Post-diagnosis serum 25-hydroxyvitamin D concentrations in women treated for breast cancer participating in a lifestyle trial in Italy.

OBJECTIVE: To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. METHODS: Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects' characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher's exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. RESULTS: Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. CONCLUSIONS: Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.

Dietary patterns derived by reduced rank regression are associated with lipid disorders among Korean adults: a cross-sectional analysis.

BACKGROUND: Lipid disorders are a potent risk factor for cardiovascular diseases. Moreover, the intake of dietary fatty acids has been closely related to blood lipid levels. Therefore, this cross-sectional study examined the associations between dietary patterns related to fatty acid intake and lipid disorders in Korean adults. METHODS: From the 2013-2019 Korea National Health and Nutrition Examination Surveys data, 8399 men and 11404 women (aged ≥ 19 years) were selected. Reduced rank regression was employed to identify dietary patterns from 26 food groups, aiming to explain the maximum variation in the intake of saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), omega-3 fatty acids, and the PUFA/SFA ratio. Associations of quintiles (Q) of dietary pattern scores with lipid disorders were examined using multiple logistic regression stratified by sex. RESULTS: Three dietary patterns were identified: dietary pattern 1 showed positive factor loadings for vegetable oils, seasonings, legumes, nuts, and fish; dietary pattern 2 was high in consumption of red meat, bread and snacks, and milk and dairy products; and dietary pattern 3 was rich in fish and milk and dairy products. In men, dietary pattern 3 was inversely associated with elevated triglycerides (Q5 vs. Q1: odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.69-0.97, P-trend = 0.008). In women, dietary pattern 2 was positively associated with elevated total cholesterol (OR = 1.31, 95% CI = 1.12-1.52, P-trend < 0.001) but inversely associated with low HDL-cholesterol (OR = 0.70, 95% CI = 0.59-0.83, P-trend < 0.001). CONCLUSION: In this study, dietary patterns explaining the intake of various types of fatty acids were differentially associated with lipid disorders in Korean adults. Dietary pattern characterized by higher intakes of red meat, bread and snacks and milk and dairy products were positively associated with elevated total cholesterol, whereas dietary pattern rich in fish consumption showed an inverse association with elevated triglycerides. These findings could be instrumental in developing dietary guidelines and strategies for preventing and managing lipid disorders in this population.

Fish Oil Derivatives in Hypertriglyceridemia: Mechanism and Cardiovascular Prevention: What Do Studies Say?

Hypertriglyceridemia is a type of dyslipidemia characterized by high triglyceride levels in the blood and increases the risk of cardiovascular disease. Conventional management includes antilipidemic medications such as statins, lowering LDL and triglyceride levels as well as raising HDL levels. However, the treatment may be stratified using omega-3 fatty acid supplements such as eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA), aka fish oil derivatives. Studies have shown that fish oil supplements reduce the risk of cardiovascular diseases; however, the underlying mechanism and the extent of reduction in CVD need more clarification. Our paper aims to review the clinical trials and observational studies in the current literature, investigating the use of fish oil and its benefits on the cardiovascular system as well as the proposed underlying mechanism.

How to Handle Elevated Triglycerides: Life after PROMINENT.

PURPOSE OF REVIEW: Hypertriglyceridaemia (HTG) is a common condition characterised by elevated levels of plasma triglycerides (TG), which are transported in the blood mainly by TG-rich lipoproteins (TRL). Elevated TG levels (150-400 mg/dL) are associated with increased cardiovascular risk. Severe HTG (>880 mg/dL) is associated with a risk of acute pancreatitis only. Randomised clinical trials investigating the clinical benefit of TG-lowering drugs in patients with elevated TG levels have provided conflicting results. RECENT FINDINGS: Elevated TG levels are only one marker of altered lipid/lipoprotein metabolism and indeed reflect altered concentrations of one or more classes or subfractions of TRL, which in turn may have a different association with CV risk. Fibrates, the drugs most commonly used to treat HTG, provide cardiovascular benefits to only a specific subgroup of patients. The lack of clinical benefit from pemafibrate has emphasised the concept that lowering TG levels is not sufficient to reduce the CV risk unless it is accompanied by a reduction in the number of circulating atherogenic lipoproteins, which can be assessed by determining apolipoprotein B levels. Treatment with omega-3 fatty acids was also ineffective in reducing CV risk, with the exception of icosapent ethyl, which, however, appears to have beneficial effects beyond lipids. New drugs are currently being developed that aim to lower TG levels by targeting apolipoprotein C-III or angiopoietin-like-3, both of which are involved in the metabolism of TGs. TG reduction can be achieved by various drugs, but most of them are ineffective in reducing CV risk. The results of outcome studies on new TG-lowering drugs will clarify whether lowering apoB levels is critical to achieve clinical benefit.

