Effect of garlic on the components of metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials.
Journal of ethnopharmacology. 2024;(Pt B):116960
ETHNOPHARMACOLOGICAL RELEVANCE Metabolic diseases are the major causes of macrovascular and microvascular complications which lead to morbidity and mortality. Traditionally, garlic has been used as food and medicine for more than 5000 years. However, efficacy studies have shown conflicting results regarding the garlic effect. AIM OF THE STUDY This study aims to evaluate the efficacy of garlic on the components of metabolic syndrome (MetS) in metabolic disease patients. MATERIALS AND METHODS This study was a systematic review and meta-analysis of randomized controlled trials (RCTs). Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), and Google scholar were searched till December 25, 2021 for identifying the relevant studies that have shown the effects of garlic on components of metabolic syndrome in metabolic disease patients. The mean difference with 95% CI was calculated using fixed-effect or random-effect models. RESULTS The effect of garlic has shown significant changes on waist circumference (p-value= <0.0001), total cholesterol (p < 0.0001), low density lipoprotein (p = 0.01), high density lipoprotein (p < 0.00001), triglycerides (p < 0.00001), systolic blood pressure (p < 0.00001), diastolic blood pressure (p < 0.00001), glucose (p < 0.00001), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (p = 0.04), C-reactive protein (p < 0.00001), tumor necrosis factor (TNF)-α (p = 0.002), interleukin (IL)-6 (p = 0.0001). Subgroup analysis has shown the favorable effects of garlic in metabolic disease patients. CONCLUSION Our meta-analysis results confirm the findings that garlic could be useful as an anti-hyperlipidemic, anti-hyperglycemic, anti-hypertensive and anti-inflammatory drug.
Phthalate exposure and risk of metabolic syndrome components: A systematic review.
Environmental pollution (Barking, Essex : 1987). 2024;(Pt 1):122714
Metabolic syndrome is a cluster of conditions that increase the risk of cardiovascular disease, i.e. obesity, insulin resistance, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-c) levels and arterial hypertension. Phthalates are environmental chemicals which might influence the risk of the aforementioned disturbances, although the evidence is still controversial. The objective of this work was to synthesize the evidence on the association between human phthalate exposure and metabolic syndrome or any of its components. In this systematic review, the PRISMA guidelines were followed and the literature was search in PubMed, Web of Science and Scopus. Longitudinal and cross-sectional studies were included, the later only if a subclinical marker of disease was evaluated. The methodological quality was assessed with the Newcastle Ottawa Scale and a checklist for Analytical Cross-Sectional Studies developed in the Joanna Briggs Institute. A total of 58 articles were identified that showed high heterogenicity in the specific phthalates assessed, time-window of exposure and duration of follow-up. The quality of the studies was evaluated as high (n = 46, score >7 points) or medium (n = 12, score 4-6). The most frequently studied phthalates were DEHP-MEHP, MBzP and MEP. The evidence revealed a positive association between prenatal (in utero) exposure to most phthalates and markers of obesity in the offspring, but contradictory results when postnatal exposure and obesity were assessed. Moreover, postnatal phthalate exposure showed positive and very consistent associations with markers of diabetes and, to a lesser extent, with triglyceride levels. However, fewer evidence and contradictory results were found for HDL-c levels and markers of hypertension. The suggested mechanisms for these metabolic effects include transcription factor PPAR activation, antagonism of thyroid hormone function, antiandrogenic effects, oxidative stress and inflammation, and epigenetic changes. Nevertheless, as the inconsistency of some results could be related to differences in the study design, future research should aim to standardise the exposure assessment.
The influence of epigenetics and inflammation on cardiometabolic risks.
