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Assessment of polyunsaturated fatty acids: A self-report and biomarker assessment with a racially and ethnically diverse sample of women.
Lc, R, B, S, D, A, Db, H, Pg, H, Ar, P
Prostaglandins, leukotrienes, and essential fatty acids. 2021;:102214
Abstract
Polyunsaturated fatty acids (PUFAs) play an important role in human health, influencing chronic disease and mortality. Food Frequency Questionnaires (FFQs) are widely used to assess self-reported diet, but they can be subject to a variety of errors. Accordingly, an accurate assessment of diet is crucial in nutrition research. This study examined the association between a widely-used self-report measure of PUFAs (Diet History Questionnaire-II: DHQ-II) with the proportion of PUFA in red blood cell (RBC) membranes, and examined whether this relationship was moderated by race/ethnicity. In a racially and ethnically diverse sample of 132 female participants (Mage = 21.97±3.98, range 18 to 42 years), bivariate correlations and linear regression analyses demonstrated associations between DHQ-II and proportion of nutrients in RBCs for omega-3 fatty acids EPA (r = 0.39, ß = 0.38, p < .01), DHA (r = 0.48, ß = 0.47, p < .01), and EPA+DHA (r = 0.51, β = 0.49, p < .01). No associations were found for omega-3 fatty acid ALA or omega-6 fatty acids LA or ARA. DHQ-II and RBC associations for EPA, DHA, and EPA+DHA were moderated by race/ethnicity, controlling for age. Self-report of EPA was most consistent with RBC proportions for Caucasian individuals, and less consistent for Black/African American individuals. Self-reports of DHA and EPA+DHA were most consistent with RBC proportions for Caucasian individuals, and less consistent for Black/African American individuals and Hispanic/Latina individuals, although still statistically significant. No associations were detected for Hispanic/Latina individuals (for EPA only), Asian/Pacific Islanders or individuals of mixed/other descent. The present study found that when compared to PUFA biomarkers, the DHQ-II did not assess PUFAs consistently across all racial/ethnic groups in this sample of women. Further research is needed to determine what factors contribute to weak or lacking correlations between reported fat intake and corresponding values in RBCs, including but not limited to recall errors, underestimations of fatty acids in food composition databases, insufficient DHQ-II assessment of fatty acids in general and from particular cultures, and genetic differences in fat metabolism.
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GlucoTRIG: a novel tool to determine the nutritional quality of foods and meals in general population.
Thota, RN, Moughan, PJ, Singh, H, Garg, ML
Lipids in health and disease. 2020;(1):83
Abstract
BACKGROUND This study aimed to develop a novel criterion, GlucoTRIG, to rank meals for healthiness, that considers both glycaemic (serum insulin) and lipaemic (serum triglycerides) responses. METHODS Healthy volunteers (n = 10) were recruited with the aim of deriving a standard GlucoTRIG value for a reference meal. Volunteers consumed the reference meal (2 regular slices of wholemeal bread; 250 mL chocolate flavoured milk; 7 g butter and 11 g peanut butter) comprising of carbohydrate, fat and protein (41, 40 and 16% energy respectively) on three different occasions with a minimum washout period of 3 days. The GlucoTRIG value was determined as the difference between the product of insulin and triglyceride obtained from venous blood samples at baseline and the product of insulin and triglyceride at 180 min. RESULTS There were no significant differences in the participants' dietary intakes and their metabolic parameters between three visits (P > 0.005). The GlucoTRIG value obtained from three mean values of the reference meal was found to be 19 ± 3.5. There were no significant (P = 0.2303) differences observed between the GlucoTRIG values for the three visits. CONCLUSION GlucoTRIG, consisting of both glycaemic and lipaemic responses, may be a physiologically relevant tool to rank foods and meals for reducing the risk of metabolic diseases. TRIAL REGISTRATION ACTRN12619000973112.
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Effect of food on the pharmacokinetics of omeprazole, pantoprazole and rabeprazole.
