Flaxseed Oil Alleviates Trimethyltin-Induced Cell Injury and Inhibits the Pro-Inflammatory Activation of Astrocytes in the Hippocampus of Female Rats.

Exposure to the neurotoxin trimethyltin (TMT) selectively induces hippocampal neuronal injury and astrocyte activation accompanied with resultant neuroinflammation, which causes severe behavioral, cognitive, and memory impairment. A large body of evidence suggests that flaxseed oil (FSO), as one of the richest sources of essential omega-3 fatty acids, i.e., α-linolenic acids (ALA), displays neuroprotective properties. Here, we report the preventive effects of dietary FSO treatment in a rat model of TMT intoxication. The administration of FSO (1 mL/kg, orally) before and over the course of TMT intoxication (a single dose, 8 mg/kg, i.p.) reduced hippocampal cell death, prevented the activation of astrocytes, and inhibited their polarization toward a pro-inflammatory/neurotoxic phenotype. The underlying protective mechanism was delineated through the selective upregulation of BDNF and PI3K/Akt and the suppression of ERK activation in the hippocampus. Pretreatment with FSO reduced cell death and efficiently suppressed the expression of inflammatory molecules. These beneficial effects were accompanied by an increased intrahippocampal content of n-3 fatty acids. In vitro, ALA pretreatment prevented the TMT-induced polarization of cultured astrocytes towards the pro-inflammatory spectrum. Together, these findings support the beneficial neuroprotective properties of FSO/ALA against TMT-induced neurodegeneration and accompanied inflammation and hint at a promising preventive use of FSO in hippocampal degeneration and dysfunction.

Osteosarcopenic adiposity (OSA) phenotype and its connection with cardiometabolic disorders: Is there a cause-and-effect?

The objectives were to examine if there is a causal relationship between osteosarcopenic adiposity (OSA) syndrome (coexistence of osteopenia/osteoporosis, sarcopenia, and excess adiposity) and cardiometabolic disorders or if these disorders initiate the development of OSA and its worsening. The search was conducted in PubMed, Scopus, and Web of Science to include articles up to the end of 2023. Of n=539 articles retrieved, n=15 met the eligibility criteria. Only studies conducted in adults and with all three body composition compartments (bone, muscle/lean, adipose) measured were considered. The results revealed that several cardiometabolic disorders, namely, hypertension, dyslipidemia (elevated total and LDL-cholesterol, lower HDL-cholesterol), insulin resistance, hyperglycemia, lower serum vitamin D, and some inflammatory markers were accompanied by OSA. In most cases, the OSA phenotype was associated with worse outcomes than cases with healthy or less impaired body composition. Our initial questions about the reciprocal cause-and-effect relationships could be surmised with more certainty for the OSA and some cardiovascular risks (hypertension, dyslipidemia) and some metabolic abnormalities (several inflammatory markers). The results of this review underscore the importance of body composition in health and from a clinical perspective, all three body composition compartments should be measured by standardized technologies using regulated diagnostic criteria to identify OSA. Randomized trials and prospective studies in diverse groups of older and younger individuals are necessary to determine if the relationships between OSA and clinical endpoints are causal and reversible through intervention and to uncover the mechanisms.

Perceptions on support, challenges and needs among parents and caregivers of children with developmental disabilities in Croatia, North Macedonia and Serbia: a cross-sectional study.

