Physiologic Adaptation to Macronutrient Change Distorts Findings from Short Dietary Trials: Reanalysis of a Metabolic Ward Study.

An influential 2-wk cross-over feeding trial without a washout period purported to show advantages of a low-fat diet (LFD) compared with a low-carbohydrate diet (LCD) for weight control. In contrast to several other macronutrient trials, the diet order effect was originally reported as not significant. In light of a new analysis by the original investigative group identifying an order effect, we aimed to examine, in a reanalysis of publicly available data (16 of 20 original participants; 7 female; mean BMI, 27.8 kg/m2), the validity of the original results and the claims that trial data oppose the carbohydrate-insulin model of obesity (CIM). We found that energy intake on the LCD was much lower when this diet was consumed first compared with second (a difference of -1164 kcal/d, P = 3.6 × 10-13); the opposite pattern was observed for the LFD (924 kcal/d, P = 2.0 × 10-16). This carry-over effect was significant (P interaction = 0.0004) whereas the net dietary effect was not (P = 0.4). Likewise, the between-arm difference (LCD - LFD) was -320 kcal/d in the first period and +1771 kcal/d in the second. Body fat decreased with consumption of the LCD first and increased with consumption of this diet second (-0.69 ± 0.33 compared with 0.57 ± 0.32 kg, P = 0.007). LCD-first participants had higher ß-hydroxybutyrate levels while consuming the LCD and lower respiratory quotients while consuming LFD when compared with LFD-first participants on their respective diets. Change in insulin secretion as assessed by C-peptide in the first diet period predicted higher energy intake and less fat loss in the second period. These findings, which tend to support rather than oppose the CIM, suggest that differential (unequal) carry-over effects and short duration, with no washout period, preclude causal inferences regarding chronic macronutrient effects from this trial.

Adherence to a low-fat dietary pattern reduces head and neck cancer risk: evidence from the PLCO trial.

PURPOSE: Low-fat dietary (LFD) pattern refers to a dietary structure with reduced fat intake. The aim was to investigate the association between LFD pattern and risk of head and neck cancer (HNC). METHODS: Data were derived from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. LFD score was used to assess adherence to an LFD pattern, with higher scores indicating greater adherence. Cox regression was used to evaluate the association between LFD score and risk of HNC and its subtypes. To visualize the trend in risk of HNC and its subtypes with changing LFD score, restricted cubic spline plots were utilized. A series of subgroup analyses were conducted to identify potential confounders. Sensitivity analyses were performed to assess the robustness of the results. RESULTS: Among 98,459 participants of PLCO trial, 268 cases with HNC were identified during an average of 8.8 years of follow-up. In the fully adjusted model, participants in the highest compared with the lowest quartiles of LFD score had a lower risk of HNC (HR Q4 vs. Q1: 0.60; 95% CI: 0.40-0.90; P for trend = 0.026) and larynx cancer (HRQ4 vs. Q1: 0.46; 95% CI: 0.22-0.96; P for trend = 0.039). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of HNC and its subtypes (all P for nonlinearity > 0.05). The primary association remained robust in the sensitivity analysis. CONCLUSION: Our findings suggest that adherence to an LFD pattern may lower the risk of HNC in the US population.

Low-carbohydrate diets, low-fat diets, and mortality in middle-aged and older people: A prospective cohort study.

BACKGROUND: Short-term clinical trials have shown the effectiveness of low-carbohydrate diets (LCDs) and low-fat diets (LFDs) for weight loss and cardiovascular benefits. We aimed to study the long-term associations among LCDs, LFDs, and mortality among middle-aged and older people. METHODS: This study included 371,159 eligible participants aged 50-71 years. Overall, healthy and unhealthy LCD and LFD scores, as indicators of adherence to each dietary pattern, were calculated based on the energy intake of carbohydrates, fat, and protein and their subtypes. RESULTS: During a median follow-up of 23.5 years, 165,698 deaths were recorded. Participants in the highest quintiles of overall LCD scores and unhealthy LCD scores had significantly higher risks of total and cause-specific mortality (hazard ratios [HRs]: 1.12-1.18). Conversely, a healthy LCD was associated with marginally lower total mortality (HR: 0.95; 95% confidence interval: 0.94, 0.97). Moreover, the highest quintile of a healthy LFD was associated with significantly lower total mortality by 18%, cardiovascular mortality by 16%, and cancer mortality by 18%, respectively, versus the lowest. Notably, isocaloric replacement of 3% energy from saturated fat with other macronutrient subtypes was associated with significantly lower total and cause-specific mortality. For low-quality carbohydrates, mortality was significantly reduced after replacement with plant protein and unsaturated fat. CONCLUSIONS: Higher mortality was observed for overall LCD and unhealthy LCD, but slightly lower risks for healthy LCD. Our results support the importance of maintaining a healthy LFD with less saturated fat in preventing all-cause and cause-specific mortality among middle-aged and older people.

