Efficacy of silymarin in patients with non-alcoholic fatty liver disease - the Siliver trial: a study protocol for a randomized controlled clinical trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases globally. Pharmacological treatments for NAFLD are still limited. Silymarin, a compound extracted from Silybum marianum, is an herbal supplement traditionally used in folk medicine for liver disorders. It has been proposed that silymarin may possess hepatoprotective and anti-inflammatory properties. The present trial aims to assess the efficacy of silymarin supplementation in the adjuvant treatment of NAFLD in adult patients. METHOD: This is a randomized double-blind placebo-controlled clinical trial recruiting adult NAFLD patients in therapy on an outpatient basis. Participants are randomized to an intervention (I) or control (C) group. Both groups receive identical capsules and are followed for 12 weeks. I receives 700mg of silymarin + 8mg vitamin E + 50mg phosphatidylcholine daily, while C receives 700mg maltodextrin + 8mg vitamin E + 50mg phosphatidylcholine daily. Patients undergo a computerized tomography (CT) scan and blood tests at the beginning and end of the study. Monthly face-to-face consultations and weekly telephone contact are carried out for all participants. The primary outcome assessed will be change in NAFLD stage, if any, assessed by the difference in attenuation coefficient between liver and spleen, obtained by upper abdomen CT. DISCUSSION: The results of this study may provide a valuable opinion on whether silymarin can be used as adjuvant therapy for the management or treatment of NAFLD. The data presented on the efficacy and safety of silymarin may provide more foundation for further trials and for a possible use in clinical practice. TRIAL REGISTRATION: This study has been approved by the Research Ethics Committee of the Professor Edgard Santos University Hospital Complex, Salvador BA, Brazil, under protocol 2.635.954. The study is carried out according to guidelines and regulatory standards for research involving humans, as set out in Brazilian legislation. Trial registration - ClinicalTrials.gov : NCT03749070. November 21, 2018.

A Reflection on the Tensions of Acting in Dual Roles of Doctoral Researcher and Practitioner when Evaluating a Lifestyle Intervention for Breast Cancer Patients.

This reflection was completed as part of a doctoral project to develop and trial a lifestyle intervention for people following the completion of their treatment for breast cancer. In this study the graduate student acted in the dual roles of nutrition practitioner and researcher. This article uses the experience, reflection, action (ERA) cycle of reflection to consider some of the tensions faced due to the divergent priorities and requirements of these two roles. One challenge occurred during study recruitment when a few potential participants did not meet the inclusion criteria for the study but still wished to attend the intervention sessions. It was also a challenge to mitigate the risks of distress of potentially vulnerable participants during group intervention sessions. In both instances there was a potential conflict between the needs of patients and research requirements. This reflection concluded that the obligations of both roles should be adhered to where possible, but if in doubt, the needs of the participants were paramount.

The effectiveness of automated digital health solutions at successfully managing obesity and obesity-associated disorders: A PICO-structured investigation.

Most adults in the UK and USA are classified as overweight or obese. Recent studies suggest that the prevalence of obesity has further increased during the SARS-CoV-2 pandemic and associated lockdowns. Digital technologies may be effective at managing obesity and related comorbidities, a potential further justified by social isolation and distancing circumstances. This review of published literature employed a Patient-Intervention-Comparison-Outcome structured approach on the use of digital solutions to determine the effectiveness of their use in the management and treatment of obesity, hypertension, and type 2 diabetes and included commercially available, automated devices and applications that did not require intervention from a clinician. Our search covered studies published between January 2004 and February 2019, and 18 papers were included in the final analysis. The digital solutions reviewed were smartphone applications, wearable activity trackers, and 'digital medicine offerings' (DMO), including ingestible sensors and wearable patches. This study found that not all interventions were effective at encouraging the lifestyle changes required for the management of obesity. Smartphone applications requiring interaction from the patient appeared to be more effective at encouraging engagement with treatment interventions than more passive wearable activity trackers. Automated feedback from smartphone applications was effective at managing type 2 diabetes, while DMO were effective at reducing blood pressure. With the advancement of new technologies alongside a rapid increase in the prevalence of obesity and associated disorders, further studies comparing the various technologies available in larger sample populations for longer periods would help determine the most cost-effective preventive and therapeutic strategies.