BACKGROUND: Parents/caregivers of children with developmental disabilities (CDD) have a wide range of support needs and there are various interventions available. Support, challenges, and needs among parents/caregivers of CDD likely vary in different geographical settings. This study aimed to analyze the perceptions of support, challenges, and needs among parents/caregivers of CDD in Croatia, North Macedonia, and Serbia. METHODS: We conducted a cross-sectional study in March-April 2023 within the Erasmus + SynergyEd project. The eligible participants were parents and caregivers of CDD in Croatia, North Macedonia, and Serbia, who filled out a modified Caregiver Needs Survey online. RESULTS: Among 953 participants, 542 (57%) were from Croatia, 205 (21%) were from North Macedonia and 206 (22%) were from Serbia. The most common diagnosis of participants' children was autism spectrum disorder (26%). The child most often received the first diagnosis at the median of 2 years, diagnosed by a team of professionals. More than half (58%) of children attended preschool and public school, while 22% did not attend any schooling. Additional support from the state/city/county was received by 66% of CDD. Most participants declared not participating in association/organization for family support. Participants mostly (68%) used experts who work with the child as a source of information about their child's condition, followed by the Internet (53%). In the last 12 months, 60% of participants had difficulties with the availability of services in their area or problems getting appointments. The biggest problem in getting support was ensuring the child's basic rights were protected. Participants stated that ensuring greater rights for CDD was the greatest need for their families. CONCLUSION: Parents/caregivers of CDD in Croatia, North Macedonia, and Serbia faced multiple challenges, but most of them were satisfied with the services provided to their children. Future efforts to develop policies and services related to CDD should consider the opinions of their parents/caregivers and disparities in access to services.

Polyphenol-rich black currant and cornelian cherry juices ameliorate metabolic syndrome induced by a high-fat high-fructose diet in Wistar rats.

Diets high in fat and sugar lead to metabolic syndrome (MetS) and related chronic diseases. We investigated the effects of commercially available, cold-pressed polyphenol-rich black currant (BC) and cornelian cherry (CC) juices on the prevention of MetS in Wistar rats induced by a 10-weeks high-fat high-fructose (HFF) diet. Juice consumption, either BC or CC, with a HFF diet resulted in lower serum triglycerides compared to only the HFF consumption. Both juices also mitigated the effects of HFF on the liver, pancreas, and adipose tissue, by preserving liver and pancreas histomorphology and reducing visceral fat and adipocyte size. Furthermore, supplementation with both juices reduced glucagon and up-regulated insulin expression in the pancreas of the rats on the HFF diet, whereas the BC also showed improved glucose regulation. BC juice also reduced the expression of IL-6 and hepatic inflammation compared to the group only on HFF diet. Both juices, especially BC, could be a convenient solution for the prevention of MetS in humans.

Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause.

Herb-induced liver injury (HILI) caused by herbal supplements, natural products, and products used in traditional medicine are important for differential diagnoses in patients with acute liver injury without an obvious etiology. The root of Withania somnifera (L.) Dunal, commonly known as ashwagandha, has been used in Ayurvedic medicine for thousands of years to promote health and longevity. Due to various biological activities, ashwagandha and its extracts became widespread as herbal supplements on the global market. Although it is generally considered safe, there are several reported cases of ashwagandha-related liver injury, and one case ended with liver transplantation. In this paper, we review all reported cases so far. Additionally, we describe two new cases of ashwagandha hepatotoxicity. In the first case, a 36-year-old man used ashwagandha capsules (450 mg, three times daily) for 6 months before he developed nausea, pruritus, and dark-colored urine. In the second case, a 30-year-old woman developed pruritus after 45 days of using ashwagandha capsules (450 mg). In both cases, serum bilirubin and liver enzymes (aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were increased. The liver injury pattern was hepatocellular (R-value 11.1) and mixed (R-value 2.6), respectively. The updated Roussel Uclaf Causality Assessment Method (RUCAM) (both cases with a score of seven) indicated a "probable" relationship with ashwagandha. Clinical and liver function improvements were observed after the discontinuation of ashwagandha supplement use. By increasing the data related to ashwagandha-induced liver injury, these reports support that consuming ashwagandha supplements is not without its safety concerns.

Disturbed Plasma Lipidomic Profiles in Females with Diffuse Large B-Cell Lymphoma: A Pilot Study.

