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BACKGROUND: Gut lactobacilli can affect the metabolic functions of healthy humans. We tested whether a 1500 kcal/d diet supplemented with cheese containing the probiotic Lactobacillus plantarum TENSIA (Deutsche Sammlung für Mikroorganismen, DSM 21380) could reduce some symptoms of metabolic syndrome in Russian adults with obesity and hypertension. METHODS: In this 3-week, randomized, double-blind, placebo-controlled, parallel pilot study, 25 subjects ingested probiotic cheese and 15 ingested control cheese. Fifty grams of each cheese provided 175 kcal of energy. Blood pressure (BP), anthropometric characteristics, markers of liver and kidney function, metabolic indices (plasma glucose, lipids, and cholesterol), and urine polyamines were measured. Counts of fecal lactobacilli and L. plantarum TENSIA were evaluated using molecular methods. The data were analyzed by t-test for independent samples and Spearman’s partial correlation analysis. RESULTS: The probiotic L. plantarum TENSIA was present in variable amounts (529.6 ± 232.5 gene copies) in 16/25 (64%) study subjects. Body mass index (BMI) was significantly reduced (p = 0.031) in the probiotic cheese group versus the control cheese group. The changes in BMI were closely associated with the water content of the body (r = 0.570, p = 0.0007) when adjusted for sex and age. Higher values of intestinal lactobacilli after probiotic cheese consumption were associated with higher BMI (r = 0.383, p = 0.0305) and urinary putrescine content (r = 0.475, p = 0.006). In patients simultaneously treated with BP-lowering drugs, similar reductions of BP were observed in both groups. A positive association was detected between TENSIA colonization and the extent of change of morning diastolic BP (r = 0.617, p = 0.0248) and a trend toward lower values of morning systolic BP (r = −0.527, p = 0.0640) at the end of the study after adjusting for BMI, age, and sex. CONCLUSION: In a pilot study of obese hypertensive patients, a hypocaloric diet supplemented with a probiotic cheese helps to reduce BMI and arterial BP values, recognized symptoms of metabolic syndrome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76271778

Background/Objectives: Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite from L-carnitine and choline (abundant in meat and eggs), is linked to CVD and T2D. This study investigated whether TMAO responses to animal-based foods differ between individuals with and without metabolic syndrome (MetS), in relation to their gut microbiota composition. Subjects/Methods: In a randomized crossover trial, 12 MetS (≥3 criteria according to the Adult Treatment Panel III: elevated waist circumference, fasting glucose, triglycerides, and blood pressure or reduced HDL cholesterol) and 21 non-MetS subjects consumed two test meals (3 hard-boiled eggs or 170 g meat balls) after overnight fasting, with ≥1-week washout. Blood was collected at baseline and 0.5, 1, 2, 4, and 6 h postprandially; urine was collected over 6 h. Fecal samples (collected pre-first day of intervention) underwent 16S rRNA sequencing. Plasma and urinary TMAO, TMA, choline, and carnitine were quantified using UPLC-MS/MS. Results: MetS subjects exhibited a non-significant trend towards higher incremental AUCs for plasma TMA, TMAO, choline, and carnitine after consuming both foods, with a 30–50% higher urinary TMAO excretion (but similar for TMA) versus non-MetS subjects. This exploratory analysis also indicated that MetS subjects had reduced gut microbial diversity, featuring decreased Blautia glucerasea (butyrate producer) and increased Ruminococcus torques (pro-inflammatory), a profile associated with inflammation but not TMA production. Conclusion: No significant increase in plasma methylamines after choline and carnitine challenge was observed in subjects with MetS compared with non-MetS. In MetS subjects (without CVD and T2D), gut microbiota composition was characterized by increased pro-inflammatory bacteria rather than TMAO-generating bacteria. The lack of statistical significance with regard to plasma TMAO response could be due to an insufficient sample size rather than the absence of an effect. Nevertheless, the observed elevation might still be clinically relevant, supported by concurrent differences in microbiota composition. These preliminary findings warrant validation in larger cohorts due to sample size limitations.

