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• Bodal, Elen; Olsen, Nora Marie Temte; Olsen, Thomas; Edvardsen, Hilde Marie Erøy; Clausen, Thomas & Skurtveit, Svetlana Ondrasova [Show all 8 contributors for this article] (2026). Medical and non-medical gabapentinoid use in fatal drug poisonings in Norway: Linked postmortem toxicology and prescription data. Forensic Science International. ISSN 0379-0738. 389, p. 1–8. doi: 10.1016/j.forsciint.2026.113143. Full text in Research Archive
• Olsen, Thomas; Elshorbagy, Amany; Tore, Elena C.; Bastani, Nasser Ezzatkhah; Stolt, Emma Theresia Kjelland & Blokland, Gabriëlla A.M. [Show all 16 contributors for this article] (2026). Higher plasma serine levels are associated with favorable values of metabolic health markers among middle-aged and older adults in The Maastricht Study. GeroScience. ISSN 2509-2715. doi: 10.1007/s11357-026-02237-4. Full text in Research Archive Show summary

  Laboratory studies indicate a mechanistic role for serine in the metabolic benefits induced by dietary restriction of methionine and cysteine. To investigate the association of plasma serine with metabolic health markers in humans, we conducted a cross-sectional analysis of a subset of data from The Maastricht Study (n = 1199). Linear regression analyses (adjusted for confounding variables) were conducted to investigate whether plasma serine is associated with markers of lipid metabolism, glucose homeostasis, and body composition. Interaction analyses were conducted to investigate whether sex, diabetes status, and plasma total cysteine modify the association of serine with metabolic markers. Correlations between dietary intake of sulfur amino acids and plasma amino acids, including methionine and total cysteine, were also investigated. Elevated plasma serine was associated with favorable changes in markers of lipid metabolism (triglycerides, total cholesterol, and indices of multiple fatty acid desaturases), glucose homeostasis (insulin resistance and glucose tolerance), fat utilization (β-hydroxybutyrate, acetoacetate, and acetone), and body composition (visceral and subcutaneous adipose depots, liver fat, and body mass index). Some associations were stronger in males than in females and in individuals with prediabetes and diabetes than in those without diabetes. Associations of plasma serine with body mass index, total fat mass, total lean mass, and subcutaneous adipose tissue weakened as plasma cysteine increased. Combined methionine and cysteine intake was inversely associated with plasma serine. Findings suggest that plasma serine is strongly associated with improved metabolic health in humans. Additional studies are required to confirm whether the associations are causal.

• Eklo, Rakel R.; Alavi, Dena Treider; Konglevoll, Dina Moxness; Kolle, Åshild; Henriksen, Hege Berg & Rising, Russell [Show all 8 contributors for this article] (2026). Predictive equations commonly used in clinics underestimate resting energy expenditure compared with whole-room indirect calorimetry in colorectal cancer survivors. American Journal of Clinical Nutrition. ISSN 0002-9165. doi: 10.1016/j.ajcnut.2026.101209. Full text in Research Archive Show summary

  Background: Accurate methods for estimating resting energy expenditure (REE) are important to ensure adequate nutritional treatment in colorectal cancer (CRC) survivors. Objective: To determine the agreement between REE estimated by commonly used predictive equations and by whole-room indirect calorimetry (WRIC). Design: This cross-sectional study included 31 CRC survivors (age: 53–78 years; mean (standard deviation (SD)) body mass index (BMI) 28.7 (4.28) kg/m2), who underwent curative surgery. Body composition was measured by dual-energy x-ray absorptiometry (DXA). Predicted REE from equations in clinical use and derived from DXA and bioelectrical impedance analysis (BIA) were compared against REE measured by 30-min WRIC. Equations included Harris-Benedict, Mifflin-St. Jeor, FAO/WHO/UNU, Henry, Mifflin-St. JeorDXA, and FAO/WHO/UNUBIA. Paired sample t-test, Lin’s concordance correlation coefficient (CCC) and Bland-Altman analysis were used to determine the agreement between measured REEWRIC and predicted REE. Accuracy was defined as the percentage of predicted REE values that fell within ± 10 % of REEWRIC. Results: Mean (SD) REEWRIC was 1710 kcal/d (353), and respiratory quotient (RQ) was 0.79 (0.05). Most equations underestimated REE. On average, Harris-Benedict, Henry, and FAO/WHO/UNUBIA showed the best overall agreement with REEWRIC. However, these equations showed low accuracy with 65 %, 68 %, and 62 % of predicted REE values within ± 10 % of REEWRIC, respectively. Conclusions: Most predictive equations tended to underestimate REE in CRC survivors compared with REEWRIC. The Harris-Benedict, Henry and FAO/WHO/UNUBIA equations showed both best accuracy and agreement with WRIC. They were still inaccurate, with individual variability for a relevant part of the sample. Future studies need to develop improved predictive equations for CRC survivors.

• Olsen, Thomas; Elshorbagy, Amany; Johnson, Jay E.; Nichenametla, Sailendra N.; Dong, Zhen & Sambamurti, Kumar [Show all 8 contributors for this article] (2025). Sulfur amino acids, metabolic health and beyond: Recent advances, translational implications, and future research considerations. Analytical Biochemistry. ISSN 0003-2697. 709. doi: 10.1016/j.ab.2025.116008. Full text in Research Archive Show summary

  Dietary restriction of the sulfur amino acids methionine and cysteine (sulfur amino acid restriction [SAAR]) is a well-established paradigm for delaying disease onset and the aging process in several experimental models. In vivo, SAAR's anti-aging effects appear to be mediated by decreased growth hormone/insulin-like growth factor-1 (GH/IGF-1) signaling, along with improvement in insulin sensitivity and overall metabolic health. SAAR-fed animals also exhibit reduced regional and total adiposity, as well as oxidative stress and inflammation. Recent experimental studies suggest that SAAR improves cognition, induces significant changes in gut microbiome composition, and that its benefits may depend on the age at which the intervention begins. In humans, observational studies have shown that higher plasma total cysteine levels are positively correlated with adiposity, insulin resistance, and an increased incidence of diabetes. Likewise, high dietary methionine and cysteine intake has been linked to increased risk of cardiovascular disease and diabetes-related mortality. Human dietary intervention studies have only been partly successful in translating the benefits of SAAR, and practical challenges for implementation remain to be addressed. This review summarizes recent advances in the SAAR field and discusses its translational potential for promoting metabolic health and reducing the risk of age-related diseases.

• Hernández-Arciga, Ulalume; Stamenkovic, Ceda; Yadav, Shweta; Nicoletti, Chiara; Albalawy, Wafaa N. & hammood, Farazdaq Al [Show all 44 contributors for this article] (2025). Dietary methionine restriction started late in life promotes healthy aging in a sex-specific manner. Science Advances. 11(16). doi: 10.1126/sciadv.ads1532. Full text in Research Archive Show summary

  Aging is associated with dysregulated methionine metabolism and increased levels of enzymes in the tyrosine degradation pathway (TDP). To investigate the efficacy of targeting either methionine metabolism or the TDP for healthspan improvement in advanced age, we initiated dietary MetR or TDP inhibition in 18-month-old C57BL/6J mice. MetR significantly improved neuromuscular function, metabolic health, lung function, and frailty. In addition, we confirmed improved neuromuscular function from dietary MetR in 5XFAD mice, whose weight was not affected by MetR. We did not observe benefits with TDP inhibition. Single-nucleus RNA and ATAC sequencing of muscle revealed cell type–specific responses to MetR, although MetR did not significantly affect mouse aging epigenetic clock markers. Similarly, an 8-week MetR intervention in a human trial (NCT04701346) showed no significant impact on epigenetic clocks. The observed benefits from late-life MetR provide translational rationale to develop MetR mimetics as an antiaging intervention.

• Kacerova, Tereza; Yates, Abi G.; Dai, Jiayi; Shepherd, Dawn; Pires, Elisabete & Jel, Sebastian de [Show all 16 contributors for this article] (2025). Role of B vitamins in modulating homocysteine and metabolic pathways linked to brain atrophy: Metabolomics insights from the VITACOG trial. Alzheimer's & Dementia. ISSN 1552-5260. 21(7). doi: 10.1002/alz.70521. Full text in Research Archive Show summary

  Abstract INTRODUCTION Elevated total homocysteine (tHcy) is a major predictor of brain atrophy, cognitive decline, and Alzheimer's disease (AD) progression. The VITACOG trial, a randomized, placebo‐controlled study in mild cognitive impairment (MCI), previously showed that B vitamin supplementation lowered tHcy, slowing brain atrophy and cognitive decline; however, the underlying mechanisms remained unclear. METHODS We used untargeted, multi‐platform metabolomics, with nuclear magnetic resonance and liquid chromatography‐mass spectrometry to analyze serum samples from 89 B vitamin–treated and 84 placebo‐treated MCI participants over a 2 year follow‐up period. RESULTS Multivariate modeling distinguished treated from placebo groups with 91.2 ± 1.8% accuracy. B vitamin supplementation induced significant metabolic reprogramming, lowering quinolinic acid, α‐ketoglutarate, α‐ketobutyrate, glucose, and glutamate. DISCUSSION These findings reveal that B vitamins influence metabolic pathways beyond tHcy reduction, particularly the tricarboxylic acid cycle and glutamine–glutamate cycling, critical for brain energy homeostasis and neurotransmission. This metabolic signature supports B vitamin supplementation as a strategy for slowing MCI progression. Highlights Nuclear magnetic resonance and multi‐platform liquid chromatography tandem mass spectrometry metabolomics were performed on serum samples from 89 B vitamin–treated and 84 placebo participants in the VITACOG trial. Multi‐platform metabolomics revealed B vitamin–driven metabolic reprogramming, achieving 91% classification accuracy. B vitamin supplementation modulates key neuroprotective metabolic pathways. Regulation of energy metabolism and neurotransmission by B vitamins contributes to brain health in elderly individuals. B vitamins demonstrate potential as an adjunct therapy in mild cognitive impairment, potentially mitigating progression to Alzheimer's disease.

• Olsen, Thomas; Stolt, Emma Theresia Kjelland; Øvrebø, Bente; Elshorbagy, Amany; Tore, Elena C. & Lee-Ødegård, Sindre [Show all 20 contributors for this article] (2024). Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial. Journal of Translational Medicine. 22(40). doi: 10.1186/s12967-023-04833-w. Full text in Research Archive Show summary

  Background Dietary sulfur amino acid restriction (SAAR) improves metabolic health in animals. In this study, we investigated the effect of dietary SAAR on body weight, body composition, resting metabolic rate, gene expression profiles in white adipose tissue (WAT), and an extensive blood biomarker profile in humans with overweight or obesity. Methods N = 59 participants with overweight or obesity (73% women) were randomized stratified by sex to an 8-week plant-based dietary intervention low (~ 2 g/day, SAAR) or high (~ 5.6 g/day, control group) in sulfur amino acids. The diets were provided in full to the participants, and both investigators and participants were blinded to the intervention. Outcome analyses were performed using linear mixed model regression adjusted for baseline values of the outcome and sex. Results SAAR led to a ~ 20% greater weight loss compared to controls (β 95% CI − 1.14 (− 2.04, − 0.25) kg, p = 0.013). Despite greater weight loss, resting metabolic rate remained similar between groups. Furthermore, SAAR decreased serum leptin, and increased ketone bodies compared to controls. In WAT, 20 genes were upregulated whereas 24 genes were downregulated (FDR < 5%) in the SAAR group compared to controls. Generally applicable gene set enrichment analyses revealed that processes associated with ribosomes were upregulated, whereas processes related to structural components were downregulated. Conclusion Our study shows that SAAR leads to greater weight loss, decreased leptin and increased ketone bodies compared to controls. Further research on SAAR is needed to investigate the therapeutic potential for metabolic conditions in humans. Trial registration: ClinicalTrials.gov identifier: NCT04701346, registered Jan 8th 2021, https://www.clinicaltrials.gov/study/NCT04701346

• Lee-Ødegård, Sindre; Hjorth, Marit; Olsen, Thomas; Moen, Gunn-Helen Øiseth; Daubny, Emily & Evans, David M [Show all 17 contributors for this article] (2024). Serum proteomic profiling of physical activity reveals CD300LG as a novel exerkine with a potential causal link to glucose homeostasis. eLIFE. 13, p. 1–25. doi: 10.7554/ELIFE.96535. Full text in Research Archive Show summary