A low-fat diet improves fatigue in multiple sclerosis: Results from a randomized controlled trial.

BACKGROUND: Fatigue can be a disabling multiple sclerosis (MS) symptom with no effective treatment options. OBJECTIVE: Determine whether a low-fat diet improves fatigue in people with MS (PwMS). METHODS: We conducted a 16-week randomized controlled trial (RCT) and allocated PwMS to a low-fat diet (active, total daily fat calories not exceeding 20%) or wait-list (control) group. Subjects underwent 2 weeks of baseline diet data collection (24-hour diet recalls (24HDRs)), followed by randomization. The active group received 2 weeks of nutrition counseling and underwent a 12-week low-fat diet intervention. One set of three 24HDRs at baseline and week 16 were collected. We administered a food frequency questionnaire (FFQ) and Modified Fatigue Impact Scale (MFIS) every 4 weeks. The control group continued their pre-study diet and received diet training during the study completion. RESULTS: We recruited 39 PwMS (20-active; 19-control). The active group decreased their daily caloric intake by 11% (95% confidence interval (CI): -18.5%, -3.0%) and the mean MFIS by 4.0 (95% CI: -12.0, 4.0) compared to the control (intent-to-treat). Sensitivity analysis strengthened the association with a mean MFIS difference of -13.9 (95% CI: -20.7, -7.2). CONCLUSIONS: We demonstrated a significant reduction in fatigue with a low-fat dietary intervention in PwMS.

A Mediterranean and low-fat dietary intervention in non-alcoholic fatty liver disease patients: Exploring participant experience and perceptions about dietary change.

BACKGROUND: A Mediterranean diet (MD) appears to be beneficial in non-alcoholic fatty liver disease (NAFLD) patients in Mediterranean countries; however, the acceptability of a MD in non-Mediterranean populations has not been thoroughly explored. The present study aimed to explore the acceptability through understanding the barriers and enablers of the MD and low-fat diet (LFD) interventions as perceived by participating Australian adults from multicultural backgrounds with NAFLD. METHODS: Semi-structured telephone interviews were performed with 23 NAFLD trial participants at the end of a 12-week dietary intervention in a multicentre, parallel, randomised clinical trial. Data were analysed using thematic analysis. RESULTS: Participants reported that they enjoyed taking part in the MD and LFD interventions and perceived that they had positive health benefits from their participation. Compared with the LFD, the MD group placed greater emphasis on enjoyment and intention to maintain dietary changes. Novelty, convenience and the ability to swap food/meals were key enablers for the successful implementation for both of the dietary interventions. Flavour and enjoyment of food, expressed more prominently by MD intervention participants, were fundamental components of the diets with regard to reported adherence and intention to maintain dietary change. CONCLUSIONS: Participants randomised to the MD reported greater acceptability of the diet than those randomised to the LFD, predominantly related to perceived novelty and palatability of the diet.

Effects of different diets on glycemic control among patients with type 2 diabetes: A literature review.

