Search Results (5,823)

Background/Objectives: This secondary and exploratory meta-analysis re-evaluated 30 randomized controlled trials on free and added sugars (FS) detailed in the European Food Safety Authority’s (EFSA) report on the tolerable upper intake level for dietary sugars, focusing on the influence of food source (beverages, foods, or mixed) on cardiometabolic and anthropometric health. Methods: The EFSA’s method of analyzing the relative FS intake (difference between treatment and comparator arms, Δ%E^fs) was used, with further adjustment for the reported intake of all sources of FS and energy. The EFSA’s “high vs. low” random-effects meta-analysis comparing groups with the highest and lowest FS intake was replicated, and additional exploratory dose–response meta-regressions (linear and non-linear) were performed, stratified by food source. Given the secondary and observational nature of the analysis, all source-stratified findings should be interpreted as hypothesis-generating, rather than causal. Results: There were no interactions between Δ%E^fs and food source for any outcome, and within a source there were linearly positive and statistically significant regressions for body weight (mixed), low-density lipoprotein cholesterol (LDL-C, foods), and uric acid (beverages). Across 13 outcomes, Δ%E^fs was positively and linearly related to greater fasting glucose, high-density lipoprotein cholesterol (HDL-C), and LDL-C, and non-linearly to body weight. However, the data were limited in their representation of FS intake at typical population levels, and there were insufficient data to investigate the effect of FS from foods on most anthropometric outcomes. Conclusions: Meta-regressive dose–responses revealed little relationship between Δ%E^fs from specific food sources and health outcomes, but such effects might be masked by confounding factors. Future trials that test realistic intakes of FS across diverse food matrices and account for dietary compensation would help to overcome limitations in the body of evidence. Full article

Background/Objectives: The relationship between P-wave dispersion (Pd) and disease status in patients with Familial Mediterranean Fever (FMF) undergoing colchicine treatment is unclear in the literature, and results are contradictory. This study aimed to evaluate P-wave dispersion in patients with Familial Mediterranean Fever receiving regular long-term colchicine treatment and to compare these findings with those of age- and sex-matched individuals without FMF. Methods: A cross-sectional and observational study included 97 individuals with positive FMF and 97 individuals with negative FMF. FMF diagnosis was confirmed according to the Tel-HaShomer criteria, and all patients received regular colchicine treatment and were evaluated during the attack-free period. P maximum, P minimum, and Pd were measured using standard 12-lead electrocardiography (ECG); clinical, laboratory, and drug data were recorded. Pd associations were analyzed using correlation and multivariable regression. Results: Pd was found to be significantly higher in FMF (+) patients (47 vs. 39 ms, p < 0.001). Pd showed a positive correlation with FMF status (r = 0.508, p < 0.001), colchicine dose (r = 0.476, p < 0.001), white blood cell (WBC) (r = 0.209, p = 0.005) and high-density lipoprotein cholesterol (HDL-C) (r = 0.156, p = 0.037) and a negative correlation with calcium channel blocker use (r = −0.245, p = 0.001). In multivariate analysis, FMF increased Pd by 10.17 ms, while calcium channel blockers decreased it by 11.78 ms (p < 0.001). Age, WBC and HDL-C also had independent positive effects on Pd (p < 0.001, p = 0.017, p = 0.040, respectively). Conclusions: These findings suggest that FMF is associated with increased P-wave dispersion despite regular colchicine treatment, indicating persistent subclinical atrial conduction heterogeneity. Full article

