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Reducing Cholesterol and Fat Intake Improves Glucose Tolerance by Enhancing β Cell Function in Nondiabetic Subjects.
Tricò, D, Trifirò, S, Mengozzi, A, Morgantini, C, Baldi, S, Mari, A, Natali, A
The Journal of clinical endocrinology and metabolism. 2018;(2):622-631
Abstract
CONTEXT A diet low in cholesterol and fat is commonly recommended to prevent metabolic and cardiovascular diseases; however, its effect on glucose tolerance is largely unknown. OBJECTIVE We examined whether and by which mechanisms a chronic reduction of cholesterol and fat intake affects glucose tolerance in nondiabetic individuals, independently of weight changes. DESIGN AND PARTICIPANTS In this crossover, randomized clinical trial, 30 healthy subjects, including 15 with family history of type 2 diabetes (T2D) (T2D offspring), underwent a 75-g oral glucose tolerance test (OGTT) after two 14-day isocaloric high-cholesterol, high-fat (HChF) or low-cholesterol, and low-fat (LChF) diets. MAIN OUTCOME MEASURES We evaluated changes in glucose tolerance, β cell function, insulin clearance, and insulin sensitivity by modeling plasma glucose, insulin, and C-peptide levels during the OGTT. RESULTS The shift from the HChF to the LChF diet was neutral on body weight but increased glucose tolerance (mean glucose -5%, P = 0.01) and three components of β cell function: glucose sensitivity (+17%, P = 0.01), insulin secretion at fasting glucose (+20%, P = 0.02), and potentiation (+19%, P = 0.03). The LChF diet improved insulin sensitivity (+7%, P = 0.048) only in T2D offspring, who tended to be more susceptible to the positive effect of the diet on glucose tolerance. CONCLUSIONS A chronic and isocaloric decrease in dietary cholesterol and fat intake improves glucose tolerance by diffusely ameliorating β cell function in nondiabetic subjects. Individuals genetically predisposed to develop T2D tend to be more susceptible to the positive effect of this dietary intervention on glucose tolerance and insulin sensitivity.
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Ketogenic diets for drug-resistant epilepsy.
Martin-McGill, KJ, Jackson, CF, Bresnahan, R, Levy, RG, Cooper, PN
The Cochrane database of systematic reviews. 2018;(11):CD001903
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BACKGROUND Ketogenic diets (KDs), being high in fat and low in carbohydrates, have been suggested to reduce seizure frequency in people with epilepsy. At present, such diets are mainly recommended for children who continue to have seizures despite treatment with antiepileptic drugs (AEDs) (drug-resistant epilepsy). Recently, there has been interest in less restrictive KDs, including the modified Atkins diet (MAD), and the use of these diets has extended into adult practice. This is an update of a review first published in 2003 and last updated in 2016. OBJECTIVES To assess the effects of KDs for drug-resistant epilepsy by reviewing the evidence from randomised controlled trials. SEARCH METHODS For the latest update we searched the Cochrane Epilepsy Group's Specialized Register (11 April 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 11 April 2017), MEDLINE (Ovid, 11 April 2017), ClinicalTrials.gov (11 April 2017) and the WHO International Clinical Trials Registry Platform (ICTRP, 11 April 2017). We imposed no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies. SELECTION CRITERIA Randomised controlled trials or quasi-randomised controlled trials of ketogenic diets for people with drug-resistant epilepsy. DATA COLLECTION AND ANALYSIS Two review authors independently applied predefined criteria to extract data and assessed study quality. MAIN RESULTS We identified 11 randomised controlled trials (RCTs) that generated 15 publications.All trials applied an intention-to-treat analysis with varied randomisation methods. The 11 studies recruited 778 patients; 712 children and adolescents and 66 adults. We assessed all 11 studies to be at low to unclear risk of bias for the following domains: random sequence generation, allocation concealment and selective reporting. For the other domains (blinding, incomplete outcome data, other bias) assessments were varied (low, unclear and high risk of bias). We could not conduct a meta-analysis due to the heterogeneity of the studies and the quality of the evidence was low to very low (GRADE ratings).Reported rates of seizure freedom reached as high as 55% in a classical 4:1 KD group after three months and reported rates of seizure reduction reached as high as 85% in a classical 4:1 KD group after three months (GRADE rating low).One trial found no significant difference between the fasting-onset and gradual-onset KD for rates of seizure freedom, and reported a greater rate of seizure reduction in the gradual-onset KD group.Studies assessing the efficacy of the MAD reported seizure freedom rates