  Background: Physical activity has been associated with preventing the development of type 2 diabetes and atherosclerotic cardiovascular disease. However, our understanding of the precise molecular mechanisms underlying these effects remains incomplete and good biomarkers to objectively assess physical activity are lacking. Methods: We analyzed 3072 serum proteins in 26 men, normal weight or overweight, undergoing 12 weeks of a combined strength and endurance exercise intervention. We estimated insulin sensitivity with hyperinsulinemic euglycemic clamp, maximum oxygen uptake, muscle strength, and used MRI/MRS to evaluate body composition and organ fat depots. Muscle and subcutaneous adipose tissue biopsies were used for mRNA sequencing. Additional association analyses were performed in samples from up to 47,747 individuals in the UK Biobank, as well as using two-sample Mendelian randomization and mice models. Results: Following 12 weeks of exercise intervention, we observed significant changes in 283 serum proteins. Notably, 66 of these proteins were elevated in overweight men and positively associated with liver fat before the exercise regimen, but were normalized after exercise. Furthermore, for 19.7 and 12.1% of the exercise-responsive proteins, corresponding changes in mRNA expression levels in muscle and fat, respectively, were shown. The protein CD300LG displayed consistent alterations in blood, muscle, and fat. Serum CD300LG exhibited positive associations with insulin sensitivity, and to angiogenesis-related gene expression in both muscle and fat. Furthermore, serum CD300LG was positively associated with physical activity and negatively associated with glucose levels in the UK Biobank. In this sample, the association between serum CD300LG and physical activity was significantly stronger in men than in women. Mendelian randomization analysis suggested potential causal relationships between levels of serum CD300LG and fasting glucose, 2 hr glucose after an oral glucose tolerance test, and HbA1c. Additionally, Cd300lg responded to exercise in a mouse model, and we observed signs of impaired glucose tolerance in male, but not female, Cd300lg knockout mice. Conclusions: Our study identified several novel proteins in serum whose levels change in response to prolonged exercise and were significantly associated with body composition, liver fat, and glucose homeostasis. Serum CD300LG increased with physical activity and is a potential causal link to improved glucose levels. CD300LG may be a promising exercise biomarker and a therapeutic target in type 2 diabetes.

• Jeevanathan, Janeni; Blom, Sigrid Marie; Olsen, Thomas; Holven, Kirsten Bjørklund; Arnesen, Erik Kristoffer & Trydal, Torleif [Show all 11 contributors for this article] (2024). Real-world impact of transitioning from one lipoprotein(a) assay to another in a clinical setting. American Journal of Preventive Cardiology. 19. doi: 10.1016/j.ajpc.2024.100726. Full text in Research Archive Show summary

  Background and aims: Different lipoprotein(a) [Lp(a)] assays may affect risk stratification of individuals and thus clinical decision-making. We aimed to investigate how transitioning between Lp(a) assays at a large central laboratory affected the proportion of individuals with Lp(a) result above clinical thresholds. Methods: We studied nationwide clinical laboratory data including 185,493 unique individuals (47.7 % women) aged 18-50 years with 272,463 Lp(a) measurements using Roche (2000-2009) and Siemens Lp(a) assay (2009-2019). Results: While the majority of individuals (66-75 %) had low levels of Lp(a) (<30 mg/dL) independent of the assay used, the Roche assay detected 20 % more individuals with Lp(a) >50 mg/dL, 40 % more individuals with Lp(a) >100 mg/dL and 80 % more individuals with Lp(a) >180 mg/dL than the currently used Siemens assay, likely due to calibration differences. Conclusion: Transitioning from one Lp(a) immunoassay to another had significant impact on Lp(a) results, particularly in individuals approaching clinically relevant Lp(a) thresholds.

• Olsen, Thomas; Vinknes, Kathrine Jørgensen; Barvíková, Kristýna; Stolt, Emma Theresia Kjelland; Lee-Ødegård, Sindre & Troensegaard, Hannibal [Show all 18 contributors for this article] (2024). Dietary sulfur amino acid restriction in humans with overweight and obesity: Evidence of an altered plasma and urine sulfurome, and a novel metabolic signature that correlates with loss of fat mass and adipose tissue gene expression. Redox Biology. 73. doi: 10.1016/j.redox.2024.103192. Full text in Research Archive Show summary

  Background In animals, dietary sulfur amino acid restriction (SAAR) improves metabolic health, possibly mediated by altering sulfur amino acid metabolism and enhanced anti-obesogenic processes in adipose tissue. Aim To assess the effects of SAAR over time on the plasma and urine SAA-related metabolites (sulfurome) in humans with overweight and obesity, and explore whether such changes were associated with body weight, body fat and adipose tissue gene expression. Methods Fifty-nine subjects were randomly allocated to SAAR (∼2 g SAA, n = 31) or a control diet (∼5.6 g SAA, n = 28) consisting of plant-based whole-foods and supplemented with capsules to titrate contents of SAA. Sulfurome metabolites in plasma and urine at baseline, 4 and 8 weeks were measured using HPLC and LC-MS/MS. mRNA-sequencing of subcutaneous white adipose tissue (scWAT) was performed to assess changes in gene expression. Data were analyzed with mixed model regression. Principal component analyses (PCA) were performed on the sulfurome data to identify potential signatures characterizing the response to SAAR. Results SAAR led to marked decrease of the main urinary excretion product sulfate (p < 0.001) and plasma and/or 24-h urine concentrations of cystathionine, sulfite, thiosulfate, H2S, hypotaurine and taurine. PCA revealed a distinct metabolic signature related to decreased transsulfuration and H2S catabolism that predicted greater weight loss and android fat mass loss in SAAR vs. controls (all pinteraction < 0.05). This signature correlated positively with scWAT expression of genes in the tricarboxylic acid cycle, electron transport and β-oxidation (FDR = 0.02). Conclusion SAAR leads to distinct alterations of the plasma and urine sulfurome in humans, and predicted increased loss of weight and android fat mass, and adipose tissue lipolytic gene expression in scWAT. Our data suggest that SAA are linked to obesogenic processes and that SAAR may be useful for obesity and related disorders.

• Olsen, Thomas; Refsum, Helga & R., Eiser Arnold (2024). Hyperhomocysteinemia Is Associated With a Myriad of Age-Related Illnesses: A Potential Role for Metal Toxicity. Mayo Clinic proceedings. ISSN 0025-6196. doi: 10.1016/j.mayocp.2024.04.016. Full text in Research Archive
• Viken, Jonas Krag; Olsen, Thomas; Drevon, Christian André; Hjorth, Marit; Birkeland, Kåre Inge & Norheim, Frode Amador [Show all 7 contributors for this article] (2024). Intra-Individual Variations in How Insulin Sensitivity Responds to Long-Term Exercise: Predictions by Machine Learning Based on Large-Scale Serum Proteomics. Metabolites. 14(6). doi: 10.3390/metabo14060335. Full text in Research Archive Show summary

  Physical activity is effective for preventing and treating type 2 diabetes, but some individuals do not achieve metabolic benefits from exercise (“non-responders”). We investigated non-responders in terms of insulin sensitivity changes following a 12-week supervised strength and endurance exercise program. We used a hyperinsulinaemic euglycaemic clamp to measure insulin sensitivity among 26 men aged 40–65, categorizing them into non-responders or responders based on their insulin sensitivity change scores. The exercise regimen included VO2max, muscle strength, whole-body MRI scans, muscle and fat biopsies, and serum samples. mRNA sequencing was performed on biopsies and Olink proteomics on serum samples. Non-responders showed more visceral and intramuscular fat and signs of dyslipidaemia and low-grade inflammation at baseline and did not improve in insulin sensitivity following exercise, although they showed gains in VO2max and muscle strength. Impaired IL6-JAK-STAT3 signalling in non-responders was suggested by serum proteomics analysis, and a baseline serum proteomic machine learning (ML) algorithm predicted insulin sensitivity responses with high accuracy, validated across two independent exercise cohorts. The ML model identified 30 serum proteins that could forecast exercise-induced insulin sensitivity changes.

• Karlsson, Cecilia; Johnsen, Line Kristin; Greasley, Peter; Retterstøl, Kjetil; Hedberg, Jonatan & Hall, Martin [Show all 18 contributors for this article] (2024). Gastric Bypass vs Diet and Cardiovascular Risk Factors: A Nonrandomized Controlled Trial. JAMA Surgery. ISSN 2168-6254. 159(9), p. 971–980. doi: 10.1001/jamasurg.2024.2162. Full text in Research Archive Show summary

  Importance Roux-en-Y gastric bypass (RYGB) is associated with reduced cardiovascular (CV) risk factors, morbidity, and mortality. Whether these effects are specifically induced by the surgical procedure or the weight loss is unclear. Objective To compare 6-week changes in CV risk factors in patients with obesity undergoing matching caloric restriction and weight loss by RYGB or a very low-energy diet (VLED). Design, Setting, and Participants This nonrandomized controlled study (Impact of Body Weight, Low Calorie Diet, and Gastric Bypass on Drug Bioavailability, Cardiovascular Risk Factors, and Metabolic Biomarkers [COCKTAIL]) was conducted at a tertiary care obesity center in Norway. Participants were individuals with severe obesity preparing for RYGB or a VLED. Recruitment began February 26, 2015; the first patient visit was on March 18, 2015, and the last patient visit (9-week follow-up) was on August 9, 2017. Data were analyzed from April 30, 2021, through June 29, 2023. Interventions VLED alone for 6 weeks or VLED for 6 weeks after RYGB; both interventions were preceded by 3-week LED. Main Outcomes and Measures Between-group comparisons of 6-week changes in CV risk factors. Results Among 78 patients included in the analyses, the mean (SD) age was 47.5 (9.7) years; 51 (65%) were women, and 27 (35%) were men. Except for a slightly higher mean (SD) body mass index of 44.5 (6.2) in the RYGB group (n = 41) vs 41.9 (5.4) in the VLED group (n = 37), baseline demographic and clinical characteristics were similar between groups. Major atherogenic blood lipids (low-density lipoprotein cholesterol, non–high-density lipoprotein cholesterol, apolipoprotein B, lipoprotein[a]) were reduced after RYGB in comparison with VLED despite a similar fat mass loss. Mean between-group differences were −17.7 mg/dL (95% CI, −27.9 to −7.5), −17.4 mg/dL (95% CI, −29.8 to −5.0) mg/dL, −9.94 mg/dL (95% CI, −15.75 to −4.14), and geometric mean ratio was 0.55 U/L (95% CI, 0.42 to 0.72), respectively. Changes in glycemic control and blood pressure were similar between groups. Conclusions and Relevance This study found that clinically meaningful reductions in major atherogenic blood lipids were demonstrated after RYGB, indicating that RYGB may reduce CV risk independent of weight loss. Trial Registration ClinicalTrials.gov Identifier: NCT02386917

• Olsen, Thomas; Christensen, Jacob Juel; Arnesen, Erik Kristoffer; Lysne, Vegard & Blomhoff, Rune (2024). Preparatory work for the update of the tolerable upper intake levels for vitamin A. EFSA Supporting publication. ISSN 2397-8325. doi: 10.2903/sp.efsa.2024.EN-8651. Full text in Research Archive
• Bråtveit, Marianne; Parys, Anthea van; Olsen, Thomas; Strand, Elin; Marienborg, Ingvild & Laupsa-Borge, Johnny [Show all 14 contributors for this article] (2024). Association between dietary macronutrient composition and plasma one-carbon metabolites and B-vitamin cofactors in patients with stable angina pectoris. British Journal of Nutrition. ISSN 0007-1145. 131(10), p. 1678–1690. doi: 10.1017/S0007114524000473. Full text in Research Archive Show summary

  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 analysed 1928 patients with suspected stable angina pectoris (geometric mean age 61), representing elevated CVD risk, to assess associations between dietary macronutrient composition (FFQ) and plasma one-carbon metabolites and related B-vitamin status markers (GC–MS/MS, LC–MS/MS or microbiological assay). Diet-metabolite associations were modelled on the continuous scale, adjusted for age, sex, BMI, smoking, alcohol and total energy intake. Average (geometric mean (95 % prediction interval)) intake was forty-nine (38, 63) energy percent (E%) from carbohydrate, thirty-one (22, 45) E% from fat and seventeen (12, 22) E% from protein. The strongest associations were seen for higher protein intake, i.e. with higher plasma pyridoxal 5’-phosphate (PLP) (% change (95 % CI) 3·1 (2·1, 4·1)), cobalamin (2·9 (2·1, 3·7)), riboflavin (2·4 (1·1, 3·7)) and folate (2·1 (1·2, 3·1)) and lower total homocysteine (tHcy) (–1·4 (–1·9, −0·9)) and methylmalonic acid (MMA) (–1·4 (–2·0, −0·8)). Substitution analyses replacing MUFA or PUFA with SFA demonstrated higher plasma concentrations of riboflavin (5·0 (0·9, 9·3) and 3·3 (1·1, 5·6)), tHcy (2·3 (0·7, 3·8) and 1·3 (0·5, 2·2)) and MMA (2·0 (0·2, 3·9) and 1·7 (0·7, 2·7)) and lower PLP (–2·5 (–5·3, 0·3) and −2·7 (–4·2, −1·2)). In conclusion, a higher protein intake and replacing saturated with MUFA and PUFA were associated with a more favourable metabolic phenotype regarding metabolites associated with CVD risk.