Evaluation of the Needs and Experiences of Patients with Hypertriglyceridemia: Social Media Listening Infosurveillance Study.

BACKGROUND: Hypertriglyceridemia is a risk factor for cardiovascular diseases. Internet usage in China is increasing, giving rise to large-scale data sources, especially to access, disseminate, and discuss medical information. Social media listening (SML) is a new approach to analyze and monitor online discussions related to various health-related topics in diverse diseases, which can generate insights into users' experiences and expectations. However, to date, no studies have evaluated the utility of SML to understand patients' cognizance and expectations pertaining to the management of hypertriglyceridemia. OBJECTIVE: The aim of this study was to utilize SML to explore the disease cognition level of patients with hypertriglyceridemia, choice of intervention measures, and the status quo of online consultations and question-and-answer (Q&A) search platforms. METHODS: An infosurveillance study was conducted wherein a disease-specific comprehensive search was performed between 2004 and 2020 in Q&A search and online consultation platforms. Predefined single and combined keywords related to hypertriglyceridemia were used in the search, including disease, symptoms, diagnosis, and treatment indicators; lifestyle interventions; and therapeutic agents. The search output was aggregated using an aggregator tool and evaluated. RESULTS: Disease-specific consultation data (n=69,845) and corresponding response data (n=111,763) were analyzed from 20 data sources (6 Q&A search platforms and 14 online consultation platforms). Doctors from inland areas had relatively high voice volumes and appear to exert a substantial influence on these platforms. Patients with hypertriglyceridemia engaging on the internet have an average level of cognition about the disease and its intervention measures. However, a strong demand for the concept of the disease and "how to treat it" was observed. More emphasis on the persistence of the disease and the safety of medications was observed. Young patients have a lower willingness for drug interventions, whereas patients with severe hypertriglyceridemia have a clearer intention to use drug intervention and few patients have a strong willingness for the use of traditional Chinese medicine. CONCLUSIONS: Findings from this disease-specific SML study revealed that patients with hypertriglyceridemia in China actively seek information from both online Q&A search and consultation platforms. However, the integrity of internet doctors' suggestions on lifestyle interventions and the accuracy of drug intervention recommendations still need to be improved. Further, a combined prospective qualitative study with SML is required for added rigor and confirmation of the relevance of the findings.

5-Fluorouracil-associated severe hypertriglyceridaemia with positive rechallenge.

Chemotherapy-induced hypertriglyceridaemia (HTG) is a potential serious adverse event. Severe HTG with triglycerides (TG) >11.3 mmol/L (1000 mg/dL) can cause acute pancreatitis in addition to cardiovascular diseases such as coronary artery disease. While the association of capecitabine (5-fluorouracil (5-FU) prodrug) with clinically relevant HTG is a well-known adverse reaction, 5-FU is not typically associated with HTG. We here report the case of a patient who developed 5-FU-associated grade 4 HTG with TG level raising up to 37.1 mmol/L (3286 mg/dL) occurring after the ninth cycle of adjuvant FOLFOX (Fluorouracil and Oxaliplatin) chemotherapy. Fenofibrate treatment and diet were started. Chemotherapy was postponed and then resumed for two additional cycles. However, severe HTG recurred shortly after. Chemotherapy was therefore permanently stopped. Approximately 8 weeks after chemotherapy discontinuation, TG fell back to range at 2.1 mmol/L (189 mg/dL) allowing interruption of fenofibrate without HTG recurrence at 3 months.