Background Fructose intake, mainly as table sugar or high fructose corn syrup, has increased in recent decades and is associated with increased risk for kidney stones. We hypothesized that fructose intake alters serum and urinary components involved in stone formation. Methods We analyzed a previously published randomized controlled study that included 33 healthy male adults (40–65 years of age) who ingested 200 g of fructose (supplied in a 2-L volume of 10% fructose in water) daily for 2 weeks. Participants were evaluated at the Unit of Nephrology of the Mateo Orfila Hospital in Menorca. Changes in serum levels of magnesium, calcium, uric acid, phosphorus, vitamin D, and intact PTH levels were evaluated. Urine magnesium, calcium, uric acid, phosphorus, citrate, oxalate, sodium, potassium, as well as urinary pH, were measured. Results Ingestion of fructose was associated with an increased serum level of uric acid ( p  < 0.001), a decrease in serum ionized calcium ( p  = 0.003) with a mild increase in PTH ( p  < 0.05) and a drop in urinary pH ( p  = 0.02), an increase in urine oxalate ( p  = 0.016) and decrease in urinary magnesium ( p  = 0.003). Conclusions Fructose appears to increase urinary stone formation in part via effects on urate metabolism and urinary pH, and also via effects on oxalate. Fructose may be a contributing factor for the development of kidney stones in subjects with metabolic syndrome and those suffering from heat stress. Trial registration ClinicalTrials.gov NCT00639756 March 20, 2008.

Metabolic syndrome is a multiplex disorder and puts patients on the road to type 2 diabetes and atherosclerotic cardiovascular diseases. However, a surrogate biomarker in plasma or urine in fully reflecting features of metabolic syndrome has not been explored. Urine metabolomics has potential utility in metabolic profiling because urine metabolites analysis reflects global outflux of metabolic change. Accordingly, we collected data on subjects (n = 99) with overweight, dyslipidemia, hypertension or impaired glucose tolerance and took a metabolomics approach to analyze the metabolites of urine revealed in metabolic syndrome by high-performance liquid chromatography-time-of-flight mass spectrometry and elicit potential biomarkers to picture metabolic syndrome. Our results revealed that the urine nicotinuric acid value of subjects with diabetes (HbA1c ≥ 6.5% or those receiving diabetes medications) (n = 25) was higher than subjects without diabetes (n = 37) (221 ± 31 vs. 152 ± 13 × 10(3) mAU, P = 0.0268). Moreover, urinary nicotinuric acid level was positively correlated with body mass index, blood pressure, total cholesterol, low-density lipoprotein cholesterol, triacylglycerol and high sensitivity C-reactive protein, but negatively correlated with high-density lipoprotein cholesterol. This is the first study, to our knowledge, to propose that nicotinuric acid represents an important pathogenic mechanism in process from metabolic syndrome to diabetes and atherosclerotic cardiovascular disease.

We assess the repeatability and relative validity of a Spanish beverage intake questionnaire for assessing water intake from beverages. The present analysis was performed within the framework of the PREDIMED-PLUS trial. The study participants were adults (aged 55–75) with a BMI ≥27 and <40 kg/m2, and at least three components of Metabolic Syndrome (MetS). A trained dietitian completed the questionnaire. Participants provided 24-h urine samples, and the volume and urine osmolality were recorded. The repeatability of the baseline measurement at 6 and 1 year was examined by paired Student’s t-test comparisons. A total of 160 participants were included in the analysis. The Bland–Altman analysis showed relatively good agreement between total daily fluid intake assessed using the fluid-specific questionnaire, and urine osmolality and 24-h volume with parameter estimates of −0.65 and 0.22, respectively (R2 = 0.20; p < 0.001). In the repeatability test, no significant differences were found between neither type of beverage nor total daily fluid intake at 6 months and 1-year assessment, compared to baseline. The proposed fluid-specific assessment questionnaire designed to assess the consumption of water and other beverages in Spanish adult individuals was found to be relatively valid with good repeatability.