of up to 25% and seizure reduction rates of up to 60% in children. One study used a simplified MAD (sMAD) and reported seizure freedom rates of 15% and seizure reduction rates of 56% in children. One study utilised a MAD in adults and reported seizure reduction rates of 35%, but no patients became seizure free (GRADE rating low).Adverse effects of the dietary interventions were experienced in all studies. The most commonly reported adverse effects were gastrointestinal syndromes. It was common that adverse effects were the reason for participants dropping out of trials (GRADE rating low). Other reasons for dropout included lack of efficacy and non-acceptance of the diet (GRADE rating low).Although there was some evidence for greater antiepileptic efficacy for a classical 4:1 KD over lower ratios, the classical 4:1 KD was consistently associated with more adverse effects.One study assessed the effect of dietary interventions on quality of life, cognition and behavioural functioning, reporting participants in the KD group to be more active, more productive and less anxious after four months, compared to the control group. However, no significant difference was found in quality-adjusted life years (QALYs) between the KD group and control group at four or 16 months (GRADE rating very low). AUTHORS' CONCLUSIONS The RCTs discussed in this review show promising results for the use of KDs in epilepsy. However, the limited number of studies, small sample sizes and the limited studies in adults, resulted in a low to very low overall quality of evidence.There were adverse effects within all of the studies and for all KD variations, such as short-term gastrointestinal-related disturbances and increased cholesterol. However, study periods were short, therefore the long-term risks associated with these adverse effects is unknown. Attrition rates remained a problem with all KDs and across all studies; reasons for this being lack of observed efficacy and dietary tolerance.Only one study reported the use of KDs in adults with epilepsy; therefore further research would be of benefit.Other more palatable but related diets, such as the MAD, may have a similar effect on seizure control as the classical KD, but this assumption requires more investigation. For people who have medically intractable epilepsy or people who are not suitable for surgical intervention, KDs remain a valid option; however, further research is required.
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Response of fibroblast growth factor 19 and bile acid synthesis after a body weight-adjusted oral fat tolerance test in overweight and obese NAFLD patients: a non-randomized controlled pilot trial.
Friedrich, D, Marschall, HU, Lammert, F
BMC gastroenterology. 2018;(1):76
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is common both in obese and overweight patients. Fibroblast growth factor 19 (FGF19), an intestinal hormone, could play a role in the complex pathogenesis of NAFLD. The aim of our study was to investigate responses of FGF19 and bile acid (BA) synthesis after a body weight-adjusted oral fat tolerance test (OFTT) in overweight and obese NAFLD patients. METHODS For this study, we recruited 26 NAFLD patients; 14 overweight (median BMI 28.3 kg/m2), 12 obese (35.3 kg/m2) and 16 healthy controls (24.2 kg/m2). All individuals received 1 g fat (Calogen®) per kg body weight orally. Serum concentrations of FGF19 were determined by ELISA. Concentrations of BAs and BA synthesis marker 7α-hydroxy-4-cholesten-3-one (C4) were measured by gas chromatography-mass spectrometry and high-performance liquid chromatography, respectively; all at 0 (baseline), 2, 4 and 6 h during the OFTT. RESULTS BMI correlated negatively with fasting FGF19 concentrations (rho = - 0.439, p = 0.004). FGF19 levels of obese NAFLD patients were significantly (p = 0.01) lower in the fasting state (median 116.0 vs. 178.5 pg/ml), whereas overweight NAFLD patients had significantly (p = 0.004) lower FGF19 concentrations 2 h after the fat load (median 163.0 vs. 244.5 pg/ml), and lowest values at all postprandial time points as compared to controls. Baseline BA concentrations correlated positively with FGF19 values (rho = 0.306, p = 0.048). In all groups, we observed BA increases during the OFTT with a peak at 2 h but no change in C4 levels in overweight/obese NAFLD patients. CONCLUSIONS Reduced basal gastrointestinal FGF19 secretion and decreased postprandial response to oral fat together with blunted effect on BA synthesis indicate alterations in intestinal or hepatic FXR signaling in overweight and obese NAFLD subjects. The precise mechanism of FGF19 signaling after oral fat load needs further evaluation. TRIAL REGISTRATION We have registered the trial retrospectively on 30 Jan 2018 at the German clinical trials register ( http://www.drks.de /), and the following number has been assigned DRKS00013942 .