Anthocyanins of Hierbamora (Solanum nigrescens): Revealing their Nutraceutical Potential for Controlling Hypertriglyceridemia and Helicobacter pylori Viability.

We present the inhibitory properties of the Solanum nigrescens anthocyanin fraction (SNAF) and its major constituents on alpha-glucosidase (AG), pancreatic lipase (PL), HMG-CoA reductase, and ornithine decarboxylase (ODC). The effect of SNAF was simultaneously evaluated in ICR male mice exposed to triglyceride charge test (TCT). HPLC-MS profiling revealed the presence cyanidin-3-O-rutinoside-5-glucoside (CRG), delphinidin-3-(p-coumaroyl)-rutinoside-5-glucoside (DCRG), and petunidin-3-(cis-p-coumaroyl)-rutinoside-5-glucoside (PCRG) as major constituents of the fraction. SNAF, CRG, and specially PCRG, induced strong non-competitive inhibition on PL (IC50 , 33-86 µg mL-1 ). The results of TCT confirmed their capacity to ameliorate (p <0.001) hypertriglyceridemia during postprandial and interdigestive stages. SNAF, CRG, DCRG, and PCRG caused negligible growth inhibition (MIC>600 µg mL-1 ) on beneficial bacteria whereas SNAF and DCRG exerted inhibitory activity on Helicobacter pylori ATCC 53504 (MIC,187-64 µg mL-1 ). Additional exploration revealed that SNAF and DCRG produced non-competitive activity on H. pylori urease, which facilitates bacterial growth under acidic conditions.

Long-Term Treatment of Lipoprotein Lipase Deficiency with Medium-Chain Triglyceride-Enriched Diet: A Case Series.

Background: Lipoprotein lipase (LPL) deficiency is a genetic condition. Affected individuals typically develop symptoms related to severe and persistent hypertriglyceridemia, such as abdominal pain and recurrent pancreatitis, before 10 years of age. No pharmacological treatment sustainably lowering triglycerides (TGs) in LPL deficiency patients has been proven to be effective. This study investigated whether a long-chain triglyceride (LCT)-restricted, medium-chain triglyceride (MCT)-supplemented diet enables a meaningful reduction in TGs and reduces LPL-related symptoms in children with LPL deficiency. Methods: A single-center retrospective case series study of LPL deficiency patients treated at the Hospital of Sick Children between January 2000 and December 2022 was carried out. Data, extracted from hospital charts, included demographics, diagnosis confirmation, clinical and imaging observations, and biochemical profiles. Results: Seven patients with hypertriglyceridemia > 20 mmol/L suspected of an LPL deficiency diagnosis were included. Six patients had a confirmed molecular diagnosis of LPL deficiency, and one had glycogen storage disease type 1a (GSD1a). Clinical presentation was at a median of 30 days of age (range 1-105), and treatment start, excluding one late-treated patient, was at a median of 42 days (range 2-106). The observation and treatment period of the LPL patients was 48.0 patient years (median 7.1, range 4.3-15.5). The LCT-restricted and MCT-supplemented diet led to an immediate drop in TGs in six out of six LPL patients. TGs improved from a median of 40.9 mmol/L (range 11.4-276.5) pre-treatment to a median of 12.0 mmol/L (range 1.1-36.6) during treatment, total cholesterol from 7.6 mmol/L (4.9-27.0) to 3.9 mmol/L (1.7-8.2), and pancreatic lipase from 631 IU/L (30-1200) to 26.5 IU/L (5-289). In 48 patient years, there was only one complication of pancreatitis and no other disease-specific manifestations or complications. Catch-up growth was observed in one late-treated patient. All patients maintained normal growth and development. As expected, the diet failed to treat hypertriglyceridemia in the GSD1a patient. Conclusions: The dietary restriction of LCT in combination with MCT supplementation as long-term management of pediatric patients with LPL deficiency was feasible, well tolerated, and clinically effective in reducing TG levels and in preventing LPL-related complications.

Association of gestational hypertriglyceridemia, diabetes with serum ferritin levels in early pregnancy: a retrospective cohort study.

