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The carbohydrate–insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of 27.8 ± 1.3 kg m−2 were admitted as inpatients to the National Institutes of Health Clinical Center and randomized to consume ad libitum either a minimally processed, plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with high glycemic load (85 g 1,000 kcal−1) or a minimally processed, animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with low glycemic load (6 g 1,000 kcal−1) for 2 weeks followed immediately by the alternate diet for 2 weeks. One participant withdrew due to hypoglycemia during the low-carbohydrate diet. The primary outcomes compared mean daily ad libitum energy intake between each 2-week diet period as well as between the final week of each diet. We found that the low-fat diet led to 689 ± 73 kcal d−1 less energy intake than the low-carbohydrate diet over 2 weeks (P

To formulate precision nutrition prescriptions, it is essential to understand the relationship between dietary assessment, ethnicity and cardiometabolic disease. Erythrocyte (RBC) fatty acid (FA) profiles reflect long-term dietary fat intake but have not been rigorously compared with short-term FA intake in women of African ancestry who have paradoxically low triglycerides with high fat intake. We compared the type of dietary fat consumed (proportion of total fat) using food records with fasting RBC FA (mol%) determined by gas chromatography in 130 female, healthy, federal employees without diabetes (12% African Immigrants (AI), 47% African Americans (AA), 41% White Americans (WA)); mean age 43+10 y and BMI 30 + 6 kg/m2). Diet quality and home prepared meals were similar across ethnicities. AI reported the lowest energy intake. Regardless of absolute energy intake, macronutrient distributions were similar. Fat intake differed by ethnicity; WA had the highest saturated FA (SFA) and lowest eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and omega-3 index (EPA + DHA), while AI and AA had similar SFA, EPA and DHA intake. AI women had the highest RBC DHA and omega-3 index. Associations between FA intake and RBC profiles were significant for DHA (r=0.3, p Disclosure A. B. Courville: None. S. T. Chung: None. S. Yang: None. L. Mabundo: None. C. K. Cravalho: None. S. Matta: None. A. Villalobos-perez: None. J. M. Dawson: None. A. H. Lichtenstein: None. A. E. Sumner: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases

A ketogenic diet lowered benzodiazepine use during withdrawal in patients with AUD and blunted alcohol administration in rats., Individuals with alcohol use disorder (AUD) show elevated brain metabolism of acetate at the expense of glucose. We hypothesized that a shift in energy substrates during withdrawal may contribute to withdrawal severity and neurotoxicity in AUD and that a ketogenic diet (KD) may mitigate these effects. We found that inpatients with AUD randomized to receive KD (n = 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet (n = 14). Over a 3-week treatment, KD compared to SA showed lower “wanting” and increased dorsal anterior cingulate cortex (dACC) reactivity to alcohol cues and altered dACC bioenergetics (i.e., elevated ketones and glutamate and lower neuroinflammatory markers). In a rat model of alcohol dependence, a history of KD reduced alcohol consumption. We provide clinical and preclinical evidence for beneficial effects of KD on managing alcohol withdrawal and on reducing alcohol drinking.

OBJECTIVES: To investigate differences in ad libitum energy intake when inpatient adults were exposed to diets with equal calories and protein but varied widely in the ratio of carbohydrate to fat. METHODS: 16 adults without diabetes were admitted to the Metabolic Clinical Research Unit in the NIH Clinical Center for four continuous weeks and were randomized to receive either a plant-based, low-fat (LF) diet or an animal-based, low-carbohydrate (LC) diet for two weeks, followed by the alternate diet for two weeks. The LF diet was ∼75% carbohydrate and ∼10% fat, whereas the LC was ∼10% carbohydrate and ∼75% fat. The LF diet had ∼4-fold more fiber and was ∼60% of the energy density of the LC diet. Both diets were matched for protein and the presented calories were double each subject's maintenance energy requirements, as calculated from their measured resting energy expenditure multiplied by 1.6. Participants received three daily meals, had continuous access to snacks, and were instructed to eat as much or as little as they wanted. Leftovers were weighed to determine food intake. ProNutra software was used to calculate energy and nutrient intake. RESULTS: The study enrolled 9 men and 7 women with an age (mean ± SE) of 29 ± 1.7 years and body mass index (BMI) of 27.5 ± 1.5. During exposure to the LF diet, participants consumed 726 ± 84 kcal/d less than during the LC diet (P

