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Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. Several studies suggest that the improvement of oxidative stress is suggested as a possible therapeutic strategy for pediatric nonalcoholic steatohepatitis. We performed a randomized, double-blind placebo-controlled trial to test the potential efficacy, assessed by improvement of oxidative stress parameters and liver ultrasound, and tolerability of a mixture of vitamin E and hydroxytyrosol (HXT) in adolescents with biopsy-proven NAFLD. Four hundred forty consecutive patients were screened, 80 of these with biopsy-proven NAFLD were enrolled. Forty patients received an oral dose of HXT and vitamin E and 40 children received the capsules of placebo for 4 months. Seventy patients completed the study. Patients in the treatment arm showed a decrease of insulin resistance (IR), triglyceride levels, oxidative stress parameters, and steatosis grade. Noteworthy, the steatosis improvement correlates with the levels of advanced glycation end products and carbonylated proteins. The HXT and vitamin E treatment improved the main oxidative stress parameters, IR, and steatosis in children with NAFLD. The use of two natural molecules that may have antioxidant effects seems a promising strategy that could be easily diet integrated to improve NAFLD-related liver damage in children. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver diseases, and is closely related to metabolic syndrome and its related conditions, diabetes mellitus and dyslipidemia. On the other hand, NAFLD as a multisystem disease increases the risk of several chronic diseases include type 2 diabetes mellitus, cardiovascular disease (CVD), and chronic kidney disease. The main objective was to review the efficacy of bioactive natural compounds assessed by clinical trials. Search literature using four databases (PubMed, EBSCO, Web of Science, and Ovid Medline) to review publications that focused on the impact of bioactive natural compounds in NAFLD treatment. Due to the lack of effective pharmacological treatments available for NAFLD, lifestyle modifications such as following a healthy diet, vigorous physical activity, and weight reduction remain the first line of treatment for NAFLD. However, due to the poor adherence to this type of treatment, especially for long-term weight loss diets some of which may have harmful effects on the liver, finding novel therapeutic agents for NAFLD treatment and/or preventing NAFLD progression has garnered significant interest. Although the therapeutic agents of NAFLD treatment have been reviewed previously, to date, no summary has been conducted of clinical trials examining the effects of herbal compounds on NAFLD-related biomarkers. This review highlights the beneficial role of herbal bioactives and medicinal plants in NAFLD treatment, particularly as complementary to a healthy lifestyle. All natural products described in this review seem to have some benefits to improve oxidative stress, cellular inflammation and insulin-resistance, which always remain as the “primum movens” of NAFLD pathogenesis. [ABSTRACT FROM AUTHOR]

Introduction: Non-alcoholic fatty liver disease (NAFLD) represents a spectrum, including ‘simple’ steatosis, non-alcoholic steatohepatitis (NASH), and fibrosis. Increasing prevalence of NAFLD has followed the international rise in obesity and lifestyle modification is the mainstay therapy for children. To date, pharmacological trials have had varying efficacy but a large number of new agents are in early phase trials for adults. Areas covered: This review explores the effect of current and potential future paediatric NAFLD treatments in terms of histological and biochemical endpoints. The potential for the extension of adult treatments to children is discussed, as well as what limits the use of certain agents in children. Expert commentary: No drugs have yet to be licenced for NAFLD. Trial heterogeneity makes comparison of drugs between studies challenging. FXR agonists are yet to be trialled in children but may represent a safe and potentially efficacious therapy. Future treatments would likely encompass a multimodal approach that may include bariatric surgery. [ABSTRACT FROM AUTHOR]