Atherosclerotic cardiovascular disease (ASCVD) is increasingly recognized not merely as a lipid-storage disorder but as a chronic, lipid-driven inflammatory condition of the arterial wall. Despite the widespread use of statins and other lipid-lowering therapies, a substantial “residual inflammatory risk” persists, propelling the search for targeted immunopharmacological interventions. At the forefront of this inflammatory cascade is the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which serves as a central orchestrator of vascular inflammation by linking metabolic dysregulation to the innate immune response. Atherogenic danger signals—such as oxidized low-density lipoprotein (ox-LDL) and cholesterol crystals—trigger NLRP3 activation through reactive oxygen species (ROS) generation, lysosomal rupture, and potassium efflux. This, in turn, drives the maturation of pro-inflammatory cytokines (IL-1β and IL-18) and initiates macrophage pyroptosis. In this review, we systematically evaluate the immunomodulatory potential of natural products—both complex extracts and single bioactive compounds—in inhibiting the NLRP3 inflammasome axis. We detail the pharmacological mechanisms by which these natural agents intercept inflammatory signaling at multiple stages: suppressing TLR4/NF-κB-mediated priming, scavenging mitochondrial ROS, and restoring autophagic flux via AMPK/mTOR pathways to prevent inflammasome assembly. By critically analyzing these pathways, we highlight natural product-derived inhibitors as a promising class of immunomodulators capable of attenuating atherosclerotic progression and addressing the persistent challenge of residual inflammatory risk. Full article

Saskatoon berry (SB), a traditional food of Indigenous people, has been associated with cardiometabolic benefits in animal models; however, its effects on humans remain unclear. This study investigated the effects of dried SB consumption on cardiometabolic outcomes, gut microbiota, and short-chain fatty acids (SCFAs) profiles in healthy adults. In a 10-week, single-arm, and open-label trial, 20 healthy adults consumed 40 g/day of freeze-dried whole SB. Biochemical measures, physical exams, dietary records, participant feedback, and fecal samples were collected before and after the intervention. Gut microbiota composition and fecal SCFAs were profiled using 16S-rRNA sequencing and gas chromatography–mass spectrometry, respectively. SB intake significantly reduced fasting plasma glucose, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), non-high-density lipoprotein-cholesterol (non-HDL-c), systolic blood pressure, and high-sensitivity C-reactive protein, while increasing dietary fiber intake. Fiber intake was negatively correlated with TC, LDL-c and non-HDL-c (p < 0.05). The relative abundance of fecal Prevotellaceae increased after SB consumption and was positively correlated with multiple fecal SCFAs (p < 0.05–0.0001), while being negatively associated with lipid profiles and blood pressure. No adverse cardiovascular, hepatic, or renal dysfunction were observed; however, the significant increase in sugar intake may pose a risk for elevated blood glucose. Therefore, limiting other high-sugar foods during SB supplementation may be advisable for individuals with glucose intolerance. Overall, SB intake improved glucose and lipid metabolism and lowered blood pressure and inflammatory markers in healthy adults. These cardiometabolic benefits may be mediated by fiber and anthocyanins in SB and through modulation of gut microbiota and SCFA production; however, further confirmation is needed in subsequent randomized controlled trials. Full article

Background/Objectives: Cardiovascular diseases are the leading cause of mortality worldwide, with coronary artery disease (CAD) being the most prevalent. An atherogenic diet contributes to oxidative stress by promoting lipid peroxidation in lipoproteins and cellular membranes, thereby compromising membrane integrity, which is reflected in lower phase angle (PhA) values. Dietary antioxidants play a crucial role in cellular health and in reducing atherosclerotic risk; therefore, the Dietary Antioxidant Index (DAI) is an important measure, as dietary antioxidants may counteract oxidative damage. This study aimed to assess the association between anthropometric, PhA, and biochemical variables across groups classified according to DAI. Methods: This was an analytical cross-sectional study. A total of 107 subjects, with and without CAD, were included. Oxidized LDL (oxLDL) and oxidized HDL (oxHDL) were determined using the ELISA technique. PhA was measured by bioelectrical impedance analysis, and DAI was calculated using the formula proposed by Wright et al. Results: DAI was positively associated with HDL concentrations in women with CAD, indicating that HDL levels increased by 5.8 mg/dL for each unit increase in DAI (R² = 0.625, p = 0.001). Furthermore, for each unit increase in DAI, the TC/HDL ratio decreased by 0.3 (R² = 0.625, p = 0.006), and the LDL/HDL ratio decreased by 0.2 (R² = 0.506, p = 0.012). Conclusions: A higher DAI is associated with a more favorable lipid profile in women with CAD, particularly with higher HDL concentrations and lower TC/HDL and LDL/HDL ratios. Full article