Lipidome dysregulation is a hallmark of cancer and inflammation. The global plasma lipidome and sub-lipidome of inflammatory pathways have not been reported in diffuse large B-cell lymphoma (DLBCL). In a pilot study of plasma lipid variation in female DLBCL patients and BMI-matched disease-free controls, we performed targeted lipidomics using LC-MRM to quantify lipid mediators of inflammation and immunity, and those known or hypothesised to be involved in cancer progression: sphingolipids, resolvin D1, arachidonic acid (AA)-derived oxylipins, such as hydroxyeicosatetraenoic acids (HETEs) and dihydroxyeicosatrienoic acids, along with their membrane structural precursors. We report on the role of the eicosanoids in the separation of DLBCL from controls, along with lysophosphatidylinositol LPI 20:4, implying notable changes in lipid metabolic and/or signalling pathways, particularly pertaining to AA lipoxygenase pathway and glycerophospholipid remodelling in the cell membrane. We suggest here the set of S1P, SM 36:1, SM 34:1 and PI 34:1 as DLBCL lipid signatures which could serve as a basis for the prospective validation in larger DLBCL cohorts. Additionally, untargeted lipidomics indicates a substantial change in the overall lipid metabolism in DLBCL. The plasma lipid profiling of DLBCL patients helps to better understand the specific lipid dysregulations and pathways in this cancer.

Plasma fatty acid composition and some markers of dietary habits are associated with cardiovascular disease risk determined by an atherogenic plasma index in postmenopausal women.

It is hypothesized that plasma proportion of selected fatty acids (FAs) and dietary habits are linked with the risk of cardiovascular disease (CVD) in postmenopausal women. Therefore, this study was designed to determine the association of plasma FA composition and markers of dietary habits with an atherogenic index of plasma (AIP), a predictor of CVD risk in postmenopausal women. In total, 87 postmenopausal women with an average age of 57 ± 7 years were recruited and their dietary intake, anthropometric and biochemical parameters, and FA status in total plasma lipid proportions were determined, showing that 65.5% of the participants had a high risk of CVD according to their AIP value. After adjusting for some confounders (age, body mass index, and physical activity level), the risk of CVD was only positively associated with the frequency of consumption of animal fat spreads (butter and lard) of terrestrial origin. Regarding the FA profile, CVD risk was positively associated with the percentages of vaccenic acid, dihomo-γ-linolenic acid, and monounsaturated fatty acids (MUFA; mainly n-7) in total FA, as well as the MUFA/SFA ratio in total plasma and stearoyl-CoA desaturase-16 activity (16:1/16:0 ratio). In contrast, the risk of CVD was negatively associated with percentages of α-linolenic acid, total polyunsaturated fatty acids (PUFA), and PUFA/MUFA ratio in total plasma lipid, and the estimated activity of Δ5-desaturase (20:4/20:3 n-6 ratio). These results support the current recommendations to decrease the frequency of animal fat spread intake because it is associated with a reduced CVD risk based on AIP in postmenopausal women. In accordance with these plasma percentages of ALA, vaccenic acid, dihomo-γ-linolenic acid, PUFA, PUFA/MUFA ratio, and 16:1/16:0 ratio may be important parameters in CVD risk assessment.

Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats.

A Western-style diet, rich in fat and simple sugars, is the main risk factor for a significant number of chronic diseases and disorders, as well as for a progression of metabolic syndrome (MetS). One of the key mechanisms involved in MetS development is increased oxidative stress caused by the accumulation of body fat. Some dietary polyphenols have shown a protective role in preventing oxidative-stress-induced damage. We investigated the difference in the oxidative response of plasma, liver, and visceral adipose tissue in rats fed with a high-fat high-fructose (HFF) diet for ten weeks, and the effectiveness of polyphenol-rich juices (black currant (BC) and cornelian cherry (CC)) in HFF-diet-induced oxidative stress prevention. The most prominent impact of the HFF diet on redox parameters was recorded in the liver, whereas adipose tissue showed the most potent protection mechanisms against oxidative stress. Consumption of both juices decreased advanced oxidation protein product (AOPP) level in plasma, increased paraoxonase1 (PON1) activity in the liver, and significantly decreased total oxidative status (TOS) in adipose tissue. BC exerted stronger antioxidative potential than CC and decreased the superoxide anion radical (O2•-) level in the liver. It also reduced TOS, total antioxidative status (TAS), and malondialdehyde (MDA) concentration in adipose tissue. The multiple linear regression analysis has shown that the best predictors of MetS development, estimated through the increase in visceral adiposity, were superoxide dismutase (SOD), AOPP, TOS, and TAS. The consumption of polyphenol-rich juices may provide a convenient approach for the systemic reduction of oxidative stress parameters.