Micro-albuminuria has been well established as one of the risk factors of metabolic syndrome (MetS). However, the association of MetS and its components with low-grade albuminuria among those with normal urinary albumin excretion has not been clearly elucidated in Chinese population. A cross-sectional study was conducted among 9,579 participants with normal urinary albumin excretion, who were recruited from Jia Ding District, Shanghai, China. The single-void first morning urine sample was collected for urinary albumin and creatinine measurements, and urinary albumin-to-creatinine ratio (UACR) was calculated as urinary albumin divided by creatinine. Low-grade albuminuria was classified as sex-specific upper UACR quartile in this population. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The prevalence of MetS and its components increased across the UACR quartiles (all P trend <0.01). A multivariable adjusted logistic regression analysis revealed that the prevalence of MetS was gradually elevated according to the UACR quartiles (adjusted odds ratios [ORs] were 1.14, 1.24 and 1.59 for UACR quartiles 2, 3 and 4, compared with the lowest quartile; P trend<0.0001). In the further stratified logistic regression analyses, the associations between low-grade albuminuria and MetS were significant in both sex strata (male and female), both age strata (<60 and ≥60 years), both body mass index strata (<24 and ≥24 kg/m(2)), and both diabetes strata (yes and no). Compared to the lowest UACR quartile, the participants in the highest quartile of UACR had the highest prevalence of central obesity (OR = 1.43; 95%CI = 1.25-1.63), high blood pressure (OR = 1.64; 95%CI = 1.43-1.87), hyperglycemia (OR = 1.52; 95%CI = 1.30-1.78) and high triglycerides (OR = 1.19; 95%CI = 1.04-1.37). Low-grade albuminuria was significantly associated with the increasing prevalence of MetS and its components in the middle-aged and elderly Chinese population with normal urinary albumin excretion.

Polycyclic aromatic hydrocarbons (PAH) are both man-made and naturally occurring environmental pollutants that may be related to cardiometabolic health risk. To determine whether PAH is associated with obesity in the adult population and to examine whether urinary concentrations of PAH metabolites are associated with differences in how obesity relates to 3 or more risk factors for the metabolic syndrome (3RFMetS), type 2 diabetes (T2D), hypertension, and dyslipidemia. A total of 4765 adult participants from the 2001-2008 National Health and Nutrition Examination Survey were examined. The association between 8 urinary hydroxylated PAH metabolites, obesity, and health were examined using weighted logistic regressions adjusting for age, sex, ethnicity, PIR, smoking status, and urinary creatinine. There was a positive dose-dependent association between obesity and 2-phenanthrene quintiles (P trend <0.0001). Contrarily, higher quintiles of 1-naphthalene were associated with lower risk of obesity (P trend = 0.0004). For a given BMI, those in the highest quintile of 2-naphthalene, 2-fluorene, 3-fluorene and 2-phenanthrene had a 66-80% greater likelihood of 3RFMetS (P≤0.05) compared to low levels. Higher quintiles of 1-naphthalene, 2-naphthalene, 2-phenanthrene and 1-pyrene were associated with a 78-124% greater likelihood of T2D (P≤0.05) compared to low levels while high 1-naphthalene, 2-naphthalene, 2-fluorene, 3-fluorene and 2-phenanthrene were associated with a 38-68% greater likelihood of dyslipidemia (P≤0.05) compared to lower levels. Finally, 2-naphthalene and 2-phenanthrene were positively associated with hypertension (P trend = 0.008 and P trend = 0.02 respectively). PAH is related to obesity and the expression of a number of obesity-related cardiometabolic health risk factors. Future research is needed to bring to light the mechanistic pathways related to these findings.