OBJECTIVES: To explore postprandial responses to isocaloric meals after ∼2 weeks on an ad libitum Low Carbohydrate (LC) diet vs. a Low Fat (LF) diet. METHODS: 16 healthy volunteers without diabetes were admitted to the NIH Clinical Center and randomized to consume a LC or LF diet for 2 weeks immediately followed by 2 weeks of the alternate diet. The LC diet was composed of ∼75% fat, ∼10% carbohydrate, and ∼15% protein; the LF diet was ∼75% carbohydrate, ∼10% fat, and ∼15% protein. Daily meals and snacks were matched for presented calories and participants were instructed to consume as much or as little as desired. On day 13 of each diet after an 8 hour fast, participants consumed a liquid meal containing 30% of energy requirements with a macronutrient composition corresponding to the prevailing diet. Blood was drawn at 0, 10, 20, 30, 60, 90, 120, 180, 240, 300, 360 minutes post meal consumption. Plasma concentrations of glucose, lactate, insulin, c-peptide, free fatty acids, and triglycerides were measured. RESULTS: 7 females and 9 males with an age of (mean ± SE) 28.7 ±1.7 y and BMI of 27.5 ± 1.5 kg/m(2) completed the study. During the LC diet, baseline levels of triglycerides and lactate were significantly lower (−33.5 ± 9.1 mg/dl; P = 0.003, −0.18 ± 0.05 mM; P = 0.002, respectively) and glucose, insulin, and c-peptide also tended to be lower (−3.7 ± 2.0 mg/dl; P = 0.09, −2.2 ± 1.2 µU/ml; P = 0.08, −0.35 ± 0.17 ng/ml; P = 0.06, respectively) whereas free fatty acids were significantly higher (0.28 ± 0.06 mM; P = 0.0005) compared to the LF diet. Average postprandial levels of glucose, lactate, insulin, and c-peptide were significantly lower following the LC meal (−11 ± 3 mg/dl; P = 0.003, −0.88 ± 0.06 mM; P

Metformin is the only approved oral agent for youth with type 2 diabetes but its mechanism of action remains controversial. Recent data in adults suggest a primary role for the enteroinsular pathway, but there are no data in youth, in whom metformin efficacy is only ~50%. Our objectives were to compare incretin concentrations and rates of glucose production and gluconeogenesis in youth with type 2 diabetes before and after short-term metformin therapy compared with peers with normal glucose tolerance (NGT). This is a case–control observational study in youth with type 2 diabetes who were not on metformin (n = 18) compared with youth with NGT (n = 10) who were evaluated with a 2 day protocol. A 75 g OGTT was administered to measure intact glucagon-like 1 peptide (iGLP-1), gastric inhibitory polypeptide (GIP) and peptide YY (PYY). Insulinogenic index (IGI) and whole-body insulin sensitivity were calculated using glucose and insulin levels from the OGTT. Basal rates of gluconeogenesis (2H2O), glucose production ([6,6-2H2]glucose) and whole-body lipolysis ([2H5]glycerol) were measured after an overnight fast on study day 2. Youth with type 2 diabetes (n = 9) were subsequently evaluated with an identical 2 day protocol after 3 months on the metformin study. Compared with individuals with NGT, those with type 2 diabetes had higher fasting (7.8 ± 2.5 vs 5.1 ± 0.3 mmol/l, mean ± SD p = 0.002) and 2 h glucose concentrations (13.8 ± 4.5 vs 5.9 ± 0.9 mmol/l, p = 0.001), higher rates of absolute gluconeogenesis (10.0 ± 1.7 vs 7.2 ± 1.1 μmol [kg fat-free mass (FFM)]−1 min−1, p

Rationale: In black women, triglycerides are paradoxically normal in the presence of insulin resistance. This relationship may be explained by race-related differences in central adiposity and SCD (stearoyl-CoA desaturase)-1 enzyme activity index. Objective: In a cross-sectional study, to compare fasting and postprandial triglyceride-rich lipoprotein particle (TRLP) concentrations and size in black compared with white pre- and postmenopausal women and determine the relationship between TRLP subfractions and whole-body insulin sensitivity, hepatic and visceral fat, and SCD-1 levels. Methods and Results: In 122 federally employed women without diabetes mellitus, 73 black (58 African American and 15 African immigrant) and 49 white; age, 44±10 (mean±SD) years; body mass index, 30.0±5.6 kg/m 2 , we measured lipoprotein subfractions using nuclear magnetic resonance. Hepatic fat was measured by proton magnetic resonance spectroscopy, insulin sensitivity index calculated by minimal modeling from a frequently sampled intravenous glucose test, and red blood cell fatty acid profiles were measured by gas chromatography and were used to estimate SCD-1 indices. Hepatic fat, insulin sensitivity index, and SCD-1 were similar in black women and lower than in whites, regardless of menopausal status. Fasting and postprandial large, medium, and small TRLPs, but not very small TRLPs, were lower in black women. Fasting large, medium, and very small TRLPs negatively correlated with insulin sensitivity index and positively correlated with visceral and hepatic fat and SCD-1 activity in both groups. In multivariate models, visceral fat and SCD-1 were associated with total fasting TRLP concentrations (adjR2, 0.39; P =0.001). Black women had smaller postprandial changes in large ( P =0.005) and medium TRLPs ( P =0.007). Conclusions: Lower visceral fat and SCD-1 activity may contribute to the paradoxical association of lower fasting and postprandial TRLP subfractions despite insulin resistance in black compared with white pre- and postmenopausal women. Similar concentrations of very small TRLPs are related to insulin resistance and could be important mediators of cardiometabolic disease risk in women. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01809288.