• Parlesak, Alexandr; Masino, Talia Theresa; Reis, Kia Daniela; Pettersen, Caroline Filskov; Christensen, Jacob Juel & Olsen, Thomas [Show all 7 contributors for this article] (2024). Preparatory work for the update of the tolerable upper intake levels for iron. EFSA Supporting publication. ISSN 2397-8325. doi: 10.2903/sp.efsa.2024.EN-8661. Full text in Research Archive
• Majtan, Tomas; Olsen, Thomas; Sokolova, Jitka; Krijt, Jakub; Krizkova, Michaela & Ida, Tomoaki [Show all 15 contributors for this article] (2024). Deciphering pathophysiological mechanisms underlying cystathionine beta-synthase-deficient homocystinuria using targeted metabolomics, liver proteomics, sphingolipidomics and analysis of mitochondrial function. Redox Biology. 73. doi: 10.1016/j.redox.2024.103222. Full text in Research Archive Show summary

  Background Cystathionine β-synthase (CBS)-deficient homocystinuria (HCU) is an inherited disorder of sulfur amino acid metabolism with varying severity and organ complications, and a limited knowledge about underlying pathophysiological processes. Here we aimed at getting an in-depth insight into disease mechanisms using a transgenic mouse model of HCU (I278T). Methods We assessed metabolic, proteomic and sphingolipidomic changes, and mitochondrial function in tissues and body fluids of I278T mice and WT controls. Furthermore, we evaluated the efficacy of methionine-restricted diet (MRD) in I278T mice. Results In WT mice, we observed a distinct tissue/body fluid compartmentalization of metabolites with up to six-orders of magnitude differences in concentrations among various organs. The I278T mice exhibited the anticipated metabolic imbalance with signs of an increased production of hydrogen sulfide and disturbed persulfidation of free aminothiols. HCU resulted in a significant dysregulation of liver proteome affecting biological oxidations, conjugation of compounds, and metabolism of amino acids, vitamins, cofactors and lipids. Liver sphingolipidomics indicated upregulation of the pro-proliferative sphingosine-1-phosphate signaling pathway. Liver mitochondrial function of HCU mice did not seem to be impaired compared to controls. MRD in I278T mice improved metabolic balance in all tissues and substantially reduced dysregulation of liver proteome. Conclusion The study highlights distinct tissue compartmentalization of sulfur-related metabolites in normal mice, extensive metabolome, proteome and sphingolipidome disruptions in I278T mice, and the efficacy of MRD to alleviate some of the HCU-related biochemical abnormalities.

• Olsen, Thomas; Elshorbagy, Amany; Stolt, Emma Theresia Kjelland; Åsberg, Anders; Zare, Hasse Khiabani & Bastani, Nasser Ezzatkhah [Show all 9 contributors for this article] (2024). Acute effects of oral mesna administration on the full amino acid profile and 3-methylhistidine: secondary results from the CYLOB dose-finding study. Amino Acids. ISSN 0939-4451. 56. doi: 10.1007/s00726-024-03398-2. Full text in Research Archive Show summary

  Plasma total cysteine (tCys) is strongly associated with fat mass in humans. Mesna lowers plasma tCys in a dose-dependent manner, but it is not known whether it interferes with metabolism of other amino acids or protein. In this Phase-1 study, we show that a single dose of mesna administered at 400, 800, 1200 or 1600 mg to 6–7 individuals per dose only slightly affects amino acid profiles, with increases in plasma valine across dose levels. There were no effects of mesna on 3-methylhistidine, a marker of protein breakdown.

• Tore, Elena C.; Adriaans, Bregje C.; Olsen, Thomas; Vinknes, Kathrine Jørgensen; Kooi, M. Eline & Elshorbagy, Amany [Show all 15 contributors for this article] (2024). Estimated stearoyl-CoA desaturase activity mediates the associations of total cysteine with adiposity: The Maastricht Study. Journal of Clinical Lipidology. ISSN 1933-2874. 19(2), p. 348–357. doi: 10.1016/j.jacl.2024.11.005. Full text in Research Archive Show summary

  Background Plasma sulfur amino acids (SAAs), particularly cysteine, are associated with obesity. One proposed mechanism is the altered regulation of the stearoyl-CoA desaturase (SCD) enzyme. Changes in the SCD enzyme activity have been linked to obesity, as well as to plasma SAA concentrations. Objective This study aimed to investigate whether estimated SCD activity mediates the associations between plasma SAAs and measures of overall adiposity and specific fat depots. Methods We examined cross-sectional data from a subset of the Maastricht Study (n=1129, 50.7% men, 56.7% with (pre)diabetes). Concentrations of methionine, total homocysteine, cystathionine, total cysteine (tCys), total glutathione (tGSH) and taurine were measured in fasting plasma. Outcomes included measures of overall, peripheral and central adiposity, and liver fat. SCD activity was estimated by ratios of serum fatty acids as SCD16 and SCD18 indices. The associations between plasma SAAs and measures of adiposity or liver fat were examined with multiple linear regression analysis. Multiple mediation analysis was used to investigate whether the significant associations were mediated by SCD16 and SCD18 indices. Results Plasma tCys was positively associated with all adiposity measures (β ranged from 0.15 to 0.30). SCD16 significantly mediated all associations (proportion mediated ranged from 5.1% to 9.7%). Inconsistent mediation effects were found for SCD18. Despite a significant inverse association of plasma tGSH with all adiposity measures (β ranged from -0.08 to -0.16), no significant mediation effect was found. Conclusions Plasma tCys may promote excessive body fat accumulation via upregulation of SCD activity.

• Henriksen, Hege Berg; Henriksen, Christine; Sousa, Ana Rita Sequeira de; Alavi, Dena Helene; Augestad, Elin Maria Sandstad & Rising, Russell [Show all 12 contributors for this article] (2023). Validity and reproducibility of a whole-room indirect calorimeter for the estimation of VO<inf>2</inf>, VCO<inf>2</inf>, and resting metabolic rate. Physiological Reports. 11(7). doi: 10.14814/phy2.15658. Full text in Research Archive Show summary

  Abstract Whole‐room indirect calorimeters (WRICs) provide accurate instruments for the measurement of respiratory exchange, energy expenditure, and macronutrient oxidation. Here, we aimed to determine the validity and reproducibility of a 7500 L WRIC for the measurement of ventilation rates and resting metabolic rate (RMR). Technical validation was performed with propane combustion tests ( n  = 10) whereas biological reproducibility was tested in healthy subjects (13 women, 6 men, mean ± SD age 39.6 ± 15.3) in two 60 min measurements separated by 24 h. Subjects followed a run‐in protocol prior to measurements. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for ventilation rates of O2 (VO2), CO2 (VCO2), the respiratory quotient (RQ; VCO2/VO2), and RMR. Technical validation showed good validity with CVs ranging from 0.67% for VO 2 to 1.00% for energy expenditure. For biological reproducibility, CVs were 2.89% for VO 2 ; 2.67% for VCO 2 ; 1.95% for RQ; and 2.68% for RMR. With the exception of RQ (74%), ICCs were excellent for VO 2 (94%), VCO 2 (96%) and RMR (95%). Excluding participants that deviated from the run‐in protocol did not alter results. In conclusion, the 7500 L WRIC is technically valid and reproducible for ventilation rates and RMR.

• Lamberg-Allardt, Christel; Adebayo, Folasade; Peltonen, Henna; Christensen, Jacob Juel & Olsen, Thomas (2023). Preparatory work for the update of the tolerable upper intake levels for vitamin D. EFSA Supporting publication. ISSN 2397-8325. doi: 10.2903/sp.efsa.2023.EN-7941. Full text in Research Archive
• Dhar, Indu; Lysne, Vegard; Ulvik, Arve; Svingen, Gard Frodahl Tveitevåg; Pedersen, Eva Kristine Ringdal & Bjørnestad, Espen Øglænd [Show all 15 contributors for this article] (2023). Plasma methylmalonic acid predicts risk of acute myocardial infarction and mortality in patients with coronary heart disease: A prospective 2-cohort study. Journal of Internal Medicine. ISSN 0954-6820. 293(4), p. 508–519. doi: 10.1111/joim.13610. Full text in Research Archive Show summary

  Background Elevated plasma methylmalonic acid (MMA) is reported in patients with established coronary heart disease (CHD) and is considered a marker of vitamin B12 deficiency. Moreover, MMA-dependent reactions have been linked to alterations in mitochondrial energy metabolism and oxidative stress, key features in the pathophysiology of cardiovascular diseases (CVDs). Objectives We examined whether plasma MMA prospectively predicted the long-term risk of acute myocardial infarction (AMI) and mortality. Methods and results Using Cox modeling, we estimated hazard ratios (HRs) for endpoints according to per 1-SD increment of log-transformed plasma MMA in two independent populations: the Western Norway Coronary Angiography Cohort (WECAC) (patients evaluated for CHD; n = 4137) and the Norwegian Vitamin Trial (NORVIT) (patients hospitalized with AMI; n = 3525). In WECAC and NORVIT, 12.8% and 18.0% experienced an AMI, whereas 21.8% and 19.9% died, of whom 45.5% and 60.3% from CVD-related causes during follow-up (range 3–11 years), respectively. In WECAC, age- and gender-adjusted HRs (95% confidence interval) were 1.18 (1.09–1.28), 1.25 (1.18–1.33), and 1.28 (1.17–1.40) for future AMI, total mortality, and CVD mortality, respectively. Corresponding risk estimates were 1.19 (1.10–1.28), 1.22 (1.14–1.31), and 1.30 (1.19–1.42) in NORVIT. These estimates were only slightly attenuated after multivariable adjustments. Across both cohorts, the MMA-risk association was stronger in older adults, women, and non-smokers. Conclusions Elevated MMA was associated with an increased risk of AMI and mortality in patients with suspected or verified CHD.

• Tore, Elena C.; Eussen, Simone; Bastani, Nasser Ezzatkhah; Dagnelie, Pieter; Elshorbagy, Amany K & Grootswagers, Pol [Show all 14 contributors for this article] (2023). The Associations of Habitual Intake of Sulfur Amino Acids, Proteins and Diet Quality with Plasma Sulfur Amino Acid Concentrations: The Maastricht Study. Journal of Nutrition. ISSN 0022-3166. 153(7), p. 2027–2040. doi: 10.1016/j.tjnut.2023.05.008. Full text in Research Archive
• Vinknes, Kathrine Jørgensen; Olsen, Thomas; Zare, Hasse Khiabani; Bastani, Nasser Ezzatkhah; Stolt, Emma Theresia Kjelland & Dahl, Anja Falkenhaug [Show all 11 contributors for this article] (2023). Cysteine-lowering treatment with mesna against obesity: Proof of concept and results from a human phase I, dose-finding study. Diabetes, obesity and metabolism. ISSN 1462-8902. 25(11), p. 3161–3170. doi: 10.1111/dom.15210. Full text in Research Archive Show summary

  Abstract Aim To investigate whether mesna—sodium‐2‐mercaptoethane sulfonate) can reduce diet‐induced fat gain in mice, and to assess the safety of single ascending mesna doses in humans to find the dose associated with lowering of plasma tCys by at least 30%. Methods C3H/HeH mice were shifted to a high‐fat diet ± mesna in drinking water; body composition was measured at weeks 0, 2 and 4. In an open, phase I, single ascending dose study, oral mesna (400, 800, 1200, 1600 mg) was administered to 17 men with overweight or obesity. Mesna and tCys concentrations were measured repeatedly for a duration of 48 hours postdosing in plasma, as well as in 24‐hour urine. Results Compared with controls, mesna‐treated mice had lower tCys and lower estimated mean fat mass gain from baseline (week 2: 4.54 ± 0.40 vs. 6.52 ± 0.36 g; week 4: 6.95 ± 0.35 vs. 8.19 ± 0.34 g; P overall  = .002), but similar lean mass gain. In men with overweight, mesna doses of 400‐1600 mg showed dose linearity and were well tolerated. Mesna doses of 800 mg or higher decreased plasma tCys by 30% or more at nadir (4h post‐dosing). With increasing mesna dose, tCys AUC 0‐12h decreased ( P trend  &lt; .001), and urine tCys excretion increased ( P trend  = .004). Conclusions Mesna reduces diet‐induced fat gain in mice. In men with overweight, single oral doses of mesna (800‐1600 mg) were well tolerated and lowered plasma tCys efficiently. The effect of sustained tCys‐lowering by repeated mesna administration on weight loss in humans deserves investigation.

