Docosahexaenoic and Eicosapentaenoic Intervention Modifies Plasma and Erythrocyte Omega-3 Fatty Acid Profiles But Not the Clinical Course of Children With Autism Spectrum Disorder: A Randomized Control Trial.

Background: The pathogenesis of autism spectrum disorder (ASD) is under investigation and one of the main alterations relates to the metabolic and inflammatory system dysfunctions. Indeed, based on a possible deficit of omega-3 fatty acids (FAs) of patients with ASD and looking for an anti-inflammatory effect, dietary supplements with omega-3 fatty acids have been proposed. We aimed to evaluate differences in plasma and erythrocyte FA profiles and plasma cytokines in patients with infantile ASD after supplementation with docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids or placebo and both compared at baseline with a reference healthy group. Methods: A double-blind, randomized placebo-controlled intervention with DHA/EPA for 6 months was carried out in 54 children between 2 and 6 years diagnosed with ASD. They were selected and randomly assigned into two groups: 19 children received 800 mg/day of DHA and 25 mg/day of EPA, or placebo. In addition, another reference group of 59 healthy children of the same age was included. Plasma lipids and cytokines, and FA profiles in plasma and erythrocytes were measured at baseline and after 6 months of treatment in ASD children, and at baseline in the reference group. Results: There were no differences in demographic, anthropometric characteristics, and omega-3 intake between the healthy reference group and the ASD children at baseline. Children with ASD showed the higher plasma percentages of palmitic acid and total saturated FA and lower total omega-6 polyunsaturated FA (PUFA) compared with healthy children. An increased level of DHA and reduced EPA level in erythrocytes were detected in the ASD group vs. the reference group. After 6 months of treatment, the ASD group that received DHA enriched product significantly increased the plasma and erythrocyte percentages of DHA, but no differences were observed in the clinical test scores and other parameters as plasma cytokines between the two groups of ASD related to the intervention. Conclusion: Spanish children with ASD exhibit an appropriate omega-3 FA status in plasma and erythrocytes. Neither a clinical improvement of ASD children nor a better anti-inflammatory or fatty acid state has been found after an intervention with DHA/EPA for 6 months. So, the prescription of n-3 LC-PUFA and other dietary supplements in ASD should be only indicated after a confirmed alteration of FA metabolism or omega-3 LC-PUFA deficiency evaluated by specific erythrocyte FA. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03620097].

The Metabolic Impact of Two Different Parenteral Nutrition Lipid Emulsions in Children after Hematopoietic Stem Cell Transplantation: A Lipidomics Investigation.

Hematopoietic stem cell transplantation (HSCT) involves the infusion of either bone marrow or blood cells preceded by toxic chemotherapy. However, there is little knowledge about the clinical benefits of parenteral nutrition (PN) in patients receiving high-dose chemotherapy during HSCT. We investigated the lipidomic profile of plasma and the targeted fatty acid profiles of plasma and erythrocytes in children after HSCT using PN with either a fish oil-based lipid emulsion or a classic soybean oil emulsion. An untargeted liquid chromatography high-resolution mass spectrometry platform connected with a novel in silico annotation algorithm was utilized to determine the most relevant chemical subclasses affected. In addition, we explored the interrelation between the lipidomics profile in plasma, the targeted fatty acid profile in plasma and erythrocytes, several biomarkers of inflammation, and antioxidant defense using an innovative data integration analysis based on Latent Components. We observed that the fish oil-based lipid emulsion had an impact in several lipid subclasses, mainly glycerophosphocholines (PC), glycerophosphoserines (PS), glycerophosphoethanolamines (PE), oxidized PE (O-PE), 1-alkyl,2-acyl PS, lysophosphatidylethanolamines (LPE), oxidized PS (O-PS) and dicarboxylic acids. In contrast, the classic soybean oil emulsion did not. Several connections across the different blocks of data were found and aid in interpreting the impact of the lipid emulsions on metabolic health.

Cardioprotective Effect of a Virgin Olive Oil Enriched with Bioactive Compounds in Spontaneously Hypertensive Rats.