Seminars in cell & developmental biology. 2024;(Pt C):175-184
Cardiometabolic diseases include metabolic syndrome, obesity, type 2 diabetes mellitus, and hypertension. Epigenetic modifications participate in cardiometabolic diseases through several pathways, including inflammation, vascular dysfunction, and insulin resistance. Epigenetic modifications, which encompass alterations to gene expression without mutating the DNA sequence, have gained much attention in recent years, since they have been correlated with cardiometabolic diseases and may be targeted for therapeutic interventions. Epigenetic modifications are greatly influenced by environmental factors, such as diet, physical activity, cigarette smoking, and pollution. Some modifications are heritable, indicating that the biological expression of epigenetic alterations may be observed across generations. Moreover, many patients with cardiometabolic diseases present with chronic inflammation, which can be influenced by environmental and genetic factors. The inflammatory environment worsens the prognosis of cardiometabolic diseases and further induces epigenetic modifications, predisposing patients to the development of other metabolism-associated diseases and complications. A deeper understanding of inflammatory processes and epigenetic modifications in cardiometabolic diseases is necessary to improve our diagnostic capabilities, personalized medicine approaches, and the development of targeted therapeutic interventions. Further understanding may also assist in predicting disease outcomes, especially in children and young adults. This review describes epigenetic modifications and inflammatory processes underlying cardiometabolic diseases, and further discusses advances in the research field with a focus on specific points for interventional therapy.
Association between vitamin D and cardiovascular health: Myth or Fact? A narrative review of the evidence.
Women's health (London, England). 2023;:17455057231158222
Vitamin D deficiency is prevalent worldwide. Since the discovery of the expression of vitamin D receptor in ventricular cardiomyocytes, fibroblasts, and blood vessels, there has been a growing body of literature assessing the link between vitamin D status and cardiovascular health from one side, and the effect of vitamin D supplementation on prevention of cardiovascular diseases from the other side. In this review, we summarized studies highlighting the role of vitamin D on cardiovascular health, namely atherosclerosis, hypertension, heart failure, and metabolic syndrome, a recognized significant risk factor for cardiovascular diseases. Studies showed discrepancies between findings from cross-sectional and longitudinal cohorts and those from interventional trials, but also between one outcome and another. Cross-sectional studies found a strong association between low 25 hydroxyvitamin D (25(OH)D3) and acute coronary syndrome, and heart failure. These findings encouraged the promotion for vitamin D supplementation as a preventive measure for cardiovascular diseases in the elderly, namely in women. This fact, however, turned out into a myth with the results of large interventional trials that did not show any benefit from vitamin D supplementation in reducing ischemic events, heart failure or its outcomes, or hypertension. Although some clinical studies showed beneficial effect of vitamin D supplementation on insulin sensitivity and metabolic syndrome, this effect was not consistent across all studies.
Carriers of autosomal recessive conditions: are they really 'unaffected?'.
Journal of medical genetics. 2023
Mendel's Law of Dominance suggests that recessive disease expression requires the inheritance of two mutated alleles as the dominant, wildtype allele suppresses disease presentation leading to the expression of physiological normal phenotypes. However, there is existing evidence that challenges this school of thought. Here, we summarise existing literature evaluating metabolic and health impacts among carriers of autosomal recessive conditions, focusing on phenylketonuria (PKU), classical homocystinuria, galactosemia and Usher syndrome as examples. Our findings suggest that carriers, often described as 'unaffected', may actually display attenuated symptoms for the recessive disease they are carrying. For instance, PKU is an inborn error of metabolism characterised by the build-up of plasma phenylalanine attributed to the deficiency of the phenylalanine hydroxylase (PAH) enzyme. While less severe, PKU carriers also exhibit this impaired enzymatic activity, leading to elevated plasma phenylalanine levels, especially after phenylalanine consumption. Related to these metabolic alterations in the PAH pathway, there is early evidence to suggest that PKU carriers may have compromised cognitive and mental health outcomes. Overall, research on the health and metabolic impacts of PKU carriers is sparse, with most studies conducted several decades ago. However, early evidence suggests that intermediate phenotypes among carriers of autosomal recessive conditions are plausible. The illustrated possible intermediate phenotypes observed among carriers necessitates future research to determine possible clinical implications among this population.
Acute and long-term exercise adaptation of adipose tissue and skeletal muscle in humans: a matched transcriptomics approach after 8-week training-intervention.
