidation and tryptophan degradation pathways have been linked to lifestyle diseases and dietary habits. This study aimed to investigate how krill oil, a source of ω-3 polyunsaturated fatty acids (PUFAs) with a high phosphatidylcholine content, affected these parameters. The pilot study was con...

Background: Plasma trimethylamine-N-oxide (TMAO) is associated with cardiovascular disease; however specific relationships with cardiac arrhythmias are unknown. We evaluated the association between plasma TMAO and incident atrial fibrillation (AF). Methods: Risk associations were explored among 3797 patients with suspected stable angina in the W...

Objectives No individual homocysteine (Hcy) metabolite has been studied as a risk marker for coronary artery disease (CAD). Our objective was to examine Hcy‐thiolactone, a chemically reactive metabolite generated by methionyl‐tRNA synthetase and cleared by the kidney, as a risk predictor of incident acute myocardial infarction (AMI) in the Western...

Background Cystathionine is an intermediate product in the transsulfuration pathway and formed during the B6‐dependent conversion of methionine to cysteine. Elevated plasma cystathionine has been related to atherosclerosis, which is a major etiological factor for ischemic stroke. However, the role of cystathionine in stroke development is unknown....

Background The Healthy Nordic Food Index (HNFI) has been associated with beneficial effects on markers of cardiovascular disease (CVD). Whether such effects are present among patients with established coronary heart disease is unknown. In the present study, we investigated the association between adherence to the HNFI and the risk of acute myocardi...

Background Plasma total homocysteine (tHcy) has been implicated in the development of cardiovascular disease, but the mechanisms remain unclear. Vitamin A (Vit-A) is involved in homocysteine metabolism and we therefore explored the potential interaction between plasma tHcy and serum Vit-A in relation to incident acute myocardial infarction. Method...

In patients with stable angina, the association between high-sensitivity cardiac troponin T (hs-cTnT) and incident acute myocardial infarction (AMI), as well as pathophysiologic mechanisms accounting for an adverse prognosis, remain to be determined. We explored the association between hs-cTnT and future AMI among 3,882 patients evaluated for suspe...

Aims/hypothesis: Ceramide lipids have a role in the development of insulin resistance, diabetes and risk of cardiovascular disease. Here we investigated four ceramides and their ratios to find the best predictors of incident diabetes. Methods: A validated mass-spectrometric method was applied to measure Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:...

Genetic or nutritional deficiencies in 1 carbon and homocysteine (Hcy) metabolism elevate Hcy-thiolactone levels and are associated with cardiovascular and neurologic diseases. Hcy-thiolactone causes protein damage, cellular toxicity, and proatherogenic changes in gene expression in human cells and tissues. A polymorphic cardio-protective enzyme, p...

Background: Coffee is a widely consumed beverage, and studies suggest that drinking coffee has beneficial health effects. The phytohormone trigonelline is present in large amounts in coffee beans, and circulating concentrations of trigonelline have been shown to be positively related to dietary intake of coffee and to increase significantly after...

Table S1. HRs and 95% CIs Using Time‐Dependent Covariates for Associations Between GH in at Least 1 Pregnancy During 1980–2009 and Risk of CVD Among 577 185 Women

Background: Preeclampsia and gestational hypertension (GH) are the most common hypertensive pregnancy disorders. Preeclampsia has been linked to increased risk of cardiovascular disease (CVD), but a similar association for GH has not been established. We aimed to determine the association between GH and subsequent CVD, and explore the additional r...

Background: Although choline metabolism has been associated with atherosclerotic heart disease, less research attention has been paid to the associations of choline and its oxidative metabolite betaine with cardiac arrhythmias. Methods and results: We evaluated associations of plasma concentrations and dietary intakes of choline and betaine with...

Background Cystathionine is a thio-ether and a metabolite formed from homocysteine during transsulfuration. Elevated plasma cystathionine levels are reported in patients with cardiovascular disease; however prospective relationships with acute myocardial infarction (AMI) are unknown. We investigated associations between plasma cystathionine and AMI...

Background Link between inflammation and atrial fibrillation (AF) has been increasingly recognized. Neopterin, a biomarker of cellular immune activation, may be associated with incident AF. Objective To investigate the association between plasma neopterin levels and risk of an inpatient hospital diagnosis of AF, and to evaluate a joint association...

Background and aims: Methionine (Met) is an essential amino acid involved in methylation reactions and lipid metabolism. A Met-deficient diet may cause hepatic lipid accumulation, which is considered an independent risk factor for atherosclerosis. However, the prospective relationship between circulating Met and incident acute myocardial infarctio...

Systemic fibrinogen and neopterin are related to inflammation. We investigated the prognostic utility and possible interactions of these biomarkers in stable coronary artery disease (SCAD) patients undergoing coronary angiography. We included 3,545 patients with suspected stable angina with a median follow-up of 7.3 and 10.2 years for incident acut...

Objective Obesity is associated with increased inflammation and insulin resistance. In conditions with chronic immune activation, low plasma vitamin B6-levels are described, as well as an increased kynurenine:tryptophan-ratio (KTR). We investigated circulating tryptophan, kynurenine and its metabolites, neopterin, B-vitamins, CRP, and HbA1c in indi...

Background Vitamin B-6 homeostasis is altered during inflammation and immune activation. It is unknown whether altered vitamin B-6 homeostasis is associated with the risk of stroke. Objective We investigated the relation between the ratio plasma 4-pyridoxic acid: (pyridoxal + pyridoxal-5′-phosphate) (PAr) as an indicator of altered vitamin B-6 hom...

Context and objective Vitamin D status may affect cardiovascular disease (CVD) development and survival. We studied the relationship between concentrations of the circulating biomarker 25-hydroxyvitamin D (25OHD) and all-cause and cardiovascular mortality risk. Design, Setting, Participants and main Outcome Measures 25OHD, the sum of 25-hydroxyvit...

Context Carnitine and its metabolites are centrally involved in fatty acid metabolism. While elevated circulating concentrations have been observed in obesity and insulin resistance, prospective studies examining whether these metabolites are associated with incident type 2 diabetes mellitus (T2D) are sparse. Objective We performed a comprehensive...