Nutrition and Physical Activity as Modulators of Osteosarcopenic Adiposity: A Scoping Review and Recommendations for Future Research.

Osteosarcopenic adiposity (OSA) syndrome denotes the confluence of bone, muscle, and adipose tissue deterioration. Being a complex entity, numerous uncertainties about OSA still exist, despite the extensive research on the topic. Our objectives were to evaluate human studies addressing dietary intake/nutritional status and the quantity/types of physical activity related to OSA. The search in PubMed, Scopus, and Web of Science databases was conducted to examine relevant articles published from inception to the end of December 2022, utilizing the MeSH strings in the search strategy. Only studies published in English and conducted in humans (≥18 years) without chronic conditions (cancers, kidney/liver disease) or pregnancy were used. Book chapters, abstracts-only, and studies in which participants did not have all three body composition components measured to identify OSA or when body composition components could not be related to the independent/exposure variables were excluded. A total of n = 1020 articles were retrieved from all three databases and eight more from the reference lists. After the exclusion of duplicates and other unsuitable articles, n = 23 studies were evaluated. Among those, eleven were from epidemiological or cross-sectional studies relating nutrients/dietary intake or nutritional status with OSA. Another four examined the relationship between serum biomarkers (vitamin D and ferritin) with OSA, while eight articles presented the results of the interventional studies with resistance training. Overall, higher protein, calcium, potassium, and vitamins D and C intakes emerged as nutrients positively modifying OSA, along with a diet higher in fruits and low-fat dairy foods. Higher serum vitamin D and ferritin were respectively positively and negatively related to OSA. Resistance training was a safe intervention yielding several beneficial outcomes for the OSA syndrome in older women.

Anti-inflammatory effect of combining fish oil and evening primrose oil supplementation on breast cancer patients undergoing chemotherapy: a randomized placebo-controlled trial.

Breast cancer is the most common malignant tumor and one of the leading causes of cancer-related death in women throughout the world. This study is a parallel, randomized, double-blind, controlled, 12-week supplementation trial, investigating the anti-inflammatory effects of dietary intake of fish oil and evening primrose oil (EPO), in patients with breast cancer undergoing chemotherapy. The primary outcomes were changes in the nutritional status and inflammatory cytokines of patients during the study. The secondary outcomes were changes in hematological and biochemical parameters and fatty acid profile. Of the 32 eligible patients, half of them is randomly assigned to a treatment arm with fish oil and EPO (n = 16), or a control arm (n = 16) with mineral oil as a placebo. The intervention group was taking 2 gel capsules of fish oil and 3 gel capsules of EPO (400 mg eicosapentaenoic acid, 600 mg docosahexaenoic acid, and 351 mg gamma-linolenic acid) fish oil and evening primrose oil for 12 weeks, during their chemotherapy. The control/placebo group was taking 5 gel capsules of 1g of mineral oil. One of the patients dropped out due to discontinuation of the treatment (in the placebo group) and two did not show up at the post-treatment measurements (in the intervention group), thus, 29 women completed the study. The results showed an increase in plasma levels of docosapentaenoic acid (22:5n-3), docosahexaenoic acid (22:6n-3), total n-3PUFA, vaccenic acid (18:1n-7), and a decrease in n-6/n-3 PUFA ratio in the intervention group. An increase in the plasma level of dihomo-gamma-linolenic acid (20:3n-6) was observed in the placebo group. There was no difference in plasma levels of interleukin (IL) IL-8, IL-10, and tumor necrosis factor-alpha, while the level of IL-6 decreased in both groups and was significantly lower in the intervention group at the end of the study. In conclusion, this supplementation improved the PUFA status and decreased the level of IL-6 in breast cancer patients undergoing chemotherapy. Consequently, this treatment may help reduce cancer complications resulting from impaired lipid metabolism and inflammation. ClinicalTrials.gov Identifier: NCT03516253. Date of registration 04/05/2018.