Ochoa, D, Román, M, Cabaleiro, T, Saiz-Rodríguez, M, Mejía, G, Abad-Santos, F
BMC pharmacology & toxicology. 2020;(1):54
Abstract
BACKGROUND The pharmacokinetics of proton pump inhibitors (PPIs) may be affected by food intake. We aimed to evaluate the effect of food on the pharmacokinetics of omeprazole, rabeprazole, and pantoprazole. SETTING The study population comprised 186 healthy volunteers participating in 6 bioequivalence clinical trials. METHOD Subjects were evaluated to determine the effect of a high-fat breakfast on the pharmacokinetics of omeprazole (n = 36), rabeprazole (n = 69), and pantoprazole (n = 81). MAIN OUTCOME MEASURE Drug plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry. RESULTS Food affected the pharmacokinetics of omeprazole (increased Tmax and decreased AUC and Cmax), pantoprazole (increased Tmax and decreased AUC), and rabeprazole (increased Tmax, Cmax and half-life). Food increased variability in Tmax for all 3 drugs, delaying absorption around 3 to 4 h and until 20 h in some subjects. CONCLUSION As food delays the absorption of PPIs and increases their variability, it would be better to administer these drugs under fasting conditions. TRIAL REGISTRATION European Union Drug Regulating Authorities Clinical Trials Database: EudraCT : 2004-003863-59 (registration date 05/MAR/2004), EudraCT 2006-001162-17 (registration date 17-MAR-2006), EudraCT: 2007-002489-37 (registration date 12-JUN-2007), EudraCT: 2007-002490-31 (registration date 12-JUN-2007), EudraCT: 2010-024029-19 (registration date 23-NOV-2010).
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Postprandial Lipemic Responses to Various Sources of Saturated and Monounsaturated Fat in Adults.
Sciarrillo, CM, Koemel, NA, Tomko, PM, Bode, KB, Emerson, SR
Nutrients. 2019;(5)
Abstract
BACKGROUND Postprandial lipemia (PPL) is a cardiovascular disease risk factor. However, the effects of different fat sources on PPL remain unclear. We aimed to determine the postprandial response in triglycerides (TG) to four dietary fat sources in adults. METHODS Participants completed four randomized meal trials. For each meal trial, participants (n = 10; 5M/5F) consumed a high-fat meal (HFM) (13 kcal/kg; 61% of total kcal from fat) with the fat source derived from butter, coconut oil, olive oil, or canola oil. Blood was drawn hourly for 6 h post-meal to quantify PPL. RESULTS Two-way ANOVA of TG revealed a time effect (p < 0.0001), but no time-meal interaction (p = 0.56), or meal effect (p = 0.35). Meal trials did not differ with regard to TG total (p = 0.33) or incremental (p = 0.14) area-under-the-curve. When stratified by sex and the TG response was averaged across meals, two-way ANOVA revealed a time effect (p < 0.0001), time-group interaction (p = 0.0001), and group effect (p = 0.048), with men exhibiting a greater response than women, although this difference could be attributed to the pronounced difference in BMI between men and women within the sample. CONCLUSION In our sample of young adults, postprandial TG responses to a single HFM comprised of different fat sources did not differ.
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Effect of Food on the Pharmacokinetics of Ertugliflozin and Its Fixed-Dose Combinations Ertugliflozin/Sitagliptin and Ertugliflozin/Metformin.