Phospholipid transfer protein (PLTP) is a lipid transfer protein classically studied in the context of plasma lipoprotein metabolism, high-density lipoprotein (HDL) remodeling, and cardiovascular disease risk. PLTP facilitates phospholipid transfer between lipoproteins and regulates HDL particle size and composition through interactions with apolipoprotein A-I and apolipoprotein A-II. While its systemic roles in cholesterol handling, reverse cholesterol transport, and inflammatory signaling are well established, the cell-autonomous functions of PLTP within cardiomyocytes remain poorly defined, particularly in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Extensive experimental and clinical studies demonstrate that PLTP enhances ABCA1-dependent cholesterol efflux primarily by stabilizing ABCA1 at the plasma membrane and by promoting the generation of lipid-poor apolipoprotein A-I and pre-β HDL particles, which serve as efficient cholesterol acceptors; the magnitude of these effects depends on cellular context, PLTP expression levels, and the availability of lipid acceptors. PLTP expression is metabolically regulated and widely distributed across tissues, including macrophages and other non-hepatic cells, supporting roles beyond circulating lipoprotein remodeling. Altered PLTP activity has been linked to atherosclerosis, cardiovascular disease, and inflammatory pathways, underscoring its relevance to cardiac pathophysiology. Emerging evidence further suggests that intracellular cholesterol distribution, rather than total cholesterol content alone, critically influences mitochondrial membrane composition, bioenergetics, and stress signaling in cardiomyocytes. These observations raise the possibility that PLTP-regulated lipid flux may indirectly shape mitochondrial function by modulating cellular cholesterol homeostasis. This review synthesizes current knowledge of PLTP biology, cholesterol metabolism, and lipoprotein remodeling, and integrates these concepts with emerging frameworks in cardiomyocyte lipid metabolism and mitochondrial physiology. We highlight human iPSC-derived cardiomyocytes as a strategic and translationally relevant platform to investigate PLTP’s non-canonical, cell-intrinsic roles, identify critical knowledge gaps, and propose future directions for elucidating how PLTP may influence mitochondrial function in human cardiac cells. Full article

Hypertriglyceridemia is a well-recognized contributor to residual atherosclerotic cardiovascular disease risk and a predisposing factor for acute pancreatitis. Despite the availability of currently available pharmacologic agents and lifestyle interventions, patients with severe and refractory hypertriglyceridemia often fail to achieve adequate control. Recent advances in the molecular understanding of triglyceride metabolism have driven the development of targeted therapies that selectively modulate key regulatory pathways. This study sought to provide an overview of triglyceride regulation, the atherogenic role of remnant lipoproteins, and clinical evidence of emerging triglyceride-lowering therapies. Lipoprotein metabolism is regulated by a complex network of regulatory proteins that include lipoprotein lipase (LPL), apolipoproteins such as apolipoprotein C-III (ApoC-III), and angiopoietin-like proteins (ANGPTLs). Targeting these proteins in the metabolic cascade has shown promising results in reducing triglyceride levels. Emerging therapies such as antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) directed against ApoC-III (volanesorsen, olezarsen, and plozasiran), inhibitors of ANGPTL3 (evinacumab and zodasiran), and fibroblast growth factor 21 (FGF-21) analogs (pegozafermin) have demonstrated substantial triglyceride-lowering efficacy. These agents have achieved reductions in triglyceride levels of up to 80 percent in clinical trials. Additionally, preliminary evidence suggests that these agents may also reduce the incidence of acute pancreatitis and improve cardiometabolic risk profiles, although dedicated trials are still needed to confirm these outcomes. The therapeutic landscape for hypertriglyceridemia is rapidly evolving. Integrating these novel agents into clinical practice will require individualized treatment plans, sustained lifestyle modification, and careful safety monitoring. Full article