Crosstalk between dietary patterns, obesity and nonalcoholic fatty liver disease.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is rising worldwide, paralleling the epidemic of obesity. The liver is a key organ for the metabolism of proteins, fats and carbohydrates. Various types of fats and carbohydrates in isocaloric diets differently influence fat accumulation in the liver parenchyma. Therefore, nutrition can manage hepatic and cardiometabolic complications of NAFLD. Even moderately reduced caloric intake, which leads to a weight loss of 5%-10% of initial body weight, is effective in improving liver steatosis and surrogate markers of liver disease status. Among dietary patterns, the Mediterranean diet mostly prevents the onset of NAFLD. Furthermore, this diet is also the most recommended for the treatment of NAFLD patients. However, clinical trials based on the dietary interventions in NAFLD patients are sparse. Since there are only a few studies examining dietary interventions in clinically advanced stages of NAFLD, such as active and fibrotic steatohepatitis, the optimal diet for patients in these stages of the disease must still be determined. In this narrative review, we aimed to critically summarize the associations between different dietary patterns, obesity and prevention/risk for NAFLD, to describe specific dietary interventions' impacts on liver steatosis in adults with NAFLD and to provide an updated overview of dietary recommendations that clinicians potentially need to apply in their daily practice.

Trans fatty acids in frequently consumed products from Serbian and Slovenian market.

OBJECTIVES: Industrially produced trans fatty acid (iTFA) have adverse health effects and thus their consumption should be limited. The aim of this study was to determine and compare the iTFA content in frequently consumed food products by young adults from the Serbian and Slovenian market with supposedly elevated iTFA content in 2015. At the time of this study, there was no recommended limit of iTFA in both countries, and reduction of iTFA in foods was on voluntary basis. METHODS: We determined iTFA content in food products, 19 from the Serbian and 22 from the Slovenian market, blinded and analysed in the same analytical run. Contents of fatty acids (FA) methyl esters were analysed by capillary gas chromatography with a flame ionisation detector. Heptadecanoic acid was used as internal standard. Individual FA along with TFA were expressed as percentages of total measured FA. The amount of each FA in the sample was then calculated from the response factor and the transformation factor of the FA from the FA methyl ester content. RESULTS: Elaidic acid (C18:1t) was found as the most abundant TFA in analysed products, ranging from 0.52 g/100 g of total FA in chocolate candy up to 60.4 g/100 g in a salami from Serbian market. In Slovenian products, the values for elaidic acid were lower, 0.04-3.95 g/100 g of total FA, except in one type of wafers (24.3 g/100 g). CONCLUSIONS: The majority of analysed products from the Serbian and three from Slovenian market exceeded the recommended WHO and EU limit of 2% iTFA of total fat in foods. Samples of frequently consumed salami, wafers, tea biscuits, and snacks were identified as products with potentially higher burden of iTFA in diets of young adults in Serbia.

A prospective, randomized, double-blind, placebo-controlled trial of polyphenols on the outcomes of inflammatory factors and oxidative stress in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is commonly associated with hyperglycemia, dyslipidemia, oxidative stress and inflammation which are well known cardiovascular risk factors. Pomegranate peel polyphenols have a proven hypolipemic, antioxidant and anti-inflammatory activity. However, there is a lack of clinical studies that would confirm its antioxidant and anti-inflammatory effects in diabetic patients. The potential of pomegranate peel extract (PoPEx) to counteract inflammation and oxidative stress in T2DM patients was investigated. For this purpose, a randomized, double-blind placebo-controlled study involving adult T2DM patients treated with PoPEx or placebo for eight-weeks was conducted. METHODS: Patients were randomly divided into two groups: the first group (n = 30) received capsules containing PoPEx 250 mg twice daily, while the placebo group (n = 30) received placebo capsules twice daily. Plasma concentration of inflammatory factors (interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and high sensitivity C reactive protein (hsCRP)), oxidative stress biomarkers (thiobarbituric acid reactive substances (TBARS), nitrites (NO2-), superoxide anion radical (O2-), hydrogen peroxide (H2O2), total antioxidant capacity (TAC)), homocysteine and lipid profile were analyzed. RESULTS: The PoPEx treatment showed a significant reduction of inflammatory factors (IL-6, TNF-α, hsCRP), oxidative stress biomarkers (TBARS, NO2-, O2-) and homocysteine, while the TAC was increased. Moreover, a significant improvement in lipid profile was observed in the PoPEx group. Additional analysis showed a significant inverse correlation between the decrements of all measured inflammatory markers and TAC in the PoPEx group. CONCLUSIONS: The study demonstrated that eight-week-long PoPEx administration had favorable effects on inflammatory status and oxidative stress biomarkers in diabetic patients.