Metabolic and nutritional triggers associated with increased risk of liver complications in SARS-CoV-2.

Obesity, diabetes, cardiovascular and respiratory diseases, cancer and smoking are risk factors for negative outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can quickly induce severe respiratory failure in 5% of cases. Coronavirus disease-associated liver injury may occur during progression of SARS-CoV-2 in patients with or without pre-existing liver disease, and damage to the liver parenchyma can be caused by infection of hepatocytes. Cirrhosis patients may be particularly vulnerable to SARS-CoV-2 if suffering with cirrhosis-associated immune dysfunction. Furthermore, pharmacotherapies including macrolide or quinolone antibiotics and steroids can also induce liver damage. In this review we addressed nutritional status and nutritional interventions in severe SARS-CoV-2 liver patients. As guidelines for SARS-CoV-2 in intensive care (IC) specifically are not yet available, strategies for management of sepsis and SARS are suggested in SARS-CoV-2. Early enteral nutrition (EN) should be started soon after IC admission, preferably employing iso-osmolar polymeric formula with initial protein content at 0.8 g/kg per day progressively increasing up to 1.3 g/kg per day and enriched with fish oil at 0.1 g/kg per day to 0.2 g/kg per day. Monitoring is necessary to identify signs of intolerance, hemodynamic instability and metabolic disorders, and transition to parenteral nutrition should not be delayed when energy and protein targets cannot be met via EN. Nutrients including vitamins A, C, D, E, B6, B12, folic acid, zinc, selenium and ω-3 fatty acids have in isolation or in combination shown beneficial effects upon immune function and inflammation modulation. Cautious and monitored supplementation up to upper limits may be beneficial in management strategies for SARS-CoV-2 liver patients.

A poorer nutritional status impacts quality of life in a sample population of elderly cancer patients.

RATIONALE: Quality of Life (QoL) is impaired in cancer, and the elderly are particularly vulnerable to malnutrition. A diagnosis of cancer in elderly patients further exacerbates risks of negative health outcomes. Here we investigated associations between QoL and nutritional status in a sample population of mostly socially deprived elderly cancer patients. METHOD: 432 cancer patients were recruited for this cross-sectional study at point of admission to a tertiary referral hospital for cancer treatment. Patient-generated subjective global assessment (PG-SGA) assessed nutritional status. Functional assessment of cancer therapy- general (FACT-G) quantified QoL. Relationship between PG-SGA and QoL was assessed by Spearman correlation. PG-SGA outcomes were compared against FACT-G scores employing Mann-Whitney test. Bivariate Linear Regression Model was employed to investigate influences of sociodemographic, clinical and nutritional status upon QoL. RESULTS: 37.5% of participants were malnourished or at risk. 39% were illiterate and 54.6% had family income lower than minimum wage. Malnourished patients showed lower FACT-G scores (76.8 vs. 84.7; p = 0.000). Poor nutritional diagnosis was inversely correlated with all QoL domains. Bivariate regression analysis showed that lower PG-SGA scores (ßo = - 1.00; p = 0.000) contributed to FACT-G score deterioration, the male gender showed better QoL scores, and other clinical and sociodemographic variables did not show relationship. CONCLUSION: Poorer nutritional status was significantly associated with worsened physical, social, emotional and functional well-being QoL domains in elderly cancer patients. Poorer nutritional status is an independent risk factor for worsened QoL. Future policies aimed at particularly vulnerable populations may improve QoL and health outcomes.

Oestrogen replacement fails to fully revert ovariectomy-induced changes in adipose tissue monoglycerides, diglycerides and cholesteryl esters of rats fed a lard-enriched diet.