Background: Globally, type 2 diabetes mellitus (T2DM) is one of the most common diseases, and the incidence is gradually increasing. Diet management could improve the elevated HbA1c levels. Aim: This review aims to examine the effects of different types of diets on glycemic control in patients with T2DM. Methods: PubMed and Google scholar databases were searched. Reports published from the years 1991 to 2021 that focused on the effect of different diets on diabetes control were selected. Results: All the studies reported that the type of diet can affect insulin secretion and glycemic control in patients with diabetes. The recommended macronutrient distribution for patients with diabetes is 30% of fat, 45-60% of carbohydrates, and 15-35% of protein. Consuming more or less of these macronutrients may lead to changes in glucose metabolism and may affect insulin secretion. In fact, following alow-fat diet improves glycemic control and decreases HbA1c levels. Studies reported that a low-carbohydrate diet had the greatest effect on improving glycemic control and insulin parameters. A low-calorie diet reduced fasting plasma glucose, while a very low-calorie diet resulted in a long-term decrease in HbA1c level. A healthy diet free of processed foods and sugar, and rich in nutrients such as fiber, vitamins, and minerals contributed to maintaining controlled blood sugar and lipid plasma levels. Although studies show a low-salt diet improves blood pressure, which is common inT2DM, other findings show that restricting salt intake is associated with increased sugar consumption. Conclusion: Healthy diet with adequate intake of energy and low-fat and low-sugar foods can enhance the glycemic control and reduce T2DM complications.

A High-Fat Western Diet Attenuates Intestinal Changes in Mice with DSS-Induced Low-Grade Inflammation.

BACKGROUND: A Western diet (WD) is associated with increased inflammation in the large intestine, which is often ascribed to the high dietary fat content. Intestinal inflammation in rodents can be induced by oral administration of dextran sodium sulfate (DSS). However, most studies investigating effects of WD and DSS have not used appropriate low-fat diets (LFDs) as control. OBJECTIVES: To compare the effects of a WD with those of an LFD on colon health in a DSS-induced low-grade colonic inflammation mouse model. METHODS: Six-week-old male C57BL/6JRj mice were fed an LFD (fat = 10.3% energy, n = 24) or a WD (fat = 41.2% energy, n = 24) for 15 wk [Experiment 1 (Exp.1)]. Half the mice on each diet (n = 12) then received 1% DSS in water for 6 d with the remainder (n = 12 in each diet) administered water. Disease activity, proinflammatory genes, inflammatory biomarkers, and fecal microbiota (16S rRNA) were assessed (Exp.1). Follow-up experiments (Exp.2 and Exp.3) were performed to investigate whether fat source (milk or lard; Exp.2) affected outcomes and whether a shift from LFD to WD 1 d prior to 1% DSS exposure caused an immediate effect on DSS-induced inflammation (Exp.3). RESULTS: In Exp.1, 1% DSS treatment significantly increased disease score in the LFD group compared with the WD group (2.7 compared with 0.8; P < 0.001). Higher concentrations of fecal lipocalin (11-fold; P < 0.001), proinflammatory gene expression (≤82-fold), and Proteobacteria were observed in LFD-fed mice compared with the WD group. The 2 fat sources in WDs (Exp.2) revealed the same low inflammation in WD+DSS mice compared with LFD+DSS mice. Finally, the switch from LFD to WD just before DSS exposure resulted in reduced colonic inflammation (Exp.3). CONCLUSIONS: Herein, WDs (with milk or lard) protected mice against DSS-induced colonic inflammation compared with LFD-fed mice. Whether fat intake induces protective mechanisms against DSS-mediated inflammation or inhibits establishment of the DSS-induced colitis model is unclear.

One size does not fit all; practical, personal tailoring of the diet to NAFLD patients.

Different dietary regimens for weight loss have developed over the years. Since the most evidenced treatment for non-alcoholic fatty liver disease (NAFLD) is weight reduction, it is not surprising that more diets targeting obesity are also utilized for NAFLD treatment. However, beyond the desired weight loss effects, one should not ignore the dietary composition of each diet, which may not necessarily be healthy or safe over the long term for hepatic and extrahepatic outcomes, especially cardiometabolic outcomes. Some of these diets are rich in saturated fat and red meat, are very strict, and require close medical supervision. Some may also be very difficult to adhere to for long periods, thus reducing the patient's motivation. The evidence for a direct benefit to NAFLD by restrictive diets such as very-low-carb, ketogenic, very-low-calorie diets, and intermittent fasting is scarce, and the long-term safety has not been tested. Nowadays, the approach is that the diet should be tailored to the patient's cultural and personal preferences. There is strong evidence for the independent protective association of NAFLD with a diet based on healthy eating patterns of minimally-processed foods, low in sugar and saturated fat, high in polyphenols, and healthy types of fats. This leads to the conclusion that a Mediterranean diet should serve as a basis that can be restructured into other kinds of diets. This review will elaborate on the different diets and their role in NAFLD. It will provide a practical guide to tailor the diet to the patients without compromising its composition and safety.