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Background: There are no licensed treatments for non alcoholic fatty liver disease (NAFLD) in adults or children. In NAFLD, several studies have shown a benefit of omega-3 fatty acid treatment on lipid profile, insulin-sensitivity and hepatic steatosis and it has also been suggested that Vitamin D treatment has potential antifibrotic properties in liver disease. Trial Design: To date, however, there are no studies that have tested the combination of Docosahexanoic acid (DHA) and vitamin D treatment which may benefit the whole spectrum of disease in NAFLD. Our aim therefore, was to test the effect of daily DHA (500 mg) plus vitamin D (800 IU) treatment, in obese children with biopsy-proven NAFLD and vitamin D deficiency, in a randomized, double-blind placebo-controlled trial. Methods: The 41/43 patients completed the study (18-treatment, 23-placebo). At 12 months: i) the main outcome was liver histology improvement, defined by NAS; ii) the secondary outcome was amelioration of metabolic parameters. Results: DHA plus vitamin D treatment reduced the NAFLD Activity Score (NAS), in the treatment group (5.4 v1.92; p<0.001 for baseline versus end of study). There was no change in fibrosis score, but a reduction of the activation of hepatic stellate cells (HSC) and fibrillar collagen content was noted (3.51±1.66 v. 1.59±1.37; p = 0.003) in treatment group. Moreover, the triglycerides (174.5 vs. 102.15 mg/dl), ALT (40.25 vs. 24.5 UI/l) and HOMA-IR (4.59 vs. 3.42) were all decreased with treatment. Conclusion: DHA plus vitamin D treatment improved insulin-resistance, lipid profile, ALT and NAS. There was also decreased HSC activation and collagen content with treatment. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is currently considered the main cause of chronic liver disease worldwide. Mechanisms leading to the development and progression of this disease are topics of great interest for researchers and clinicians. The current multi-hit hypothesis has thrown the crosstalk between liver and adipose tissue into sharp focus. It is well known that adipose tissue produces circulating factors, known as adipocytokines, which exert several effects on liver cells, promoting the onset of NAFLD and its progression to non-alcoholic steatohepatitis in obese subjects. In a similar way, hepatocytes may also respond to obesogenic stimuli by producing and releasing hepatokines into the circulation. Here, the authors provide an overview of recent advances in our understanding of the role of the most relevant adipocytokines and hepatokines in NAFLD pathogenesis, highlighting their possible molecular and functional interactions. [ABSTRACT FROM PUBLISHER]

Chronic liver diseases in children represent a rising problem with significant effects on public health. In fact, several pediatric liver diseases are precursors of adult chronic hepatopathies, cirrhosis and hepatocellular carcinoma. The prevalence of liver diseases in children is unknown. In the USA, every year, 15,000 children are hospitalized for liver diseases, but these disorders continue to be under-recognized or diagnosed late. The main reason is due to the frequent absence of symptoms in the vast majority of liver diseases, especially in the early stages. In the last few decades several advances have been made in understanding the pathogenesis of liver diseases, permitting the discovery of new therapeutic targets to treat liver diseases, thus improving the natural history of these disorders. In this article we discuss the most recent advances in the understanding of the pathogenesis, diagnosis and treatment of the most frequent pediatric liver diseases. [ABSTRACT FROM PUBLISHER]

Background: There is an urgent need to develop alternatives to liver biopsy in children to diagnose nonalcoholic steatohepatitis (NASH), the aggressive form of nonalcoholic fatty liver disease (NAFLD). Increased hepatocyte apoptosis plays a central role in the development of NASH. Aims: To evaluate the plasma levels of two markers of apoptosis, soluble Fas (sFas) and soluble Fas ligand (sFasL), in children with NAFLD and assess their utility as biomarkers of disease severity. Methods: Children with biopsy-proven NAFLD were included, and blood samples were collected. Patients were divided into NASH and 'not NASH.' We measured plasma sFas and sFasL using specific ELISA immunoassays. Results: One hundred and seventeen children with NAFLD were recruited. Average age was 12.2 ± 2.9 years, 67 % were male, and 58 % had NASH. Patients with NASH had significantly higher levels of sFas and sFasL than patients in the 'not NASH' group (686.0 ± 186.5 pg/mL versus 594.2 ± 244.9, p = 0.023 for sFas and 324.9 ± 146.5 pg/mL versus 221.4 ± 134.0, p < 0.001 for sFasL). sFasL was found to have higher accuracy for predicting the presence of NASH on liver biopsy with an AUC (95 % CI) of 0.714 (0.618, 0.810). A prediction model, the NASH apoptosis score, was generated consisting of plasma sFasL, age, ferritin, transferrin, and triglyceride levels. The area under receiver operating characteristic curve was 0.78 (95 % CI 0.0.69, 0.87). Conclusions: Markers of the extrinsic pathway of hepatocyte apoptosis are elevated in children with NASH. sFasL and the NASH apoptosis score are potential novel biomarkers for NASH. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnoea syndrome (OSAS) is a common sleep disorder, affecting over 4% of the general population, and is associated with metabolic syndrome and cardiovascular disease, independent of obesity and traditional risk factors. OSAS has been recently connected to nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in the world, which can be found in 30% of the general adult population. Several studies suggest that the chronic intermittent hypoxia (CIH) of OSAS patients may per se trigger liver injury, inflammation, and fibrogenesis, promoting NAFLD development and the progression from steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In NAFLD patients, liver disease may be caused by hypoxia both indirectly by promoting inflammation and insulin resistance and directly by enhancing proinflammatory cytokine production and metabolic dysregulation in liver cells. In this review, we focus on molecular mechanisms linking OSAS to NAFLD, including hypoxia inducible factor (HIF), nuclear factor kappa B (NF-κB), YKL-40, unfolded protein response, and hypoxic adipose tissue inflammation, which all could provide novel potential therapeutic approaches for the management of NAFLD patients with OSAS. [ABSTRACT FROM AUTHOR]