Menopause may be accompanied by abdominal obesity and inflammation, conditions accentuated by high-fat intake, especially of saturated fat (SFA)-rich diets. We investigated the consequences of high-SFA intake on the fatty acid (FA) profile of monoglycerides, diglycerides and cholesteryl esters from retroperitoneal white adipose tissue (RET) of rats with ovariectomy-induced menopause, and the effect of oestradiol replacement. Wistar rats were either ovariectomized (Ovx) or sham operated (Sham) and fed either standard chow (C) or lard-enriched diet (L) for 12 weeks. Half of the Ovx rats received 17ß-oestradiol replacement (Ovx + E2). Body weight and food intake were measured weekly. RET neutral lipids were chromatographically separated and FAs analysed by gas chromatography. Ovariectomy alone increased body weight, feed efficiency, RET mass, leptin and insulin levels, leptin/adiponectin ratio, HOMA-IR and HOMA-ß indexes. OvxC + E2 showed attenuation in nearly all blood markers. HOMA-ß index was restored in OvxL + E2. OvxC showed significantly disturbed SFA and polyunsaturated FA (PUFA) profile in RET cholesteryl esters (CE). OvxC also showed increased monounsaturated FA (MUFA) in the monoglyceride diglyceride (Mono-Di) fraction. Similar changes were not observed in OvxL, although increased SFA and decreased PUFA was observed in Mono-Di. Overall, HRT was only partially able to revert changes induced by ovariectomy. There appears to be increased mobilization of essential FA in Ovx via CE, which is a dynamic lipid species. The same results were not found in Mono-Di, which are more inert. HRT may be helpful to preserve FA profile in visceral fat, but possibly not wholly sufficient in reverting the metabolic effects induced by menopause.

The usefulness of melatonin in the field of obstetrics and gynecology.

Disorders of the female reproductive system, including those associated with hormone regulation, fertility rate and fetal health, are issues of great concern worldwide. More recently, melatonin supplementation has been suggested as a therapeutic approach in gynecological practice. In both animal models and in women, melatonin supplementation suggests a therapeutic and preventative potential, effects attributed mainly to its antioxidant properties and action as hormone modulator. The aim of this literature review is to further investigate the evidence available on the effects of melatonin supplementation in animal and human studies, focusing on its potential application to gynecology. Melatonin-containing supplements are easily found in online and high street retailers, and despite its supplementation deemed to be relatively safe, no consensus has been reached on effective dosage and supplementation period. Short term supplementation studies, of up to six months, suggest that a daily posology of 2-18 mg of melatonin may have the potential to improve fertility rate, oocyte quality, maturation and number of embryos. However, the evidence available so far on the effects of melatonin supplementation covering gestational age and gestational outcomes is very scarce. Clinical trials and longer-term supplementation studies are required to assess any clinical outcome associated with melatonin supplementation in the field of gynecology.

The effect of artichoke on lipid profile: A review of possible mechanisms of action.

Cardiovascular disease is a highly prevalent issue worldwide, and one of its main manifestations, dyslipidaemia, needs more attention. Cooked artichoke (Cynara scolymus) hearts or artichoke leaf extract (ALE) are believed to be helpful in the treatment of dyslipidaemia. In this narrative review, we provide a brief overview of the potential impact of artichoke consumption on lipid profile. We appraised the Cochrane, MEDLINE and Web of Science databases, and included articles published between 2000 and June 2018 on intervention in humans only. The main potential of ALE administration observed on lipid profile relates to decreased serum LDL, total cholesterol and triglyceride concentrations, although no strong evidence for increasing HDL appears to exist. Evidence suggests that decreases of 8-49 mg/dL for LDL concentration, 12-55 mg/dL for total cholesterol, and 11-51 mg/dL for triglycerides, can be attributed to 2 to 3 g/d of ALE, in which its components luteolin and chlorogenic acid may play a key role. On the other hand, the effects of cooked artichoke hearts can be attributed mainly to its soluble fibres, particularly inulin. Despite the convincing evidence on its health benefits, additional long-term clinical trials are pivotal to fully elucidate the potential effects of ALE administration on positive cardiovascular outcomes.

Gut microbiota, probiotics and diabetes.

Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic ß cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gut microbiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes.

White adipose tissue re-growth after partial lipectomy in high fat diet induced obese wistar rats.