Aims: Previous studies showed conflicting results linking body iron stores to the risk of gestational diabetes mellitus (GDM) and dyslipidemia. We aim to investigate the relationship between serum ferritin, and the prevalence of GDM, insulin resistance (IR) and hypertriglyceridemia. Methods: A total of 781 singleton pregnant women of gestation in Shanghai General Hospital took part in the retrospective cohort study conducted. The participants were divided into four groups by quartiles of serum ferritin levels (Q1-4). Binary logistic regressions were used to examine the strength of association between the different traits and the serum ferritin (sFer) quartiles separately, where Q1 (lowest ferritin quartile) was taken as the base reference. One-way ANOVA was adopted to compare the averages of the different variables across Sfer quartiles. Results: Compared with the lowest serum ferritin quartile (Q1), the ORs for Q3, and Q4 in our population were 1.79 (1.01-2.646), and 2.07 (1.089-2.562) respectively and this trend persisted even after adjusted for age and pre-BMI. Women with higher serum ferritin quartile including Q3 (OR=2.182, 95%CI=1.729-5.527, P=0.003) and Q4(OR=3.137, 95%CI=3.137-8.523, P<0.01)are prone to develop insulin resistance disorders. No significant difference was observed between sFer concentrations and gestational hypertriglyceridemia(GTG) in the comparison among these 4 groups across logistic regressions but TG was found positively correlated with increased ferritin values in the second trimester. Conclusions: Increased concentrations of plasma ferritin in early pregnancy are significantly and positively associated with insulin resistance and incidence of GDM but not gestational dyslipidemia. Further clinical studies are warranted to determine whether it is necessary to encourage pregnant women to take iron supplement as a part of routine antenatal care.

Very severe hypertriglyceridemia complicating pediatric acute lymphoblastic leukemia treatment: a call for management guidelines.

OBJECTIVES: Severe and very severe hypertriglyceridemia although rare within the pediatric population occur more often among oncology patients, secondary to chemotherapeutic agents. Currently there exists minimal literature to guide management of severe hypertriglyceridemia among pediatric patients. Very-low-fat dietary restriction should be considered over nil per os (NPO) for initial management of severe hypertriglyceridemia in stable pediatric patients. Pediatricians caring for oncology patients must consider chylomicronemia as a potential etiology for presenting symptoms. Pediatric severe hypertriglyceridemia management guidelines are needed as pediatricians must currently rely on anecdotal experiences for management decisions. CASE PRESENTATION: Three children receiving treatment for acute lymphoblastic leukemia required hospitalization for very severe hypertriglyceridemia. Management varied among the cases but included: NPO or very-low-fat diet, insulin, intravenous fluids, fibrates, and omega-3 fatty acids. CONCLUSIONS: These cases suggest that pediatric severe hypertriglyceridemia management, in the absence of pancreatitis should allow a very-low-fat diet initially rather than NPO followed by pharmacologic therapies.

Fibrates, Hypertriglyceridemia, and CVD Risk: Where Do We Stand After the PROMINENT Trial for Triglyceride Lowering?

PURPOSE OF REVIEW: To evaluate recent clinical trials focusing on patients with hypertriglyceridemia. RECENT FINDINGS: Randomized clinical trials have recently been undertaken in hypertriglyceridemic patients to determine whether effective reductions in triglycerides would improve cardiovascular disease (CVD) outcomes. However, the fibric acid derivative, pemafibrate, failed to reduce cardiovascular events despite significant reductions (~ 25-35%) in triglyceride levels and despite background statin therapy. In contrast, icosapent ethyl, a highly purified omega-3 fatty acid was previously shown to reduce CVD events in hypertriglyceridemic patients, despite more modest reductions (~ 20%) in triglyceride levels in statin treated patients. The divergent results obtained in patients with hypertriglyceridemia (HTG), a group at particularly high risk of CVD, especially when coupled with other risk factors, indicates that triglyceride lowering in of itself is insufficient to offset CVD risk. Rather, the effectiveness of therapy in this high-risk cohort may be the result of the suppression of the inherent atherogenic properties associated with HTG.

Medical management of hypertriglyceridemia in pancreatitis.