• Åkesson, Agneta; Söderlund, Fredrik; Bärebring, Linnea; Christensen, Jacob Juel; Olsen, Thomas & Witthöft, Cornelia M (2023). Preparatory work for the update of the tolerable upper intake levels for folic acid/folate. EFSA Supporting publication. ISSN 2397-8325. doi: 10.2903/sp.efsa.2023.EN-7940. Full text in Research Archive
• Moore, Timothy M.; Lee-Ødegård, Sindre; Olsen, Thomas; Morselli, Marco; Strumwasser, Alexander R. & Lin, Amanda J. [Show all 40 contributors for this article] (2023). Conserved multi-tissue transcriptomic adaptations to exercise training in humans and mice. Cell reports. 42(5). doi: 10.1016/j.celrep.2023.112499. Full text in Research Archive Show summary

  Physical activity is associated with beneficial adaptations in human and rodent metabolism. We studied over 50 complex traits before and after exercise intervention in middle-aged men and a panel of 100 diverse strains of female mice. Candidate gene analyses in three brain regions, muscle, liver, heart, and adipose tissue of mice indicate genetic drivers of clinically relevant traits, including volitional exercise volume, muscle metabolism, adiposity, and hepatic lipids. Although ∼33% of genes differentially expressed in skeletal muscle following the exercise intervention are similar in mice and humans independent of BMI, responsiveness of adipose tissue to exercise-stimulated weight loss appears controlled by species and underlying genotype. We leveraged genetic diversity to generate prediction models of metabolic trait responsiveness to volitional activity offering a framework for advancing personalized exercise prescription. The human and mouse data are publicly available via a user-friendly Web-based application to enhance data mining and hypothesis development.

• Olsen, Thomas & Lerner, Ulf H. (2023). Vitamin A – a scoping review for Nordic nutrition Recommendations 2023. Food & Nutrition Research (FNR). ISSN 1654-6628. 67. doi: 10.29219/fnr.v67.10229. Full text in Research Archive Show summary

  Vitamin A refers to a group of fat-soluble compounds with retinol activity, including all-trans retinol and pro-vitamin A carotenoids. Bioactive compounds include retinal and all-trans retinoic acid with important functions in vision, immune function, growth, and development. The literature search that was performed for the current scoping review yielded a total of seven publications relevant to setting the recommended daily intake for vitamin A. In total, six publications assessed the relationship of serum retinol and/or dietary vitamin A intake with fracture risk (n = 2), cancer (n = 3), and deficiency after bariatric surgery (n = 1). One additional report by the European Food Safety Administration (EFSA) with updated average requirements was included. The outcomes-based systematic reviews and meta-analyses showed positive associations for vitamin A intake and serum retinol with risk of hip fracture. Weak or inconclusive associations were observed for cancer or obesity. One publication by EFSA with updated estimated average requirements and population reference intakes for dietary vitamin A intakes was published in 2015. The EFSA recommendations and estimated average requirements are based on a European reference population, with body weights derived from an assumed body mass index of 22, which might be too low and not representative of the Nordic and Baltic populations, and consequently resulting in lower estimated average requirements and recommendations. In conclusion, there were limited new outcomes-based data for vitamin A and health outcomes.

• Parys, Anthea van; Sæle, Jostein; Puaschitz, Nathalie Genevieve; Anfinsen, Åslaug Matre; Karlsson, Therese & Olsen, Thomas [Show all 12 contributors for this article] (2022). The association between dairy intake and risk of cardiovascular disease and mortality in patients with stable angina pectoris. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 30(3), p. 219–229. doi: 10.1093/eurjpc/zwac217. Full text in Research Archive Show summary

  Aims The association of dairy products with cardiovascular disease and mortality risk remains heavily debated. We aimed to investigate the association between intake of total dairy and dairy products and the risk of acute myocardial infarction (AMI), stroke, and cardiovascular and all-cause mortality. Methods and results We included 1929 patients (80% men, mean age 62 years) with stable angina pectoris from the Western Norway B-vitamin Intervention Trial. Dietary data were obtained via a 169-item food frequency questionnaire. Risk associations were estimated using Cox proportional hazard regression models adjusted for relevant covariates. Non-linear associations were explored visually. The mean (±SD) dairy intake in the study population was 169 ± 108 g/1000 kcal. Median follow-up times were 5.2, 7.8, and 14.1 years for stroke, AMI, and mortality, respectively. Higher intake of total dairy and milk were positively associated with stroke risk [HR (95% CI): 1.14 (1.02, 1.27) and 1.13 (1.02, 1.27), cardiovascular mortality 1.06 (1.00, 1.12) and 1.07 (1.01, 1.13)] and all-cause mortality [1.07 (1.03, 1.11) and 1.06 (1.03, 1.10)] per 50 g/1000 kcal. Higher cheese intake was inversely associated with AMI risk [0.92 (0.83, 1.02)] per 10 g/1000 kcal. Butter was associated with increased AMI risk [1.10 (0.97, 1.24)] and all-cause mortality [1.10 (1.00, 1.20) per 5 g/1000 kcal. Conclusion Higher dairy and milk consumption were associated with increased risk of mortality and stroke. Cheese was associated with decreased, and butter with increased, risk of AMI. Dairy is a heterogenous food group with divergent health effects and dairy products should therefore be investigated individually.

• Lee-Ødegård, Sindre; Olsen, Thomas; Norheim, Frode Amador; Drevon, Christian A & Birkeland, Kåre Inge (2022). Potential Mechanisms for How Long-Term Physical Activity May Reduce Insulin Resistance. Metabolites. 12(3)(208). doi: 10.3390/metabo12030208. Full text in Research Archive Show summary

  Insulin became available for the treatment of patients with diabetes 100 years ago, and soon thereafter it became evident that the biological response to its actions differed markedly between individuals. This prompted extensive research into insulin action and resistance (IR), resulting in the universally agreed fact that IR is a core finding in patients with type 2 diabetes mellitus (T2DM). T2DM is the most prevalent form of diabetes, reaching epidemic proportions worldwide. Physical activity (PA) has the potential of improving IR and is, therefore, a cornerstone in the prevention and treatment of T2DM. Whereas most research has focused on the acute effects of PA, less is known about the effects of long-term PA on IR. Here, we describe a model of potential mechanisms behind reduced IR after long-term PA to guide further mechanistic investigations and to tailor PA interventions in the therapy of T2DM. The development of such interventions requires knowledge of normal glucose metabolism, and we briefly summarize an integrated physiological perspective on IR. We then describe the effects of long-term PA on signaling molecules involved in cellular responses to insulin, tissue-specific functions, and whole-body IR.

• Hustad, Kristin Solheim; Ottestad, Inger; Olsen, Thomas; Sæther, Thomas; Ulven, Stine Marie & Holven, Kirsten Bjørklund (2022). Salmon fish protein supplement increases serum vitamin B12 and selenium concentrations: secondary analysis of a randomised controlled trial. European Journal of Nutrition. ISSN 1436-6207. 61(6), p. 3085–3093. doi: 10.1007/s00394-022-02857-4. Full text in Research Archive Show summary

  Abstract Purpose The main aim of the present study was to examine the effect of a fish protein supplement made from by-products from production of Atlantic salmon, on blood concentration of micronutrients. Methods We conducted an 8-week double-blind parallel-group randomised controlled trial. In total, 88 adults were randomised to a salmon fish protein supplement or placebo, and 74 participants were included in the analysis of vitamin D, omega-3, vitamin B12, selenium, folate, zinc, homocysteine and mercury. Results During the intervention period, geometric mean (GSD) of serum vitamin B12 concentrations increased from 304 (1.40) to 359 (1.42) pmol/L in the fish protein group ( P vs. controls = 0.004) and mean (SD) serum selenium increased from 1.18 (0.22) to 1.30 (0.20) μmol/L ( P vs. controls = 0.002). The prevalence of low vitamin B12 status (B12 &lt; 148–221 &gt; pmol/L) decreased from 15.4 to 2.6% in the fish protein group, while increasing from 5.9 to 17.6% in the placebo group ( P  = 0.045). There was no difference between the groups in serum levels of the other micronutrients measured. Conclusion Including a salmon fish protein supplement in the daily diet for 8 weeks, increases serum vitamin B12 and selenium concentrations. From a sustainability perspective, by-products with high contents of micronutrients and low contents of contaminants, could be a valuable dietary supplement or food ingredient in populations with suboptimal intake. Trail Registration The study was registered at ClinicalTrials.gov (ID: NCT03764423) on June 29th 2018.

• Tore, Elena C.; Elshorbagy, Amany K.; Bakers, Frans CH; Brouwers, Marin C.G.J.; Dagnelie, Pieter & Eussen, Simone J. [Show all 17 contributors for this article] (2022). Associations between plasma sulfur amino acids and specific fat depots in two independent cohorts: CODAM and The Maastricht Study. European Journal of Nutrition. ISSN 1436-6207. doi: 10.1007/s00394-022-03041-4. Full text in Research Archive Show summary

  Abstract Purpose Sulfur amino acids (SAAs) have been associated with obesity and obesity-related metabolic diseases. We investigated whether plasma SAAs (methionine, total cysteine (tCys), total homocysteine, cystathionine and total glutathione) are related to specific fat depots. Methods We examined cross-sectional subsets from the CODAM cohort ( n  = 470, 61.3% men, median [IQR]: 67 [61, 71] years) and The Maastricht Study (DMS; n  = 371, 53.4% men, 63 [55, 68] years), enriched with (pre)diabetic individuals. SAAs were measured in fasting EDTA plasma with LC–MS/MS. Outcomes comprised BMI, skinfolds, waist circumference (WC), dual-energy X-ray absorptiometry (DXA, DMS), body composition, abdominal subcutaneous and visceral adipose tissues (CODAM: ultrasound, DMS: MRI) and liver fat (estimated, in CODAM, or MRI-derived, in DMS, liver fat percentage and fatty liver disease). Associations were examined with linear or logistic regressions adjusted for relevant confounders with z-standardized primary exposures and outcomes. Results Methionine was associated with all measures of liver fat, e.g ., fatty liver disease [CODAM: OR = 1.49 (95% CI 1.19, 1.88); DMS: OR = 1.51 (1.09, 2.14)], but not with other fat depots. tCys was associated with overall obesity, e.g., BMI [CODAM: β  = 0.19 (0.09, 0.28); DMS: β  = 0.24 (0.14, 0.34)]; peripheral adiposity, e.g., biceps and triceps skinfolds [CODAM: β  = 0.15 (0.08, 0.23); DMS: β  = 0.20 (0.12, 0.29)]; and central adiposity, e.g., WC [CODAM: β  = 0.16 (0.08, 0.25); DMS: β  = 0.17 (0.08, 0.27)]. Associations of tCys with VAT and liver fat were inconsistent. Other SAAs were not associated with body fat. Conclusion Plasma concentrations of methionine and tCys showed distinct associations with different fat depots, with similar strengths in the two cohorts.

• Svendsen, Karianne; Olsen, Thomas; Vinknes, Kathrine Jørgensen; Mundal, Liv; Holven, Kirsten Bjørklund & Bogsrud, Martin Prøven [Show all 9 contributors for this article] (2022). Risk of stroke in genetically verified familial hypercholesterolemia: A prospective matched cohort study. Atherosclerosis. ISSN 0021-9150. 358, p. 34–40. doi: 10.1016/j.atherosclerosis.2022.08.015. Full text in Research Archive Show summary

  Background and aims: Individuals with familial hypercholesterolemia (FH), causing severely elevated LDL-C, are expected to have a higher risk of ischemic stroke. The risk of hemorrhagic stroke and impact of statin use are, however, not known. We aimed to investigate the risk of incident total, ischemic and hemorrhagic stroke in individuals with FH compared to controls, and to explore the association between cumulative statin use and risk of total stroke in FH. Methods: This prospective cohort study consists of 4186 individuals with genetically verified FH and 82 180 age and sex matched controls followed from 2008 to 2018 for incident stroke. Daily defined doses (DDD) described cumulative statin exposure: 0–5000 DDD (“low”), 5000–10,000 DDD (“intermediate”), and >10 000 DDD (“high”). Results were presented as hazard ratio (95% CI) derived from Cox proportional hazards models. Results: Individuals with FH did not have a higher risk of total stroke (1.16 (0.95–1.43) nor ischemic stroke (1.11 (0.88–1.38). Excess risk of hemorrhagic stroke was observed (1.63 (1.07, 2.48) but attenuated after adjusting for antithrombotic medication (1.25 (0.81, 1.93). Among individuals with FH, there was no association between statin use and total stroke for intermediate vs. low DDD [0.69 (0.32, 1.48)] or for high vs. low DDD [0.83 (0.41, 1.67)]. Conclusions: No significant excess risk of incident total and ischemic stroke in FH, and no difference in total stroke risk among the FH population with low, intermediate, and high statin exposure were observed. The observed relationship between FH and hemorrhagic stroke was no longer significant after adjusting for use of anti- thrombotic medication.