Role of Corticosteroids in Drug-Induced Liver Injury. A Systematic Review.

Introduction: Apart from cessation of the implicated agent leading to drug-induced liver injury (DILI), there is no standard therapy for DILI. Corticosteroids have been used in DILI, although their efficacy is unclear. Published data showed either beneficial effects or no improvement associated with steroid therapy. The aim of the current study was to perform a systematic review of the role of corticosteroids in the treatment of DILI. Methods: A search was performed in PubMed, searching for the terms: "corticosteroids" and "drug-induced liver injury". Observation studies were included, but case reports excluded. Results: A total of 24 papers were retrieved. Most of these were observational studies on the effects of corticosteroids in moderate/severe DILI (n = 8), reports on the corticosteroid treatment in patients with drug-induced autoimmune hepatitis (DI-AIH) (n = 5), and effects of corticosteroids in drug-induced fulminant acute liver failure (ALF, n = 2). Furthermore, treatment of corticosteroids in patients with liver injury due to check point inhibitors (CPIs) was addressed in nine studies. In moderate/severe DILI, six out of eight studies suggested steroid treatment to be beneficial, whereas two studies showed negative results. All five observational studies on the effects of corticosteroids in DI-AIH showed good therapeutic response with rapid and long lasting effects after discontinuation of corticosteroids and without evidence of relapse. Steroid therapy was not associated with improved overall survival in patients with drug-induced fulminant ALF. CPIs-induced liver injury was found to improve spontaneously in 33-50% without corticosteroids, and the rate of patients who were treated responded to steroids in 33-100% (mean 72%). Conclusions: The majority of studies analyzing the effects of corticosteroids in moderate/severe DILI have demonstrated beneficial effects. However, this was not the case in drug-induced fulminant ALF. Patients with DI-AIH had an excellent response to corticosteroids. The majority of those with CPIs-induced liver injury responded to corticosteroids; however, patients without treatment usually recovered spontaneously. The observational design and comparison with historical controls in these studies makes it very difficult to draw conclusions on the efficacy of corticosteroids in DILI. Therefore, there is a strong need for a randomized controlled trial to properly assess the role of corticosteroids in DILI.

EFFICACY OF A LIPID-LOWERING DIET ON KEY FATTY ACID RATIOS AND OMEGA-3 INDEX IN HYPERLIPIDEMIC SUBJECTS.

Polyunsaturated fatty acid (PUFA) dietary intake, status and serum key fatty acid (FA) ratios may aid in cardiovascular disease-related risk assessment. The aim of this study was to investigate the effects of lipid-lowering diet on key FA ratios in serum phospholipids and omega-3 index in erythrocyte phospholipids in moderately hyperlipidemic subjects. The study included 41 subjects, mean age 56±6 years. Nutritional habits were evaluated by food frequency questionnaire. Participants followed lipid lowering diet for 12 weeks. Energy intake of omega-6 and omega-3 FA was changed from 7.6% and 0.6% to 5.7% and 1.2%, respectively. Marked decrease in four FA ratios in serum phospholipids, i.e., omega-6/omega-3, arachidonic acid (AA)/eicosapentaenoic acid (EPA), AA/docosahexaenoic acid (DHA), AA/(EPA+DHA) and omega-3 index (EPA+DHA) was found in study subjects after lipid-lowering diet. Total cholesterol/high-density lipoprotein (HDL), low-density lipoprotein (LDL)/HDL and triacylglycerol/HDL-cholesterol ratios positively correlated with all FA ratios, and negatively correlated with total omega-3 levels in serum phospholipids and omega-3 index in erythrocytes. Total serum omega-3 levels showed strongest association with lipoprotein ratios and positive correlation with homeostatic model assessment (HOMA) index. In conclusion, lipid-lowering diet resulted in decreased serum key FA ratios, increased omega-3 levels, and improved insulin sensitivity that may lead to a lower risk of cardiovascular disease in subjects with moderate hyperlipidemia.

