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Effects of Delayed-Release Olive Oil and Hydrolyzed Pine Nut Oil on Glucose Tolerance, Incretin Secretion and Appetite in Humans.
Sørensen, KV, Kaspersen, MH, Ekberg, JH, Bauer-Brandl, A, Ulven, T, Højlund, K
Nutrients. 2021;(10)
Abstract
BACKGROUND To investigate the potential synergistic effects of olive oil releasing 2-oleoylglycerol and hydrolyzed pine nut oil containing 20% pinolenic acid on GLP-1 secretion, glucose tolerance, insulin secretion and appetite in healthy individuals, when delivered to the small intestine as potential agonists of GPR119, FFA1 and FFA4. METHODS Nine overweight/obese individuals completed three 6-h oral glucose tolerance tests (OGTTs) in a crossover design. At -30 min, participants consumed either: no oil, 6 g of hydrolyzed pine nut oil (PNO-FFA), or a combination of 3 g hydrolyzed pine nut oil and 3 g olive oil (PNO-OO) in delayed-release capsules. Repeated measures of glucose, insulin, C-peptide, GLP-1, GIP, ghrelin, subjective appetite and gastrointestinal tolerability were done. RESULTS PNO-FFA augmented GLP-1 secretion from 0-360 min compared to no oil and PNO-OO (p < 0.01). GIP secretion was increased from 240-360 min after both PNO-FFA and PNO-OO versus no oil (p < 0.01). Both oil treatments suppressed subjective appetite by reducing hunger and prospective food consumption and increasing satiety (p < 0.05). CONCLUSIONS In support of previous findings, 6 g of delayed-release hydrolyzed pine nut oil enhanced postprandial GLP-1 secretion and reduced appetite. However, no synergistic effect of combining hydrolyzed pine nut oil and olive oil on GLP-1 secretion was observed. These results need further evaluation in long-term studies including effects on bodyweight and insulin sensitivity.
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Supplementation with oil rich in eicosapentaenoic acid, but not in docosahexaenoic acid, improves global cognitive function in healthy, young adults: results from randomized controlled trials.
Patan, MJ, Kennedy, DO, Husberg, C, Hustvedt, SO, Calder, PC, Khan, J, Forster, J, Jackson, PA
The American journal of clinical nutrition. 2021;(3):914-924
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Abstract
BACKGROUND Evidence regarding the effects of the omega-3 (ɷ-3) PUFAs (n-3 PUFAs) DHA and EPA on cognition is lacking. OBJECTIVES We investigated whether supplementation with oils rich in EPA or DHA improves cognition, prefrontal cortex (PFC) hemoglobin (Hb) oxygenation, and memory consolidation. METHODS Healthy adults (n = 310; age range: 25-49 y) completed a 26-wk randomized controlled trial in which they consumed either 900 mg DHA/d and 270 mg EPA/d (DHA-rich oil), 360 mg DHA/d and 900 mg EPA/d (EPA-rich oil), or 3000 mg/d refined olive oil (placebo). Cognitive performance and memory consolidation were assessed via computerized cognitive test battery. PFC Hb oxygenation was measured using near infrared spectroscopy (NIRS). RESULTS Both global accuracy and speed improved with EPA-rich oil compared with placebo and DHA-rich oil [EPA vs. placebo accuracy: estimated marginal mean (EMM) = 0.17 (95% CI: 0.09, 0.24) vs. EMM = 0.03 (95% CI = -0.04, 0.11); P = 0.044; EPA vs. placebo speed: EMM = -0.15 (95% CI: -0.22, -0.07) vs. EMM = 0.03 (95% CI: -0.05, 0.10); P = 0.003]. Accuracy of memory was improved with EPA compared with DHA [EMM = 0.66 (95% CI: 0.26, 1.06) vs. EMM = -0.08 (95% CI: -0.49, 0.33); P = 0.034]. Both EPA- and DHA-rich oils showed trends towards reduced PFC oxygenated Hb (oxy-Hb) compared with placebo [placebo: EMM = 27.36 µM (95% CI: 25.73, 28.98); DHA: EMM = 24.62 µM (95% CI: 22.75, 26.48); P = 0.060; EPA: EMM = 24.97 µM (95% CI: 23.35, 26.59); P = 0.082]. CONCLUSIONS EPA supplementation improved global cognitive function and was superior to the oil enriched with DHA. Interpreted within a neural efficiency framework, reduced PFC oxygenated Hb suggests that n-3 PUFAs may be associated with increased efficiency.These trials were registered in the clinical trials registry (https://clinicaltrials.gov/) as NCT03158545, NCT03592251, NCT02763514.