• Doncheva, Atanaska Ivanova; Romero, Silvana Angelica Troncoso; Ramirez-Garrastacho, Manuel; Lee-Ødegård, Sindre; Kolnes, Kristoffer Jensen & Tangen, Daniel S. [Show all 11 contributors for this article] (2022). Extracellular vesicles and microRNAs are altered in response to exercise, insulin sensitivity and overweight. Acta Physiologica. ISSN 1748-1708. 236(4). doi: 10.1111/apha.13862. Full text in Research Archive Show summary

  Abstract: Extracellular vesicles induced by exercise have emerged as potential mediators of tissue crosstalk. Extracellular vesicles and their cargo miRNAs have been linked to dysglycemia and obesity in animal models, but their role in humans is unclear. Aim: The aim of the study was to characterize the miRNA content in plasma extracellular vesicle isolates after acute and long-term exercise and to study associations between extracellular vesicle miRNAs, mRNA expression in skeletal muscle and adipose tissue, and cardiometabolic risk factors. Methods: Sedentary men with or without dysglycemia and overweight underwent an acute bicycle test and a 12-week exercise intervention with extensive metabolic phenotyping. Gene expression in m. vastus lateralis and subcutaneous adipose tissue was measured with RNA sequencing. Extracellular vesicles were purified from plasma with membrane affinity columns or size exclusion chromatography. Results: Extracellular vesicle miRNA profiling revealed a transient increase in the number of miRNAs after acute exercise. We identified miRNAs, such as miR-652-3p, that were associated to insulin sensitivity and adiposity. By performing explorative association analyses, we identified two miRNAs, miR-32-5p and miR-339-3p, that were strongly correlated to an adipose tissue macrophage signature. Conclusion: Numerous miRNAs in plasma extracellular vesicle isolates were increased by exercise, and several miRNAs correlated to insulin sensitivity and adiposity. Our findings warrant future studies to characterize exercise-induced extracellular vesicles and cargo miRNA to clarify where exercise-induced extracellular vesicles originate from, and to determine whether they influence metabolic health or exercise adaptation.

• Dörner, Rebecca; Hägele, Franziska A.; Koop, Jana; Rising, Russell; Foerster, Thomas & Olsen, Thomas [Show all 9 contributors for this article] (2022). Validation of energy expenditure and macronutrient oxidation measured by two new whole-room indirect calorimeters. Obesity. ISSN 1930-7381. 30(9), p. 1796–1905. doi: 10.1002/oby.23527. Full text in Research Archive Show summary

  Objective The aim of this study was to validate two new whole-room indirfect calorimeters according to Room Indirect Calorimetry Operating and Reporting Standards (RICORS 1.0). Methods For technical validation, 16 propane combustion tests were performed to determine accuracy and precision of energy expenditure (EE) and ventilation rates of oxygen (VO2), carbon dioxide (VCO2), and respiratory exchange ratio (VCO2/VO2). For biological validation, eight participants (mean [SD], age 24.1 [2.5] years; BMI 24.3 [3.1] kg/m2) underwent four 24-hour protocols under highly standardized conditions: (1) isocaloric sedentary, (2) fasting sedentary, (3) isocaloric active, and (4) fasting active. Reliability (coefficients of variation [CV]) and minimal detectable changes (MDC) were calculated for 24-hour EE, sleeping metabolic rate (SMR), physical activity energy expenditure (PAEE), thermic effect of food (TEF), and macronutrient oxidation rates. Results Technical validation showed high reliability and recovery rates for VO2 (0.75% and 100.8%, respectively), VCO2 (0.49% and 100.6%), and EE (0.54% and 98.2%). Biological validation revealed CV and MDC for active conditions of 1.4% and 4.3% for 24-hour EE, 1.7% and 5.9% for SMR, and 30.2% and 38.4% for TEF, as well as 5.8% and 10.5% for PAEE, respectively. Mean CV and MDC for macronutrient oxidation rates were 9.9% and 22.9%, respectively. Conclusions The precision of 24-hour EE and SMR was high, whereas it was lower for PAEE and poor for TEF.

• Nichenametla, Sailendra N.; Mattocks, Dwight A.L.; Cooke, Diana; Midya, Vishal; Malloy, Virginia L. & Mansilla, Wilfredo [Show all 18 contributors for this article] (2022). Cysteine restriction-specific effects of sulfur amino acid restriction on lipid metabolism. Aging Cell. ISSN 1474-9718. 21(12). doi: 10.1111/acel.13739. Full text in Research Archive Show summary

  Decreasing the dietary intake of methionine exerts robust anti-adiposity effects in rodents but modest effects in humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing methionine and eliminating cysteine. Such diets exert both methionine restriction (MR) and cysteine restriction (CR), that is, sulfur amino acid restriction (SAAR). Contrarily, SAAR diets formulated for human consumption included cysteine, and thus might have exerted only MR. Epidemiological studies positively correlate body adiposity with plasma cysteine but not methionine, suggesting that CR, but not MR, is responsible for the anti-adiposity effects of SAAR. Whether this is true, and, if so, the underlying mechanisms are unknown. Using methionine- and cysteine-titrated diets, we demonstrate that the anti-adiposity effects of SAAR are due to CR. Data indicate that CR increases serinogenesis (serine biosynthesis from non-glucose substrates) by diverting substrates from glyceroneogenesis, which is essential for fatty acid reesterification and triglyceride synthesis. Molecular data suggest that CR depletes hepatic glutathione and induces Nrf2 and its downstream targets Phgdh (the serine biosynthetic enzyme) and Pepck-M. In mice, the magnitude of SAAR-induced changes in molecular markers depended on dietary fat concentration (60% fat >10% fat), sex (males > females), and age-at-onset (young > adult). Our findings are translationally relevant as we found negative and positive correlations of plasma serine and cysteine, respectively, with triglycerides and metabolic syndrome criteria in a cross-sectional epidemiological study. Controlled feeding of low-SAA, high-polyunsaturated fatty acid diets increased plasma serine in humans. Serinogenesis might be a target for treating hypertriglyceridemia.

• Elshorbagy, Amany; Bastani, Nasser Ezzatkhah; Lee-Ødegård, Sindre; Øvrebø, Bente; Yasein, Nadia Haj & Svendsen, Karianne [Show all 10 contributors for this article] (2022). The association of fasting plasma thiol fractions with body fat compartments, biomarker profile, and adipose tissue gene expression. Amino Acids. ISSN 0939-4451. doi: 10.1007/s00726-022-03229-2. Full text in Research Archive Show summary

  Abstract People with high plasma total cysteine (tCys) have higher fat mass and higher concentrations of the atherogenic apolipoprotein B (apoB). The disulfide form, cystine, enhanced human adipogenesis and correlated with total fat mass in a Middle-Eastern cohort. In 35 European adults with overweight (88.6% women) and with dual-X-ray absorptiometry measurements of regional fat, we investigated how cystine compared to other free disulfides in their association with total regional adiposity, plasma lipid and glucose biomarkers, and adipose tissue lipid enzyme mRNA ( n  = 19). Most total plasma homocysteine (tHcy) (78%) was protein-bound; 63% of total glutathione (tGSH) was reduced. tCys was 49% protein-bound, 30% mixed-disulfide, 15% cystine, and 6% reduced. Controlling for age and lean mass, cystine and total free cysteine were the fractions most strongly associated with android and total fat: 1% higher cystine predicted 1.97% higher android fat mass (95% CI 0.64, 3.31) and 1.25% (0.65, 2.98) higher total fat mass (both p  = 0.005). A positive association between tCys and apoB ( β : 0.64%; 95% CI 0.17, 1.12%, p  = 0.009) was apparently driven by free cysteine and cystine; cystine was also inversely associated with the HDL-associated apolipoprotein A1 ( β : −0.57%; 95% CI −0.96, −0.17%, p  = 0.007). No independent positive associations with adiposity were noted for tGSH or tHcy fractions. Plasma cystine correlated with CPT1a mRNA (Spearman’s r  = 0.68, p  = 0.001). In conclusion, plasma cystine—but not homocysteine or glutathione disulfides—is associated with android adiposity and an atherogenic plasma apolipoprotein profile. The role of cystine in human adiposity and cardiometabolic risk deserves investigation. ClinicalTrials.gov identifiers: NCT02647970 and NCT03629392.

• Matre, Åslaug Oddsdatter; Parys, Anthea Van; Olsen, Thomas; Haugsgjerd, Teresa Risan; Baravelli, Carl Michael & Nygård, Ottar [Show all 8 contributors for this article] (2021). The Association of Meat Intake With All-Cause Mortality and Acute Myocardial Infarction Is Age-Dependent in Patients With Stable Angina Pectoris. Frontiers in Nutrition. 8, p. 1–10. doi: 10.3389/fnut.2021.642612. Full text in Research Archive Show summary

  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 association between total meat intake and risk of all-cause mortality, acute myocardial infarction, cancer, and gastrointestinal cancer in patients with stable angina pectoris. We also investigated whether age modified these associations. Materials and Methods: This prospective cohort study consisted of 1,929 patients (80% male, mean age 62 years) with stable angina pectoris from the Western Norway B-Vitamin Intervention Trial. Dietary assessment was performed by the administration of a semi-quantitative food frequency questionnaire. Cox proportional hazards models were used to investigate the association between a relative increase in total meat intake and the outcomes of interest. Results: The association per 50 g/1,000 kcal higher intake of total meat with morbidity and mortality were generally inconclusive but indicated an increased risk of acute myocardial infarction [HR: 1.26 (95% CI: 0.98, 1.61)] and gastrointestinal cancer [1.23 (0.70, 2.16)]. However, we observed a clear effect modification by age, where total meat intake was associated with an increased risk of mortality and acute myocardial infarction among younger individuals, but an attenuation, and even reversal of the risk association with increasing age. Conclusion: Our findings support the current dietary guidelines emphasizing a restricted meat intake in cardiovascular disease patients but highlights the need for further research on the association between meat intake and health outcomes in elderly populations. Future studies should investigate different types of meat separately in other CVD-cohorts, in different age-groups, as well as in the general population.

• Dhar, Indu; Svingen, Gard Frodahl Tveitevåg; Olsen, Thomas; Lysne, Vegard; Bjørnestad, Espen Øglænd & Ueland, Per Magne [Show all 7 contributors for this article] (2021). β-blocker use and risk of all-cause mortality in patients with coronary heart disease: effect modification by serum vitamin A. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 28(17), p. 1897–1902. doi: 10.1093/eurjpc/zwaa158. Full text in Research Archive Show summary

  Aims  Blockade of β-adrenoceptors reduces sympathetic nervous system activity and improves survival in patients with heart failure with reduced left ventricular ejection fraction (HFrEF); however, any improvement in longevity among patients with coronary heart disease (CHD) but without HFrEF remains uncertain. Vitamin A has been linked to the activation of tyrosine hydroxylase, the rate‐limiting enzyme in the catecholamine synthesis pathway. We investigated if vitamin A status modified the association of β-blocker use with the risk of all-cause mortality. Methods and results  A total of 4118 patients undergoing elective coronary angiography for suspected stable angina pectoris, of whom the majority had normal left ventricular ejection fraction (LVEF) were studied. Hazard ratios (HRs) of all-cause mortality comparing treatment vs. non-treatment of β-blockers according to the tertiles of serum vitamin A were explored in Cox proportional hazards regression models. During a median follow-up of 10.3 years, 897 patients (21.8%) died. The overall LVEF was 65% and 283 (6.9%) had anamnestic HF. After multivariable adjustments for traditional risk factors, medical history, and drug therapies of cardiovascular disease, β-blocker treatment was inversely associated with the risk of all-cause mortality [HR : 0.84; 95% CI (confidence interval), 0.72–0.97]. However, the inverse association was generally stronger among patients in the upper serum vitamin A tertile (HR :0.66; 95% CI, 0.50–0.86; Pinteraction = 0.012), which remained present after excluding patients with LVEF < 40%. Conclusion  In patients with suspected CHD, β-blocker treatment was associated with improved survival primarily among patients with high serum vitamin A levels.

