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.

Many Paths to Alzheimer's Disease: A Unifying Hypothesis Integrating Biological, Chemical, and Physical Risk Factors.

Sporadic Alzheimer's disease (AD) is a complex, multifactorial disease. We should therefore expect to find many factors involved in its causation. The known neuropathology seen at autopsy in patients dying with AD is not consistently seen in all patients with AD and is sometimes seen in patients without dementia.

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.

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 of Circulating Amino Acids and Dietary Inflammatory Potential with Muscle Health in Chinese Community-Dwelling Older People.

Amino acids (AAs) and dietary inflammatory potential play essential roles in muscle health. We examined the associations of dietary inflammatory index (DII) of habitual diet with serum AA profile, and ascertained if the associations between DII and muscle outcomes were mediated by serum AAs, in 2994 older Chinese community-dwelling men and women (mean age 72 years) in Hong Kong. Higher serum branched chain AAs (BCAAs), aromatic AAs and total glutathione (tGSH) were generally associated with better muscle status at baseline.

The association of serum sulfur amino acids and related metabolites with incident diabetes: a prospective cohort study.

Aim: Plasma total cysteine (tCys) is associated with fat mass and insulin resistance, whereas taurine is inversely related to diabetes risk. We investigated the association of serum sulfur amino acids (SAAs) and related amino acids (AAs) with incident diabetes.

Methods: Serum AAs were measured at baseline in 2997 subjects aged ≥ 65 years.

Extracellular cystine influences human preadipocyte differentiation and correlates with fat mass in healthy adults.

Plasma cysteine is associated with human obesity, but it is unknown whether this is mediated by reduced, disulfide (cystine and mixed-disulfides) or protein-bound (bCys) fractions. We investigated which cysteine fractions are associated with adiposity in vivo and if a relevant fraction influences human adipogenesis in vitro. In the current study, plasma cysteine fractions were correlated with body fat mass in 35 adults.

Changes in plasma fatty acids and related biomarkers during transition to an exclusively plant- and fish-based diet in healthy adults.

Objective: The aim of this study was to examine the time scale of plasma fatty acid changes during transition to an exclusively plant- and fish-based diet in healthy individuals and determine whether there are associated alterations in arachidonic acid (ARA)-derived inflammatory mediators, estimated stearoyl coenzyme A desaturase (SCD) activity, and blood pressure.

Methods: In pursuit of a religious fast, 36 adults abstained  from eating poultry, meat, dairy products, and eggs, while increasing fish intake for 6 wk. Participants were assessed 1 wk before (W0) and 1 (W1) and 6 (W6) weeks after the diet change.

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.

Association of Maternal Plasma Total Cysteine and Growth among Infants in Nepal: A Cohort Study.

Cysteine is a semi-essential amino acid that has been positively associated with growth in children. However, transgenerational effects remain unclear. The aim of this analysis was to assess whether maternal plasma total cysteine (tCys) concentration is associated with various growth indicators in infants living in peri-urban settings in Bhaktapur, Nepal.

Blood pressure measurement protocol determines hypertension phenotypes in a Middle Eastern population.

Clinic blood pressure (BP) measurement remains a crucial step in managing hypertension. While the number of measures recorded in different settings varies, with typically 1-3 measures, there has been no prior justification for the actual number of measures required. We investigated the pattern of BP variability over 5 consecutive automated readings (R1-R5) and the influence of patient characteristics on this pattern to identify the phenotype of hypertension in a Middle Eastern population.

Body mass index determines the response of plasma sulfur amino acids to methionine loading.

Evidence from human, animal and cellular studies suggests that high plasma total cysteine (tCys) is causally linked to human obesity, but determinants of population tCys variability are unknown. We hypothesized that tCys elevation in obesity may be mediated by an altered tCys response to intake of its precursor, methionine. We investigated whether BMI influences the change in plasma tCys, total homocysteine (tHcy) and total cysteinylglycine (tCysGly) 6h following a 100 mg/kg oral methionine load in 800 healthy subjects and 750 cardiovascular disease (CVD) cases.