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Dietary unsaturated fat increases HDL metabolic pathways involving apoE favorable to reverse cholesterol transport.
Morton, AM, Furtado, JD, Mendivil, CO, Sacks, FM
JCI insight. 2019;(7)
Abstract
BACKGROUND HDL that contains apolipoprotein E (apoE) is a subspecies especially active in steps in reverse cholesterol transport, a process that brings cholesterol from peripheral cells to the liver. Here, we studied the effect of dietary unsaturated fat compared with carbohydrate on the metabolism of HDL containing apoE. METHODS We enrolled 9 adults who were overweight or obese and had below-average HDL-cholesterol in a crossover study of a high-fat diet, primarily unsaturated, and a low-fat, high-carbohydrate diet. A metabolic tracer study was performed after each diet period. RESULTS Dietary fat increased the secretion, metabolism, and clearance of HDL subspecies containing apoE. Dietary fat increased the rate of clearance of large cholesterol-rich HDL containing apoE and increased their conversion to small HDL containing apoE, indicating selective cholesterol ester delivery to the liver. The high-unsaturated-fat diet did not affect the metabolism of HDL lacking apoE. CONCLUSION HDL containing apoE is a diet-responsive metabolic pathway that renders HDL more biologically active in reverse cholesterol transport. This may be a mechanism by which unsaturated fat protects against coronary heart disease. Protein-based HDL subspecies such as HDL containing apoE may be used to identify additional atheroprotective treatment targets not evident in the total HDL-cholesterol measurement. TRIAL REGISTRATION ClinicalTrials.gov NCT01399632. FUNDING NIH and the National Center for Advancing Translational Science.
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Investigation of the effect of dietary docosahexaenoic acid (DHA) supplementation on macular function in subjects with autosomal recessive Stargardt macular dystrophy.
MacDonald, IM, Sieving, PA
Ophthalmic genetics. 2018;(4):477-486
Abstract
PURPOSE To test the effect of docosahexanoic acid (DHA) dietary supplementation on macular function in patients with Stargardt disease. MATERIALS AND METHODS A single center, double-masked, randomized placebo-controlled trial of 11 subjects (2 males, 9 females) with Stargardt disease in a crossover design (NCT00060749). Six participants were randomized to two sequences of three month periods of DHA supplementation (2000 mg/day) followed by three months of placebo. Five participants were randomized to the opposite sequence. All participants were evaluated with a food frequency and NEI-VF25 questionnaires, complete ophthalmic examination, multifocal electroretinography (ERG, primary outcome), 30-Hz flicker ERG, Humphrey 10-2 visual field, D15 color tests and serum lipid analysis. RESULTS During periods of DHA supplementation, serum rose and then fell with transition to periods of placebo. None of the participants experienced greater than 20% change from baseline values of the mfERG during periods of DHA supplementation or placebo, while the average change in peak amplitude and phase angle of the flicker ERG remained similar at all visits. No significant change was observed for any of the secondary outcome measures. Eight adverse events occurred but these were not considered to be due to the treatment. CONCLUSIONS No perceived effect of DHA supplementation on macular function was observed in a small sample of Stargardt patients who were compliant with the protocol as estimated by changes in serum DHA. This study will help design future studies of the effect of DHA supplementation on retinal function in cohorts with retinal dystrophies.