• Olsen, Thomas; Øvrebø, Bente; Turner, Cheryl; Bastani, Nasser Ezzatkhah; Refsum, Helga & Vinknes, Kathrine (2021). Effects of short-term methionine and cysteine restriction and enrichment with polyunsaturated fatty acids on oral glucose tolerance, plasma amino acids, fatty acids, lactate and pyruvate: results from a pilot study. BMC Research Notes. 14(43). doi: 10.1186/s13104-021-05463-5. Full text in Research Archive Show summary

  Objective In this 7-day pilot study we randomized healthy, normal-weight men and women to either a dietary intervention with methionine and cysteine restriction enriched in PUFA (Met/Cyslow + PUFA, n = 7) or with high contents of methionine, cysteine and SFA (Met/Cyshigh + SFA, n = 7). The objective was to describe the short-term responses in oral glucose tolerance, amino acid profile, total fatty acid profile, pyruvate and lactate following a Met/Cyslow + PUFA diet vs. Met/Cyshigh + SFA. Results The diet groups consisted of five women and two men, aged 20–38 years. After the 7-d intervention median pre- and post-oral glucose tolerance test (OGTT) glucose concentrations were 5 mmol/L and 4 mmol/L respectively in the Met/Cyslow + PUFA group. In the Met/Cyshigh + SFA group, median pre- and post-OGTT glucose concentrations were 4.8 mmol/L and 4.65 mmol/L after the 7-d intervention. The responses in the amino acid profiles were similar in both groups during the intervention with the exception of serine. Fatty acids decreased from baseline to day 7 in both groups. Plasma lactate and pyruvate were similar for both groups with an increase to day 3 before approaching baseline values at day 7. Trial registration ClinicalTrials.gov: NCT02647970, registration date: January 6th 2016.

• Stolt, Emma Theresia Kjelland; Olsen, Thomas; Elshorbagy, Amany; Kozich, Viktor; Greevenbroek, Marleen M.J. Van & Øvrebø, Bente [Show all 10 contributors for this article] (2021). Sulfur amino acid restriction, energy metabolism and obesity: a study protocol of an 8-week randomized controlled dietary intervention with whole foods and amino acid supplements. Journal of Translational Medicine. 19. doi: 10.1186/s12967-021-02824-3. Full text in Research Archive Show summary

  Background Dietary sulfur amino acid (SAA) restriction is an established animal model for increasing lifespan and improving metabolic health. Data from human studies are limited. In the study outlined in this protocol, we will evaluate if dietary SAA restriction can reduce body weight and improve resting energy expenditure (REE) and parameters related to metabolic health. Method/design Men and women (calculated sample size = 60), aged 18–45 years, with body mass index of 27–35 kg/m2 will be included in a double-blind 8-week dietary intervention study. The participants will be randomized in a 1:1 manner to a diet with either low or high SAA. Both groups will receive an equal base diet consisting of low-SAA plant-based whole foods and an amino acid supplement free of SAA. Contrasting SAA contents will be achieved using capsules with or without methionine and cysteine (SAAhigh, total diet SAA ~ 50–60 mg/kg body weight/day; SAAlow, total diet SAA ~ 15–25 mg/kg body weight/day). The primary outcome is body weight change. Data and material collection will also include body composition (dual X-ray absorptiometry), resting energy expenditure (whole-room indirect calorimetry) and samples of blood, urine, feces and adipose tissue at baseline, at 4 weeks and at study completion. Measures will be taken to promote and monitor diet adherence. Data will be analyzed using linear mixed model regression to account for the repeated measures design and within-subject correlation. Discussion The strength of this study is the randomized double-blind design. A limitation is the restrictive nature of the diet which may lead to poor compliance. If this study reveals a beneficial effect of the SAAlow diet on body composition and metabolic health, it opens up for new strategies for prevention and treatment of overweight, obesity and its associated disorders. Trial registration ClinicalTrials.gov: NCT04701346, Registration date: January 8th, 2021

• Parys, Anthea van; Karlsson, Therese; Vinknes, Kathrine; Olsen, Thomas; Øyen, Jannike & Dierkes, Jutta [Show all 8 contributors for this article] (2021). Food Sources Contributing to Intake of Choline and Individual Choline Forms in a Norwegian Cohort of Patients With Stable Angina Pectoris. Frontiers in Nutrition. 8, p. 1–8. doi: 10.3389/fnut.2021.676026. Full text in Research Archive Show summary

  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 Nordic countries. A higher intake of lipid-soluble choline forms has been associated with increased risk of acute myocardial infarction, highlighting the need for knowledge about food sources of the individual choline forms. In general, little is known about the habitual intake and food sources of choline, and individual choline forms. Objective: Investigate foods contributing to the intake of total choline and individual choline forms. Design: The study population consisted of 1,929 patients with stable angina pectoris from the Western Norway B Vitamin Intervention Trial. Dietary intake data was obtained through a 169-item food frequency questionnaire. Intake of total choline and individual choline forms was quantified using the USDA database, release 2. Results: The geometric mean (95% prediction interval) total choline intake was 287 (182, 437) mg/d. Phosphatidylcholine accounted for 42.5% of total choline intake, followed by free choline (25.8%) and glycerophosphocholine (21.2%). Phosphocholine and sphingomyelin contributed 4.2 and 4.5%, respectively. The main dietary choline sources were eggs, milk, fresh vegetables, lean fish, and bread. In general, animal food sources were the most important contributors to choline intake. Conclusion: This study is, to the best of our knowledge, the first to assess the intake of all choline forms and their dietary sources in a European population. Most choline was consumed in the form of phosphatidylcholine and animal food sources contributed most to choline intake. There is a need for accurate estimates of the dietary intake of this essential nutrient to issue appropriate dietary recommendations.

• Olsen, Thomas; Turner, Cheryl; Øvrebø, Bente; Bastani, Nasser Ezzatkhah; Refsum, Helga & Vinknes, Kathrine (2020). Postprandial effects of a meal low in sulfur amino acids and high in polyunsaturated fatty acids compared to a meal high in sulfur amino acids and saturated fatty acids on stearoyl CoA-desaturase indices and plasma sulfur amino acids: a pilot study. BMC Research Notes. 13. doi: 10.1186/s13104-020-05222-y. Full text in Research Archive Show summary

  Objective The sulfur amino acid (SAA) cysteine is positively related, whereas polyunsaturated fatty acids (PUFAs) are inversely related to activity of the lipogenic enzyme stearoyl-CoA desaturase (SCD). High SCD activity promotes obesity in animals, and plasma activity indices positively associates with fat mass in humans. SCD may thus be a target for dietary intervention with SAA restriction and PUFA enrichment with unknown potential benefits for body composition. We randomized ten healthy individuals to a meal restricted in SAAs and enriched with PUFAs (Cys/Metlow + PUFA) (n = 5) or a meal enriched in SAA and saturated fatty acids (Cys/Methigh + SFA) (n = 5). We measured plasma SCD activity indices (SCD16 and SCD18) and SAAs response hourly from baseline and up to 4 h postprandial. Results SCD16 was unchanged whereas SCD18 tended to increase in the Cys/Metlow + PUFA compared to the Cys/Methigh + SFA group (ptime*group interaction = 0.08). Plasma concentrations of total cysteine fractions including free and reduced cysteine decreased in the Cys/Metlow + PUFA compared to the Cys/Methigh + SFA group (both ptime*group interaction < 0.001). In conclusion, a meal low in SAA but high in PUFAs reduced plasma cysteine fractions but not SCD activity indices. This pilot study can be useful for the design and diet composition of future dietary interventions that targets SCD and SAA. Trial registration ClinicalTrials.gov: NCT02647970, registration date: 6 January 2016

• Svendsen, Karianne; Vinknes, Kathrine; Retterstøl, Kjetil & Olsen, Thomas (2020). Why we can probably trust public policy dietary guidelines for prevention. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. doi: 10.1093/eurjpc/zwaa008. Full text in Research Archive
• Svendsen, Karianne; Olsen, Thomas; Rusvik, Tove Caroline Nordstrand; Ulven, Stine Marie; Holven, Kirsten Bjørklund & Retterstøl, Kjetil [Show all 7 contributors for this article] (2020). Fatty acid profile and estimated desaturase activities in whole blood are associated with metabolic health. Lipids in Health and Disease. 19. doi: 10.1186/s12944-020-01282-y. Full text in Research Archive Show summary

  Background: The aim was to investigate if fatty acid profile and estimated desaturase activities; stearoyl CoAdesaturase (SCD), delta-5-desaturase and delta-6-desaturase (D5D; D6D), differ between individuals with metabolically healthy (MH) and unhealthy (MU) phenotypes. We also explored these associations according to BMI categories. Methods: Men and women at moderately elevated risk of cardiovascular disease were included in this crosssectional study (n=321). If subjects met ≥4 out of 5 criteria (elevated triglycerides, total and LDL-cholesterol, HbA1c and low HDL-cholesterol), they were classified as MU (n=52). If levels were within reference ranges for ≥3 of the same criteria, subjects were classified as MH (n=150). Utilizing the entire population, a score ranging from 0 to 5 denoting the number of MU criteria met was computed. Estimated desaturase activities were calculated as productto-precursor ratio of fatty acids in whole blood (SCD16 [16:1n7/16:0], SCD18 [18:1n9/18:0], D5D [18:3n6/18:2n6], D6D [20:4n6/20:3n6]). Results: Individuals with MH had lower estimated SCD16 and SCD18 activities, whereas estimated D6D activity was higher compared to MU. Similar, SCD16 and SCD18 increased, whereas D6D decreased with increasing criteria of MU. Trends were similar across BMI categories. Conclusions: This study supports the notion of estimated desaturase activities as possible novel biomarkers of metabolic health irrespectively of BMI.

• Olsen, Thomas; Sollie, Ove; Nurk, Eha; Turner, Cheryl; Jernerén, Fredrik & Ivy, John L. [Show all 10 contributors for this article] (2020). Exhaustive Exercise and Post-exercise Protein Plus Carbohydrate Supplementation Affect Plasma and Urine Concentrations of Sulfur Amino Acids, the Ratio of Methionine to Homocysteine and Glutathione in Elite Male Cyclists. Frontiers in Physiology. 11(2020). doi: 10.3389/fphys.2020.609335. Full text in Research Archive Show summary

  Plasma and tissue sulfur amino acid (SAA) availability are crucial for intracellular methylation reactions and cellular antioxidant defense, which are important processes during exercise and in recovery. In this randomized, controlled crossover trial among eight elite male cyclists, we explored the effect of exhaustive exercise and post-exercise supplementation with carbohydrates and protein (CHO+PROT) vs. carbohydrates (CHO) on plasma and urine SAAs, a potential new marker of methylation capacity (methionine/total homocysteine ratio [Met/tHcy]) and related metabolites. The purpose of the study was to further explore the role of SAAs in exercise and recovery. Athletes cycled to exhaustion and consumed supplements immediately after and in 30 min intervals for 120 min post-exercise. After ~18 h recovery, performance was tested in a time trial in which the CHO+PROT group cycled 8.5% faster compared to the CHO group (41:53 ± 1:51 vs. 45:26 ± 1:32 min, p

• Olsen, Thomas; Øvrebø, Bente; Yasein, Nadia Haj; Lee-Ødegård, Sindre; Svendsen, Karianne & Hjorth, Marit [Show all 11 contributors for this article] (2020). Effects of dietary methionine and cysteine restriction on plasma biomarkers, serum fibroblast growth factor 21, and adipose tissue gene expression in women with overweight or obesity: a double-blind randomized controlled pilot study. Journal of Translational Medicine. 18(122). doi: 10.1186/s12967-020-02288-x. Full text in Research Archive Show summary

  Background Dietary restriction of methionine and cysteine is a well-described model that improves metabolic health in rodents. To investigate the translational potential in humans, we evaluated the effects of dietary methionine and cysteine restriction on cardiometabolic risk factors, plasma and urinary amino acid profile, serum fibroblast growth factor 21 (FGF21), and subcutaneous adipose tissue gene expression in women with overweight and obesity in a double-blind randomized controlled pilot study. Methods Twenty women with overweight or obesity were allocated to a diet low (Met/Cys-low, n = 7), medium (Met/Cys-medium, n = 7) or high (Met/Cys-high, n = 6) in methionine and cysteine for 7 days. The diets differed only by methionine and cysteine content. Blood and urine were collected at day 0, 1, 3 and 7 and subcutaneous adipose tissue biopsies were taken at day 0 and 7. Results Plasma methionine and cystathionine and urinary total cysteine decreased, whereas FGF21 increased in the Met/Cys-low vs. Met/Cys-high group. The Met/Cys-low group had increased mRNA expression of lipogenic genes in adipose tissue including DGAT1. When we excluded one participant with high fasting insulin at baseline, the Met/Cys-low group showed increased expression of ACAC, DGAT1, and tendencies for increased expression of FASN and SCD1 compared to the Met/Cys-high group. The participants reported satisfactory compliance and that the diets were moderately easy to follow. Conclusions Our data suggest that dietary methionine and cysteine restriction may have beneficial effects on circulating biomarkers, including FGF21, and influence subcutaneous adipose tissue gene expression. These results will aid in the design and implementation of future large-scale dietary interventions with methionine and cysteine restriction. Trial registration ClinicalTrials.gov Identifier: NCT03629392, registration date: 14/08/2018 https://clinicaltrials.gov/ct2/show/NCT03629392.

