Acute effects of oral mesna administration on the full amino acid profile and 3-methylhistidine: secondary results from the CYLOB dose-finding study.

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.

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.

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.

Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial.

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.

Cysteine-lowering treatment with mesna against obesity: Proof of concept and results from a human phase I, dose-finding study.

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.

The association of fasting plasma thiol fractions with body fat compartments, biomarker profile, and adipose tissue gene expression.

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.

Cysteine restriction-specific effects of sulfur amino acid restriction on lipid metabolism.

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).

Associations between plasma sulfur amino acids and specific fat depots in two independent cohorts: CODAM and The Maastricht Study.

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.

The association between dairy intake and risk of cardiovascular disease and mortality in patients with stable angina pectoris.

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.

Risk of stroke in genetically verified familial hypercholesterolemia: A prospective matched cohort study.

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.

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.

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.

Food Sources Contributing to Intake of Choline and Individual Choline Forms in a Norwegian Cohort of Patients With Stable Angina Pectoris.

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.

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.

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.

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.

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/Cys + PUFA, n = 7) or with high contents of methionine, cysteine and SFA (Met/Cys + 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/Cys + PUFA diet vs. Met/Cys + SFA.

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.

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.

Plasma Sulfur Amino Acids and Risk of Cerebrovascular Diseases: A Nested Case-Control Study in the EPIC-Norfolk Cohort.

Background And Purpose: B-vitamin supplements lower circulating concentrations of homocysteine and may reduce stroke incidence. Homocysteine concentrations are associated with the incidence of stroke but other sulfur-containing compounds in the related metabolic pathway have not yet been investigated for an association with incident cerebrovascular diseases.

Methods: Nested within the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Norfolk cohort, we established a case-control study with 480 incident cases of cerebrovascular diseases and 480 controls matched by age, sex, and year of baseline examination (1993-1997).

Intake of carbohydrates and SFA and risk of CHD in middle-age adults: the Hordaland Health Study (HUSK).

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.

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.

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.

Association of dietary vitamin K and risk of coronary heart disease in middle-age adults: the Hordaland Health Study Cohort.

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.

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.

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 n = 7), medium (Met/Cys n = 7) or high (Met/Cys n = 6) in methionine and cysteine for 7 days.

Creatinine, total cysteine and uric acid are associated with serum retinol in patients with cardiovascular disease.

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.

Does Lifestyle Intervention After Gastric Bypass Surgery Prevent Weight Regain? A Randomized Clinical Trial.

Background: Weight regain after bariatric surgery often starts after 1-2 y, but studies evaluating strategies to prevent weight regain are lacking. The aim of this intervention was to evaluate the efficacy of a 2-y-group-based lifestyle intervention starting approximately 2 y after Roux-en-Y gastric bypass (RYGB) compared with usual care on weight regain and related metabolic risk factors.

Methods: A total of 165 patients with a mean of 21 months (range 14-32) after RYGB were randomized to a lifestyle intervention group (LIG) or a usual care group (UCG).

Plasma Sulphur-Containing Amino Acids, Physical Exercise and Insulin Sensitivity in Overweight Dysglycemic and Normal Weight Normoglycemic Men.

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 ( = 13) and normoglycemic ( = 13) men underwent 45 min cycling before and after 12 weeks exercise intervention.