The effects of partial removal of epididymal (EPI) and retroperitoneal (RET) adipose tissues (partial lipectomy) on the triacylglycerol deposition of high fat diet induced obese rats were analyzed, aiming to challenge the hypothesized body fat regulatory system. Male 28-day-old wistar rats received a diet enriched with peanuts, milk chocolate and sweet biscuits during the experimental period. At the 90th day of life, rats were submitted to either lipectomy (L) or sham surgery. After 7 or 30 days, RET, EPI, liver, brown adipose tissue (BAT), blood and carcass were obtained and analyzed. Seven days following surgery, liver lipogenesis rate and EPI relative weight were increased in L. After 30 days, L, RET and EPI presented increased lipogenesis, lipolysis and percentage of small area adipocytes. L rats also presented increased liver malic enzyme activity, BAT lipogenesis, and triacylglycerol and corticosterone serum levels. The partial removal of visceral fat pads affected the metabolism of high fat diet obese rats, which leads to excised tissue re-growth and possibly compensatory growth of non-excised depots at a later time.

Exercise training in rats impairs the replenishment of white adipose tissue after partial lipectomy.

The aim of this study was to evaluate the effect of exercise training on the metabolism of rats following the partial removal of fat pads. Three-month-old male Wistar rats were subjected to the partial removal (L) of retroperitoneal white adipose tissue (RET) and epididymal white adipose tissue (EPI), or a sham operation (Sh). Seven days after surgery, both sets of rats were subdivided into exercised (LE or ShE) (swimming 90 min/day, 5 days/week, 6 weeks) and sedentary (LS or ShS) groups. Partial removal of the fat pads increased the lipogenesis rates in both the RET and EPI and decreased the weight and lypolysis rate of the EPI, while the RET weight was not significantly affected by lipectomy. In both lipectomized and sham-operated groups, exercise training caused a reduction in carcass lipid content, food intake, RET and EPI weights, and RET lipogenesis rate. On the other hand, the exercise training increased the percentage of diet-derived lipid accumulation in both tissues, either in sham and lipectomized rats. These results confirmed that regrowth is not uniform and depends on the particular fat pad that is excised. They also demonstrated that exercise training following the partial removal of fat pads modified adipose tissue metabolism, impaired the replenishment of adipose tissue, and decrease body adiposity.

Long chain saturated fatty acids increase haptoglobin gene expression in C57BL/6J mice adipose tissue and 3T3-L1 cells.

BACKGROUND: Dietary lipids are directly related to the composition of adipose tissue, aetiology of obesity and arousal of obesity-related pathologies, like chronic inflammation states. Haptoglobin is an acute phase protein secreted by the liver and white adipose tissue, and its blood levels vary according to the volume of fat in the body. AIM OF THE STUDY: To investigate the effect of diets enriched with large amounts of dietary fats, which differ in their fatty acid composition, on the haptoglobin gene expression by visceral and subcutaneous adipose tissue of mice fed for 2 days or 8 weeks. 3T3-L1 cells were treated with fatty acids that are found in those types of dietary fats. METHODS: Mice were treated acutely (for 2 days) or chronically (for 8 weeks) with diets enriched with soybean oil, fish oil, coconut oil or lard. 3T3-L1 cells were treated with six different fatty acids. Haptoglobin gene expression was quantified by northern blotting. RESULTS: Both chronic and acute treatment with lard, which is rich in long chain saturated fatty acids, increased the haptoglobin mRNA expression in the retroperitoneal and epidydimal white adipose tissues. Chronic treatment with coconut oil, which is rich in medium chain saturated fatty acids, increased the haptoglobin expression in the epidydimal and subcutaneous depots. In 3T3-L1, palmitic acid increased the haptoglobin gene expression. CONCLUSION: The type of lipids in the diet can differently modulate the white adipose tissue gene expression of haptoglobin, and saturated fatty acids play a major role in promoting a pro-inflammatory environment. This response is fat pad specific and dependant on the duration of treatment.

Effects of different fatty acids and dietary lipids on adiponectin gene expression in 3T3-L1 cells and C57BL/6J mice adipose tissue.