Background/Objectives: Vitamin D plays an important role in glucose metabolism, lipid regulation, and inflammatory processes, and has been implicated in cardiometabolic health. However, its associations with specific metabolic biomarkers remain inconsistent, particularly in older adults. This study aimed to examine whether vitamin D deficiency is differentially associated with multiple metabolic biomarkers in a nationally representative sample of older adults. Methods: This cross-sectional study used data from the 2024 Korea National Health and Nutrition Examination Survey, including 1806 adults aged ≥65 years. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D levels < 20 ng/mL. Metabolic biomarkers included fasting glucose, glycated hemoglobin (HbA1c), triglycerides, C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C), waist circumference, and body mass index (BMI). Complex sample linear regression analyses were performed with sequential adjustment for sociodemographic factors, health behaviors, and comorbidities. Results: In unadjusted analyses, vitamin D deficiency was associated with adverse metabolic profiles, including higher fasting glucose, HbA1c, triglycerides, waist circumference, and CRP levels, and lower HDL-C levels. After adjustment for sociodemographic factors, health behaviors, and comorbidities, significant associations remained for HbA1c (β = 0.10, p = 0.034), triglycerides (β = 0.10, p = 0.003), and waist circumference (β = 1.21, p = 0.040). No significant associations were observed for fasting glucose, HDL-C, CRP, or BMI. Conclusions: Vitamin D deficiency was independently associated with poorer long-term glycemic status, hypertriglyceridemia, and central adiposity in older adults, but not with other metabolic markers after adjustment. These findings suggest that the metabolic correlates of vitamin D deficiency may be domain-specific rather than generalized. Longitudinal and interventional studies are needed to clarify causality and underlying mechanisms. Full article

Thyroid hormones regulate a complex and interconnected network of metabolic signaling. Thyroid dysfunction is, at present, defined and monitored through circulating thyroid-stimulating hormone (TSH) and free thyroid hormones. However, biochemical normalization does not entirely indicate restoration of metabolic homeostasis. This discrepancy highlights a critical limitation of the current TSH-centric paradigm, which also fails to explain the heterogeneity in cardiometabolic outcomes observed among patients with similar biochemical profiles. Metabolomics, through the analysis of tissue-specific biofluids, could aid in capturing the complex metabolic perturbations that characterize this disease. In this review, we summarize metabolomic signatures typical of thyroid dysfunction, perform a critical evaluation of limitations and variability across studies, and explore the clinical and translational implications of metabolomics in thyroid pathology. In addition, five metabolic hubs influenced by thyroid hormone activity are summarized: (i) lipid and lipoprotein remodeling; (ii) mitochondrial energetics and redox balance; (iii) amino acid metabolism and protein turnover; (iv) gut–liver–thyroid axis and (v) biological impact of subclinical thyroid diseases. Taken together, these findings challenge the sufficiency of a diagnostic model based on TSH measurement and pose metabolomics as a promising tool to refine risk stratification, uncover subclinical vulnerability and guide patient-centered management of thyroid disease. Despite its promise, clinical adoption of metabolomics is hindered by a lack of standardization and complex data interpretation. To overcome these limitations, coupling metabolomics with genomics and transcriptomics may allow its translation into practical application. Full article

Background/Objectives: The guideline targets for blood pressure (BP), hemoglobin A1c (HbA1c), and low-density lipoprotein cholesterol (LDL-C) are frequently unmet, and physicians often misjudge control. This study aimed to characterize the real-world control of BP, HbA1c, and LDL-C in patients with type 2 diabetes (T2D) and hypertension, herein called cardiometabolic multimorbidity (CMM), and to compare guideline-based versus physician-perceived disease control. Methods: We conducted SNAPSHOT–Brazil, a nationwide, multicenter, cross-sectional study to gather real-world data on patients with CMM. The ESC guidelines defined the cardiovascular (CV) risk and control targets. Results: We included 451 patients with hypertension and T2D (median age 65 years; 60% female; 54% White). Most patients (98%) were on pharmacotherapy and reported high adherence (according to the Hill–Bone Medication Adherence Scale). A very high CV risk predominated (78%); 22% of the patients were at a high risk. The guideline-defined control was achieved in 27% for BP, 34% for HbA1c, 13% for LDL-C, and 6% for both BP and LDL-C; only 3% met all three targets simultaneously. The physicians accurately stratified the CV risk in 49% of patients, while 50% had their CV risk underestimated. They systematically overestimated control in 29% of cases for BP, 35% for LDL-C, and 25% for both. The sensitivity ranged from 0.88 to 0.98; the positive predictive values ranged from 0.19 to 0.48, and the positive likelihood ratios ranged from 2.16 to 3.65. Conclusions: The SNAPSHOT–Brazil study revealed a low attainment of BP, HbA1c, and LDL-C targets, despite the widespread pharmacotherapy and the high self-reported adherence. The physicians consistently overestimated disease control and underestimated the CV risk. Full article