• Dhar, Indu; Siddique, Sumia; Pedersen, Eva Kristine Ringdal; Svingen, Gard Frodahl Tveitevåg; Lysne, Vegard & Olsen, Thomas [Show all 12 contributors for this article] (2020). Lipid parameters and vitamin A modify cardiovascular risk prediction by plasma neopterin. Heart. ISSN 1355-6037. 106, p. 1073–1079. doi: 10.1136/heartjnl-2019-316165. Full text in Research Archive Show summary

  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 risk association between neopterin and incident acute myocardial infarction (AMI). Methods We included 4130 patients with suspected stable angina pectoris (SAP), of whom 80% received lipid-lowering treatment with statins. Risk associations between plasma neopterin and AMI are given as HRs per SD increase in log-transformed neopterin. Results During a median follow-up of 7.5 years, 530 (12.8%) patients experienced an AMI. In age-adjusted and sex-adjusted analysis, plasma neopterin was positively associated with incident AMI (HR (95% CI) per SD: 1.26 (1.17 to 1.35)). However, the estimates were most pronounced in patients with serum low-density lipoprotein cholesterol (LDL-C) or apolipoprotein (apo) B100 below-median (HR (95% CI) per SD: 1.35 (1.24 to 1.48) and 1.42 (1.27 to 1.58), respectively; both pinteraction ≤0.03). We also observed a particularly strong risk association in those with above-median Vit-A (HR (95% CI) per SD: 1.32 (1.21 to 1.44); pinteraction=0.03). The estimates were slightly modified after multivariable adjustment. Conclusions In patients with suspected SAP, the majority of whom receiving statin therapy, high plasma neopterin was associated with increased risk of AMI particularly among those with low LDL-C and apoB100 or high Vit-A levels. The particularly strong relationship of plasma neopterin with residual cardiovascular risk in patients with low lipid levels should be further investigated.

• Lee-Ødegård, Sindre; Gulseth, Hanne Løvdal; Langleite, Torgrim Mikal; Norheim, Frode; Olsen, Thomas & Refsum, Helga [Show all 9 contributors for this article] (2020). Branched-chain amino acid metabolism, insulin sensitivity and liver fat response to exercise training in sedentary dysglycaemic and normoglycaemic men. Diabetologia. ISSN 0012-186X. 64(2), p. 410–423. doi: 10.1007/s00125-020-05296-0. Full text in Research Archive Show summary

  Aims/hypothesis: Obesity and insulin resistance may be associated with elevated plasma concentration of branched-chain amino acids (BCAAs) and impaired BCAA metabolism. However, it is unknown whether the insulin-sensitising effect of long-term exercise can be explained by concomitant change in BCAAs and their metabolism. Methods: We included 26 sedentary overweight and normal-weight middle-aged men from the MyoGlu clinical trial, with or without dysglycaemia, for 12 weeks of supervised intensive exercise intervention, including two endurance and two resistance sessions weekly. Insulin sensitivity was measured as the glucose infusion rate (GIR) from a hyperinsulinaemic−euglycaemic clamp. In addition, maximum oxygen uptake, upper and lower body strength and adipose tissue depots (using MRI and spectroscopy) were measured, and subcutaneous white adipose tissue (ScWAT) and skeletal muscle (SkM) biopsies were harvested both before and after the 12 week intervention. In the present study we have measured plasma BCAAs and related metabolites using CG-MS/MS and HPLC-MS/MS, and performed global mRNA-sequencing pathway analysis on ScWAT and SkM. Results: In MyoGlu, men with dysglycaemia displayed lower GIR, more fat mass and higher liver fat content than normoglycaemic men at baseline, and 12 weeks of exercise increased GIR, improved body composition and reduced liver fat content similarly for both groups. In our current study we observed higher plasma concentrations of BCAAs (14.4%, p = 0.01) and related metabolites, such as 3-hydroxyisobutyrate (19.4%, p = 0.034) in dysglycaemic vs normoglycaemic men at baseline. Baseline plasma BCAA levels correlated negatively to the change in GIR (ρ = −0.41, p = 0.037) and VO2max (ρ = −0.47, p = 0.015) after 12 weeks of exercise and positively to amounts of intraperitoneal fat (ρ = 0.40, p = 0.044) and liver fat (ρ = 0.58, p = 0.01). However, circulating BCAAs and related metabolites did not respond to 12 weeks of exercise, with the exception of isoleucine, which increased in normoglycaemic men (10 μmol/l, p = 0.01). Pathway analyses of mRNA-sequencing data implied reduced BCAA catabolism in both SkM and ScWAT in men with dysglycaemia compared with men with normoglycaemia at baseline. Gene expression levels related to BCAA metabolism correlated positively with GIR and markers of mitochondrial content in both SkM and ScWAT, and negatively with fat mass generally, and particularly with intraperitoneal fat mass. mRNA-sequencing pathway analysis also implied increased BCAA metabolism after 12 weeks of exercise in both groups and in both tissues, including enhanced expression of the gene encoding branched-chain α-ketoacid dehydrogenase (BCKDH) and reduced expression of the BCKDH phosphatase in both groups and tissues. Gene expression of SLC25A44, which encodes a mitochondrial BCAA transporter, was increased in SkM in both groups, and gene expression of BCKDK, which encodes BCKDH kinase, was reduced in ScWAT in dysglycaemic men. Mediation analyses indicated a pronounced effect of enhanced SkM (~53%, p = 0.022), and a moderate effect of enhanced ScWAT (~18%, p = 0.018) BCAA metabolism on improved insulin sensitivity after 12 weeks of exercise, based on mRNA sequencing. In comparison, plasma concentration of BCAAs did not mediate any effect in this regard. Conclusion/interpretation: Plasma BCAA concentration was largely unresponsive to long-term exercise and unrelated to exercise-induced insulin sensitivity. On the other hand, the insulin-sensitising effect of long-term exercise in men may be explained by enhanced SkM and, to a lesser degree, also by enhanced ScWAT BCAA catabolism.

• Olsen, Thomas & Blomhoff, Rune (2019). Retinol, Retinoic Acid, and Retinol-Binding Protein 4 are Differentially Associated with Cardiovascular Disease, Type 2 Diabetes, and Obesity: An Overview of Human Studies. Advances in Nutrition. ISSN 2161-8313. doi: 10.1093/advances/nmz131. Full text in Research Archive Show summary

  Vitamin A is a fat-soluble essential nutrient obtained from plant- and animal-based sources that has roles in growth, vision, and metabolism. Vitamin A circulates mainly as retinol bound to retinol-binding protein 4 (RBP4), and is delivered to tissues and converted to retinoic acid, which is a ligand for several nuclear receptors. In recent years, aspects of vitamin A metabolism have been under scrutiny with regards to the development of metabolic and lifestyle diseases including cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and overweight and obesity in humans. Studies have mainly focused on RBP4 in this context, whereas the major circulating form, retinol, and the major bioactive form, retinoic acid, have been overlooked in this regard until recently. As one of the main roles of RBP4 is to deliver retinol to tissues for biological action, the associations of retinol and retinoic acid with these diseases must also be considered. In this review, we summarize and discuss recent and available evidence from human studies with focus on retinol, retinoic acid, and RBP4 and provide an overview of these crucial components of vitamin A metabolism in CVD, T2DM, and obesity. In summary, retinol was found to be both inversely and positively associated with CVD whereas the associations with T2DM and obesity were less clear. Although only a few studies have been published on retinoic acid, it was inversely associated with CVD. In contrast, serum RBP4 was mostly found to be positively associated with CVD, T2DM, and obesity. At present, it is difficult to ascertain why the reported associations differ depending on the compound under study, but there is a clear imbalance in the literature in disfavor of retinol and retinoic acid, which needs to be considered in future human studies.

• Lee-Ødegård, Sindre; Olsen, Thomas; Vinknes, Kathrine; Refsum, Helga; Gulseth, Hanne Løvdal & Birkeland, Kåre I. [Show all 7 contributors for this article] (2019). Plasma Sulphur-Containing Amino Acids, Physical Exercise and Insulin Sensitivity in Overweight Dysglycemic and Normal Weight Normoglycemic Men. Nutrients. 11(1). doi: 10.3390/nu11010010. Full text in Research Archive Show summary

  Plasma sulphur-containing amino acids and related metabolites are associated with insulin sensitivity, although the mechanisms are unclear. We examined the effect of exercise on this relationship. Dysglycemic (n = 13) and normoglycemic (n = 13) men underwent 45 min cycling before and after 12 weeks exercise intervention. We performed hyperinsulinemic euglycemic clamp, mRNA-sequencing of skeletal muscle and adipose tissue biopsies, and targeted profiling of plasma metabolites by LC-MS/MS. Insulin sensitivity increased similarly in dysglycemic and normoglycemic men after 12 weeks of exercise, in parallel to similar increases in concentration of plasma glutamine, and decreased concentrations of plasma glutamate, cysteine, taurine, and glutathione. Change in plasma concentrations of cysteine and glutathione exhibited the strongest correlations to exercise-improved insulin sensitivity, and expression of a cluster of genes essential for oxidative phosphorylation and fatty acid metabolism in both skeletal muscle and adipose tissue, as well as mitochondria-related genes such as mitofilin. Forty-five min of cycling decreased plasma concentrations of glutamine and methionine, and increased plasma concentrations of glutamate, homocysteine, cystathionine, cysteine, glutathione, and taurine. Similar acute responses were seen in both groups before and after the 12 weeks training period. Both acute and long-term exercise may influence transsulphuration and glutathione biosynthesis, linking exercise-improved insulin sensitivity to oxidative stress and mitochondrial function.

• Koivisto, Anu; Olsen, Thomas; Paur, Ingvild; Paulsen, Gøran; Bastani, Nasser Ezzatkhah & Garthe, Ina [Show all 10 contributors for this article] (2019). Effects of antioxidant-rich foods on altitude-induced oxidative stress and inflammation in elite endurance athletes: A randomized controlled trial. PLOS ONE. 14(6). doi: 10.1371/journal.pone.0217895. Full text in Research Archive Show summary

  Background Various altitude training regimes, systematically used to improve oxygen carrying capacity and sports performance, have been associated with increased oxidative stress and inflammation. We investigated whether increased intake of common antioxidant-rich foods attenuates these processes. Methods In a randomized controlled trial, 31 elite endurance athletes (23 ± 5 years), ingested antioxidant-rich foods (n = 16), (> doubling their usual intake), or eucaloric control foods (n = 15) during a 3-week altitude training camp (2320 m). Fasting blood and urine samples were collected 7 days pre-altitude, after 5 and 18 days at altitude, and 7 days post-altitude. Change over time was compared between the groups using mixed models for antioxidant capacity [uric acid-free (ferric reducing ability of plasma (FRAP)], oxidative stress (8-epi-PGF2α) and inflammatory biomarkers (IFNγ, IL1α, IL1RA, IL1β, IL2, IL5, IL6, IL7, IL10, IL12p70, IL13, IL17, TNFα, MCP-1 and micro-CRP). The cytokine response to a stress-test (VO2max ramp test or 100 m swimming) was assessed at pre- and post-altitude. Results FRAP increased more in the antioxidant compared to the control group (p = 0.034). IL13 decreased in the antioxidant group, while increasing in the controls (p = 0.006). A similar trend was seen for IL6 (p = 0.062). A larger decrease in micro-CRP was detected in the antioxidant group compared to controls (β: -0.62, p = 0.02). We found no group differences for the remaining cytokines. 8-epi-PGF2α increased significantly in the whole population (p = 0.033), regardless group allocation. The stress response was significantly larger post-altitude compared with pre-altitude for IL1β, IL6, IL7, IL13, IL12p70 and TNFα, but we found no group differences. Conclusions Increased intake of antioxidant-rich foods elevated the antioxidant capacity and attenuated some of the altitude-induced systemic inflammatory biomarkers in elite athletes. The antioxidant intervention had no impact on the altitude-induced oxidative stress or changes in acute cytokine responses to exercise stress-tests.