Olive oil and its derivatives have been described to exert beneficial effects on hypertensive states and cardiovascular disease prevention. We studied the effects of chronic consumption of extra virgin olive oil (EVOO), enriched in bioactive compounds from olive fruit and leaves, on blood pressure, endothelial function, oxidative and inflammatory status, and circulating cholesterol levels, in spontaneously hypertensive rats (SHR). Thirty SHR were randomly assigned to three groups: a control untreated SHR group, an SHR group (1 mL/rat/day) of a control olive oil (17.6 mg/kg of phenolic compounds), and an SHR group (1 mL/rat/day) of the enriched EVOO (750 mg/kg of phenolic compounds) for eight weeks. Ten Wistar Kyoto rats (WKY) were included as healthy controls. Long-term administration of the enriched EVOO decreased systolic blood pressure and cardiac hypertrophy, and improved the ex vivo aortic endothelial dysfunction measured in SHR. Moreover, enriched oil supplementation reduced the plasma levels of Angiotensin II and total cholesterol, and the urinary levels of endothelin-1 and oxidative stress biomarkers, while pro-inflammatory cytokines were unaffected. In conclusion, sustained treatment with EVOO, enriched in bioactive compounds from the olive fruit and leaves, may be an effective tool for reducing blood pressure and cholesterol levels alone or in combination with pharmacological anti-hypertensive treatment.

The NUTRAOLEOUM Study, a randomized controlled trial, for achieving nutritional added value for olive oils.

BACKGROUND: Virgin olive oil, a recognized healthy food, cannot be consumed in great quantities. We aim to assess in humans whether an optimized virgin olive oil with high phenolic content (OVOO, 429 mg/Kg) and a functional one (FOO), both rich in phenolic compounds (429 mg/Kg) and triterpenic acids (389 mg/kg), could provide health benefits additional to those supplied a by a standard virgin olive oil (VOO). METHODS/DESIGN: A randomized, double-blind, crossover, controlled study will be conducted. Healthy volunteers (aged 20 to 50) will be randomized into one of three groups of daily raw olive oil consumption: VOO, OVOO, and FOO (30 mL/d). Olive oils will be administered over 3-week periods preceded by 2-week washout ones. The main outcomes will be markers of lipid and DNA oxidation, inflammation, and vascular damage. A bioavailability and dose-response study will be nested within this sustained- consumption one. It will be made up of 18 volunteers and be performed at two stages after a single dose of each olive oil. Endothelial function and nitric oxide will be assessed at baseline and at 4 h and 6 h after olive oil single dose ingestion. DISCUSSION: For the first time the NUTRAOLEUM Study will provide first level evidence on the health benefits in vivo in humans of olive oil triterpenes (oleanolic and maslinic acid) in addition to their bioavailability and disposition. TRIAL REGISTRATION: The Trial has been registered in ClinicalTrials.gov ID: NCT02520739 .

Changes in Antioxidant Defense System Using Different Lipid Emulsions in Parenteral Nutrition in Children after Hematopoietic Stem Cell Transplantation.

BACKGROUND: Traditionally, lipids used in parenteral nutrition (PN) are based on ω-6 fatty acid-rich vegetable oils, such as soybean oil, with potential adverse effects involving oxidative stress. METHODS: We evaluated the antioxidant defense system in children, after hematopoietic stem cell transplantation (HSCT), who were randomized to use a lipid emulsion with fish oil or soybean oil. Blood samples at baseline, at 10 days, and at the end of the PN were taken to analyze plasma retinol, α-tocopherol, ß-carotene, coenzyme Q9 and coenzyme Q10 levels, and catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPOX), and superoxide dismutase (SOD) levels in lysed erythrocytes. RESULTS: An increase in plasma α-tocopherol levels in the group of patients receiving the fish oil-containing emulsion (FO) compared with the group receiving the soybean emulsion was observed at day 10 of PN. Concurrently, plasma α-tocopherol increased in the FO group and ß-carotene decreased in both groups at day 10 compared with baseline levels, being more significant in the group receiving the FO emulsion. CONCLUSION: FO-containing emulsions in PN could improve the antioxidant profile by increasing levels of α-tocopherol in children after HSCT who are at higher risk of suffering oxidative stress and metabolic disorders.

Postprandial glucose, insulin and gastrointestinal hormones in healthy and diabetic subjects fed a fructose-free and resistant starch type IV-enriched enteral formula.