Ceramides, sphingolipids produced from fatty acids linked to sphingosine and an amide, are structural elements of cellular membranes and lipoproteins. These molecules also retain biological effects in key cellular pathways such as oxidative stress and inflammation, apoptosis, and fibrosis, with a role in the onset and development of many pathophysiological conditions, including obesity, diabetes, and insulin resistance. Increasing evidence suggests that different nutrients and dietary patterns may affect ceramide levels, both negatively (e.g., fructose and the Western diet), whereas others improve the ceramide profile (e.g., ω-3 PUFAs, resveratrol, vitamin D, and the Mediterranean and the Nordic diets). Thus, ceramide nutritional modulation could represent a simple, additive, and reliable tool to improve metabolic health. This review focused on the role of ceramides in the pathophysiology of diabetes and obesity, as well as their pathogenetic mechanisms of action. Ceramides are increasingly recognized as “dynamic metabolic interfaces” linking nutrition and disease. This review aims to address a critical gap by synthesizing recent evidence on how dietary interventions, in addition to pharmacological approaches, can specifically target the enzymatic pathways involved in ceramide synthesis to enhance metabolic health. Thus, this review offers a concentrated analysis of the response of specific ceramide species, such as Cer16:0 and Cer18:0, to distinct dietary factors. Additionally, it incorporates emerging evidence on the role of gut microbiota in the biotransformation of sphingolipids, thereby adding a contemporary dimension to the established nutritional perspective. Full article

Background: To investigate the association between the uric acid-to-high-density lipoprotein cholesterol ratio (UAHDLr) and the risk of new-onset atrial fibrillation (NOAF) during hospitalization in patients with non-ST-elevation myocardial infarction (NSTEMI). Methods: This retrospective cohort study included NSTEMI patients without prior atrial fibrillation. UAHDLr was log2-transformed to evaluate the effect of doubling. Feature selection was performed using least absolute shrinkage and selection operator regression. Cox proportional hazards models with sequential adjustments were applied. Nonlinear associations were assessed using restricted cubic spline analysis, and discrimination was evaluated with time-dependent receiver operating characteristic analysis. Results: UAHDLr was independently associated with in-hospital NOAF across all models. Doubling (1-unit increase) UAHDLr significantly increased NOAF risk in unadjusted (HR: 5.97, 95% CI: 3.71–9.61) and clinically adjusted models (HR: 5.98, 95% CI: 3.58–9.99). The association was stronger in the LASSO-adjusted (HR: 8.19, 95% CI: 4.13–16.24) and fully adjusted models (HR: 13.40, 95% CI: 5.90–30.44). Spline analysis showed a progressive increase in NOAF risk with higher UAHDLr values. Discrimination was stable, with an area under the curve of approximately 0.76. Conclusions: UAHDLr is a strong, easily accessible biomarker for predicting in-hospital NOAF in NSTEMI patients and may support early risk stratification. Full article

Blood metabolism in dairy cows is crucial for milk quality, functioning primarily through the “blood–milk” metabolic axis. Allium mongolicum Regel (AMR), a functional Allium herb, has been shown to regulate on ruminant lipid metabolism. This study investigated the impact of AMR ethanol extract (AME) on lactation performance, blood lipid parameters, and blood–milk metabolomes. Twelve mid-lactation Holsteins (606 ± 11 kg; milk yield 33.14 ± 2.08 kg/d) of parity 2–3 were assigned to either a basal diet (CON) or a diet supplemented with 54 g/d of AME (AEE). Results indicated that AME significantly decreased plasma triglycerides (TG), C15:0, C16:1, C18:1 n-9 c, C18:3 n-6, monounsaturated fatty acids (p < 0.05) and significantly increased C18:2 n-6 c, polyunsaturated fatty acids (p < 0.05). Lactation performance, including the average daily dry matter intake, daily yields of milk fat, protein and lactose, remained unaffected by the AME addition (p > 0.05). Metabolomic profiling revealed that AME significantly enriched the glycerophospholipid metabolism pathway in plasma, upregulating key phospholipid precursors such as L-serine and Sphinganine. Concurrently, milk metabolomics showed an upregulation of short-chain Acylcarnitines. Plasma TG correlated negatively with both plasma L-serine and milk Acylcarnitines, whereas low-density lipoprotein correlated positively with these energy-driven milk metabolites. These findings suggest that AME may contribute to remodeling the plasma lipid metabolic profile in a manner that could facilitate plasma-to-milk lipid flux. This appears to occur through enhanced hepatic lipid processing and increased mammary lipid utilization, offering preliminary insights into potential nutritional strategies for supporting lipid metabolism in dairy cows. Full article