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Association of Low-Fat Dietary Pattern With Breast Cancer Overall Survival: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trial.
Chlebowski, RT, Aragaki, AK, Anderson, GL, Simon, MS, Manson, JE, Neuhouser, ML, Pan, K, Stefanic, ML, Rohan, TE, Lane, D, et al
JAMA oncology. 2018;(10):e181212
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IMPORTANCE In a randomized clinical trial, a low-fat eating pattern was associated with lower risk of death after breast cancer. However, the extent to which results were driven by dietary influence on survival after breast cancer diagnosis was unknown. OBJECTIVE To determine the association of a low-fat dietary pattern with breast cancer overall survival (breast cancer followed by death from any cause measured from cancer diagnosis). DESIGN, SETTING, AND PARTICIPANTS This is a secondary analysis of the Women's Health Initiative randomized clinical trial that was conducted at 40 US clinical centers enrolling participants from 1993 through 1998. Participants were 48 835 postmenopausal women with no previous breast cancer and dietary fat intake of greater than 32% by food frequency questionnaire. INTERVENTIONS Participants were randomized to a dietary intervention group (40%; n = 19 541) with goals to reduce fat intake to 20% of energy and increase fruit, vegetable, and grain intake or a usual-diet comparison group (60%; n = 29 294). Dietary group participants with incident breast cancers continued to participate in subsequent dietary intervention activities. MAIN OUTCOMES AND MEASURES Breast cancer overall survival for incident breast cancers diagnosed during the 8.5-year (median) dietary intervention, examined in post hoc analyses after 11.5 years (median) postdiagnosis follow-up. RESULTS Of 1764 women diagnosed with breast cancer during the dietary intervention period, mean (SD) age at screening was 62.7 (6.7) years and age at diagnosis was 67.6 (6.9) years. With 516 total deaths, breast cancer overall survival was significantly greater for women in the dietary intervention group than in the usual-diet comparison group (10-year survival of 82% and 78%, respectively; hazard ratio [HR], 0.78; 95% CI, 0.65-0.94; P = .01). In the dietary group there were fewer deaths from breast cancer (68 vs 120; HR, 0.86; 95% CI, 0.64-1.17), other cancers (36 vs 65; HR, 0.76; 95% CI, 0.50-1.17), and cardiovascular disease (27 vs 64; HR, 0.62; 95% CI, 0.39-0.99). CONCLUSIONS AND RELEVANCE In women who received a diagnosis of breast cancer during the dietary intervention period, those in the dietary group had increased overall survival. The increase is due, in part, to better survival from several causes of death. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00000611.
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Endotoxemia is modulated by quantity and quality of dietary fat in older adults.
Lopez-Moreno, J, Garcia-Carpintero, S, Gomez-Delgado, F, Jimenez-Lucena, R, Vals-Delgado, C, Alcala-Diaz, JF, Roncero-Ramos, I, Rangel-Zuñiga, OA, Yubero-Serrano, EM, Malagon, MM, et al
Experimental gerontology. 2018;:119-125
Abstract
BACKGROUND Aging is an important determinant of the rate of atherosclerosis development, mainly through low-grade inflammation. Diet, and particularly its fat content, modulates the inflammatory response in fasting and postprandial states. OBJECTIVE We aimed to study the effects of dietary fat on endotoxemia in healthy older adults. MATERIALS AND METHODS Twenty healthy older adults were randomized to three diets, lasting three-weeks each, using a crossover design: 1. A Mediterranean diet enriched in MUFA with virgin olive oil. 2. An SFA-rich diet. 3. A low-fat high-carbohydrate diet enriched in n-3 PUFA (α-linolenic acid of plant origin) (CHO-PUFA diet). At the end of each period, after a 12-h fast, the subjects received a meal with a composition similar to the dietary period just completed. We determined the fasting and the postprandial plasma levels of lipopolysaccharide (LPS) and LPS-binding protein (LBP). RESULTS In the fasting state, we observed lower LPS plasma levels after the consumption of the CHO-PUFA diet (P=0.046) in comparison with the consumption of the Med and SFA-rich diets. In the postprandial measurements, we observed a statistically significant increase in plasma levels of LPS (P=0.044) and a decrease in LBP (P=0.003) after the intake of the CHO-PUFA meal, whereas no postprandial changes were observed after the ingestion of the Med and SFA-rich meals. CONCLUSION Our results, together with those obtained in a previous study, support the concept that the consumption of the Med Diet, in contrast to a low-fat PUFA diet, constitutes a more suitable dietary lifestyle for preventing the development of atherosclerosis in a population at risk, such as older adults.