PURPOSE OF REVIEW: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) should be considered in all cases of acute pancreatitis and triglyceride levels measured early, so that appropriate early and long-term treatment can be initiated. RECENT FINDINGS: In most cases of HTG-AP, conservative management (nothing by mouth, intravenous fluid resuscitation and analgesia) is sufficient to achieve triglyceride levels less than 500 mg/dl. Intravenous insulin and plasmapheresis are sometimes used, although prospective studies showing clinical benefits are lacking. Pharmacological management of hypertriglyceridemia (HTG) should start early and target triglyceride levels of less than 500 mg/dl to reduce the risk or recurrent acute pancreatitis. In addition to currently used fenofibrate and omega-3 fatty acids, several novel agents are being studied for long-term treatment of HTG. These emerging therapies focus mainly on modifying the action of lipoprotein lipase (LPL) through inhibition of apolipoprotein CIII and angiopoietin-like protein 3. Dietary modifications and avoidance of secondary factors that worsen triglyceride levels should also be pursued. In some cases of HTG-AP, genetic testing may help personalize management and improve outcomes. SUMMARY: Patients with HTG-AP require acute and long-term management of HTG with the goal of reducing and maintaining triglyceride levels to less than 500 mg/dl.

Indications for omega-3 fatty acid supplementation in prevention of cardiovascular disease: From fish to pharmaceuticals.

OBJECTIVE: To explore the evidence for omega-3 fatty acid (O3FA) supplementation in primary and secondary prevention of cardiovascular disease (CVD). SOURCES OF INFORMATION: PubMed, Cochrane reviews, and Google Scholar were searched for meta-analyses and reviews related to O3FAs and CVD. Salient, recent randomized controlled trials referenced in these reviews were retrieved. Current lipid guidelines were reviewed. MAIN MESSAGE: Most O3FAs are derived from marine or aquatic microalgae, which are consumed by fish. The essential fatty acids eicosapentaenoic acid and docosahexaenoic acid are mainly sourced from fish, with a small fraction coming from plants. Omega-3 fatty acids modestly lower triglyceride levels, but the major impact on CVD is through a variety of other mechanisms related to cell membrane function, antioxidant properties, and reduction of atherogenic small low-density lipoprotein cholesterol particles. Guidelines continue to recommend eating 2 servings of fish per week. There is little evidence of benefit of O3FAs in primary prevention of CVD. Given that 40% of Canadians have insufficient levels and that these low levels may be associated with other chronic diseases over time, supplementation with O3FAs could be considered, particularly in those with hypertriglyceridemia, in those who eat no fish, or for vegetarians or vegans. Doses up to 1 g daily are considered safe. For secondary prevention after statin optimization, if triglyceride levels are between 1.5 and 5.6 mmol/L, guidelines recommend with level 1A evidence taking 2 g of icosapent ethyl twice a day. This is also recommended in primary prevention for patients with diabetes and hypertriglyceridemia and additional CVD risk factors. As fish stocks dwindle over time, preserving fisheries for developing countries and obtaining O3FA from microalgal or genetically modified plant sources may become important. CONCLUSION: All guidelines recommend at least 2 servings of oily fish per week, although benefit from O3FAs is mostly seen in secondary prevention. Fish oil and combination preparations of eicosapentaenoic acid and docosahexaenoic acid have failed to show benefit at any dose at any level of prevention in patients who are appropriately prescribed statins. High-dose eicosapentaenoic acid shows substantial benefit in selected patients taking statins who have high triglyceride levels.

Nutrition interventions for adults with dyslipidemia: A Clinical Perspective from the National Lipid Association.