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Glycemic Effects of a Low-Carbohydrate Enteral Formula Compared With an Enteral Formula of Standard Composition in Critically Ill Patients: An Open-Label Randomized Controlled Clinical Trial.
van Steen, SC, Rijkenberg, S, Sechterberger, MK, DeVries, JH, van der Voort, PHJ
JPEN. Journal of parenteral and enteral nutrition. 2018;(6):1035-1045
Abstract
BACKGROUND Enteral low-carbohydrate formulas (LCFs) could serve as a noninsulin alternative for the treatment of stress hyperglycemia in critically ill patients. We compared the glycemic effects of an LCF with a standard formula. METHODS We conducted an open-label randomized trial in patients admitted to our intensive care unit between September 2015 and June 2016. Adult patients with an indication for enteral nutrition were randomized to an LCF (Glucerna 1.5 kcal) or a standard enteral formula (Fresubin Energy Fibre, with additional protein supplement). Primary outcome was glucose variability defined as mean absolute glucose (MAG) change (mmol/L/h). Secondary outcomes were mean glucose, time in target, hypoglycemic and hyperglycemic events, and insulin requirements. We assessed glycemic outcomes per blinded continuous glucose monitoring (CGM) system and compared outcomes with glucose measurements per blood gas analysis and point-of-care device. RESULTS We randomized 107 patients (LCF: n = 53; standard: n = 54). Six patients had no CGM data, leaving 101 patients (n = 52; n = 49) for the intention-to-treat analysis. MAG change and time in target range were not different between groups. LCF gave a lower mean glucose measured per point-of-care device (7.8 ± 1.0 vs 8.4 ± 1.1 mmol/L, P = .007). LCF patients required significantly less insulin on the second study day (46.8 vs 68.0 IU, P = .036). CONCLUSION LCF showed a trend toward a modestly reduced mean glucose and significantly lower insulin requirements as compared with standard feeding but had no effect on glucose variability or time in target range.
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Unsaturated Fatty Acids Improve Atherosclerosis Markers in Obese and Overweight Non-diabetic Elderly Patients.
de Oliveira, PA, Kovacs, C, Moreira, P, Magnoni, D, Saleh, MH, Faintuch, J
Obesity surgery. 2017;(10):2663-2671
Abstract
BACKGROUND Several studies have demonstrated the benefits of replacing trans and saturated fats with unsaturated fatty acids on cardiovascular diseases. We aimed to demonstrate the effect of polyunsaturated and monounsaturated fat supplementation on the biochemical and endothelial markers of atherosclerotic disease in obese or overweight non-diabetic elderly patients. METHOD Seventy-nine patients were randomly divided into three groups: flaxseed oil, olive oil, and sunflower oil; patients in each group received 30 mL of oil for 90 days. Patients were subjected to anthropometric and bioimpedance assessments; biochemical and endothelial evaluations were performed through ultrasonography of the brachial artery and carotid artery for endothelium-dependent dilation and intima-media thickness assessment, respectively, before and after the intervention. The participants' usual diet remained unchanged. RESULTS The flaxseed oil group had improved ultra-sensitive C-reactive protein levels (p = 0.074) and reduced carotid intima-media thickness (CIMT) (p = 0.028); the olive oil group exhibited an improved apolipoprotein (Apo)B/ApoA ratio (p = 0.021), reduced CIMT (p = 0.028), and improved flow-mediated vasodilation (FMV) (p = 0.054); and similarly, the sunflower oil group showed an improved ApoB/ApoA ratio (p = 0.024), reduced CIMT (p = 0.048), and improved FMV (p = 0.001). CONCLUSION Unsaturated fatty acid supplementation using the three vegetable oils attenuated pro-inflammatory properties and improved prothrombotic conditions. Therefore, introducing or replacing saturated and trans fat with unsaturated fatty acids is beneficial for cardiovascular risk reduction in obese or overweight non-diabetic elderly people. Further studies are needed to determine which unsaturated fat best prevents cardiovascular disease in elderly patients.