Liver disease and COVID-19: The link with oxidative stress, antioxidants and nutrition.

Varying degrees of liver injuries have been reported in patients infected with the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). In general, oxidative stress is actively involved in initiation and progression of liver damage. The liver metabolizes various compounds that produce free radicals. Maintaining the oxidative/antioxidative balance is important in coronavirus disease 2019 (COVID-19) patients. Antioxidant vitamins, essential trace elements and food compounds, such as polyphenols, appear to be promising agents, with effects in oxidative burst. Deficiency of these nutrients suppresses immune function and increases susceptibility to COVID-19. Daily micronutrient intake is necessary to support anti-inflammatory and antioxidative effects but for immune function may be higher than current recommended dietary intake. Antioxidant supplements (ß-carotene, vitamin A, vitamin C, vitamin E, and selenium) could have a potential role in patients with liver damage. Available evidence suggests that supplementing the diet with a combination of micronutrients may help to optimize immune function and reduce the risk of infection. Clinical trials based on the associations of diet and SARS-CoV-2 infection are lacking. Unfortunately, it is not possible to definitively determine the dose, route of administration and best timing to intervene with antioxidants in COVID-19 patients because clinical trials are still ongoing. Until then, hopefully, this review will enable clinicians to understand the impact of micronutrient dietary intake and liver status assessment in COVID-19 patients.

Neuroinflammation in Autism and Supplementation Based on Omega-3 Polyunsaturated Fatty Acids: A Narrative Review.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction across multiple contexts and restricted, repetitive patterns of behavior, interests and activities. The maternal status of polyunsaturated fatty acids (PUFA) regulates microglial activity and neuroinflammatory pathways during a child's brain development. In children with ASD, the metabolism of PUFA is thought to be deficient or abnormal, leading to increased production of proinflammatory cytokines, increased oxidative stress and an imbalance in the formation and action of neurotransmitters. In addition, nutritional deficits in omega-3 PUFA may affect gut microbiota and contribute to ASD by the gut-brain axis. The aim of this study was to review the possible role of neuroinflammation in ASD development and the effect of omega-3 PUFA supplementation in children with ASD. Due to a wide heterogeneity across RCTs, no definitive conclusion about omega-3 PUFA effects in ASD can be drawn. Supplementation with PUFA could be considered as one of the aspects in regulating the biological status of the organism and could provide added value to standard medical and psychological interventions for reducing behavioral deficits.

Memorable Food: Fighting Age-Related Neurodegeneration by Precision Nutrition.

Healthcare systems worldwide are seriously challenged by a rising prevalence of neurodegenerative diseases (NDDs), which mostly, but not exclusively, affect the ever-growing population of the elderly. The most known neurodegenerative diseases are Alzheimer's (AD) and Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis, but some viral infections of the brain and traumatic brain injury may also cause NDD. Typical for NDD are the malfunctioning of neurons and their irreversible loss, which often progress irreversibly to dementia and ultimately to death. Numerous factors are involved in the pathogenesis of NDD: genetic variability, epigenetic changes, extent of oxidative/nitrosative stress, mitochondrial dysfunction, and DNA damage. The complex interplay of all the above-mentioned factors may be a fingerprint of neurodegeneration, with different diseases being affected to different extents by particular factors. There is a voluminous body of evidence showing the benefits of regular exercise to brain health and cognitive functions. Moreover, the importance of a healthy diet, balanced in macro- and micro-nutrients, in preventing neurodegeneration and slowing down a progression to full-blown disease is evident. Individuals affected by NDD almost inevitably have low-grade inflammation and anomalies in lipid metabolism. Metabolic and lipid profiles in NDD can be improved by the Mediterranean diet. Many studies have associated the Mediterranean diet with a decreased risk of dementia and AD, but a cause-and-effect relationship has not been deduced. Studies with caloric restriction showed neuroprotective effects in animal models, but the results in humans are inconsistent. The pathologies of NDD are complex and there is a great inter-individual (epi)genetic variance within any population. Furthermore, the gut microbiome, being deeply involved in nutrient uptake and lipid metabolism, also represents a pillar of the gut microbiome-brain axis and is linked with the pathogenesis of NDD. Numerous studies on the role of different micronutrients (omega-3 fatty acids, bioactive polyphenols from fruit and medicinal plants) in the prevention, prediction, and treatment of NDD have been conducted, but we are still far away from a personalized diet plan for individual NDD patients. For this to be realized, large-scale cohorts that would include the precise monitoring of food intake, mapping of genetic variants, epigenetic data, microbiome studies, and metabolome, lipidome, and transcriptome data are needed.