Impact of a Mediterranean diet on hepatic and metabolic outcomes in non-alcoholic fatty liver disease: The MEDINA randomised controlled trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is predominantly managed by lifestyle intervention, in the absence of effective pharmacotherapies. Mediterranean diet (MedDiet) is the recommended diet, albeit with limited evidence. AIMS: To compare an ad libitum MedDiet to low-fat diet (LFD) in patients with NAFLD for reducing intrahepatic lipids (IHL) by proton magnetic resonance spectroscopy (1 H-MRS). Secondary outcomes include insulin resistance by homeostatic model of assessment (HOMA-IR), visceral fat by bioelectrical impedance analysis (BIA), liver stiffness measurement (LSM) and other metabolic outcomes. METHODS: In this parallel multicentre RCT, subjects were randomised (1:1) to MedDiet or LFD for 12 weeks. RESULTS: Forty-two participants (25 females [60%], mean age 52.3 ± 12.6 years) were included, 23 randomised to LFD and 19 to MedDiet.; 39 completed the study. Following 12 weeks, there were no between-group differences. IHL improved significantly within the LFD group (-17% [log scale]; p = .02) but not within the MedDiet group (-8%, p = .069). HOMA-IR reduced in the LFD group (6.5 ± 5.6 to 5.5 ± 5.5, p < .01) but not in the MedDiet group (4.4 ± 3.2 to 3.9 ± 2.3, p = .07). No differences were found for LSM (MedDiet 7.8 ± 4.0 to 7.6 ± 5.2, p = .429; LFD 11.8 ± 14.3 to 10.8 ± 10.2 p = .99). Visceral fat reduced significantly in both groups; LFD (-76% [log scale], p = <.0005), MedDiet (-61%, p = <.0005). CONCLUSIONS: There were no between-group differences for hepatic and metabolic outcomes when comparing MedDiet to LFD. LFD improved IHL and insulin resistance. Significant improvements in visceral fat were seen within both groups. This study highlights provision of dietary interventions in free-living adults with NAFLD is challenging.

Long-term effect of a dietary intervention with two-healthy dietary approaches on food intake and nutrient density in coronary patients: results from the CORDIOPREV trial.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of disease burden in the world by non-communicable diseases. Nutritional interventions promoting high-quality dietary patterns with low caloric intake value and high nutrient density (ND) could be linked to a better control of CVD risk and recurrence of coronary disease. This study aims to assess the effects of a dietary intervention based on MedDiet or Low-Fat dietary intervention over changes in ND and food intake after 1 and 7 years of follow-up of the CORDIOPREV study. METHODS: We prospectively analyzed the results of the 802 coronary patients randomized to two healthy dietary patterns (MedDiet = 425, Low-Fat Diet = 377) who completed the 7 years of follow-up and had all the dietary data need. Dietary intake information obtained from a validated 137-item Food Frequency Questionnaire was used to calculate 1- and 7-year changes in dietary intake and ND (measured as nutrient intake per 1000 kcal). T test was used to ascertain differences in food intake and ND between groups across follow-up time. Within-subject (dietary allocation group) differences were analyzed with ANOVA repeated measures. RESULTS: From baseline to 7 years of follow-up, significant increases of vegetables, fruits, and whole cereals within groups (p < 0.001) was found. We found a higher increase in dietary intake of certain food groups with MedDiet in comparison with Low-Fat Diet for vegetables (46.1 g/day vs. 18.1 g/day, p < 00.1), fruits (121.3 g/day vs. 72.9 g/day), legumes (4.3 g/day vs. 0.16 g/day) and nuts (7.3 g/day vs. - 3.7 g/day). There was a decrease in energy intake over time in both groups, slightly higher in Low-Fat Diet compared to MedDiet group (- 427.6 kcal/day vs. - 279.8 kcal/day at 1st year, and - 544.6 kcal/day vs. - 215.3 kcal/day after 7 years of follow-up). ND of all the nutrients increased within group across follow-up time, except for Saturated Fatty Acids (SFA), cholesterol and sodium (p < 0.001). CONCLUSIONS: A comprehensive dietary intervention improved quality of diet, reducing total energy intake and increasing the intake of healthy food groups and overall ND after 1 year and maintaining this trend after 7 years of follow-up. Our results reinforce the idea of the participation in trials, enhance nutrition literacy and produces better nutritional outcomes in adult patients with established CVD. CLINICAL TRIAL REGISTRY: The trial was registered in 2009 at ClinicalTrials.gov (number NCT00924937).