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Substituting poly- and mono-unsaturated fat for dietary carbohydrate reduces hyperinsulinemia in women with polycystic ovary syndrome.
Perelman, D, Coghlan, N, Lamendola, C, Carter, S, Abbasi, F, McLaughlin, T
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2017;(4):324-327
Abstract
OBJECTIVE Hyperinsulinemia is a prevalent feature of polycystic ovary syndrome (PCOS), contributing to metabolic and reproductive manifestations of the syndrome. Weight loss reduces hyperinsulinemia but weight regain is the norm, thus preventing long-term benefits. In the absence of weight loss, replacement of dietary carbohydrate (CHO) with mono/polyunsaturated fat reduces ambient insulin concentrations in non-PCOS subjects. The current study evaluated whether this dietary intervention could ameliorate hyperinsulinemia in women with PCOS. DESIGN/SETTING/PATIENTS Obese women with PCOS (BMI 39 ± 7 kg/m2) and insulin resistance completed a crossover study (Stanford University Clinical Research Center) comparing two isocaloric diets, prepared by research dietitians, containing 60% CHO/25% fat versus 40% CHO/45% fat (both 15% protein and ≤7% saturated fat). After 3 weeks on each diet, daylong glucose, insulin, and fasting lipid/lipoproteins were measured. RESULTS Daylong glucose did not differ according to diet. Daylong insulin concentrations were substantially (30%) and significantly lower on the low CHO/higher fat diet. Beneficial changes in lipid profile were also observed. CONCLUSIONS Replacement of dietary CHO with mono/polyunsaturated fat yields clinically important reductions in daylong insulin concentrations, without adversely affecting lipid profile in obese, insulin-resistant women with PCOS. This simple and safe dietary intervention may constitute an important treatment for PCOS. ClinicalTrials.gov Identifier: NCT00186459.
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Impact of the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on offspring neurodevelopment: 5-year follow-up of a randomized controlled trial.
Brei, C, Stecher, L, Brunner, S, Ensenauer, R, Heinen, F, Wagner, PD, Hermsdörfer, J, Hauner, H
European journal of clinical nutrition. 2017;(9):1114-1120
Abstract
BACKGROUND/OBJECTIVES Evidence regarding the effect of n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy on offspring's neurodevelopment is not conclusive. SUBJECTS/METHODS In this analysis, the effect of a reduced n-6:n-3 LCPUFA ratio in the diet of pregnant/lactating women (1.2 g n-3 LCPUFA together with an arachidonic acid (AA)-balanced diet between 15th wk of gestation-4 months postpartum vs control diet) on child neurodevelopment at 4 and 5 years of age was assessed. A child development inventory (CDI) questionnaire and a hand movement test measuring mirror movements (MMs) were applied and the association with cord blood LCPUFA concentrations examined. RESULTS CDI questionnaire data, which categorizes children as 'normal', 'borderline' or 'delayed' in different areas of development, showed no significant evidence between study groups at 4 (n=119) and 5 years (n=130) except for the area 'letters' at 5 years of age (P=0.043). Similarly, the results did not strongly support the hypothesis that the intervention has a beneficial effect on MMs (for example, at 5 years: dominant hand, fast: adjusted mean difference, -0.08 (-0.43, 0.26); P=0.631). Children exposed to higher cord blood concentrations of docosahexaenoic acid, eicosapentaenoic acid and AA, as well as a lower ratio of n-6:n-3 fatty acids appeared to show beneficial effects on MMs, but these results were largely not statistically significant. CONCLUSIONS Our results do not show clear benefits or harms of a change in the n-6:n-3 LCPUFA ratio during pregnancy on offspring's neurodevelopment at preschool age. Findings on cord blood LCPUFAs point to a potential influence on offspring development.
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Reduction of the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on offspring body composition: follow-up results from a randomized controlled trial up to 5 y of age.