Circulating amino acids are associated with bone mineral density decline and ten-year major osteoporotic fracture risk in older community-dwelling adults.

With aging, poor bone mineral density (BMD) and accelerated decrease in BMD are strong risk factors for fracture. Reports of the associations of dietary protein intake with bone strength are inconsistent, possibly owing to differences in protein sources and amino acid (AA) composition. We examined the associations of serum AA with 4-year hip BMD loss and subsequent fracture risk within 10 years in older community-dwelling adults, and further addressed whether lifestyle, dietary protein intake and its source, and body composition would affect the associations.

Cortical tau burden and behavioural dysfunctions in mice exposed to monosodium glutamate in early life.

Although monosodium glutamate (MSG)-induced neurotoxicity has been recognized for decades, the potential similarities of the MSG model to Alzheimer's disease (AD)-type neuropathology have only recently been investigated. MSG-treated mice were examined behaviourally and histologically in relation to some features of AD. Four-week old mice received 5 subcutaneous MSG (2 g/kg) injections on alternate days, or saline.

Protective effect of melatonin versus montelukast in cisplatin-induced seminiferous tubule damage in rats.

We compared the protective effects of melatonin and montelukast against cisplatin-induced testicular damage. Adult male rats were assigned to one of four groups: a control group, a cisplatin (Cis) group treated with a single intraperitoneal injection of 7 mg/kg cisplatin, a cisplatin + melatonin group (Cis-Mel) and a cisplatin + montelukast group (Cis-Mon) each treated with the same dose of cisplatin together with either oral melatonin (20 mg/kg) or oral montelukast (10 mg/kg) in 2 ml water from day 1 to day 10 starting on the day of the cisplatin injection. Cisplatin-induced oxidative stress, with a significant increase in testicular malonedialdehyde (MDA), decreased testicular glutathione (GSH), histological testicular damage and body weight loss.

Food Overconsumption in Healthy Adults Triggers Early and Sustained Increases in Serum Branched-Chain Amino Acids and Changes in Cysteine Linked to Fat Gain.

Background: Plasma concentrations of branched-chain amino acids (BCAAs) and the sulfur-containing amino acid cysteine are associated with obesity and insulin resistance. BCAAs predict future diabetes.

Objective: We investigated amino acid changes during food overconsumption.

Circulating Polyunsaturated Fatty Acids as Biomarkers for Dietary Intake across Subgroups: The CODAM and Hoorn Studies.

Aims: To evaluate whether participant characteristics and way of expressing circulating fatty acids (FA) influence the strengths of associations between self-reported intake and circulating levels of linoleic acid (LA), alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

Methods: Cross-sectional analyses were performed in pooled data from the CODAM (n = 469) and Hoorn (n = 702) studies. Circulating FA were measured by gas liquid chromatography and expressed as proportions (% of total FA) and concentrations (µg/mL).

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.

Objective: We compared Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) and body mass index (BMI) as correlates of body fat percent (BF%) and the association with future risk of cardiovascular disease (CVD) and type 2 diabetes in a Caucasian population.

Methods: We used data from 6796 individuals (born 1925-27 and 1950-52) from the Hordaland Health Study, a prospective cohort study in Norway. The study was conducted in 1992-1993 and 1997-1999.

Perturbed adipose tissue hydrogen peroxide metabolism in centrally obese men: Association with insulin resistance.

Objective: Although adipose tissue hydrogen peroxide (H2O2) and its metabolizing enzymes have been linked to obesity and insulin resistance in animal studies, this relation remains to be evaluated in humans.

Methods: Non-diabetic men (N = 43, median age, 49 (37, 54 y)) undergoing abdominal surgeries were studied. Participants were classified by body mass index (BMI) into normal-weight (N = 19), or overweight/obese (Ow/Ob; BMI ≥25; N = 24).