Effect of Atkins versus a low-fat diet on gut microbiota, and cardiometabolic markers in obese women following an energy-restricted diet: Randomized, crossover trial.

BACKGROUND AND AIMS: There is controversy about effects of the Atkins diet on cardiometabolic markers in previous studies. No study compared effects of Atkins versus a low-fat diet on gut microbiota in obese women during a weight-loss program up to date. METHODS AND RESULTS: A 6-week, randomized, crossover trial was conducted. Twenty-four healthy women with obesity (BMI≥30 kg/m2) were randomly assigned to receive the Atkins (55%, 25%, and 20% of total daily calories from fat, protein, and carbohydrates), or low-fat (20%, 15%, and 65% of total daily calories from fat, protein, and carbohydrates) diets while following a weight-loss program. Vegetable oils were used as the main source of dietary fat. Dietary groups were switched after two weeks of washout period with a weight maintenance low-fat diet. The effects of the two diets did not differ for the most endpoints. However, Gut Actinobacteria residency and serum total antioxidant capacity significantly increased in the Akins diet group compared with the low-fat one (p = 0.02 and p = 0.04). Adjusting for all parameters, gut Actinobacteria residency 1.48- and 2.5-folds decreased the serum LDL.C/HDL.C ratio and non-HDL.C levels (95%CI: 3.1, -0.22; p = 0.03 and -0.07, -0.002; p = 0.04), respectively. Decrease in gut Proteobacteria residency showed a significant reduction in serum total oxidant status (95%CI: 7.4, -0.07; p = 0.04). CONCLUSIONS: The Atkins diet, based on vegetable oils, alters gut microbiota composition, atherogenic and antioxidant parameters. REGISTRATION NUMBER FOR CLINICAL TRIAL: IRCT20200929048876N3.

The effect of a Mediterranean diet vs. a low-fat diet on non-alcoholic fatty liver disease in children: a randomized trial.

Non-alcoholic fatty liver disease (NAFLD) is becoming ever more common in children, due to the increasing global prevalence of obesity. The first-line treatment consists of weight loss through a combination of a healthy diet and exercise. The objective of this study was to determine the effects of a Mediterranean Diet or a low-fat diet on reducing hepatic steatosis and insulin resistance in children with NAFLD. This 12-week randomised clinical trial was conducted with children aged 9-17 years diagnosed with NAFLD and randomised into either a Mediterranean Diet or a low-fat diet group. By the end of the study, hepatic steatosis had decreased significantly in both groups (p < 0.001). Liver enzymes also improved significantly, while significant decreases were observed in insulin resistance in both groups, although this decrease was greater in the Mediterranean Diet group (p = 0.010). This study demonstrated that a decrease in hepatic steatosis and an improvement in insulin sensitivity can be achieved with both a Mediterranean Diet and a low-fat diet over 12 weeks, with no significant decrease in the energy required for growth, in children with NAFLD.

Protein digestibility and bioavailability in an F2 mouse cross between the selected fat mouse line and an M2 congenic line carrying the anti-obesity and anti-diabetic Tst allele.

The study was performed to investigate protein digestibility and utilization in an F2 cross (M2-F2 cross) between the selected Fat (F) line and an M2 congenic line. The congenic M2 line carried the Fob3b2 quantitative trait locus (QTL) from the selected Lean (L) line previously shown to contain the Tst gene with leanness, anti-diabetic and resistance to diet-induced obesity effects. The main objective of the study was to test if some of the effects on leanness and obesity resistance of the L-line Fob3b2 could also be due to the effect of this QTL on nutrient digestibility and bioavailability. The F2 littermates carrying either the Fat line segment within the Fob3b2 region or the L-line were compared when fed the high-fat diet. Eleven mice per genotype were individually housed in metabolic cages. In 5-day experimental period, body mass and diet intake were measured. The part of study was done on the F and L line and tested the difference in apparent protein digestibility on low-fat (LFD) and high-fat (HFD) diet. The nitrogen content was determined in the diet, faeces, and urine based on which, the apparent protein digestibility, apparent protein biological value and apparent net protein utilization were calculated There were no significant differences in any of these parameters on congenic line, confirming that the phenotypic effect on adiposity between the genotypes in the M2-F2 population was not due to the differential effect of the Fob3b2 locus carrying the Tst gene on protein utilization. We conclude that the observed phenotypic effects of this gene region are due to direct metabolic actions rather than the effects on nutrient absorption and nitrogen utilization since there were no differences in apparent protein digestibility between L and F lines, irrespective to HFD or LFD. The age of animals had significant effect on the level of digestibility.

