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• 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.

• 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.

• 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

• 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; 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.

• 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.

• 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.

• 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.

• 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.

• Vinknes, Kathrine; Refsum, Helga; Turner, Cheryl; Khaw, Kay-Tee; Wareham, Nicholas J. & Forouhi, Nita G. [Show all 7 contributors for this article] (2021). Plasma Sulfur Amino Acids and Risk of Cerebrovascular Diseases: A Nested Case-Control Study in the EPIC-Norfolk Cohort. Stroke. ISSN 0039-2499. 52(1), p. 172–180. doi: 10.1161/STROKEAHA.120.029177. Full text in Research Archive
• Parys, Anthea van; Brække, Maria Sandvik; Karlsson, Therese; Vinknes, Kathrine Jørgensen; Tell, Grethe S. & Haugsgjerd, Teresa Risan [Show all 11 contributors for this article] (2021). Assessment of dietary choline intake, contributing food items and associations with one-carbon and lipid metabolites in middle-aged and elderly adults: the Hordaland Health Study. Journal of Nutrition. ISSN 0022-3166. 152(2), p. 1–12. doi: 10.1093/jn/nxab367. Full text in Research Archive Show summary

  Background: Choline is an essential nutrient for humans and is involved in various physiologic functions. Through its metabolite betaine, it is closely connected to the one-carbon metabolism, and the fat-soluble choline form phosphatidylcholine is essential for VLDL synthesis and secretion in the liver connecting choline to the lipid metabolism. Dietary recommendations for choline are not available in the Nordic countries primarily due to data scarcity. Objectives: The aim of this study was to investigate the dietary intake of total choline and individual choline forms, dietary sources, and the association of total choline intake with circulating one-carbon metabolites and lipids. Methods: We included 5746 participants in the Hordaland Health Study, a survey including community-dwelling adults born in 1925–1927 (mean age 72 y, 55% women) and 1950–1951 (mean age 48 y, 57% women). Dietary data were obtained using a 169-item FFQ, and choline content was calculated using the USDA Database for Choline Content of Common Foods, release 2. Metabolites of the one-carbon and lipid metabolism were measured in a nonfasting blood sample obtained at baseline, and the association with total choline intake was assessed using polynomial splines. Results: The geometric mean (95% prediction interval) energy-adjusted total choline intake was 260 (170, 389) mg/d, with phosphatidylcholine being the main form (44%). The major food items providing dietary choline were eggs, low-fat milk, potatoes, and leafy vegetables. Dietary total choline was inversely associated with circulating concentrations of total homocysteine, glycine, and serine and positively associated with choline, methionine, cystathionine, cysteine, trimethyllysine, trimethylamine-N-oxide, and dimethylglycine. A weak association was observed between choline intake and serum lipids. Conclusions: Phosphatidylcholine was the most consumed choline form in community-dwelling adults in Norway. Our findings suggest that choline intake is associated with the concentration of most metabolites involved in the one-carbon and lipid metabolism.

• 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

• Haugsgjerd, Teresa Risan; Egeland, Grace M.; Nygård, Ottar; Vinknes, Kathrine; Sulo, Gerhard & Lysne, Vegard [Show all 8 contributors for this article] (2020). Association of dietary vitamin K and risk of coronary heart disease in middle-age adults: the Hordaland Health Study Cohort. BMJ Open. 10(5). doi: 10.1136/bmjopen-2019-035953. Full text in Research Archive Show summary