Lifestyle habits can have a profound impact on atherosclerotic cardiovascular disease (ASCVD) risk. The National Lipid Association previously published recommendations for lifestyle therapies to manage dyslipidemia. This Clinical Perspective provides an update with a focus on nutrition interventions for the three most common dyslipidemias in adults: 1) low-density lipoprotein cholesterol (LDL-C) elevation; 2) triglyceride (TG) elevation, including severe hypertriglyceridemia with chylomicronemia; and 3) combined dyslipidemia, with elevations in both LDL-C and TG levels. Lowering LDL-C and non-high-density lipoprotein cholesterol are the primary objectives for reducing ASCVD risk. With severe TG elevation (≥500 mg/dL), the primary objective is to prevent pancreatitis and ASCVD risk reduction is secondary. Nutrition interventions that lower LDL-C levels include reducing cholesterol-raising fatty acids and dietary cholesterol, as well as increasing intakes of unsaturated fatty acids, plant proteins, viscous fibers, and reducing adiposity for patients with overweight or obesity. Selected dietary supplements may be employed as dietary adjuncts. Nutrition interventions for all patients with elevated TG levels include restricting intakes of alcohol, added sugars, and refined starches. Additional lifestyle factors that reduce TG levels are participating in daily physical activity and reducing adiposity in patients with overweight or obesity. For patients with severe hypertriglyceridemia, an individualized approach is essential. Nutrition interventions for addressing concurrent elevations in LDL-C and TG include a combination of the strategies described for lowering LDL-C and TG. A multidisciplinary approach is recommended to facilitate success in making and sustaining dietary changes and the assistance of a registered dietitian nutritionist is highly recommended.

Effect of long-chain omega-3 polyunsaturated fatty acids on cardiometabolic factors in children with acute lymphoblastic leukemia undergoing treatment: a secondary analysis of a randomized controlled trial.

Introduction: Increased triglycerides (TGs) are a major risk factor for cardiovascular disease. Furthermore, hypertriglyceridemia is commonly associated with a reduction of high-density lipoprotein cholesterol (HDL-C) and an increase in atherogenic small-dense low-density lipoprotein (LDL-C) levels. Studies provide support that polyunsaturated omega-3 fatty acids (ω3-LCPUFAs) are cardioprotective and have antithrombotic and anti-inflammatory effects. The potential effects of ω3-LCPUFAs on cardiometabolic factors and anti-inflammatory actions in children with acute lymphoblastic leukemia (ALL) are limited. This is a secondary analysis of a previous clinical trial registered at clinical trials.gov (# NCT01051154) that was conducted to analyze the effect of ω3-LCPUFAs in pediatric patients with ALL who were receiving treatment.Objective: To examine the effect of supplementation with ω3-LCPUFAs on cardiometabolic factors in children with ALL undergoing treatment. Methods: Thirty-four children (placebo group: 20 patients; ω3-LCPUFAs group: 14 patients) aged 6.7 ± 2.7 years who were newly diagnosed with ALL were evaluated. Children were randomized to receive either ω3-LCPUFAs or placebo capsules (sunflower oil). ω3-LCPUFAs were administered in the form of 500-mg soft capsules. The ω3-LCPUFA capsules contained 225 mg of DHA, 45 mg of EPA, and 20 mg of another ω3-LCPUFAs. The omega-3 dose was administered at a rate of 0.100 g/kg of body weight/day for three months. Main outcomes: Fasting cholesterol, HDL-C, very-low-density lipoprotein (VLDL-C), TGs, atherogenic index of plasma (AIP), android/gynoid ratio (A/GR), IL-6, TNF-α, and percentage of fat mass (DXA) were measured in all patients. Fatty acid analyses in red blood cells were performed with gas chromatography. Results: We found significantly lower levels of TGs (p=0.043), VLDL-C (p=0.039), IL-6 (p=0.025), and AIP (p=0.042) in the ω3-LCPUFAs group than in the placebo group at three months. In contrast, the total cholesterol concentration was higher at 3 months in the ω3-LCPUFAs group than in the placebo group (155 mg/dl vs. 129 mg/dl, p=0.009). The number of children with hypertriglyceridemia (85% vs. 50%; p=0.054) tended to be lower between the time of diagnosis and after 3 months of supplementation with ω3-LCPUFAs. Conclusion: These findings support the use of ω3-LCPUFAs to reduce some adverse cardiometabolic and inflammatory risk factors in children with ALL. Clinical trial registration: ClinicalTrials.gov, identifier NCT01051154.

Impact of body mass index on the severity of bexarotene-associated hypertriglyceridemia: A post hoc analysis of an open-labeled clinical study of combined bexarotene and phototherapy in Japanese patients with cutaneous T-cell lymphoma.