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Pediatric Age Palm Oil Consumption.
Di Genova, L, Cerquiglini, L, Penta, L, Biscarini, A, Esposito, S
International journal of environmental research and public health. 2018;(4)
Abstract
Palm oil is widely used in the food industry for its chemical/physical properties, low cost and wide availability. Its widespread use has provoked an intense debate about whether it is a potential danger to human health. In a careful review of the scientific literature, we focused on nutritional characteristics and health effects of the use of palm oil with regards to children, seeking to determine whether there is evidence that justifies fears about the health effects of palm oil. Our review showed that palm oil represents a significant source of saturated fatty acids, to which scientific evidence attributes negative health effects when used in excess, especially with regards to cardiovascular diseases. However, to date, there is no evidence about the harmful effects of palm oil on the health of children. Nevertheless, palm oil has possible ill health effects linked to its composition of fatty acids: its consumption is not correlated to risk factors for cardiovascular diseases in young people with a normal weight and cholesterol level; the elderly and patients with dyslipidaemia or previous cardiovascular events or hypertension are at a greater risk. Therefore, the matter is not palm oil itself but the fatty-acid-rich food group to which it belongs. The most important thing is to consume no more than 10% of saturated fatty acids, regardless of their origin and regardless of one's age. Correct information based on a careful analysis of the scientific evidence, rather than a focus on a singular presumed culprit substance, should encourage better lifestyles.
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Lipids in the Stomach - Implications for the Evaluation of Food Effects on Oral Drug Absorption.
Koziolek, M, Carrière, F, Porter, CJH
Pharmaceutical research. 2018;(3):55
Abstract
Food effects on oral drug bioavailability can have significant impact on the provision of safe and reliable oral pharmacotherapy. A mechanistic understanding of the events that contribute to the occurrence of food effects is therefore critical. An increased oral bioavailability is often seen for poorly water-soluble drugs after co-administration with lipids, including lipids in food, and is commonly explained by the ability of lipids to enhance drug solubility in intestinal luminal fluids. In contrast, the impact of lipids on drug solubilisation in the stomach has received less attention. This is in spite of the fact that lipid digestion is initiated in the stomach by human gastric lipase and that gastric events also initiate emulsification of lipids in the gastrointestinal tract. The stomach therefore acts to 'pre-process' lipids for subsequent events in the intestine and may significantly affect downstream events at intestinal drug absorption sites. In this article, the mechanisms by which lipids are processed in the stomach are reviewed and the potential impact of these processes on drug absorption discussed. Attention is also focused on in vitro methods that are used to assess gastric processing of lipids and their application to better understand food effects on drug release and absorption.
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Effect of food on the pharmacokinetics of YH4808, a potassium-competitive acid blocker, after single- and multiple-oral dosing in healthy subjects.
Kim, E, Kim, A, Yi, S, Kim, YK, Jang, SB, Byun, HM, Yoon, SH, Cho, JY, Jang, IJ, Yu, KS, et al
European journal of clinical pharmacology. 2018;(10):1261-1272
Abstract
PURPOSE YH4808 is a potassium-competitive acid blocker, developed for the treatment of acid-related disorders. Two clinical studies in healthy male subjects were conducted to evaluate the effect of food on the pharmacokinetics of YH4808. METHODS The first study, a randomized, three-treatment, three-period, crossover study, compared pharmacokinetics of YH4808 (300 mg) after a single dose at fed state with a standard or a high-fat meal to those at fasted state. The second study, a randomized, two-treatment, two-period, crossover study, investigated pharmacokinetics at fasted or fed state with a standard meal after twice daily dose of YH4808 (100 mg) for 7 days. Bloods for pharmacokinetic evaluation were sampled up to 48 h post-dose and 24 h post-dose at steady state, respectively. The pharmacokinetic parameters were estimated by non-compartmental method. RESULTS After single dosing, the geometric means of maximum plasma concentration increased by 1.2 and 2.1 times in the fed states with a standard meal and a high-fat meal, respectively, of that in fasted state. Corresponding values of area under the plasma concentration-time curve (AUC) from time 0 to the last measurable time point increased by 1.8 and 2.8 times, respectively. After multiple dosing, the geometric mean for 24-h AUC at steady state slightly increased in fed state by 1.1 times of that in fasted state. CONCLUSIONS As fat content of the food increased, the systemic exposure of YH4808 after single dosing increased. However, systemic exposures at steady state after multiple dosing between fasted and fed states were similar. TRIAL REGISTRATION ClinicalTrials.gov registry no.: NCT01520012.