Childhood obesity when associated with serum lipoprotein changes triggers atherosclerosis. Evidences suggest that the atherosclerotic process begins in childhood and that the extent of early atherosclerosis of the aorta and coronary arteries can be associated with lipoprotein levels and obesity. Furthermore, many studies in childhood demonstrate an important relationship between parameters of insulin sensitivity, body fat distribution, and the development of lipid abnormalities. This review focuses on the most recent findings on the relationship between obesity, dyslipidemia, and cardiovascular risk in children. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of metabolic abnormalities ranging from simple triglyceride accumulation in the hepatocytes to hepatic steatosis with inflammation, ballooning and fibrosis. It has been demonstrated that the pathogenesis of NAFLD involves increased oxidative stress, with consumption of the major cellular antioxidant, glutathione (GSH). Liver has a fundamental role in sulfur compound metabolism, although the data reported on plasma thiols status in NAFLD are conflicting. We recruited 63 NAFLD patients, and we analyzed all plasma thiols, such as homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CysGly) and GSH, by high-performance liquid chromatography (HPLC) with fluorescence detection. Hcy, Cys and CysGly plasma levels increased in NAFLD patients (p < 0.0001); whereas GSH levels were decreased in NAFLD patients when compared to controls (p < 0.0001). On the contrary, patients with steatohepatitis exhibited lower levels of Hcy and Cys than subjects without. Furthermore, a positive correlation was found between Hcy and Cys and the presence of fibrosis in children with NAFLD. Taken together, these data demonstrated a defective hepatic sulfur metabolism in children with NAFLD, and that high levels of Hcy and Cys probably correlates with a pattern of more severe histological liver damage, due to mechanisms that require further studies. [ABSTRACT FROM AUTHOR]

Introduction: Nonalcoholic fatty liver disease (NAFLD) is one of the most important causes of liver-related morbidity and mortality in children. Recently, we have reported the effects of docosahexaenoic acid (DHA), the major dietary long-chain polyunsaturated fatty acids, in children with NAFLD. DHA exerts a potent anti-inflammatory activity through the G protein-coupled receptor (GPR)120. Our aim was to investigate in pediatric NAFLD the mechanisms underlying the effects of DHA administration on histo-pathological aspects, GPR120 expression, hepatic progenitor cell activation and macrophage pool. Patients and Methods: 20 children with untreated NAFLD were included. Children were treated with DHA for 18 months. Liver biopsies before and after the treatment were analyzed. Hepatic progenitor cell activation, macrophage pool and GPR120 expression were evaluated and correlated with clinical and histo-pathological parameters. Results: GPR120 was expressed by hepatocytes, liver macrophages, and hepatic progenitor cells. After DHA treatment, the following modifications were present: i) the improvement of histo-pathological parameters such as NAFLD activity score, ballooning, and steatosis; ii) the reduction of hepatic progenitor cell activation in correlation with histo-pathological parameters; iii) the reduction of the number of inflammatory macrophages; iv) the increase of GPR120 expression in hepatocytes; v) the reduction of serine-311-phosphorylated nuclear factor kappa B (NF-κB) nuclear translocation in hepatocytes and macrophages in correlation with serum inflammatory cytokines. Conclusions: DHA could modulate hepatic progenitor cell activation, hepatocyte survival and macrophage polarization through the interaction with GPR120 and NF-κB repression. In this scenario, the modulation of GPR120 exploits a novel crucial role in the regulation of the cell-to-cell cross-talk that drives inflammatory response, hepatic progenitor cell activation and hepatocyte survival. [ABSTRACT FROM AUTHOR]