BACKGROUND: Reducing the dietary glycaemic response has been proposed as a means of reducing the risk of diabetes. AIM: To evaluate the effects of a new diabetes-specific formula (DSF) enriched with resistant starch type IV and fructose-free on postprandial glycaemia, insulinaemia and gastrointestinal hormones in healthy volunteers and in outpatient type 2 diabetics. METHODS: (1) Twenty-four healthy volunteers were divided into two groups: Group 1 ( n = 10) was provided 50 g of the carbohydrate (CHO) constituent of the new product and 50 g of glucose separated by 1 week; Group 2 ( n = 14) was provided 400 ml of the new DSF (T-Diet Plus(®) Diabet NP) and 400 ml of a control product separated by 1 week. (2) Ten type 2 diabetic patients received 400 ml of the new DSF and two other commercially available DSF (Glucerna(®) SR and Novasource(®) Diabet) on three occasions separated by 1 week. Venous blood samples were drawn at time 0 and at different times until 120 min. Glucose, insulin and gastrointestinal hormones were determined. Glycaemic and insulinaemic indices and glycaemic load were calculated. RESULTS: The CHO constituent and the new DSF showed low glycaemic index and glycaemic load. In healthy subjects, insulin and C-peptide release were lower after administration of the CHO constituent as well as after the new DSF (P < 0.001). Ghrelin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) production were lower after intake of the CHO constituent (P ranging from <0.001 to 0.019) compared with glucose, and GIP was lower after ingestion of the new DSF (P = 0.002) than after the control product. In type 2 diabetic patients, glucose AUC was lower after the administration of the new DSF (P = 0.037) compared with the others. CONCLUSIONS: Our results indicate that this new product could be beneficial for diabetic patients.

Contribution of polyunsaturated fatty acids to intestinal repair in protein-energy malnutrition.

The aim of this study was to assess the effect of polyunsaturated fatty acids supplied in the diet on intestinal mucosa repair in a rat model of protein-energy malnutrition. Rats were fed either a standard semipurified diet or the same diet containing lactose as the only source of carbohydrate to cause protein-energy malnutrition. Diarrhea was induced within 24 h and was maintained for 2 weeks, after which both groups of rats were fed for 1 week either the standard diet or the standard diet supplemented with different sources of fatty acids, such as olive oil (OO), fish oil (FO), and purified phospholipids from pig brain (BPL). The lactose-enriched diet caused loss of enterocyte microvilli, lymphocyte infiltration, supranuclear cytoplasmic vesiculation, decreased number of goblet cells, low-density enlarged mitochondria, and less cristae. The FO diet improved the pathology score according to the histological and ultrastructural analysis, with an increased number of goblet cells, ratio of microvilli length to crypt depth, and percentage of intraepithelial lymphocytes compared to those found in rats with protein-energy malnutrition. We previously reported that chronic diarrhea depletes the antioxidant defense in rat intestine; we now show that both, the FO and the BPL diets, increase GSH levels in colon and that some antioxidant enzyme activities vary according to the source of fatty acids, with higher catalase and superoxide dismutase by the FO diet in jejunum, increased catalase by the BPL diet in jejunum, and elevated glutathione peroxidase by the OO diet in colon. The fatty acid profile of intestinal mucosa reflects the source of fat in the diet, with the lowest ratio of n-6/n-3 for rats fed the FO diet. These results suggest that dietary polyunsaturated fatty acids, particularly those in the n-3 series, may play an important role in intestinal repair in chronic diarrhea due to protein-energy malnutrition.

Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on the oxidizability and thrombogenicity of low-density lipoprotein.

Consumption of oily fish and fish oils is associated with protection against cardiovascular disease. Paradoxically, long-chain polyunsaturated fatty acids present in low-density lipoprotein (LDL) are suggested to be susceptible to oxidation. It is not clear whether eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have similar effects on the susceptibility of LDL to oxidation or whether they affect the thrombogenicity of oxidized LDL. This study examined the influence of highly purified preparations of EPA and DHA on LDL oxidizability and LDL-supported thrombin generation in healthy human volunteers. Forty-two healthy volunteers were randomly assigned to receive olive oil (placebo), an EPA-rich oil or a DHA-rich oil for 4 weeks at a dose of 9 g oil/day. EPA and DHA were incorporated into LDL phospholipids and cholesteryl esters during the supplementation period, but were progressively lost during ex vivo copper-mediated oxidation. Following supplementation, the EPA treatment significantly increased the formation of conjugated dienes during LDL oxidation compared with baseline, whereas the DHA treatment had no effect. Neither treatment significantly affected the lag time for oxidation, oxidation rate during the propagation phase or maximum diene production. Neither EPA nor DHA significantly affected the thrombotic tendency of oxidized LDL compared with the placebo, although DHA tended to decrease it. In conclusion, there are subtle differences in the effects of EPA and DHA on the oxidizability and thrombogenicity of LDL. DHA does not appear to increase the susceptibility of LDL to oxidation to the same degree as EPA and has a tendency to decrease LDL-supported thrombin generation.