Bexarotene is an effective oral drug for the treatment of cutaneous T-cell lymphoma, but careful management is required due to its various side effects. In particular, hypertriglyceridemia often requires a reduction or even suspension of bexarotene therapy. The risk factors of bexarotene-associated severe hypertriglyceridemia are not clear. Here, we conducted a post hoc analysis of the data from our previous clinical trial, which confirmed the efficacy and safety of combined bexarotene and phototherapy, to evaluate the effect of body mass index on bexarotene-associated hypertriglyceridemia. Twenty-five subjects were divided into two subgroups: normal and underweight (body mass index [BMI] <25 kg/m2 group) and overweight and obese (BMI ≥25 kg/m2 group) patients. The overall incidence of hypertriglyceridemia was 81.3% (13/16) in the BMI <25 kg/m2 group and 88.9% (8/9) in the BMI ≥25 kg/m2 group. The incidence of grade ≥3 hypertriglyceridemia (≥500 mg/dL) was 7.7% (1/13) in the BMI <25 kg/m2 group and 7/8 (87.5%) in the BMI ≥25 kg/m2 group (P < 0.001). Consequently, dose reduction in the BMI ≥25 kg/m2 group was larger than that in the BMI <25 kg/m2 group. The bexarotene-induced change in the serum triglyceride concentration was significantly increased in cutaneous T-cell lymphoma patients with a higher body mass index (ρ = 0.508, P = 0.009). The area under the curve was 0.886 (95% confidence interval 0.748-1.000, P = 0.002). With a body mass index cut-off of 24.85 kg/m2 , the sensitivity and specificity for identifying grade ≥3 hypertriglyceridemia were 0.875 and 0.882, respectively. The present findings suggest that BMI ≥25 kg/m2 is a risk factor for bexarotene-associated severe hypertriglyceridemia, therefore overweight and obese patients treated with bexarotene should receive lipid-lowering drugs prophylactically. Further studies for optimizing the initial bexarotene dose in such patients are required.

Nutritional Treatment of Hypertriglyceridemia in Childhood: From Healthy-Heart Counselling to Life-Saving Diet.

Hypertriglyceridemia is a lipid disorder with a varying prevalence; it is very common if we consider triglyceride plasma values slightly above the threshold, whereas it is extremely rare if only severely elevated triglyceride levels are considered. In most cases, severe forms of hypertriglyceridemia are caused by genetic mutations in the genes that regulate triglyceride metabolism, thus leading to extreme triglyceride plasma values and acute pancreatitis risk. Secondary forms of hypertriglyceridemia are usually less severe and are mainly associated with weight excess, but they can also be linked to liver, kidney, endocrinologic, or autoimmune diseases or to some class of drugs. Nutritional intervention is the milestone treatment for patients with hypertriglyceridemia and it has to be modulated on the underlying cause and on triglyceride plasma levels. In pediatric patients, nutritional intervention must be tailored according to specific age-related energy, growth and neurodevelopment requests. Nutritional intervention is extremely strict in case of severe hypertriglyceridemia, whereas it is similar to good healthy nutritional habits counselling for mild forms, mainly related to wrong habits and lifestyles, and to secondary causes. The aim of this narrative review is to define different nutritional intervention for various forms of hypertriglyceridemia in children and adolescents.

Strawberry, Blueberry, and Strawberry-Blueberry Blend Beverages Prevent Hepatic Steatosis in Obese Rats by Modulating Key Genes Involved in Lipid Metabolism.