  Objective: The role of vitamin K in the regulation of vascular calcification is established. However, the association of dietary vitamins K1 and K2 with risk of coronary heart disease (CHD) is inconclusive. Design: Prospective cohort study. Setting: We followed participants in the community-based Hordaland Health Study from 1997 - 1999 through 2009 to evaluate associations between intake of vitamin K and incident (new onset) CHD. Baseline diet was assessed by a past-year food frequency questionnaire. Energy-adjusted residuals of vitamin K1 and vitamin K2 intakes were categorised into quartiles. Participants: 2987 Norwegian men and women, age 46–49 years. Methods: Information on incident CHD events was obtained from the nationwide Cardiovascular Disease in Norway (CVDNOR) Project. Multivariable Cox regression estimated HRs and 95% CIs with test for linear trends across quartiles. Analyses were adjusted for age, sex, total energy intake, physical activity, smoking and education. A third model further adjusted K1 intake for energy-adjusted fibre and folate, while K2 intake was adjusted for energy-adjusted saturated fatty acids and calcium. Results: During a median follow-up time of 11 years, we documented 112 incident CHD cases. In the adjusted analyses, there was no association between intake of vitamin K1 and CHD (HRQ4vsQ1 = 0.92 (95% CI 0.54 to 1.57), p for trend 0.64), while there was a lower risk of CHD associated with higher intake of energy-adjusted vitamin K2 (HRQ4vsQ1 = 0.52 (0.29 to 0.94), p for trend 0.03). Further adjustment for potential dietary confounders did not materially change the association for K1, while the association for K2 was slightly attenuated (HRQ4vsQ1 = 0.58 (0.28 to 1.19)). Conclusions: A higher intake of vitamin K2 was associated with lower risk of CHD, while there was no association between intake of vitamin K1 and CHD.

• 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
• Haugsgjerd, Teresa Risan; Egeland, Grace M.; Nygård, Ottar; Igland, Jannicke; Sulo, Gerhard & Lysne, Vegard [Show all 9 contributors for this article] (2020). Intake of carbohydrates and SFA and risk of CHD in middle-age adults: The Hordaland Health Study (HUSK). Public Health Nutrition (PHN). ISSN 1368-9800. p. 1–15. doi: 10.1017/S1368980020003043. Full text in Research Archive Show summary

  Objective: Limiting SFA intake may minimise the risk of CHD. However, such reduction often leads to increased intake of carbohydrates. We aimed to evaluate associations and the interplay of carbohydrate and SFA intake on CHD risk. Design: Prospective cohort study. Setting: We followed participants in the Hordaland Health Study, Norway from 1997–1999 through 2009. Information on carbohydrate and SFA intake was obtained from a FFQ and analysed as continuous and categorical (quartiles) variables. Multivariable Cox regression estimated hazard ratios (HR) and 95 % CI. Theoretical substitution analyses modelled the substitution of carbohydrates with other nutrients. CHD was defined as fatal or non-fatal CHD (ICD9 codes 410–414 and ICD10 codes I20–I25). Participants: 2995 men and women, aged 46–49 years. Results: Adjusting for age, sex, energy intake, physical activity and smoking, SFA was associated with lower risk (HRQ4 v. Q1 0·44, 95 % CI 0·26, 0·76, Ptrend = 0·002). For carbohydrates, the opposite pattern was observed (HRQ4 v. Q1 2·10, 95 % CI 1·22, 3·63, Ptrend = 0·003). SFA from cheese was associated with lower CHD risk (HRQ4 v. Q1 0·44, 95 % CI 0·24, 0·83, Ptrend = 0·006), while there were no associations between SFA from other food items and CHD. A 5 E% substitution of carbohydrates with total fat, but not SFA, was associated with lower CHD risk (HR 0·75, 95 % CI 0·62, 0·90). Conclusions: Higher intake of predominantly high glycaemic carbohydrates and lower intake of SFA, specifically lower intake from cheese, were associated with higher CHD risk. Substituting carbohydrates with total fat, but not SFA, was associated with significantly lower risk of CHD.

• 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.

• Hanvold, Susanna; Vinknes, Kathrine; Løken, Elin Bjørge; Hjartåker, Anette; Klungsøyr, Ole & Birkeland, Eline [Show all 10 contributors for this article] (2019). Does Lifestyle Intervention After Gastric Bypass Surgery Prevent Weight Regain? A Randomized Clinical Trial. Obesity Surgery. ISSN 0960-8923. 29(11), p. 3419–3431. doi: 10.1007/s11695-019-04109-7. Full text in Research Archive
• 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.

• 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.