• Olsen, Thomas; Vinknes, Kathrine; Blomhoff, Rune; Lysne, Vegard; Midttun, Øivind & Dhar, Indu [Show all 12 contributors for this article] (2019). Creatinine, total cysteine and uric acid are associated with serum retinol in patients with cardiovascular disease. European Journal of Nutrition. ISSN 1436-6207. doi: 10.1007/s00394-019-02086-2. Full text in Research Archive Show summary

  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 from a subgroup of 1962 patients using a food frequency questionnaire. Potential biomarkers and dietary factors were explored using linear regression modelling adjusted for age and sex. Regression coefficients and corresponding confidence intervals (CI) are given as % change in serum retinol per unit change in the predictors. Analyses were performed in the total population and in strata of serum retinol tertiles. Results: In age- and sex-adjusted models, serum creatinine (standardized β: 0.38, 95% CI [0.35, 0.42]), plasma total cysteine (0.26, [0.23, 0.29]), serum uric acid (0.30, [0.26, 0.33]) and plasma neopterin (0.22, [0.18, 0.25]) were positively associated, whereas plasma serine (− 0.15, [− 0.18, − 0.12]) and serum C-reactive protein (− 0.15, [− 0.18, − 0.12]) were inversely associated with serum retinol. When we included the significant biomarkers in a multivariate model, the model explained 33% of the variability (R2 = 0.33) in serum retinol. The results were similar in the lower and upper tertiles of serum retinol. Weak or no associations were observed for dietary factors. Conclusions: In patients with suspected CAD, concentrations of creatinine, cysteine and uric acid were positively associated with serum retinol. Future studies should assess whether retinol concentrations are influenced by metabolic alterations in patients at risk of cardiovascular disease.

• Olsen, Thomas; Øvrebø, Bente; Turner, Cheryl; Bastani, Nasser Ezzatkhah; Refsum, Helga & Vinknes, Kathrine (2018). Combining Dietary Sulfur Amino Acid Restriction with Polyunsaturated Fatty Acid Intake in Humans: A Randomized Controlled Pilot Trial. Nutrients. 10(12), p. 1–15. doi: 10.3390/nu10121822. Full text in Research Archive
• Olsen, Thomas; Vinknes, Kathrine; Svingen, Gard Frodahl Tveitevåg; Pedersen, Eva Ringdal; Dhar, Indu & Tell, Grethe S. [Show all 11 contributors for this article] (2018). The risk association of plasma total homocysteine with acute myocardial infarction is modified by serum vitamin A. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 25(15), p. 1612–1620. doi: 10.1177/2047487318788587. Full text in Research Archive Show summary

  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. Methods. Cox proportional hazards models were used to assess the prospective relationships between tHcy and acute myocardial infarction in 2205 patients from Western Norway undergoing elective coronary angiography for suspected stable angina pectoris. Results are reported as hazard ratio per standard deviation increase in log-transformed tHcy. An interaction term for tHcy × Vit-A was added to multivariate models including age, sex, smoking, apolipoprotein B fasting, statin and aspirin prescription and estimated glomerular filtration rate.  Results. Geometric mean (geometric standard deviation) age of the participants (64.3% men) was 62.3 (1.24) years. Plasma tHcy was higher among participants in the upper versus lower Vit-A tertile. During 7 (2.4) years of follow-up, 15.1% suffered an AMI. A significant association of plasma tHcy with AMI in the total study population was observed. When we stratified the population according to Vit-A tertiles, plasma tHcy was associated with acute myocardial infarction only in the upper Vit-A tertile (hazard ratio per SD: 1.25, 95% confidence interval: 1.04–1.53, pinteraction = 0.03). Conclusions. The risk relationship between plasma tHcy and acute myocardial infarction was modified by serum concentrations of Vit-A in patients with suspected stable angina pectoris. This finding may clarify the relationship between tHcy and cardiovascular disease.

• Olsen, Thomas; Vinknes, Kathrine; Svingen, Gard Frodahl Tveitevåg; Pedersen, Eva Ringdal; Tell, Grethe S. & Blomhoff, Rune [Show all 11 contributors for this article] (2017). Cardiovascular disease risk associated with serum apolipoprotein B is modified by serum vitamin A. Atherosclerosis. ISSN 0021-9150. p. 325–330. doi: 10.1016/j.atherosclerosis.2017.07.020. Full text in Research Archive
• Strand, Elin; Pedersen, Eva Ringdal; Svingen, Gard Frodahl Tveitevåg; Olsen, Thomas; Bjørndal, Bodil & Karlsson, Therese [Show all 13 contributors for this article] (2017). Serum acylcarnitines and risk of cardiovascular death and acute myocardial infarction in patients with stable angina pectoris. Journal of the American Heart Association (JAHA). 6:e003620(2), p. 1–28. doi: 10.1161/JAHA.116.003620. Full text in Research Archive Show summary

  Background: Excess levels of serum acylcarnitines, which are intermediate products in metabolism, have been observed in metabolic diseases such as type 2 diabetes mellitus. However, it is not known whether acylcarnitines may prospectively predict risk of cardiovascular death or acute myocardial infarction in patients with stable angina pectoris. Methods and Results: This study included 4164 patients (median age, 62 years; 72% men). Baseline serum acetyl‐, octanoyl‐, palmitoyl‐, propionyl‐, and (iso)valerylcarnitine were measured using liquid chromatography/tandem mass spectrometry. Hazard ratios (HRs) and 95% CIs for quartile 4 versus quartile 1 are reported. The multivariable model included age, sex, body mass index, fasting status, current smoking, diabetes mellitus, apolipoprotein A1, apolipoprotein B, creatinine, left ventricular ejection fraction, extent of coronary artery disease, study center, and intervention with folic acid or vitamin B6. During median 10.2 years of follow‐up, 10.0% of the patients died of cardiovascular disease and 12.8% suffered a fatal or nonfatal acute myocardial infarction. Higher levels of the even‐chained acetyl‐, octanoyl‐, and palmitoyl‐carnitines were significantly associated with elevated risk of cardiovascular death, also after multivariable adjustments (HR [95% CI]: 1.52 [1.12, 2.06]; P=0.007; 1.73 [1.23, 2.44]; P=0.002; and 1.61 [1.18, 2.21]; P=0.003, respectively), whereas their associations with acute myocardial infarction were less consistent. Conclusions: Among patients with suspected stable angina pectoris, elevated serum even‐chained acylcarnitines were associated with increased risk of cardiovascular death and, to a lesser degree with acute myocardial infarction, independent of traditional risk factors.

• Lysne, Vegard; Strand, Elin; Svingen, Gard Frodahl Tveitevåg; Bjørndal, Bodil; Pedersen, Eva Ringdal & Midttun, Øivind [Show all 10 contributors for this article] (2016). Peroxisome Proliferator-Activated Receptor Activation is Associated with Altered Plasma One-Carbon Metabolites and B-Vitamin Status in Rats. Nutrients. 8(1). doi: 10.3390/nu8010026. Full text in Research Archive Show summary

  Plasma concentrations of metabolites along the choline oxidation pathway have been linked to increased risk of major lifestyle diseases, and peroxisome proliferator-activated receptors (PPARs) have been suggested to be involved in the regulation of key enzymes along this pathway. In this study, we investigated the effect of PPAR activation on circulating and urinary one-carbon metabolites as well as markers of B-vitamin status. Male Wistar rats (n = 20) received for 50 weeks either a high-fat control diet or a high-fat diet with tetradecylthioacetic acid (TTA), a modified fatty acid and pan-PPAR agonist with high affinity towards PPAR. Hepatic gene expression of PPARα, PPARβ/δ and the enzymes involved in the choline oxidation pathway were analyzed and concentrations of metabolites were analyzed in plasma and urine. TTA treatment altered most biomarkers, and the largest effect sizes were observed for plasma concentrations of dimethylglycine, nicotinamide, methylnicotinamide, methylmalonic acid and pyridoxal, which were all higher in the TTA group (all p < 0.01). Hepatic Pparα mRNA was increased after TTA treatment, but genes of the choline oxidation pathway were not affected. Long-term TTA treatment was associated with pronounced alterations on the plasma and urinary concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats.

• Mathisen, Therese Fostervold & Olsen, Thomas (2016). Når kroppsfokus blir patologisk: Sosiale medier, fitness og spiseforstyrret atferd. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. p. 6–11. Full text in Research Archive

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• Strømland, Stine Sofie; Aspholm, Trude; Fjørtoft, Jenny; Brønner, Charlotte Utheim; Stolt, Emma & Snipen, Lars-Gustav [Show all 12 contributors for this article] (2024). Effects of sulfur amino acid restriction on gut microbiota and inflammation in people with overweight and obesity: an 8-week randomized controlled dietary intervention study. Full text in Research Archive
• Elshorbagy, Amany; Bastani, Nasser Ezzatkhah; Lee-Ødegård, Sindre; Øvrebø, Bente; Yasein, Nadia Haj & Svendsen, Karianne [Show all 10 contributors for this article] (2023). Correction to: The association of fasting plasma thiol fractions with body fat compartments, biomarker profile, and adipose tissue gene expression (Amino Acids, (2022), 10.1007/s00726-022-03229-2). Amino Acids. ISSN 0939-4451. 55, p. 547–548. doi: 10.1007/s00726-023-03244-x. Full text in Research Archive
• Svendsen, Karianne; Vinknes, Kathrine Jørgensen; Retterstøl, Kjetil & Olsen, Thomas (2022). Why we can probably trust public policy dietary guidelines for prevention. 29(6), p. e209–e210. doi: 10.1093/eurjpc/zwaa008. Full text in Research Archive
• Svendsen, Karianne; Olsen, Thomas; Vinknes, Kathrine Jørgensen; Mundal, Liv; Holven, Kirsten Bjørklund & Bogsrud, Martin Prøven [Show all 9 contributors for this article] (2022). No increased risk of stroke in genetically verified familial hypercholesterolemia: a prospective matched cohort study. Full text in Research Archive
• Bastani, Nasser Ezzatkhah; Refsum, Helga; Olsen, Thomas; Vinknes, Kathrine Jørgensen; Retterstøl, Kjetil & Zare, Hasse Khiabani (2022). Determination of plasma thiols using LC-MS/MS: Cysteine-lowering treatment with mesna against obesity: Preliminary results from a phase I dose-finding stud. Full text in Research Archive
• Kværner, Ane Sørlie; Svendsen, Karianne & Olsen, Thomas (2022). Ny teori utfordrer den tradisjonelle energibalansemodellen – men møter kritikk fra fagmiljøet. Full text in Research Archive
• Svendsen, Karianne; Vinknes, Kathrine; Retterstøl, Kjetil & Olsen, Thomas (2020). Why we can probably trust public policy dietary guidelines for prevention. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. doi: 10.1093/EURJPC/ZWAA008. Full text in Research Archive
• Lysne, Vegard; Olsen, Thomas; Christensen, Jacob J. & Arnesen, Erik (2018). Ja, det er et poeng å bytte til lettbrus! Dagbladet. ISSN 0805-3766. Full text in Research Archive
• Olsen, Thomas; Øvrebø, Bente; Arnesen, Erik & Lysne, Vegard (2018). Ikke skrot BMI! Full text in Research Archive
• Olsen, Thomas; Lysne, Vegard & Dahl, Helene (2018). Bedre mot overvekt, bedre for tennene. Kunstig sukker er et folkehelsetiltak. Full text in Research Archive
• Lysne, Vegard & Olsen, Thomas (2018). Feilkilder i ernæringsepidemiologi. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. Full text in Research Archive
• Øvrebø, Bente; Olsen, Thomas & Vinknes, Kathrine (2017). Stearoyl-CoA desaturase og energimetabolisme – et prosjekt ved Universitetet i Oslo. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. p. 20–22. Full text in Research Archive
• Lysne, Vegard & Olsen, Thomas (2017). Konfidensintervaller – hva kan de fortelle deg? Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. p. 28–31. Full text in Research Archive
• Lysne, Vegard & Olsen, Thomas (2016). P-verdier. Veiledende eller villedende? En simulert studie. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. p. 28–31. Full text in Research Archive

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