There is an increasing interest in developing natural herb-infused functional beverages with health benefits; therefore, in this study, we aimed to evaluate the effect of strawberry, blueberry, and strawberry-blueberry blend decoction-based functional beverages on obesity-related metabolic alterations in high-fat and high-fructose diet-fed rats. The administration of the three berry-based beverages for eighteen weeks prevented the development of hypertriglyceridemia in obese rats (1.29-1.78-fold) and hepatic triglyceride accumulation (1.38-1.61-fold), preventing the development of hepatic steatosis. Furthermore, all beverages significantly down-regulated Fasn hepatic expression, whereas the strawberry beverage showed the greatest down-regulation of Acaca, involved in fatty acid de novo synthesis. Moreover, the strawberry beverage showed the most significant up-regulation of hepatic Cpt1 and Acadm (fatty acid ß-oxidation). In contrast, the blueberry beverage showed the most significant down-regulation of hepatic Fatp5 and Cd36 (fatty acid intracellular transport). Nevertheless, no beneficial effect was observed on biometric measurements, adipose tissue composition, and insulin resistance. On the other hand, several urolithins and their derivatives, and other urinary polyphenol metabolites were identified after the strawberry-based beverages supplementation. In contrast, enterolactone was found significantly increase after the intake of blueberry-based beverages. These results demonstrate that functional beverages elaborated with berry fruits prevent diet-induced hypertriglyceridemia and hepatic steatosis by modulating critical genes involved in fatty acid hepatic metabolism.

Triglyceride-rich lipoproteins, remnant-cholesterol, and atherosclerotic cardiovascular disease.

PURPOSE OF REVIEW: Despite indisputable role of LDL-C lowering, a considerable residual risk for atherosclerotic cardiovascular disease (ASCVD) persists. The precise mechanism(s) underlying this phenomenon remain unclear. Triglyceride-rich lipoproteins (TRL) appear to be one of the main mediators, based on the genetic and epidemiologic data. However, whether this is caused by direct effects of Triglycerides or other components of TRL remains uncertain. The cholesterol component of TRL remnants (Rem-C) has been proposed as a more pertinent mediator of the increased risk associated with high triglycerides. RECENT FINDINGS: Several long-term observational studies have shown a significant relationship between Rem-C and ASCVD events, compared with other triglyceride-related parameters. Recent trials have shown that lowering of triglyceride levels by various agents, including fibrates and omega-3 fatty acids, in statin-treated subjects, did not explain the reduction in ASCVD events. In a large clinical trial with pemafibrate, a highly selective PPAR-α agonist, in type 2 diabetes and elevated triglycerides, the reduction in triglycerides was accompanied by a significant increase in LDL-C and Apo-B levels, despite a reduction in Rem-C, and no effect on ASCVD events. SUMMARY: Elevated Rem-C as a risk determinant, with LDL-C at goal, requires additional studies in clinical trials. Standardization and accuracy of Rem-C assays (calculated versus direct method) is also needed.

Effect of omega-3 supplementation on lipid profile in children and adolescents: a systematic review and meta-analysis of randomized clinical trials.

PURPOSE: Dyslipidemia is considered as a known risk factor for cardiovascular disease. Yet various trials with wide ranges of doses and durations have reported contradictory results. We undertook this meta-analysis of randomized controlled trials (RCTs) to determine whether omega-3 supplementation can affect lipid profile in children and adolescents. METHODS: Cochrane Library, Embase, PubMed, and Scopus databases were searched up to March 2021. Meta-analysis was performed using random-effect method. Effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity was assessed using the I2 index. In order to identification of potential sources of heterogeneity, predefined subgroup and meta-regression analysis was conducted. RESULTS: A total of 14 RCTs with 15 data sets were included. Based on the combination of effect sizes, there was a significant reduction in TG levels (WMD: -15.71 mg/dl, 95% CI: -25.76 to -5.65, P=0.002), with remarkable heterogeneity (I2=88.3%, P<0.001). However, subgroup analysis revealed that omega-3 supplementation significantly decreased TG only in studies conducted on participants ≤13 years old (WMD=-25.09, 95% CI: -43.29 to -6.90, P=0.007), (I2=84.6%, P<0.001) and those with hypertriglyceridemia (WMD=-28.26, 95% CI: -39.12 to -17.41, P<0.001), (I2=0.0%, P=0.934). Omega-3 supplementation had no significant effect on total cholesterol, HDL, and LDL levels. Also, results of nonlinear analysis showed significant effect of treatment duration on HDL status (Pnon-linearity=0.047). CONCLUSION: Omega-3 supplementation may significantly reduce TG levels in younger children and those with hypertriglyceridemia. Also, based on the HDL-related results, clinical trials with longer duration of intervention are recommended in this population.