-
1.
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.
-
2.
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).
-
3.
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.
-
4.
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
-
-
Free full text
-
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.
-
5.
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.
-
6.
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
-
-
Free full text
-
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.
-
7.
Assessment of effect of CYP3A inhibition, CYP induction, OATP1B inhibition, and high-fat meal on pharmacokinetics of the JAK1 inhibitor upadacitinib.
Mohamed, MF, Jungerwirth, S, Asatryan, A, Jiang, P, Othman, AA
British journal of clinical pharmacology. 2017;(10):2242-2248
-
-
Free full text
-
Abstract
AIMS: Upadacitinib (ABT-494) is a selective Janus kinase 1 inhibitor being developed for treatment of auto-immune inflammatory disorders. This work evaluated effects of high-fat meal, cytochrome P450 (CYP) 3A inhibition, CYP induction, and organic anion transporting polypeptide (OATP) 1B inhibition on upadacitinib pharmacokinetics. METHODS Two Phase 1 evaluations were conducted, each in 12 healthy subjects. In Study 1, using a randomized, two-sequence crossover design, a 3 mg dose of upadacitinib (immediate-release capsules) was administered alone under fasting conditions, after high-fat meal, or on Day 4 of a 6-day regimen of 400 mg once-daily ketoconazole. In Study 2, a 12 mg upadacitinib dose was administered alone, with the first, and with the eighth dose of a 9-day regimen of rifampin 600 mg once daily. Upadacitinib plasma concentrations were characterized. RESULTS Administration of upadacitinib immediate-release capsules after a high-fat meal decreased upadacitinib Cmax by 23% and had no impact on upadacitinib AUC relative to the fasting conditions. Ketoconazole (strong CYP3A inhibitor) increased upadacitinib Cmax and AUC by 70% and 75%, respectively. Multiple doses of rifampin (broad CYP inducer) decreased upadacitinib Cmax and AUC by approximately 50% and 60%, respectively. A single dose of rifampin (also an OATP1B inhibitor) had no effect on upadacitinib AUC. Upadacitinib was well tolerated when co-administered with ketoconazole, rifampin, or after a high-fat meal. CONCLUSIONS Strong CYP3A inhibition and broad CYP induction result in a weak and moderate effect, respectively, on upadacitinib exposures. OATP1B inhibition and administration of upadacitinib immediate-release formulation with food does not impact upadacitinib exposure.
-
8.
Effects of a very high saturated fat diet on LDL particles in adults with atherogenic dyslipidemia: A randomized controlled trial.
Chiu, S, Williams, PT, Krauss, RM
PloS one. 2017;(2):e0170664
Abstract
BACKGROUND Previous studies have shown that increases in LDL-cholesterol resulting from substitution of dietary saturated fat for carbohydrate or unsaturated fat are due primarily to increases in large cholesterol-enriched LDL, with minimal changes in small, dense LDL particles and apolipoprotein B. However, individuals can differ by their LDL particle distribution, and it is possible that this may influence LDL subclass response. OBJECTIVE The objective of this study was to test whether the reported effects of saturated fat apply to individuals with atherogenic dyslipidemia as characterized by a preponderance of small LDL particles (LDL phenotype B). METHODS Fifty-three phenotype B men and postmenopausal women consumed a baseline diet (55%E carbohydrate, 15%E protein, 30%E fat, 8%E saturated fat) for 3 weeks, after which they were randomized to either a moderate carbohydrate, very high saturated fat diet (HSF; 39%E carbohydrate, 25%E protein, 36%E fat, 18%E saturated fat) or low saturated fat diet (LSF; 37%E carbohydrate, 25%E protein, 37%E fat, 9%E saturated fat) for 3 weeks. RESULTS Compared to the LSF diet, consumption of the HSF diet resulted in significantly greater increases from baseline (% change; 95% CI) in plasma concentrations of apolipoprotein B (HSF vs. LSF: 9.5; 3.6 to 15.7 vs. -6.8; -11.7 to -1.76; p = 0.0003) and medium (8.8; -1.3 to 20.0 vs. -7.3; -15.7 to 2.0; p = 0.03), small (6.1; -10.3 to 25.6 vs. -20.8; -32.8 to -6.7; p = 0.02), and total LDL (3.6; -3.2 to 11.0 vs. -7.9; -13.9 to -1.5; p = 0.03) particles, with no differences in change of large and very small LDL concentrations. As expected, total-cholesterol (11.0; 6.5 to 15.7 vs. -5.7; -9.4 to -1.8; p<0.0001) and LDL-cholesterol (16.7; 7.9 to 26.2 vs. -8.7; -15.4 to -1.4; p = 0.0001) also increased with increased saturated fat intake. CONCLUSIONS Because medium and small LDL particles are more highly associated with cardiovascular disease than are larger LDL, the present results suggest that very high saturated fat intake may increase cardiovascular disease risk in phenotype B individuals. This trial was registered at clinicaltrials.gov (NCT00895141). TRIAL REGISTRATION Clinicaltrials.gov NCT00895141.
-
9.
Gut Microbe-Generated Trimethylamine N-Oxide From Dietary Choline Is Prothrombotic in Subjects.
Zhu, W, Wang, Z, Tang, WHW, Hazen, SL
Circulation. 2017;(17):1671-1673
-
10.
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.