Sahasrabudhe, V, Fediuk, DJ, Matschke, K, Shi, H, Liang, Y, Hickman, A, Bass, A, Terra, SG, Zhou, S, Krishna, R, et al
Clinical pharmacology in drug development. 2019;(5):619-627
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Abstract
Ertugliflozin, an inhibitor of sodium-glucose cotransporter 2, is approved in the United States and European Union for the treatment of type 2 diabetes in adults, both as monotherapy and as part of fixed-dose combination (FDC) therapies with either sitagliptin or immediate-release metformin. The effect of a standard, high-fat breakfast on the pharmacokinetics of the highest strengths of ertugliflozin monotherapy (15 mg), ertugliflozin/sitagliptin FDC (15-/100-mg), and ertugliflozin/metformin FDC (7.5-/1000-mg) tablets was evaluated. In 3 separate open-label, 2-period, 2-sequence, single-dose, crossover studies, 14 healthy subjects per study were randomized to receive either ertugliflozin monotherapy or FDC tablets comprising ertugliflozin and sitagliptin or ertugliflozin and metformin under fasted and fed (or vice versa) conditions. Food did not meaningfully affect the pharmacokinetics of ertugliflozin, sitagliptin, or metformin. For FDCs, the effect of food was consistent with that described for individual components. All treatments were well tolerated. Ertugliflozin and ertugliflozin/sitagliptin FDC tablets can be administered without regard to meals. As metformin is administered with meals because of its gastrointestinal side effects, the ertugliflozin/metformin FDC should also be administered with meals.
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Effects of medium chain triglycerides supplementation on insulin sensitivity and beta cell function: A feasibility study.
Thomas, DD, Stockman, MC, Yu, L, Meshulam, T, McCarthy, AC, Ionson, A, Burritt, N, Deeney, J, Cabral, H, Corkey, B, et al
PloS one. 2019;(12):e0226200
Abstract
OBJECTIVE Medium chain triglycerides (MCT) have unique metabolic properties which may improve insulin sensitivity (Si) and beta cell function but data in humans are limited. We conducted a 6-week clinical trial of MCT oil supplementation. METHODS 22 subjects without diabetes (8 males, 14 females, mean ± standard error age 39±2.9 years, baseline BMI 27.0±1.4 kg/m2) were counseled to maintain their body weight and physical activity (PA) during the trial. Dietary intake, PA data, body composition, and resting energy expenditure (REE) were obtained through dietary recall, international PA questionnaire, dual x-ray absorptiometry, and indirect calorimetry, respectively. MCT prescriptions were given based on REE and PA to replace part of dietary fat with 30 grams of MCT per 2000 kcal daily. Insulin-modified frequently sampled intravenous glucose tolerance tests were performed before and after MCT to measure changes in Si, acute insulin response (AIR), disposition index (DI), and glucose effectiveness (Sg). RESULTS MCT were well tolerated and weight remained stable (mean change 0.3 kg, p = 0.39). Fasting REE, respiratory quotient, and body composition were stable during the intervention. There were no significant changes in mean fasting glucose, insulin, insulin resistance, fasting total ketones, Si, AIR, DI, Sg, leptin, fructosamine, and proinsulin. The mean change in Si was 0.5 10-4 min-1 per mU/L (95% CI: -1.4, 2.4), corresponding to a 12% increase from baseline, and the range was -4.7 to 12.9 10-4 min-1 per mU/L. Mean total adiponectin decreased significantly from 22925 ng/mL at baseline to 17598 ng/mL at final visit (p = 0.02). The baseline clinical and laboratory parameters were not significantly associated with the change in Si. DISCUSSION There were a wide range of changes in the minimal model parameters of glucose and insulin metabolism in subjects following 6 weeks of MCT as an isocaloric substitution for part of usual dietary fat intake. Since this was a single-arm non-randomized study without a control group, it cannot be certain whether these changes were due to MCT so further randomized controlled trials are warranted.
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Vitamin E absorption and kinetics in healthy women, as modulated by food and by fat, studied using 2 deuterium-labeled α-tocopherols in a 3-phase crossover design.