International journal of obesity (2005). 2023;(4):313-324
BACKGROUND Exercise exerts many health benefits by directly inducing molecular alterations in physically utilized skeletal muscle. Molecular adaptations of subcutaneous adipose tissue (SCAT) might also contribute to the prevention of metabolic diseases. AIM: To characterize the response of human SCAT based on changes in transcripts and mitochondrial respiration to acute and repeated bouts of exercise in comparison to skeletal muscle. METHODS Sedentary participants (27 ± 4 yrs) with overweight or obesity underwent 8-week supervised endurance exercise 3×1h/week at 80% VO2peak. Before, 60 min after the first and last exercise bout and 5 days post intervention, biopsies were taken for transcriptomic analyses and high-resolution respirometry (n = 14, 8 female/6 male). RESULTS In SCAT, we found 37 acutely regulated transcripts (FC > 1.2, FDR < 10%) after the first exercise bout compared to 394, respectively, in skeletal muscle. Regulation of only 5 transcripts overlapped between tissues highlighting their differential response. Upstream and enrichment analyses revealed reduced transcripts of lipid uptake, storage and lipogenesis directly after exercise in SCAT and point to β-adrenergic regulation as potential major driver. The data also suggest an exercise-induced modulation of the circadian clock in SCAT. Neither term was associated with transcriptomic changes in skeletal muscle. No evidence for beigeing/browning was found in SCAT along with unchanged respiration. CONCLUSIONS Adipose tissue responds completely distinct from adaptations of skeletal muscle to exercise. The acute and repeated reduction in transcripts of lipid storage and lipogenesis, interconnected with a modulated circadian rhythm, can counteract metabolic syndrome progression toward diabetes.
The effects of a 6-month intervention aimed to reduce sedentary time on skeletal muscle insulin sensitivity: a randomized controlled trial.
American journal of physiology. Endocrinology and metabolism. 2023;(2):E152-E162
Sedentary behavior (SB) and physical inactivity associate with impaired insulin sensitivity. We investigated whether an intervention aimed at a 1-h reduction in daily SB during 6 mo would improve insulin sensitivity in the weight-bearing thigh muscles. Forty-four sedentary inactive adults [mean age 58 (SD 7) yr; 43% men] with metabolic syndrome were randomized into intervention and control groups. The individualized behavioral intervention was supported by an interactive accelerometer and a mobile application. SB, measured with hip-worn accelerometers in 6-s intervals throughout the 6-mo intervention, decreased by 51 (95% CI 22-80) min/day and physical activity (PA) increased by 37 (95% CI 18-55) min/day in the intervention group with nonsignificant changes in these outcomes in the control group. Insulin sensitivity in the whole body and in the quadriceps femoris and hamstring muscles, measured with hyperinsulinemic-euglycemic clamp combined with [18F]fluoro-deoxy-glucose PET, did not significantly change during the intervention in either group. However, the changes in hamstring and whole body insulin sensitivity correlated inversely with the change in SB and positively with the changes in moderate-to-vigorous PA and daily steps. In conclusion, these results suggest that the more the participants were able to reduce their SB, the more their individual insulin sensitivity increased in the whole body and in the hamstring muscles but not in quadriceps femoris. However, according to our primary randomized controlled trial results, this kind of behavioral interventions targeted to reduce sedentariness may not be effective in increasing skeletal muscle and whole body insulin sensitivity in people with metabolic syndrome at the population level.NEW & NOTEWORTHY Aiming to reduce daily SB by 1 h/day had no impact on skeletal muscle insulin sensitivity in the weight-bearing thigh muscles. However, successfully reducing SB may increase insulin sensitivity in the postural hamstring muscles. This emphasizes the importance of both reducing SB and increasing moderate-to-vigorous physical activity to improve insulin sensitivity in functionally different muscles of the body and thus induce a more comprehensive change in insulin sensitivity in the whole body.
Incorrect analysis in "Effects of the application of a food processing-based classification system in obese women: A randomized controlled pilot study" has resulted in incorrect conclusions of demonstrated effects where no such effects have been demonstrated.
