Heterozygous Mutations in Both the and Genes: Double Haploinsufficiency as an Unusual Cause of Vitamin B Deficiency-A Case Report.

Vitamin B deficiency is usually simple to diagnose. However, our patient demonstrates that in difficult cases, the ordinary clinician may need a transdisciplinary approach. The finding of a double haploinsufficiency as a possible cause of vitamin B deficiency in our patient, illustrates the usefulness of performing large panel clinical exome sequencing.

Elevated homocysteine is associated with increased rates of epigenetic aging in a population with mild cognitive impairment.

Elevated plasma total homocysteine (tHcy) is associated with the development of Alzheimer's disease and other forms of dementia. In this study, we report the relationship between tHcy and epigenetic age in older adults with mild cognitive impairment from the VITACOG study. Epigenetic age and rate of aging (ROA) were assessed using various epigenetic clocks, including those developed by Horvath and Hannum, DNAmPhenoAge, and with a focus on Index, a new principal component-based epigenetic clock that, like DNAmPhenoAge, is trained to predict an individual's "PhenoAge.

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.

Determination of underivatized amino acids in human plasma using ion pair liquid chromatography/tandem mass spectrometry.

Accurate quantification of amino acids (AA) is essential for several applications, including clinical research, food analysis, and pharmaceutical studies. In this study, we developed an analytical method based on liquid chromatography with electrospray ionization coupled to tandem mass spectrometry detection (LC-ESI-MS/MS). This method was devised to accurately quantify a spectrum of amino acids, notably taurine, creatinine, glutathione (GSH), and sulfur-containing amino acids (SAAs) such as methionine, cysteine, and homocysteine, using only 10 μL of human plasma.

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 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.

The dihydrofolate reductase 19-bp deletion modifies the beneficial effect of B-vitamin therapy in mild cognitive impairment: pooled study of two randomized placebo-controlled trials.

Background: Higher serum homocysteine is associated with cognitive decline in older people. But homocysteine-lowering trials including folic acid (FA) show inconsistent results on cognitive decline. The reduction of FA to dihydrofolate by dihydrofolate reductase (DHFR) is slow in humans.

B Vitamins Prevent Iron-Associated Brain Atrophy and Domain-Specific Effects of Iron, Copper, Aluminum, and Silicon on Cognition in Mild Cognitive Impairment.

Background:: Metals, silicon, and homocysteine are linked to Alzheimer’s disease. B vitamin therapy lowers homocysteine and slows brain atrophy and cognitive decline in mild cognitive impairment (MCI).

Objective:: Examine metals and silicon as predictors of cognition/brain atrophy in MCI, their interaction with homocysteine and cysteine, and how B vitamins affect these relationships.

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.

Paraoxonase 1, B Vitamins Supplementation, and Mild Cognitive Impairment.

Background: Identification of modifiable risk factors that affect cognitive decline is important for the development of preventive and treatment strategies. Status of paraoxonase 1 (PON1), a high-density lipoprotein-associated enzyme, may play a role in the development of neurological diseases, including Alzheimer's disease.

Objective: We tested a hypothesis that PON1 status predicts cognition in individuals with mild cognitive impairment (MCI).