Background/Objectives: this study evaluated the effects of a 12-week multicomponent training (MCT) program combined with multiprofessional interventions (nutritional and psychoeducational) on body composition, lipid profiles, fasting glucose levels, and arterial stiffness in Brazilian older women stratified by nutritional status. Methods: thirty-six older women, who were classified as normal weight (n = 8; mean age: 69.2 ± 7.2 years), overweight (n = 13; mean age: 72.1 ± 5.3 years), or obese (n = 15; mean age: 70.3 ± 4.6 years), were included in the study. The outcomes included body fat percentage (BFP), visceral fat level, fat-free mass (FFM), fasting glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and arterial stiffness, as determined by pulse wave velocity (PWV). Results: BFP was reduced in all groups (p < 0.001), but in the overweight and obese groups, these decreases were greater. Visceral fat level decreased significantly in all groups (p < 0.001), with greater decreases in the obese group compared with the normal weight and overweight groups (p < 0.001), and greater reductions in the normal weight group compared to the overweight group (p < 0.05). A significant reduction in PWV was observed only in the overweight group (p < 0.05), while greater improvements were observed in the overweight group compared to the normal weight group (p < 0.05) in FFM, lipid profiles, and fasting glucose. Conclusions: an MCT combined with multiprofessional intervention effectively reduced BFP and arterial stiffness in Brazilian older women with excess adiposity. Full article

Background: Postprandial triglyceride (TG) metabolism represents a dynamic dimension of lipid physiology that complements conventional fasting lipid assessment. Although low-density lipoprotein cholesterol (LDL-C) remains the primary therapeutic target in cardiovascular prevention, residual cardiovascular risk persists in many individuals despite apparently adequate fasting lipid control. Because most individuals spend the majority of their waking hours in a fed state, postprandial TG responses may provide clinically relevant insight into metabolic flexibility, dietary exposure, and the efficiency of TG-rich lipoprotein clearance. Methods: This narrative review was conducted using a literature search guided by predefined themes, keywords, and databases, without following a formal systematic review protocol. Randomized controlled trials, observational studies, meta-analyses, and major reviews addressing postprandial lipid metabolism, dietary determinants, and cardiometabolic risk were included, with priority given to human studies. Results: Postprandial TG responses are strongly influenced by dietary composition, eating patterns, and metabolic health. Individuals with insulin resistance, type 2 diabetes, obesity, and metabolic-associated steatotic liver disease (MASLD) frequently demonstrate exaggerated or prolonged postprandial lipemia even when fasting TG concentrations appear acceptable. While circulating TGs serve as practical clinical markers of postprandial lipid handling, cholesterol-enriched remnant lipoproteins more closely reflect atherogenic burden. Nutritional interventions, weight management, and physical activity consistently improve postprandial TG dynamics, whereas pharmacologic therapy provides additional benefit in selected high-risk patients. Non-fasting TG measurements may provide additional insight into postprandial lipid metabolism and residual cardiovascular risk, although standardized protocols and validated clinical thresholds remain to be established. Conclusions: Postprandial TG metabolism provides clinically meaningful information beyond fasting lipid measurements and represents a useful adjunct for refining residual cardiovascular risk assessment. Although standardized protocols remain limited, integrating nutritional and clinical perspectives may support a more comprehensive and individualized approach to cardiometabolic prevention. Full article