EFFECT OF 20-HOUR FASTING AND LOW FAT DIET ON GHRELIN HORMONE, GLUCOSE LEVEL AND LIVER FUNCTION IN ALBINO RATS MALE.

OBJECTIVE: The aim: It aims to study the effect of fasting and low fat diet on ghrelin hormone, glucose level, the liver enzymes AST and ALT. PATIENTS AND METHODS: Materials and methods: The experimental study was conducted using 24 healthy young male albino rat weighing 95±5 gram and age 2 month, one-way (ANOVA) were employed to determine a significance of differences. RESULTS: Results: A significant increase p≤0.05 in glucose level of non-fasting control group compere with non-fasting low fat diet group, significant increase p≤0.05 in glucose level of control group fasting for 20h compared with low fat diet fasting for 20h group, significant decrease p≤0.05 when compares non-fasting low fat diet compares to 20h fasting low fat diet and significant decrease p≤0.05 when compares non-fasting control compares to 20h fasting control, while the effect of fasting and low fat diet on ghrelin hormone. A significant decrease p≤0.05 in ghrelin hormone level of non-fasting control group compere with non-fasting low fat diet group, significant increase p≤0.05 in ghrelin hormone of control group fasting for 20h compared with low fat diet fasting for 20h group, non-fasting control compares to 20h fasting control show a significant (p≤0.05) increase, Fasting with low fat diet cause a significant decrease p≤0.05 in ALT level, also in AST level there was a significant decrease p≤0.05 after 20h fasting. CONCLUSION: Conclusions: The fasting and low fat diet have effected on ghrelin hormone, glucose level and fasting with low fat diet cause decrease in ALT level, also in AST level decrease after 20h fasting in male albino rats.

Targeted and Untargeted Mass Spectrometry Reveals the Impact of High-Fat Diet on Peripheral Amino Acid Regulation in a Mouse Model of Alzheimer's Disease.

Recent research regarding amino acid metabolism has shown that there may be a link between obesity and Alzheimer's disease (AD). This work reports a metabolomics study using targeted and untargeted mass spectrometry-based metabolomic strategies to investigate this link. Targeted hydrophilic interaction liquid chromatography-triple quadrupole mass spectrometry and untargeted reversed-phase liquid chromatography-high resolution tandem mass spectrometry assays were developed to analyze the metabolic changes that occur in AD and obesity. APPSwe/PS1ΔE9 (APP/PSEN1) transgenic mice (to represent familial or early-onset AD) and wild-type littermate controls were fed either a high-fat diet (HFD, 60% kcal from lard) or a low-fat diet (LFD, 10% kcal from lard) from 2 months of age or a reversal diet (HFD, followed by LFD from 9.5 months). For targeted analyses, we applied the guidelines outlined in the Clinical and Laboratory Standards Institute (CLSI) LC-MS C62-A document and the U.S. Food and Drug Administration (FDA) bioanalytical method validation guidance for industry to evaluate the figures of merit of the assays. Our targeted and untargeted metabolomics results suggest that numerous peripheral pathways, specifically amino acid metabolism and fatty acid metabolism, were significantly affected by AD and diet. Multiple amino acids (including alanine, glutamic acid, leucine, isoleucine, and phenylalanine), carnitines, and members of the fatty acid oxidation pathway were significantly increased in APP/PSEN1 mice on HFD compared to those on LFD. More substantial effects and changes were observed in the APP/PSEN1 mice than in the WT mice, suggesting that they were more sensitive to an HFD. These dysregulated peripheral pathways include numerous amino acid pathways and fatty acid beta oxidation and suggest that obesity combined with AD further enhances cognitive impairment, possibly through aggravated mitochondrial dysfunction. Furthermore, partial reversibility of many altered pathways was observed, which highlights that diet change can mitigate the metabolic effects of AD. The same trends in individual amino acids were observed in both strategies, highlighting the biological validity of the results.