Traber, MG, Leonard, SW, Ebenuwa, I, Violet, PC, Wang, Y, Niyyati, M, Padayatty, S, Tu, H, Courville, A, Bernstein, S, et al
The American journal of clinical nutrition. 2019;(5):1148-1167
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Abstract
BACKGROUND Determining the human vitamin E [α-tocopherol (α-T)] requirement is difficult, and novel approaches to assess α-T absorption and trafficking are needed. OBJECTIVE We hypothesized that the dual-isotope technique, using 2 deuterium-labeled [intravenous (IV) d6- and oral d3-] α-T, would be effective in determining α-T fractional absorption. Further, defined liquid meal (DLM) fat or fasting would modulate α-T fractional absorption and lipoprotein transport. METHODS A 3-phase cr ossover design was used. At 0 h, participants received IV d6-α-T and consumed d3-α-T with a 600-kcal DLM (40% or 0% fat) followed by controlled meals or by the 0% fat DLM, a 12-h fast, and then controlled meals. Blood samples and fecal samples were collected at intervals and analyzed by LC-MS. Pharmacokinetic parameters were calculated from plasma tracer concentrations and enrichments. Fractional absorption was calculated from d3- to d6-α-T areas under the curve, from a novel mathematical model, and from the balance method (oral d3-α-T minus fecal d3-α-T excreted). RESULTS Estimated α-T fractional absorption during the 40% fat intervention was 55% ± 3% (mean ± SEM; n = 10), which was 9% less than during the 0% fat intervention (64% ± 3%, n = 10; P < 0.02). Fasting had no apparent effect (56% ± 3%, n = 7), except it slowed plasma oral d3-α-T appearance. Both balance data and model outcomes confirmed that the DLM fat did not potentiate d3-α-T absorption. During the IV emulsion clearance, HDL rapidly acquired d6-α-T (21 ± 2 nmol/L plasma per minute). During the first 8 h postdosing, triglyceride-rich lipoproteins (TRLs) were preferentially d3-α-T enriched relative to LDL or HDL, showing the TRL precursor role. CONCLUSIONS Quantitatively, α-T absorption is not limited by fat absence or by fasting. However, α-T leaves the intestine by a process that is prolonged during fasting and potentiated by eating, suggesting that α-T absorption is highly dependent on chylomicron assembly processes. This trial was registered at clinicaltrials.gov as NCT00862433.
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Effects of a High-fat Meal on the Pharmacokinetics of the VEGFR Inhibitor Fruquintinib: A Randomized Phase I Study in Healthy Subjects.
Qian, H, Fan, S, Li, K, Sai, Y, Su, W, Chen, Q, Liu, Y, Li, T, Wang, W, Jia, J, et al
Clinical therapeutics. 2019;(8):1537-1544
Abstract
PURPOSE Fruquintinib is a potent and highly selective oral small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor and demonstrates promising activity against a broad spectrum of cancer types. The objective of the study was to investigate the tolerability and effect of high-fat food on the pharmacokinetic profile of a fruquintinib capsule in healthy Chinese subjects. METHODS Healthy Chinese male subjects aged between 18 and 45 years were enrolled in the study. The study included 2 phases: a dose-escalation phase and a food effect-assessment phase. In the dose-escalation phase, subjects were administered a single dose of fruquintinib (2, 3, or 4 mg) in the fasted state. In the food effect-assessment phase, subjects were administered a 4-mg fruquintinib capsule in the fasted and fed states, respectively, in 2 cycles. Blood samples for pharmacokinetic analysis were collected at the designated time points. Tolerability was assessed throughout the study by physical examination including vital sign measurements, clinical laboratory tests, 12-lead ECG, clinical assessments, and monitoring for and spontaneous reporting of adverse events. FINDINGS Twenty-nine eligible male subjects were enrolled in the study, including 9 in the dose-escalation phase and 20 in the food effect-assessment phase. In the food effect-assessment phase, the ratios (90% CI) of the geometric mean AUC0-∞ and Cmax values for fruquintinib in the fed state to those observed in the fasted state were 97.2% (94.0%-100.4%) and 82.9% (76.7%-89.5%), respectively. The mean (SD) Tmax values of fruquintinib were 3.0 (1.0) and 5.6 (4.5) hours in the fasted and fed states, respectively. The most common adverse events possibly related to the study drug were elevated blood uric acid, diarrhea, and decreased white blood cell count. IMPLICATIONS The overall bioavailability of the evaluated formulation of fruquintinib was not affected by the consumption of a high-fat, high-calorie meal prior to dosing. However, the consumption of a high-fat, high-calorie meal prior to dosing prolonged the Tmax. These results indicate that the fruquintinib capsule can be administered with or without food. ClinicalTrials.gov identifier: NCT01955304.