Nutrition and health. 2023;:2601060231194653
In their 2023 Nutrition and Health paper "Effects of the application of a food processing-based classification system in obese women: A randomized controlled pilot study", Giacomello et al. investigated the effects of an educational intervention based on the Dietary Guidelines for the Brazilian Population among obese women. The authors concluded that the intervention significantly improved weight loss, quality of life, components of metabolic syndrome, and pain. However, we believe the statistical analysis employed in the study was flawed. The authors used within-group changes to draw conclusions, which is known as a difference in nominal significance error. This error has the potential to inflate Type I error rates substantially. To address this issue, we re-analyzed the data obtained from the authors. We focused on body mass and hip circumference and replicated the incorrectly chosen within-group analyses, which remained significant. However, to properly evaluate the intervention's effectiveness, it is essential to compare the differences between the groups directly. Therefore, we calculated change scores for each participant and used independent samples t-tests and linear mixed models to compare between-group differences. Both methods yielded similar non-significant p-values, indicating that there is no significant effect of treatment on body mass or hip circumference. The original paper's conclusions regarding the effectiveness of the intervention are not supported by the proper statistical analysis. The data should be re-analyzed using appropriate between-group comparisons, and the corrected results should be published, or the incorrect results and original paper should be retracted.
Past, Present, and Future Perspectives of Plasminogen Activator Inhibitor 1 (PAI-1).
Seminars in thrombosis and hemostasis. 2023;(3):305-313
Plasminogen activator inhibitor 1 (PAI-1), a SERPIN inhibitor, is primarily known for its regulation of fibrinolysis. However, it is now known that this inhibitor functions and contributes to many (patho)physiological processes including inflammation, wound healing, cell adhesion, and tumor progression.This review discusses the past, present, and future roles of PAI-1, with a particular focus on the discovery of this inhibitor in the 1970s and subsequent characterization in health and disease. Throughout the past few decades diverse functions of this serpin have unraveled and it is now considered an important player in many disease processes. PAI-1 is expressed by numerous cell types, including megakaryocytes and platelets, adipocytes, endothelial cells, hepatocytes, and smooth muscle cells. In the circulation PAI-1 exists in two pools, within plasma itself and in platelet α-granules. Platelet PAI-1 is secreted following activation with retention of the inhibitor on the activated platelet membrane. Furthermore, these anucleate cells contain PAI-1 messenger ribonucleic acid to allow de novo synthesis.Outside of the traditional role of PAI-1 in fibrinolysis, this serpin has also been identified to play important roles in metabolic syndrome, obesity, diabetes, and most recently, acute respiratory distress syndrome, including coronavirus disease 2019 disease. This review highlights the complexity of PAI-1 and the requirement to ascertain a better understanding on how this complex serpin functions in (patho)physiological processes.
Tracing angiotensin II's yin-yang effects on cardiovascular-renal pathophysiology.
Minerva medica. 2023;(1):56-67
Adverse changes in cardiovascular and renal systems are major contributors to overall morbidity and mortality. Human cardiovascular and renal systems exhibit a complex network of positive and negative feedback that is reflected in the control of vascular tone via angiotensin II (Ang II) based signaling. This review will examine in some depth, the multiple components and processes that control the status and reflect the health of these various cardiovascular and renal systems, such as pathways associated to monomeric G proteins, RhoA/Rho kinase system and ERK, oxidative stress and NO balance. It will specifically emphasize the "yin-yang" nature of Ang II signaling by comparing and contrasting the effects and activity of various systems, pathways and components found in hypertension to those found in Gitelman's and Bartter's syndromes (GS/BS), two rare autosomal recessive tubulopathies characterized by electrolytic imbalance, metabolic alkalosis, sodium wasting and prominent activation of the renin-angiotensin-aldosterone system. Notwithstanding the activation of the renin-angiotensin-aldosterone system, GS/BS are normo-hypotensive and protected from cardiovascular-renal remodeling and therefore can be considered the mirror image, the opposite of hypertension.