Modifying dietary patterns in cardiothoracic transplant patients to reduce cardiovascular risk: The AMEND-IT Trial.

BACKGROUND: Cardiovascular disease (CVD) is common after cardiothoracic transplantation and causes substantial morbidity. AIMS: To assess feasibility and potential effectiveness of dietary interventions to reduce CVD risk. MATERIALS AND METHODS: In a pilot intervention, we recruited patients from a tertiary hospital and randomly allocated them to a Mediterranean or low-fat diet for 12 months. Feasibility was measured by patient participation, retention, and adherence. Changes in weight, body mass index (BMI), heart rate, blood pressure, glucose markers, and blood lipids were assessed using longitudinal generalized estimating equation regression models with 95% confidence intervals. RESULTS: Of 56 heart and 60 lung transplant recipients, 52 (45%) consented, 41 were randomized, and 39 (95%) completed the study with good adherence to randomized diets. After 12 months, changes in many risk factors were seen in the Mediterranean and low-fat-diet groups, respectively, including mean BMI (-0.5 vs. 0.0 kg/m2 ), systolic/diastolic blood pressure +0.5/+0.1 vs -4.4/-3.5 mmHg; fasting glucose -0.26 vs -0.27 mmol/L; total cholesterol -0.56 vs -0.40 mmol/L. Changes in BMI and systolic/diastolic blood pressure in 49 eligible patients who did not take part were +0.7 kg/m2 and +2.5/+1.8 mmHg. DISCUSSION: Dietary interventions in cardiothoracic transplant patients are feasible and potentially beneficial. CONCLUSION: A definitive nutritional intervention study in these high-risk patients is warranted.

Diet- and sex-related changes of gut microbiota composition and functional profiles after 4 months of weight loss intervention.

PURPOSE: Obesity has been related to intestinal dysbiosis and the modification of gut microbiota composition by dietary strategies becomes a promising strategy to help manage obesity. The aim of the current study was to evaluate the effect of two weight-loss diets on the composition and functional profile of gut microbiota. METHODS: 55 men and 124 women with BMI > 25 kg/m2 were randomly assigned to moderately high-protein (MHP) or low-fat (LF) diet. Differences in fecal bacteria abundance (based on 16 s rRNA sequencing) between before and after 4 months of calorie restriction was analyzed using EdgeR tool in MicrobiomeAnalyst platform. Bacterial functional profile was predicted using Tax4Fun and metagenomeSeq analysis. Significant KEGG Orthology (KO) terms were selected for the metabolomic study using chromatography. RESULTS: After the intervention, MHP-men showed a significant decrease in Negativicutes, Selenomonadales, Dielma and Dielma fastidiosa. LF-men showed a significant increase in Bacilli, Lactobacillales, Christensenellaceae, Peptococcaceae, and Streptococcaceae, Peptococcus, Streptococcus and Christensenella, Duncaniella dubosii_CP039396_93.49%, Roseburia sp_AB744234_98.96% and Alistipes inops_KJ572413_99.57%. MHP-women increased Pasteurellales, Phascolarctobacterium succinatutens, Ruthenibacterium lactatiformans_LR215981_99.55% and decreased in Phascolarctobacterium succinatutens_NR112902_99.56%. Finally, LF-women presented a significant decrease in Bacteroides clarus and Erysipelothrix inopinata_CP060715_84.4%. Surprisingly, no matching bacterial changes were found between these four groups. A total of 42 KO, 10 metabolic pathways and 107 related metabolites related were found implicated in these bacterial changes. Seven metabolites were confirmed in plasma. CONCLUSION: Weight-loss-related-changes in gut microbiome composition and the functional profile occur in a sex- and diet-related manner, showing that women and men could differentially benefit from the consumption of MHP and LF diets. TRIAL REGISTRATION: NCT02737267, 10th March 2016 retrospectively registered.

The Ketogenic Diet: Evidence for Optimism but High-Quality Research Needed.