Background & aim Hepatic fat excess in non-alcoholic fatty liver disease (NAFLD) reflects an imbalance between fat accumulation and disposal. Conflicting data exist for the role of fatty acid oxidation (FAO), one of the disposal pathways, and have mostly come from the studies delivering fatty acids (FAs) intravenously. Whether FAO of orally provided FAs is affected in NAFLD is unknown. Methods We performed a breath test study to measure FAO in subjects with NAFLD and healthy controls. Subjects ingested [1-13 C] palmitic acid (PA, 10 mg/kg) in a liquid meal and the rate of 13 CO2 appearance in expired air was measured over 6 hours by a BreathID device (Exalenz) to obtain the cumulative percent dose recovered (CPDR), the total amount of ingested 13 C recovered. CPDR was corrected by the results of a [1-13 C] acetate breath test, performed 1-4 weeks later, to calculate the rate of PA β-oxidation. Results Palmitic acid oxidation was 27% lower in 43 subjects with NAFLD compared to 11 controls (CPDR 9.5 ± 2.4% vs 13.1 ± 3.7%, P = .0001) and this persisted after correcting for acetate (29.3 ± 10.5 vs 36.6 ± 13.9, P = .03). The decrease in FAO was not because of the delayed transit as the time to peak 13 C detection did not differ between groups (4.9 ± 1.2 hours vs 4.7 ± 0.8 hours, P = .7). Rates of PA oxidation were not correlated with obesity, hepatic or adipose insulin resistance, alanine aminotransferase, liver fat content and NAFLD histology. Conclusion Fatty acid oxidation of orally delivered FA is decreased in NAFLD compared to healthy controls, likely reflecting decreased β-oxidation. The use of a breath test offers non-invasive dynamic assessment of FAO.

Minimal recent research explores how alcohol use disorder (AUD) affects dietary intake during periods of alcohol consumption. Therefore, we aimed to assess the feasibility and utility of a computerized food frequency questionnaire, the Diet History Questionnaire II (DHQ II), to quantify dietary intake in adults with AUD. Participants were adult men and women seeking treatment for AUD at the National Institutes of Health Clinical Center. Participants (N = 21) were enrolled in an observational study examining the microbiome in AUD. The Web-based DHQ II, reflecting dietary intake over the past year, was administered to participants within 2 weeks of admission to an inpatient alcohol rehabilitation program. Descriptive data are reported as mean ± SEM. Analyses were run in the Statistical Package for the Social Sciences, and P .05 was considered significant. Participants (67% male) were 46.3 ± 2.8 years old with a body mass index of 23.8 ± 0.6 kg/m

OBJECTIVES: To describe the effects of ad libitum low-fat (LF) and low-carbohydrate (LC) diets on body weight and fat mass. METHODS: Sixteen adults without diabetes spent 29 continuous days residing at the Metabolic Clinical Research Unit of the NIH Clinical Center where they were fed ad libitum either an animal-based, LC diet (75% fat, 10% carbohydrates, 15% protein) or a plant-based, LF diet (75% carbohydrates, 10% fat, 15% protein). Participants were randomly assigned to one diet for the first phase of the study (14 days), after which they were switched to the other diet for the remainder of the study. Participants were given three meals daily and were provided with additional snacks amounting to 200% of their daily energy requirements as determined by their resting energy expenditure multiplied by 1.6. Subjects were told that this was not a weight loss study and were not informed about the primary study aim. They were instructed to eat as much or as little as they desired. Total body weight and fat mass were measured using a calibrated scale and dual-energy X-ray absorptiometry, respectively. Subjects were blinded to their data and wore loose-fitting scrubs to avoid any feedback regarding changes in the fit of their clothing. RESULTS: Subjects included 7 women and 9 men, with an age of (mean ± SE) 29 ± 1.7 years and BMI of 27.5 ± 1.5 at baseline. Participants lost weight on both diets, with the LC diet resulting in 1.34 ± 0.31 kg of weight loss (P = 0.0006) and the LF diet resulting in 1.09 ± 0.31 kg of weight loss (P = 0.003) which was not significantly different from the LC diet (P = 0.58). However, participants lost 0.6 ± 0.17 kg of body fat on the LF diet (P = 0.002) but the LC diet did not result in significant body fat loss (0.04 ± 0.17 kg; P = 0.8) and the difference in body fat loss between the diets was statistically significant (P = 0.03). CONCLUSIONS: While participants lost similar amounts of weight on both diets, only the LF diet led to significant body fat loss. Early weight loss with a LC diet does not necessarily reflect a similar state of negative energy balance as compared with a LF diet. FUNDING SOURCES: Intramural Research Program of the National Institutes of Diabetes and Digestive and Kidney Diseases.