Effects of Mediterranean Diet or Low-Fat Diet on Blood Fatty Acids in Patients with Coronary Heart Disease. A Randomized Intervention Study

The Mediterranean diet (MD) prevents cardiovascular disease by different putative mechanisms, including modifications in the blood fatty acid (FA) profile. Polytherapy for secondary cardiovascular prevention might mask the effect of MD on the FA profile. This study was aimed to assess whether MD, in comparison with a low-fat diet (LFD), favorably modifies the blood FA profile in patients with coronary heart disease (CHD) on polytherapy. One hundred and twenty patients with a recent history of coronary stenting, randomized to MD or to LFD, completed 3 months of this open-label dietary intervention study. Diet Mediterranean-ness was evaluated using the Mediterranean Diet Adherence Screener (MeDAS) score. Both diets significantly reduced saturated FA (p < 0.01). Putative favorable changes in total n-3 FA (p = 0.03) and eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA; p = 0.04) were significantly larger with MD than with LFD. At 3 months, in the whole cohort, the MeDAS score correlated inversely with palmitic acid (R = −0.21, p = 0.02), and with palmitoleic acid (R = −0.32, p = 0.007), and positively with total n-3 FA (R = 0.19, p = 0.03), EPA (R = 0.28, p = 0.002), and EPA + DHA (R = 0.21, p = 0.02). In CHD patients on polytherapy, both MD and LFD shift FA blood composition towards a healthier profile, with a more favorable effect of MD on omega−3 levels.     

The Effects of a Low-Carbohydrate Diet vs. a Low-Fat Diet on Novel Cardiovascular Risk Factors: A Randomized Controlled Trial

Increasing evidence supports a low-carbohydrate diet for weight loss and improvement in traditional cardiovascular disease (CVD) markers. Effects on novel CVD markers remain unclear. We examined the effects of a low-carbohydrate diet (<40 g/day; n = 75) versus a low-fat diet (<30% kcal/day from total fat, <7% saturated fat; n = 73) on biomarkers representing inflammation, adipocyte dysfunction, and endothelial dysfunction in a 12 month clinical trial among 148 obese adults free of diabetes and CVD. Participants met with a study dietitian on a periodic basis and each diet group received the same behavioral curriculum which included dietary instruction and supportive counseling. Eighty percent of participants completed the intervention. At 12 months, participants on the low-carbohydrate diet had significantly greater increases in adiponectin (mean difference in change, 1336 ng/mL (95% CI, 342 to 2330 ng/mL); p = 0.009) and greater decreases in intercellular adhesion molecule-1 concentrations (−16.8 ng/mL (−32.0 to −1.6 ng/mL); p = 0.031) than those on the low-fat diet. Changes in other novel CVD markers were not significantly different between groups. In conclusion, despite the differences in weight changes on diets, a low-carbohydrate diet resulted in similar or greater improvement in inflammation, adipocyte dysfunction, and endothelial dysfunction than a standard low-fat diet among obese persons.     

Association between Fasting Ketonuria and Advanced Liver Fibrosis in Non-Alcoholic Fatty Liver Disease Patients without Prediabetes and Diabetes Mellitus

Ketone body production, an alternative fuel upon low glucose availability, reduces hepatic fat accumulation. However, its clinical implications have not been established in patients with nonalcoholic fatty liver disease (NAFLD). We investigated the association between spontaneous fasting ketonuria and liver fibrosis in patients with NAFLD without prediabetes and diabetes mellitus (DM). A total of 6202 patients with ultrasound confirmed NAFLD without prediabetes and DM were enrolled in the study. Using low cut off values of NAFLD fibrosis score (NFS) and fibrosis-4, liver fibrosis was defined as an intermediate–high probability of advanced liver fibrosis. Of the 6202 NAFLD patients, 360 (5.8%) had ketonuria. Compared to the patients without ketonuria, patients with ketonuria were younger (41.1 vs. 44.6 years, p < 0.001), had lower levels of glucose (87.2 vs. 91.0 mg/dL, p < 0.001), and homeostatic model assessment for insulin resistance (1.0 vs. 1.5, p < 0.001). The presence of ketonuria had an inverse association with liver fibrosis, assessed using both NFS (final adjusted odds ratio [aOR], 0.67; 95% confidence interval [CI], 0.45–1.01) and fibrosis-4 (aOR, 0.58; 95% CI, 0.40–0.84). The presence of ketonuria in NAFLD patients without prediabetes and DM may have favorable metabolic effects compared to the absence of ketonuria, independent of traditional metabolic factors.     