• Puaschitz, Nathalie Genevieve; Assmus, Jörg; Strand, Elin; Karlsson, Therese; Vinknes, Kathrine & Lysne, Vegard [Show all 10 contributors for this article] (2018). Adherence to the Healthy Nordic Food Index and the incidence of acute myocardial infarction and mortality among patients with stable angina pectoris. Journal of human nutrition and dietetics. ISSN 0952-3871. 32, p. 86–97. doi: 10.1111/jhn.12592. Full text in Research Archive Show summary

  Background: The Healthy Nordic Food Index (HNFI) has been associated with beneficial effects on markers of cardiovascular disease (CVD). Whether such effects are present among patients with established coronary heart disease is unknown. In the present study, we investigated the association between adherence to the HNFI and the risk of acute myocardial infarction (AMI) (fatal or nonfatal) and death among patients with stable angina pectoris. Methods: In the Western Norway B‐vitamin Intervention Trial, participants completed a 169‐item semi‐quantitative food frequency questionnaire. The HNFI was calculated from six food groups (fish, cabbage, apples/pears, root vegetables, whole grain bread and oatmeal), scoring 0–6. Three adherence groups were defined: 0–1 points (low), 2–3 points (medium) or 4–6 points (high). Cox regression analyses investigated associations between adherence to the HNFI and outcomes. Results: Among 2019 men (79.7%) and women with mean age of 61.7 years, 307 patients experienced an AMI event during a median (25th and 75th percentiles) follow‐up of 7.5 (6.3 and 8.7) years. Median follow‐up for total mortality was 10.5 (9.3 and 11.7) years; 171 patients died from CVD and 380 from any cause. No association between HNFI and the risk of AMI was detected. However, the HNFI was associated with a reduced risk of all‐cause death, both by linear estimates [hazard ratio (95% confidence interval = 0.91 (0.84–0.98)] and by comparison of the highest with the lowest adherence group [hazard ratio (95% confidence interval = 0.70 (0.52–0.95)]. Conclusions: The results of the present study suggest that a Healthy Nordic diet may reduce mortality in patients with established CVD.

• 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
• Vinknes, Kathrine; Nurk, Eha; Tell, Grethe S.; Sulo, Gerhard; Refsum, Helga & Elshorbagy, Amany K. (2017). The relation of CUN-BAE index and BMI with body fat, cardiovascular events and diabetes during a 6-year follow-up: The hordaland health study. Clinical Epidemiology. 9, p. 555–566. doi: 10.2147/CLEP.S145130. Full text in Research Archive
• Øyen, Jannike; Gjesdal, Clara Gram; Karlsson, Therese; Svingen, Gard Frodahl Tveitevåg; Tell, Grethe S. & Strand, Elin [Show all 11 contributors for this article] (2017). Dietary choline intake is directly associated with bone mineral density in the Hordaland Health Study. Journal of Nutrition. ISSN 0022-3166. 147(4), p. 572–578. doi: 10.3945/jn.116.243006. Full text in Research Archive
• Hanvold, Susanna; Vinknes, Kathrine; Bastani, Nasser Ezzatkhah; Turner, Cheryl; Løken, Elin Bjørge & Mala, Tom [Show all 8 contributors for this article] (2017). Plasma amino acids, adiposity, and weight change after gastric bypass surgery: are amino acids associated with weight regain? European Journal of Nutrition. ISSN 1436-6207. p. 1–9. doi: 10.1007/s00394-017-1533-9. Full text in Research Archive
• Haugsgjerd, Teresa Risan; Dierkes, Jutta; Vollset, Stein Emil; Vinknes, Kathrine; Nygård, Ottar & Seifert, Reinhard [Show all 8 contributors for this article] (2016). Association between weight change and mortality in community living older people followed for up to 14 years. The Hordaland Health Study (HUSK). The Journal of Nutrition, Health & Aging. ISSN 1279-7707. 21(8), p. 909–917. doi: 10.1007/s12603-016-0866-z. Full text in Research Archive
• Mansoor, Nadia; Vinknes, Kathrine; Veierød, Marit Bragelien & Retterstøl, Kjetil (2015). Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors a meta-analysis of randomised controlled trials. British Journal of Nutrition. ISSN 0007-1145. 115(3), p. 466–479. doi: 10.1017/S0007114515004699. Full text in Research Archive
• Vinknes, Kathrine; Elshorbagy, Amany K.; Drevon, Christian A; Gjesdal, Clara Gram; Tell, Grethe S & Nygård, Ottar [Show all 8 contributors for this article] (2013). Evaluation of the body adiposity index in a caucasian population: the Hordaland Health Study. American Journal of Epidemiology. ISSN 0002-9262. 177(6), p. 586–592. doi: 10.1093/aje/kws271. Full text in Research Archive
• Vinknes, Kathrine; Dekker, Jacqueline M.; Drevon, Christian A; Refsum, Helga; Nurk, Eha & Nijpels, Giel [Show all 13 contributors for this article] (2013). Plasma sulfur amino acids and stearoyl-CoA desaturase activity in two caucasian populations. Prostaglandins Leukot Essent Fatty Acids 2. Prostaglandins, Leukotrienes and Essential Fatty Acids. ISSN 0952-3278. 89(5), p. 297–303. doi: 10.1016/j.plefa.2013.09.007. Full text in Research Archive
• Vinknes, Kathrine; Elshorbagy, Amany K.; Drevon, Christian A; Nurk, Eha; Tell, Grethe S & Nygård, Ottar [Show all 8 contributors for this article] (2013). Associations between plasma polyunsaturated fatty acids, plasma stearoyl-CoA desaturase indices and body fat. Obesity. ISSN 1930-7381. 21(9), p. E512–E519. doi: 10.1002/oby.20457. Full text in Research Archive
• Vinknes, Kathrine; Elshorbagy, Amany K; Nurk, Eha; Drevon, Christian A; Gjesdal, Clara Gram & Tell, Grethe S [Show all 9 contributors for this article] (2013). Plasma stearoyl-CoA desaturase indices: Association with lifestyle, diet and body composition. Obesity. ISSN 1930-7381. 21(3), p. E294–E302. doi: 10.1002/oby.20011. Full text in Research Archive
• Norheim, Frode; Gjelstad, Ingrid Merethe Fange; Hjorth, Marit; Vinknes, Kathrine; Langleite, Torgrim Mikal & Holen, Torgeir [Show all 12 contributors for this article] (2012). Molecular nutrition research - the modern way of performing nutritional science. Nutrients. 4(12), p. 1898–1944. doi: 10.3390/nu4121898. Full text in Research Archive Show summary