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High dietary fat intake increases fat oxidation and reduces skeletal muscle mitochondrial respiration in trained humans.
Leckey, JJ, Hoffman, NJ, Parr, EB, Devlin, BL, Trewin, AJ, Stepto, NK, Morton, JP, Burke, LM, Hawley, JA
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2018;(6):2979-2991
Abstract
High-fat, low-carbohydrate (CHO) diets increase whole-body rates of fat oxidation and down-regulate CHO metabolism. We measured substrate utilization and skeletal muscle mitochondrial respiration to determine whether these adaptations are driven by high fat or low CHO availability. In a randomized crossover design, 8 male cyclists consumed 5 d of a high-CHO diet [>70% energy intake (EI)], followed by 5 d of either an isoenergetic high-fat (HFAT; >65% EI) or high-protein diet (HPRO; >65% EI) with CHO intake clamped at <20% EI. During the intervention, participants undertook daily exercise training. On d 6, participants consumed a high-CHO diet before performing 100 min of submaximal steady-state cycling plus an ∼30-min time trial. After 5 d of HFAT, skeletal muscle mitochondrial respiration supported by octanoylcarnitine and pyruvate, as well as uncoupled respiration, was decreased at rest, and rates of whole-body fat oxidation were higher during exercise compared with HPRO. After 1 d of high-CHO diet intake, mitochondrial respiration returned to baseline values in HFAT, whereas rates of substrate oxidation returned toward baseline in both conditions. These findings demonstrate that high dietary fat intake, rather than low-CHO intake, contributes to reductions in mitochondrial respiration and increases in whole-body rates of fat oxidation after a consuming a high-fat, low-CHO diet.-Leckey, J. J., Hoffman, N. J., Parr, E. B., Devlin, B. L., Trewin, A. J., Stepto, N. K., Morton, J. P., Burke, L. M., Hawley, J. A. High dietary fat intake increases fat oxidation and reduces skeletal muscle mitochondrial respiration in trained humans.
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Heritability and responses to high fat diet of plasma lipidomics in a twin study.
Frahnow, T, Osterhoff, MA, Hornemann, S, Kruse, M, Surma, MA, Klose, C, Simons, K, Pfeiffer, AFH
Scientific reports. 2017;(1):3750
Abstract
Lipidomics have a great potential as clinical tool for monitoring metabolic changes in health and disease. Nevertheless hardly anything is known about the heritability of lipids. Therefore, it is necessary to clarify how and how much we can affect these progresses in individuals. In our interventional twin study (46 healthy, non-obese twin pairs) we investigated the lipid profile in plasma samples after switching from a low fat diet to an isocaloric high fat diet (HFD) to characterize the metabolic adaptation. Additionally we used the ACE model for Additive genetics, Common and unique Environment as well as linear mixed modelling to analyse the heritability of lipids. The heritability of lipids varied between 0-62% and applied to lipid species rather than to lipid classes. Phospholipids showed the highest inheritance. In addition, sex, body mass index (BMI) and age were important modifiers. The lipid profile changed already after one week of HFD and diverged further after 5 weeks of additional HFD. Basal concentrations of specific lipids within phospholipids are strongly inherited and are likely to be associated with heritable disease risks. BMI, sex and age were major modifiers. Nutrition strongly alters specific lipid classes, and has to be controlled in clinical association studies.