Abstract: Non-alcoholic fatty liver disease is rapidly becoming one of most common liver diseases in the paediatric population in industrialized countries due to the growing prevalence of obesity and overweight. Paediatric NAFLD is typically of primary origin and it is strongly associated with several features of the metabolic syndrome. The mainstay of NAFLD therapy is represented by lifestyle interventions on obesogenic environment and sedentary lifestyle, which aim to improve obesity, hepatic changes and quality of life as well. Unfortunately, this goal is very difficult to be achieved and pharmacological approaches have become necessary. Although in fairly recent years, many pharmacological agents, on the basis of pathogenetic mechanism of the disease, have been attempted, to date guidelines for the management of fatty liver are still lacking. Establishing effective therapeutic strategies to treat the disease represents the challenge for paediatric hepatologists in the near future. In this article, we briefly review the current knowledge and ideas concerning paediatric non-alcoholic fatty liver disease. [Copyright &y& Elsevier]

The aim of this secondary analysis of a randomized controlled trial was to test whether the I148M variant of Patatin-like phospholipase domain-containing protein-3 (PNPLA3) is associated with the response to docosahexaenoic acid (DHA) in children with non-alcoholic fatty liver disease (NAFLD). Sixty children with NAFLD were randomized in equal numbers to DHA 250 mg/day, DHA 500 mg/day or placebo. Coherently with the primary analysis, the probability of more severe steatosis after 24 months of DHA supplementation was 50% lower [95% confidence interval (CI) −59% to −42%)] in the combined DHA 250 and 500 mg/day groups versus placebo. The present secondary analysis revealed an independent effect of PNPLA3 status on the response to DHA. In fact, the probability of more severe steatosis was higher (37%, 95% CI 26-48%) for the PNPLA3 M/M versus I/M genotype and lower (−12%, 95% CI −21% to −3%) for the I/I versus I/M genotype (Somers' D for repeated measures). We conclude that the 148M allele of PNPLA3 is associated with lower response, and the 148I allele with greater response, to DHA supplementation in children with NAFLD. [ABSTRACT FROM AUTHOR]

Atypical fibroblast growth factors (FGF) 21 and 19 play a central role in energy metabolism through the mediation of Klotho coreceptor. Contradictory findings are available about the association of FGF21 and FGF19 with nonalcoholic fatty liver disease (NAFLD) in humans. We investigated the association of serum FGF21, FGF19 and liver Klotho coreceptor with non-alcoholic steatohepatitis (NASH) and fibrosis in children with NAFLD. Serum FGF21 and FGF19 were measured in 84 children with biopsy-proven NAFLD and 23 controls (CTRL). The hepatic expression of Klotho coreceptor was measured in 7 CTRL, 9 patients with NASH (NASH+) and 11 patients without NASH (NASH−). FGF21 and FGF19 showed a tendency to decrease from CTRL (median FGF21 = 196 pg/mL; median FGF19 = 201 pg/mL) to NASH− (FGF21 = 89 pg/mL; FGF19 = 81 pg/mL) to NASH+ patients (FGF21 = 54 pg/mL; FGF19 = 41 pg/mL) (p<0.001 for all comparisons) and were inversely associated with the probability of NASH and fibrosis in children with NAFLD. The hepatic expression of Klotho coreceptor was inversely associated with NASH (R2 = 0.87, p<0.0001) and directly associated with serum FGF21 (R2 = 0.57, p<0.0001) and FGF19 (R2 = 0.67, p<0.0001). In conclusion, serum FGF19 and FGF21 and hepatic Klotho expression are inversely associated with hepatic damage in children with NAFLD and these findings may have important implications for understanding the mechanisms of NAFLD progression. [ABSTRACT FROM AUTHOR]