Short-Term Consumption of Pomegranate Juice Alleviates Some Metabolic Disturbances in Overweight Patients with Dyslipidemia.

Pomegranate juice (PJ) has potential positive effects in patients with metabolic disturbances due to a high content of polyphenols. The objective of this study was to evaluate effects of a 2-week consumption of dietary doses of PJ on blood pressure, lipid metabolism, and oxidative stress markers in overweight patients with dyslipidemia. Twenty-four patients, 8 males and 16 females, 40-60 years of age, with established overweight and dyslipidemia were randomly assigned into intervention group, who consumed 300 mL of PJ daily for 2 weeks, or control group. After 2 weeks of juice intake, intervention group had significantly lower diastolic blood pressure, low-density lipoprotein cholesterol, aminotransferase, and activity of glutathione peroxidase. Furthermore, patients who consumed PJ had reduced percentage of docosahexaenoic acid (22:6n-3, DHA) in plasma phospholipids and increased estimated activity of stearoyl-CoA desaturase. In erythrocytes, we found a significant increase in the levels of dihomo-γ- linolenic acid (20:3n-6, DGLA) and DHA, as well as in estimated activity of Δ6 desaturase, and a decrease in estimated activity of Δ5 desaturase. These results show that even a short-term consumption of dietary doses of PJ exerts beneficial effects and affects lipid metabolism in overweight patients with dyslipidemia.

Metabolically healthy obesity: is there a link with polyunsaturated fatty acid intake and status?

The aim of this study was to compare dietary intake and status of polyunsaturated fatty acids (PUFA) in plasma and erythrocyte phospholipids metabolically healthy and unhealthy, and obese and nonobese persons. Metabolic health status in 171 participants was defined according to criteria for metabolic syndrome. Obese and nonobese metabolically unhealthy persons (MUHO and MUHNO) had higher energy intake of n-6 PUFA (7.82 ± 1.03 and 7.49 ± 0.86) and lower intake of n-3 PUFA (0.60 ± 0.12 and 0.62 ± 0.11) compared to obese and nonobese metabolically healthy persons (MHO and MHNO) (5.92 ± 0.63 and 5.72 ± 0.67; 1.20 ± 0.07 and 1.22 ± 0.09, respectively) and a higher n-6/n-3 PUFA ratio. The plasma level of n-6 PUFA was lower in the MUHO and MUHNO groups (38.49 ± 3.71 and 38.53 ± 2.19) compared to MHNO (40.90 ± 2.43), while n-3 PUFA status was lower in obese than in nonobese persons (3.58 ± 0.79 and 3.50 ± 1.02 vs. 4.21 ± 0.80 and 4.06 ± 1.15). The MHO group had a higher eicosapentaenoic/arachidonic acid ratio and estimated desaturase (SCD16, D6D) and elongase activity in plasma phospholipids compared to MHNO. The low intake of n-3 PUFA is directly associated with metabolic risk factors. These results indicated that obesity is closely associated with low levels of n-3 PUFA in plasma phospholipids, suggesting that dietary modifications including n-3 PUFA supplementation appear to be suitable therapeutic strategy in obese persons.