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Food and functional dyspepsia: a systematic review.
Duncanson, KR, Talley, NJ, Walker, MM, Burrows, TL
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2018;(3):390-407
Abstract
BACKGROUND Functional dyspepsia (FD) is a debilitating functional gastrointestinal disorder characterised by early satiety, post-prandial fullness or epigastric pain related to meals, which affects up to 20% of western populations. A high dietary fat intake has been linked to FD and duodenal eosinophilia has been noted in FD. We hypothesised that an allergen such as wheat is a risk factor for FD and that withdrawal will improve symptoms of FD. We aimed to investigate the relationship between food and functional dyspepsia. METHODS Sixteen out of 6451 studies identified in a database search of six databases met the inclusion criteria of studies examining the effect of nutrients, foods and food components in adults with FD or FD symptoms. RESULTS Wheat-containing foods were implicated in FD symptom induction in six studies, four of which were not specifically investigating gluten and two that were gluten-specific, with the implementation of a gluten-free diet demonstrating a reduction in symptoms. Dietary fat was associated with FD in all three studies that specifically measured this association. Specific foods reported as inducing symptoms were high in either natural food chemicals, high in fermentable carbohydrates or high in wheat/gluten. Caffeine was associated with FD in four studies, although any association with alcohol was uncertain. CONCLUSIONS Wheat and dietary fats may play key roles in the generation of FD symptoms and reduction or withdrawal eased symptoms. Randomised trials investigating the roles of gluten, FODMAPs (fermentable oligosaccharide, disaccharide, monosaccharide and polyols) and high fat ingestion and naturally occurring food chemicals in the generation of functional dyspepsia symptoms are warranted and further investigation of the mechanisms is now required.
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Genetically determined vitamin D levels and change in bone density during a weight-loss diet intervention: the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) Trial.
Zhou, T, Sun, D, Heianza, Y, Li, X, Champagne, CM, LeBoff, MS, Shang, X, Pei, X, Bray, GA, Sacks, FM, et al
The American journal of clinical nutrition. 2018;(5):1129-1134
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BACKGROUND Obesity is closely associated with bone health. Although diet and weight loss produce many metabolic benefits, studies of weight loss diets on bone health are conflicting. Genetic variations, such as vitamin D levels, may partly account for these conflicting observations by regulating bone metabolism. OBJECTIVE We investigated whether the genetic variation associated with vitamin D concentration affected changes in bone mineral density (BMD) in response to a weight-loss diet intervention. DESIGN In the 2-y Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, BMD was measured for 424 participants who were randomly assigned to 1 of 4 diets varying in macronutrient intakes. A genetic risk score (GRS) was calculated based on 3 genetic variants [i.e., 7-dehydrocholesterol reductase (DHCR7) rs12785878, cytochrome P450 2R1 (CYP2R1) rs10741657 and group-specific component globulin (GC) rs2282679] related to circulating vitamin D levels. A dual-energy X-ray absorptiometry scan was performed to assess changes in whole-body BMD over 2 y. The final analysis included 370 participants at baseline. RESULTS We found a significant interaction between dietary fat intake and vitamin D GRS on 2-y changes in whole-body BMD (P-interaction = 0.02). In the high-fat diet group, participants with higher GRS showed significantly less reduction in whole-body BMD than those with lower GRS, whereas the genetic associations were not significant in the low-fat diet group. We also found a significant interaction between dietary fat intake and the GRS on 6-mo change in femur neck BMD (P-interaction = 0.02); however, the interaction became nonsignificant at 2 y. CONCLUSION Our data indicate that dietary fat intake may modify the effect of vitamin D-related genetic variation on changes in BMD. Overweight or obese patients predisposed to sufficient vitamin D may benefit more in maintaining BMD along with weight loss by eating a low-fat diet. This trial was registered at clinicaltrials.gov as NCT03258203.