Abstract: Over the past decade, non-alcoholic fatty liver disease (NAFLD) has become one of most common chronic liver diseases in children. A greater understanding about the risk factors and molecular pathogenesis of NAFLD suggests that lifestyle interventions aiming to decrease obesity/body mass index and metabolic derangement are the first line of treatments adopted in children affected by this disease. However, because these therapeutic options are often at the beginning misjudged by the patients and their parents, the use of pharmacologic agents may help to protect the liver and other organs from further irreversible tissue damage. Pharmacologic therapies against one or more specific factors and/or molecules involved in the development of NAFLD (i.e., insulin resistance, free fatty acid lipid toxicity, and oxidative stress) also might slow the progression of this increasingly prevalent pediatric disorder. On this basis, insulin sensitizers, antioxidants, cytoprotective agents, and dietary supplementations have been evaluated in pediatric clinical trials. In this review, we discuss the efficacy of the dietary approaches, possibly coupled with regular exercise, on decreasing the metabolic and histologic damage in pediatric NAFLD. We also emphasize several advantages of the pharmacologic treatments adopted or adoptable in combination with lifestyle interventions in children with NAFLD. [Copyright &y& Elsevier]

Nonalcoholic fatty liver disease encompasses a spectrum of disease from asymptomatic steatosis, with or without elevated aminotransferases, to cirrhosis with relative complications and hepatocellular carcinoma. Owing to the increasing prevalence of nonalcoholic fatty liver disease and the potential for nonalcoholic steatohepatitis to progress to cirrhosis and liver-related mortality, more research has been focused on therapy of this important liver disease over the last two decades. To date, weight loss and physical activity represent the cornerstone of treatment, with interventions being limited to subjects at risk of disease progression, but the type of treatment remains a matter of debate. A few medications have shown promising results in preliminary pilot studies, but few agents have been tested rigorously. Today, multiple therapeutic approaches are considered the way to go in treating nonalcoholic steatohepatitis patients. In this paper we review the status of current and emerging therapeutic strategies for children and adult patients with nonalcoholic steatohepatitis. [ABSTRACT FROM AUTHOR]

Maiorana A, Nobili V, Calandra S, Francalanci P, Bernabei S, El Hachem M, Monti L, Gennari F, Torre G, de Ville de Goyet J, Bartuli A. Preemptive liver transplantation in a child with familial hypercholesterolemia. Pediatr Transplantation 2011: 15:E25-E29. © 2010 John Wiley & Sons A/S. Familial hypercholesterolemia is an autosomal codominant disorder associated with markedly elevated plasma concentration of LDL-cholesterol and increased cardiovascular risk. Homozygous patients have rapid development of atherosclerosis with death from cardiovascular disease even in childhood. Life-long recurrent apheresis to reduce plasma LDL-cholesterol is considered the gold standard for treatment. Liver transplantation can be curative for this condition, but is usually only considered after the development of cardiovascular disease. We report a 5.5-yr-old child initially misdiagnosed with heterozygous familial hypercholesterolemia and treated by low-fat diet only. In view of persistent hypercholesterolemia and development of xanthomatosis, new molecular studies indicated the presence of two different mutations in the LDL receptor gene, with one being a deletion of two exons not identifiable with standard sequencing analysis. Recurrent plasma apheresis in combination with statins lowered, but did not normalize plasma LDL-cholesterol levels. It caused progressive reduction of the size of xanthomas and prevented the development of vascular complications. After two yr, liver transplantation normalized LDL-cholesterol levels and completely resolved the skin lesions. Preemptive liver transplantation is a definitive cure of familial homozygous hypercholesterolemia and might be more effective if performed before development of vascular complications. [ABSTRACT FROM AUTHOR]