Obesity is positively correlated to dietary lipid intake, and the type of lipid may play a causal role in the development of obesity-related pathologies. A major protein secreted by adipose tissue is adiponectin, which has antiatherogenic and antidiabetic properties. The aim of this study was to evaluate the effects of four different high-fat diets (enriched with soybean oil, fish oil, coconut oil, or lard) on adiponectin gene expression and secretion by the white adipose tissue (WAT) of mice fed on a selected diet for either 2 (acute treatment) or 60 days (chronic treatment). Additionally, 3T3-L1 adipocytes were treated for 48 h with six different fatty acids: palmitic, linoleic, eicosapentaenoic (EPA), docosahexaenoic (DHA), lauric, or oleic acid. Serum adiponectin concentration was reduced in the soybean-, coconut-, and lard-enriched diets in both groups. Adiponectin gene expression was lower in retroperitoneal WAT after acute treatment with all diets. The same reduction in levels of adiponectin gene expression was observed in epididymal adipose tissue of animals chronically fed soybean and coconut diets and in 3T3-L1 cells treated with palmitic, linoleic, EPA, and DHA acids. These results indicate that the intake of certain fatty acids may affect serum adiponectin levels in mice and adiponectin gene expression in mouse WAT and 3T3-L1 adipocytes. The effects appear to be time dependent and depot specific. It is postulated that the downregulation of adiponectin expression by dietary enrichment with soybean oil or coconut oil may contribute to the development of insulin resistance and atherosclerosis.

Efeito da lipectomia sobre o metabolismo lipídico de ratos normais e obesos / Effect of lipectomy on the lipid metabolism of normal or obese rats

INTRODUÇÃO: A obesidade é uma doença que ocorre como conseqüência do desequilíbrio no balanço entre a energia ingerida e a gasta para a manutenção de processos vitais. A obesidade possui prevalência crescente, assumindo atualmente caráter epidêmico, sendo considerada um dos principais problemas de saúde pública na sociedade moderna. Ela está associada com aumento do risco de desenvolver diabetes mellitus, doenças vasculares, dislipidemias e inúmeras outras doenças crônicas. A lipectomia por sucção é um método bastante efetivo e seguro para redução da adiposidade, porém vários pesquisadores verificaram que a reposição do tecido adiposo pode ocorrer. Dados da literatura têm mostrado que o tecido adiposo é um órgão não apenas de estoque energético, mas também de produção e secreção de várias substâncias com ação local e sistêmica, como fator de necrose tumoral a, interleucinas S e 8, elementos do sistema renina-angiotensina, leptina, metalotioneína e outros. OBJETIVO: Verificar os efeitos da lipectomia após sete ou trinta dias da cirurgia sobre o metabolismo do fígado, dos tecidos adiposos brancos retroperitoneal e epididimal, do tecido adiposo marrom interescapular e da carcaça de animais normais ou tomados obesos pela administração neonatal de glutamato monossódico - MSG. MÉTODOS: Ratos Wistar normais ou MSG, com 90 dias de vida, foram anestesiados com Ketamina e Xilazina intraperitonealmente. Em seguida foi feita uma incisão longitudinal mediana no abdômen expondo a cavidade peritoneal para retirada bilateral de parte dos tecidos adiposos retroperitoneal (RET) e epididimal (EPI). Sete ou trinta dias após a lipectomia os animais foram sacrificados por decapitação, e retirados, pesados, congelados a -70ºC e posteriormente processados o RET, EPI, tecido adiposo marrom interescapular (TAM) e o fígado. RESULTADOS: O modelo de obesidade utilizado neste estudo - o MSG -foi eficaz em promover obesidade nos animais estudados. Após sete dias da lipectomia verificamos principalmente aumento na taxa de lipogênese do RET, EPI e TAM e aumento na captação de lipídio marcado pelos tecidos EPI e TAM nos animais MSG, além de aumento da trigliceridemia nos grupos normal e MSG. Após trinta dias da lipectomia verificamos aumento na taxa de...(au)