  In spite of amazing progress in food supply and nutritional science, and a striking increase in life expectancy of approximately 2.5 months per year in many countries during the previous 150 years, modern nutritional research has a great potential of still contributing to improved health for future generations, granted that the revolutions in molecular and systems technologies are applied to nutritional questions. Descriptive and mechanistic studies using state of the art epidemiology, food intake registration, genomics with single nucleotide polymorphisms (SNPs) and epigenomics, transcriptomics, proteomics, metabolomics, advanced biostatistics, imaging, calorimetry, cell biology, challenge tests (meals, exercise, etc.), and integration of all data by systems biology, will provide insight on a much higher level than today in a field we may name molecular nutrition research. To take advantage of all the new technologies scientists should develop international collaboration and gather data in large open access databases like the suggested Nutritional Phenotype database (dbNP). This collaboration will promote standardization of procedures (SOP), and provide a possibility to use collected data in future research projects. The ultimate goals of future nutritional research are to understand the detailed mechanisms of action for how nutrients/foods interact with the body and thereby enhance health and treat diet-related diseases.

• Vinknes, Kathrine; Vogel, Stefan De; Elshorbagy, Amany K; Nurk, Eha; Drevon, Christian A & Gjesdal, Clara Gram [Show all 9 contributors for this article] (2011). Dietary intake of protein is positively associated with percent body fat in middle-aged and older adults. Journal of Nutrition. ISSN 0022-3166. 141(3), p. 440–446. doi: 10.3945/jn.110.133710. 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
• 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
• 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
• Haugsgjerd, Teresa Risan; Dierkes, Jutta; Vollset, Stein Emil; Vinknes, Kathrine; Nygård, Ottar & Seifert, Reinhard [Show all 8 contributors for this article] (2016). Association between weight change and mortality in community living older people followed for up to 14 years: the Hordaland Health Study (HUSK). Full text in Research Archive
• Mansoor, Nadia; Vinknes, Kathrine; Veierød, Marit Bragelien & Retterstøl, Kjetil (2016). Low-carbohydrate diets increase LDL-cholesterol, and thereby indicate increased risk of CVD. British Journal of Nutrition. ISSN 0007-1145. 115(12), p. 2264–2266. doi: 10.1017/S0007114516001343. Full text in Research Archive

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