For >50 y, dietary guidelines in the United States have focused on reducing intakes of saturated and total fat. However, rates of obesity and diabetes rose markedly throughout this period, with potentially catastrophic implications for public health and the economy. Recently, ketogenic diets have received substantial attention from the general public and nutrition research community. These very-low-carbohydrate diets, with fat comprising >70% of calories, have been dismissed as fads. However, they have a long history in clinical medicine and human evolution. Ketogenic diets appear to be more effective than low-fat diets for treatment of obesity and diabetes. In addition to the reductions in blood glucose and insulin achievable through carbohydrate restriction, chronic ketosis might confer unique metabolic benefits of relevance to cancer, neurodegenerative conditions, and other diseases associated with insulin resistance. Based on available evidence, a well-formulated ketogenic diet does not appear to have major safety concerns for the general public and can be considered a first-line approach for obesity and diabetes. High-quality clinical trials of ketogenic diets will be needed to assess important questions about their long-term effects and full potential in clinical medicine.

Long-term dietary adherence and changes in dietary intake in coronary patients after intervention with a Mediterranean diet or a low-fat diet: the CORDIOPREV randomized trial.

PURPOSE: Adherence to a healthy dietary pattern positively influences clinical outcomes in cardiovascular prevention, but long-term adherence is difficult to maintain. We evaluated 5-year changes in dietary habits, adherence achieved, and its maintenance in a cohort of coronary patients from the CORDIOPREV study. METHODS: 1002 coronary patients were randomized to a Mediterranean diet (n = 502) or a low-fat diet (n = 500) and received individual-group-telephone visits and personalized dietary advice. A validated food-frequency questionnaire, a 14-point Mediterranean diet adherence screener, and a 9-point low-fat diet adherence score were used. Dietary adherence was categorized into Low, Medium, and High Adherence. Changes in nutrient intake, food consumption, and adherence were analyzed on a yearly basis. The maintenance of long-term dietary adherence was evaluated using data after the first year and fifth year. RESULTS: From baseline to 5 years, significant increases were observed in overall dietary adherence (Mediterranean diet from 8.9 to 11.4; low-fat diet from 3.9 to 7.1) and in the percentage of patients considered High Adherence (Mediterranean diet from 41 to 89%; low-fat diet from 4 to 67%). When we evaluated the maintenance of adherence, patients considered Low and Medium Adherence at 1 year increased their adherence at the 5 years with both diets and patients considered High Adherence maintained their adherence with a Mediterranean diet, but decreased their adherence with a low-fat diet. CONCLUSIONS: A comprehensive dietary intervention results in an overall long-term improvement and maintenance of adherence to the Mediterranean and low-fat diets. In our population, the Mediterranean diet group achieved a high level of adherence in the short term which was maintained in the long term.

Dietary α-lactalbumin alters energy balance, gut microbiota composition and intestinal nutrient transporter expression in high-fat diet-fed mice.

Recently there has been a considerable rise in the frequency of metabolic diseases, such as obesity, due to changes in lifestyle and resultant imbalances between energy intake and expenditure. Whey proteins are considered as potentially important components of a dietary solution to the obesity problem. However, the roles of individual whey proteins in energy balance remain poorly understood. This study investigated the effects of a high-fat diet (HFD) containing α-lactalbumin (LAB), a specific whey protein, or the non-whey protein casein (CAS), on energy balance, nutrient transporters expression and enteric microbial populations. C57BL/6J mice (n 8) were given an HFD containing either 20 % CAS or LAB as protein sources or a low-fat diet containing CAS for 10 weeks. HFD-LAB-fed mice showed a significant increase in cumulative energy intake (P=0·043), without differences in body weight, energy expenditure, locomotor activity, RER or subcutaneous and epididymal white adipose tissue weight. HFD-LAB intake led to a decrease in the expression of glut2 in the ileum (P=0·05) and in the fatty acid transporter cd36 (P<0·001) in both ileum and jejunum. This suggests a reduction in absorption efficiency within the small intestine in the HFD-LAB group. DNA from faecal samples was used for 16S rRNA-based assessment of intestinal microbiota populations; the genera Lactobacillus, Parabacteroides and Bifidobacterium were present in significantly higher proportions in the HFD-LAB group. These data indicate a possible functional relationship between gut microbiota, intestinal nutrient transporters and energy balance, with no impact on weight gain.