Metabolic syndrome (MetS) is a cluster of metabolic disorders associated with increased risks of cardiovascular diseases and type 2 diabetes, posing a significant public health challenge globally. Early identification of biomarkers for MetS is crucial for timely intervention. This study aimed to explore the association between 24-hour urine indicators (sodium, potassium, creatinine, and microalbumin) and MetS among Chinese adults, providing evidence for early MetS screening and intervention. A cross-sectional survey was conducted in 2017, involving 1175 Chinese residents aged 18–69 years. Data were collected via questionnaires, physical measurements, and laboratory tests, with 24-hour urine samples analyzed for sodium, potassium, creatinine, and microalbumin excretion. Participants were excluded if they had incomplete data, unqualified urine collection, or a self-reported history of hypertension or diabetes. Of the 1175 participants (median age 42 years; 48.17% male), the prevalence of MetS was 11.4%. The median 24-hour urine excretion levels were 158.42/24 hours mmol (sodium), 34.89 mmol/24 hours (potassium), 9.62 mmol/24 hours (creatinine), and 4.31 mg/24 hours (microalbumin). Specifically, 24-hour urine microalbumin excretion was significantly higher in participants with MetS (6.35 mg/24 h) than in those without (4.12 mg/24 h; P  < 0.0001), while no significant differences were observed in sodium, potassium, or creatinine excretion between the two groups. Notably, elevated microalbumin excretion was associated with MetS components: central obesity, elevated blood pressure, elevated fasting blood glucose, and elevated triglycerides (all P  < 0.05). When microalbumin excretion was divided into quartiles, adjusted odds ratios (adjusted for age, sex, and other confounders) for MetS and its component (elevated fasting blood glucose) increased with higher quartiles (MetS: 1.00, 1.53, 1.99, 2.75; P for trend = 0.0004; elevated fasting blood glucose: 1.00, 1.31, 1.35, 2.20; P for trend = 0.0005). These findings indicate that elevated 24-hour urine microalbumin excretion is independently associated with MetS in Chinese adults, suggesting its potential as a practical biomarker for early risk assessment and intervention.

Background Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner. Methods We used NMR-based metabolomics on a large cohort of donors (n = 21,323; 37.5% female) to investigate the diagnostic value of serum or serum combined with urine to estimate the MetS risk. Specifically, we have determined 41 circulating metabolites and 112 lipoprotein classes and subclasses in serum samples and this information has been integrated with metabolic profiles extracted from urine samples. Results We have developed MetSCORE, a metabolic model of MetS that combines serum lipoprotein and metabolite information. MetSCORE discriminate patients with MetS (independently identified using the WHO criterium) from general population, with an AUROC of 0.94 (95% CI 0.920–0.952, p < 0.001). MetSCORE is also able to discriminate the intermediate phenotypes, identifying the early risk of MetS in a quantitative way and ranking individuals according to their risk of undergoing MetS (for general population) or according to the severity of the syndrome (for MetS patients). Conclusions We believe that MetSCORE may be an insightful tool for early intervention and lifestyle modifications, potentially preventing the aggravation of metabolic syndrome.

Maintaining a balanced ratio between sodium and potassium intake is one of the most important dietary and lifestyle factors in the development of metabolic syndrome (MetS), but available evidence is still limited, particularly when using urine samples to estimate this ratio. We aim to evaluate the associations between the 24-h urinary sodium–potassium ratio (24hUNa/KE) and MetS risk through a large health check-up program in China. This cross-sectional study analyzed health check-up data from 59,292 participants at the Third Xiangya Hospital’s Department of Health Management in Changsha, China, from 2018 to 2021. Each participant gave one fasting urine sample to analyze sodium, potassium, and creatinine levels during the check-up. The Kawasaki formula estimated 24-h urinary sodium (24hUNaE) and potassium excretion (24hUKE), with the 24hUNa/KE ratio calculated by dividing 24hUNaE by 24hUKE. The prevalence of MetS was found to be 19.27%. Notably, the overall MetS prevalence was higher in men (28.08%) than in women (7.83%). In women, MetS prevalence increased from 6.35 to 10.30% across the lowest to highest 24hUNa/KE quartiles. A significant increase in MetS prevalence was associated with each standard deviation increase in 24hUNa/KE (adjusted odds ratio [AOR], 1.03; 95% confidence interval [CI] 1.01–1.06), particularly for central obesity (AOR, 1.04; 95% CI 1.02–1.06) and elevated blood pressure (AOR, 1.20; 95% CI 1.17–1.22). In women, a one standard deviation increase in the 24hUNa/KE ratio raised the risk of MetS by 9% (AOR, 1.09; 95% CI 1.05–1.14), but no significant link was found in men. A strong positive link exists between 24hUNa/KE and MetS and its components, especially central obesity and high blood pressure, with a more significant effect in women.