Brei, C, Stecher, L, Much, D, Karla, MT, Amann-Gassner, U, Shen, J, Ganter, C, Karampinos, DC, Brunner, S, Hauner, H
The American journal of clinical nutrition. 2016;(6):1472-81
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BACKGROUND It has been hypothesized that the n-6:n-3 (ω-6:ω-3) long-chain polyunsaturated fatty acid (LCPUFA) ratio in the maternal diet during the prenatal and early postnatal phase positively affects the body composition of the offspring. However, only limited data from prospective human intervention studies with long-term follow-up are available. OBJECTIVE We assessed the long-term effects of a reduced n-6:n-3 LCPUFA ratio in the diets of pregnant and lactating women [1020 mg docosahexaenoic acid (DHA) plus 180 mg eicosapentaenoic acid (EPA)/d together with an arachidonic acid-balanced diet compared with a control diet] on the body weights and compositions of their offspring from 2 to 5 y of age with a focus on the 5-y results. DESIGN Participants in the randomized controlled trial received follow-up assessments with annual body-composition measurements including skinfold thickness (SFT) measurements (primary outcome), a sonographic assessment of abdominal subcutaneous and preperitoneal fat, and child growth. In addition, abdominal MRI was performed in a subgroup of 5-y-old children. For the statistical analysis, mixed models for repeated measures (MMRMs) were fit with the use of data from each visit since birth (except for MRI). RESULTS Maternal LCPUFA supplementation did not significantly influence the children's sum of 4 SFTs [means ± SDs at 5 y of age: intervention, 23.9 ± 4.7 mm (n = 57); control, 24.5 ± 5.0 mm (n = 55); adjusted mean difference, -0.5 (95% CI: -2.2, 1.2)], growth, or ultrasonography measures at any time point in the adjusted MMRM model (all P values < 0.05). Results were consistent with abdominal MRI measurements (n = 44) at 5 y of age, which showed no significant differences in subcutaneous and visceral adipose tissue volumes and ratios. CONCLUSION The current study provides no evidence that a dietary reduction of the n-6:n-3 LCPUFA ratio in the maternal diet during pregnancy and lactation is a useful early preventive strategy against obesity at preschool age. This trial was registered at clinicaltrials.gov as NCT00362089.
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Dietary saturated fat and monounsaturated fat have reversible effects on brain function and the secretion of pro-inflammatory cytokines in young women.
Dumas, JA, Bunn, JY, Nickerson, J, Crain, KI, Ebenstein, DB, Tarleton, EK, Makarewicz, J, Poynter, ME, Kien, CL
Metabolism: clinical and experimental. 2016;(10):1582-8
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BACKGROUND Previous literature suggests that a higher ratio of palmitic acid (PA)/oleic acid (OA) in the diet induces inflammation, which may result in deficient brain insulin signaling, and, secondarily, impaired physical activity, sleep efficiency, and cognitive functioning. OBJECTIVE We hypothesized that lowering the typical dietary PA/OA would affect the activation of relevant brain networks during a working memory task and would also lower secretion of pro-inflammatory cytokines. DESIGN In 12 female subjects participating in a randomized, cross-over trial comparing 3-week high PA diet (HPA) and low PA and a high OA diet (HOA), we evaluated functional magnetic resonance imaging (fMRI) using an N-back test of working memory, cytokine secretion by lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC), and plasma cytokine concentrations. RESULTS Brain activation during the HPA diet compared to the HOA diet was increased in regions of the basal ganglia including the caudate and putamen (p<0.005). In addition, compared to the HOA diet, during the HPA diet, the plasma concentrations of IL-6 (p=0.04) and IL-1β (p=0.05) were higher, and there was a higher secretion of IL-18 (p=0.015) and a trend for higher IL-1β secretion (p=0.066) from LPS-stimulated PBMCs. CONCLUSIONS The HPA diet resulted in increased brain activation in the basal ganglia compared to the HOA diet as well as increased secretion of pro-inflammatory cytokines. These data provide evidence that short-term (2week) diet interventions impact brain network activation during a working memory task and that these effects are reversible since the order of the study diets was randomized. These data are consistent with the hypothesis that lowering the dietary PA content via substitution with OA also could affect cognition.