Effects of polyphenol supplementation on hepatic steatosis, intima-media thickness and non-invasive vascular elastography in obese adolescents: a pilot study protocol.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent in obese adolescents. Increased systemic inflammation and decreased gut microbial diversity linked to obesity affect the liver and are also associated with cardiovascular diseases in adulthood. However, NAFLD and vascular alterations are reversible. METHODS AND ANALYSIS: This pilot study evaluated the feasibility of a prospective open-label randomised controlled trial evaluating the effects of polyphenols on NAFLD and vascular parameters in obese adolescents. Children aged 12-18 years with hepatic steatosis (n=60) will be recruited. The participants will be randomised with a 1:1 allocation ratio to receive polyphenol supplementation one time per day for 8 weeks along with the clinician-prescribed treatment (group B, n=30) or to continue the prescribed treatment without taking any polyphenols (group A, n=30). The outcome measures will be collected from both the groups at day 1 before starting polyphenol supplementation, at day 60 after 8 weeks of supplementation and at day 120, that is, 60 days after supplementation. The changes in hepatic steatosis and vascular parameters will be measured using liver and vascular imaging. Furthermore, anthropometric measures, blood tests and stool samples for gut microbiome analysis will be collected. After evaluating the study's feasibility, we hypothesise that, as a secondary outcome, compared with group A, the adolescents in group B will have improved NAFLD, vascular parameters, systemic inflammation and gut microbiome. ETHICS AND DISSEMINATION: This study is approved by Health Canada and the hospital ethics. Participants and their parents/tutors will both provide consent. Trial results will be communicated to the collaborating gastroenterologists who follow the enrolled participants. Abstracts and scientific articles will be submitted to high-impact radiological societies and journals. CLINICALTRIALS: gov ID: NCT03994029. Health Canada authorisation referral number: 250 811. Protocole version 13, 2 June 2023. TRIAL REGISTRATION NUMBER: NCT03994029.

Non-alcoholic fatty liver disease severity and metabolic complications in obese children: impact of omega-3 fatty acids.

Although n-3 polyunsaturated fatty acids (PUFA) revealed promising therapeutic results in non-alcoholic fatty liver disease (NAFLD), which is considered as the most prevalent cause of chronic hepatic disease, inconsistencies are calling for further confirmatory trials to demonstrate therapeutic efficacy and safety. The study, registered as NCT02201160 on www.clinicaltrials.gov, was designed to compare two groups of NAFLD with a different severity, and to evaluate the efficacy of n-3 PUFA supplementation. Twenty young male participants of French Canadian origin with NAFLD were enrolled and classified into moderate (mNAFLD) and severe (sNAFLD) fatty liver groups, according to transaminase levels, ultrasonography, NAFLD Activity Score and Fatty Liver Index (FLI). The sNAFLD patients were assigned to consume 2 g of n-3 PUFA for 6 months. sNAFLD patients displayed higher insulinemia, insulin resistance (IR), oxidative stress (OxS), systolic blood pressure and the risk lipid indicators of cardiovascular diseases. Supplementation of n-3 PUFA for 6 months resulted in a significant increase in concentrations of eicosapentaenoic and docosahexaenoic acids in red blood cells along with an attenuation of hepatic steatosis as reflected by the reduction of the FLI, ALT and ALT/AST ratio. Moreover, the n-3 PUFA improved the lipid profile and carotid intima-media thickness, while reducing metabolic and OxS markers as well as raising adiponectin. In conclusion, NAFLD severity was essentially related to IR. Treatment with n-3 PUFA has an evidently beneficial effect on liver steatosis and related metabolic abnormalities. Furthermore, the cross association of omega-3 index with cardiometabolic markers may serve as a predictor for cardiovascular risk disorders in NAFLD.

Cow's Milk Allergy and Bone Mineral Density in Prepubertal Children.

BACKGROUND AND OBJECTIVES: Recent data suggest that cow's milk allergy (CMA) has become more persistent, prolonging treatment via strict elimination of cow's milk products into a period of skeletal growth. The objectives of this study were to compare bone mineral density (BMD), vitamin D status, and dietary intakes of calcium and vitamin D between prepubertal children with persistent CMA and those with non-cow's milk food allergies (NCMA) as control subjects and to assess the use of and compliance to calcium and vitamin D supplementation among children with persistent CMA. METHODS: Fifty-two children with persistent CMA and 29 with NCMA were recruited. BMD was measured by using dual energy radiograph absorptiometry, and vitamin D status was assessed by using plasma 25-hydroxyvitamin D concentrations. Calcium and vitamin D intakes, as well as compliance to calcium and vitamin D supplementation, were recorded. RESULTS: Lumbar spine BMD z scores were significantly lower in children with CMA. Low bone mass was detected in 6% of the CMA group compared with none in the NCMA group. Children with CMA displayed significantly lower calcium intakes than control subjects. Vitamin D status was not reduced in children with CMA compared with control subjects. Fewer than one-half of children with CMA reported the use of calcium and vitamin D supplements. However, adherence was high among supplement users, with a mean compliance rate of 5.5 days per week. CONCLUSIONS: These prepubertal children with persistent CMA had lower lumbar spine BMD z scores than children with NCMA, which likely resulted from lower calcium intake.

The potential efficacy of omega-3 fatty acids as anti-angiogenic agents in benign vascular tumors of infancy.

Hemangiomas of infancy are benign vascular tumors frequently encountered in pediatrics. Medical treatment (corticosteroids, interferon, chemotherapy, embolization and radiation) in high-risk hemangioma cases could greatly benefit from the addition of new and safer therapies. The rapid growth of hemangiomas during the proliferative phase occurs secondary to a process of local uncontrolled angiogenesis, involving potent mediators such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). We hypothesize that omega-3 fatty acids, naturally occurring nutrients of proven health benefit to infants, could become an alternative or an adjuvant treatment for hemangiomas, by slowing down their rapid proliferation phase through anti-angiogenic and anti-tumoral effects. Suggested mechanisms of action of omega-3 fatty acids include the downregulation of VEGF and bFGF, and the suppression of pro-angiogenic eicosanoids such as cylooxygenase-2. In this article, we review recent animal and human studies using dietary omega-3 fatty acids supplements, alone or in conjunction with chemotherapy, for the treatment of a variety of tumors dependent on angiogenesis for growth. Available murine hemangioma models offer the opportunity to determine optimal omega-3 fatty acid dose, while taking in account related immunohistochemical markers, clinical outcome and secondary effects, before planning clinical trials. Lessons learned in hemangiomas of infancy may have a broad impact in understanding the phenomenon of dysregulated angiogenesis in cancer research.