Background and Aim: Oxidative stress is an important pathophysiological mechanism in non-alcoholic steatohepatitis, where hepatocyte apoptosis is significantly increased correlating with disease severity. Protein glutathionylation occurs as a response to oxidative stress, where an increased concentration of oxidized glutathione modifies post-translational proteins by thiol disulfide exchange. In this study, we analyzed the protein glutathionylation in non-alcoholic fatty liver disease (NAFLD) and evaluated a potential association between glutathionylation, fibrosis, and vitamin E treatment. Methods: Protein glutathionylation was studied in the livers of 36 children (mean age 12.5 years, range 4–16 years) subdivided into three groups according to their NAFLD activity score (NAS) by Western blot analysis and immunohistochemistry, using a specific monoclonal antibody. In addition, we identified the hepatocyte ultrastructures involved in glutathionylation by immunogold electron microscopy. Results: Our findings showed that protein glutathionylation increases in the livers of patients with NAFLD and it is correlated with steatohepatitis and liver fibrosis. Its increase appears mainly in nuclei and cytosol of hepatocytes, and it is reversed by antioxidant therapy with reduced fibrosis. Conclusion: Protein glutathionylation significantly increases in livers with NAFLD, strongly suggesting that oxidative injury plays a crucial role in this disease. Furthermore, the marked increase of protein glutathionylation, in correlation with collagen VI immunoreactivity, suggests a link between the redox status of hepatic protein thiols and fibrosis. [ABSTRACT FROM AUTHOR]

Abstract Nonalcoholic fatty liver disease (NAFLD) is a multifaceted disorder that ranges from simple fatty liver to nonalcoholic steatohepatitis (NASH) with or without fibrosis, which may evolve toward cirrhosis and hepatocellular carcinoma. It is currently considered a "global" and "epidemic" disease, whose prevalence is progressively increasing even in pediatric age. The incidence of NAFLD is very high in overweight/obese children, and a greater risk of disease progression is associated with severe obesity, highlighting the role of nutrition. To date, for NAFLD, there are few guidelines for diagnostic and follow-up methods, and scarce validated protocols for treatment. The initial indications consist of gradual weight loss and regular exercise, but in children, the difficulty of adhering to long-term behavioral changes makes this approach limited. The purpose of this narrative review is to examine the mechanism underlying the pathogenic mechanisms that lead to NAFLD in children, with a major focus on the role of nutrition. Because this is particularly relevant in light of the absence of pharmacological treatments suitable for children, we also overview clinical studies on the potential effects of nutritional supplementations, including vitamins, docosahexaenoic acid, and probiotics.in children. To this aim, updated search was conducted on PubMed and clinicaltrials.gov databases. Future research should consider additional clinical studies in pediatric NAFLD patients to validate the benefits of dietary supplements and to define the appropriate dosage and duration for intervention. Furthermore, experimental studies with -omics approaches could be helpful to deepen the related mechanisms and to search for a possible optimal supplement combination against NAFLD in children. [ABSTRACT FROM AUTHOR]

The effects of Nigella sativa (NS) on plasma lipid concentrations are controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to obtain a conclusive result in humans. PubMed-Medline, SCOPUS, Web of Science, and Google Scholar databases were searched (up to August 2015) to identify RCTs investigating the impact of NS on total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and triglycerides concentrations. A random-effects model and the generic inverse variance weighting method were used for quantitative data synthesis. Meta-regression, sensitivity analysis, and publication bias assessments were performed using standard methods. A total of 17 RCTs examining the effects of NS on plasma lipid concentrations were included. Meta-analysis suggested a significant association between NS supplementation and a reduction in total cholesterol (weighed-mean-difference [WMD]: −15.65 mg/dL, 95% CI: −24.67, −6.63, p = 0.001), LDL-C (WMD: −14.10 mg/dL, 95% CI: −19.32, −8.88, p < 0.001), and triglyceride levels (WMD: −20.64 mg/dL, 95% CI: −30.29, −11.00, p < 0.001). No significant effect on HDL-C concentrations (WMD: 0.28 mg/dL, 95% CI: −1.96, 2.53, p = 0.804) was found. A greater effect of NS seed oil versus seed powder was observed on serum total cholesterol and LDL-C levels, and an increase in HDL-C levels was found only after NS seed powder supplementation. NS has a significant impact on plasma lipid concentrations, leading to lower total cholesterol, LDL-C, and TG levels while increased HDL-C is associated with NS powder only. Further RCTs are needed to explore the NS benefits on cardiovascular outcomes. [ABSTRACT FROM AUTHOR]