Effects of Two Months of Very Low Carbohydrate Ketogenic Diet on Body Composition,Muscle Strength,Muscle Area,and Blood Parameters in Competitive Natural Body Builders

Background: Ketogenic diet (KD) is a nutritional approach that restricts daily carbohydrates, replacing most of the reduced energy with fat, while maintaining an adequate quantity of protein. Despite the widespread use of KD in weight loss in athletes, there are still many concerns about its use in sports requiring muscle mass accrual. Thus, the present study sought to investigate the influence of a KD in competitive natural body builders. Methods: Nineteen volunteers (27.4 ± 10.5 years) were randomly assigned to ketogenic diet (KD) or to a western diet (WD). Body composition, muscle strength and basal metabolic rate were measured before and after two months of intervention. Standard blood biochemistry, testosterone, IGF-1, brain-derived neurotrophic factor (BDNF) and inflammatory cytokines (IL6, IL1β, TNFα) were also measured. Results: Body fat significantly decreased in KD (p = 0.030); whilst lean mass increased significantly only in WD (p < 0.001). Maximal strength increased similarly in both groups. KD showed a significant decrease of blood triglycerides (p < 0.001), glucose (p = 0.001), insulin (p < 0.001) and inflammatory cytokines compared to WD whilst BDNF increased in both groups with significant greater changes in KD (p < 0.001). Conclusions: KD may be used during body building preparation for health and leaning purposes but with the caution that hypertrophic muscle response could be blunted.     

Comparison of Effects of Long-Term Low-Fat vs High-Fat Diets on Blood Lipid Levels in Overweight or Obese Patients: A Systematic Review and Meta-Analysis

Dietary fat plays an important role in the primary prevention of cardiovascular disease, but long-term (≥12 months) effects of different percentages of fat in the diet on blood lipid levels remain to be established. Our systematic review and meta-analysis focused on randomized controlled trials assessing the long-term effects of low-fat diets compared with diets with high amounts of fat on blood lipid levels. Relevant randomized controlled trials were identified searching MEDLINE, EMBASE, and the Cochrane Trial Register until March 2013. Thirty-two studies were included in the meta-analysis. Decreases in total cholesterol (weighted mean difference –4.55 mg/dL [–0.12 mmol/L], 95% CI –8.03 to –1.07; P=0.01) and low-density lipoprotein (LDL) cholesterol (weighted mean difference –3.11 mg/dL [–0.08 mmol/L], 95% CI –4.51 to –1.71; P<0.0001) were significantly more pronounced following low-fat diets, whereas rise in high-density lipoprotein (HDL) cholesterol (weighted mean difference 2.35 mg/dL [0.06 mmol/L], 95% CI 1.29 to 3.42; P<0.0001) and reduction in triglyceride levels (weighted mean difference –8.38 mg/dL [–0.095 mmol/L], 95% CI –13.50 to –3.25; P=0.001) were more distinct in the high-fat diet groups. Including only hypocaloric diets, the effects of low-fat vs high-fat diets on total cholesterol and LDL cholesterol levels were abolished. Meta-regression revealed that lower total cholesterol level was associated with lower intakes of saturated fat and higher intakes of polyunsaturated fat, and increases in HDL cholesterol levels were related to higher amounts of total fat largely derived from monounsaturated fat (of either plant or animal origin) in high-fat diets (composition of which was ～17% of total energy content in the form of monounsaturated fatty acids, ～8% of total energy content in the form of polyunsaturated fatty acids), whereas increases in triglyceride levels were associated with higher intakes of carbohydrates. In addition, lower LDL cholesterol level was marginally associated with lower saturated fat intake. The results of our meta-analysis do not allow for an unequivocal recommendation of either low-fat or high-fat diets in the primary prevention of cardiovascular disease.     

Effects of Dietary Fat and Saturated Fat Content on Liver Fat and Markers of Oxidative Stress in Overweight/Obese Men and Women under Weight-Stable Conditions

Dietary fat and oxidative stress are hypothesized to contribute to non-alcoholic fatty liver disease and progression to steatohepatitis. To determine the effects of dietary fat content on hepatic triglyceride, body fat distribution and markers of inflammation and oxidative stress, overweight/obese subjects with normal glucose tolerance consumed a control diet (CONT: 35% fat/12% saturated fat/47% carbohydrate) for ten days, followed by four weeks on a low fat (LFD (n = 10): 20% fat/8% saturated fat/62% carbohydrate) or high fat diet (HFD (n = 10): 55% fat/25% saturated fat/27% carbohydrate). Hepatic triglyceride content was quantified by MRS and abdominal fat distribution by MRI. Fasting biomarkers of inflammation (plasma hsCRP, IL-6, IL-12, TNFα, IFN-γ) and oxidative stress (urinary F2-α isoprostanes) were measured. Body weight remained stable. Compared to the CONT, hepatic triglyceride decreased on the LFD (mean (95% CI): change −2.13% (−3.74%, −0.52%)), but did not change on the HFD and there was no significant difference between the LFD and HFD. Intra-abdominal fat did not change significantly on either diet, but subcutaneous abdominal fat increased on the HFD. There were no significant changes in fasting metabolic markers, inflammatory markers and urinary F2-α isoprostanes. We conclude that in otherwise healthy overweight/obese adults under weight-neutral conditions, a diet low in fat and saturated fat has modest effects to decrease liver fat and may be beneficial. On the other hand, a diet very high in fat and saturated fat had no effect on hepatic triglyceride or markers of metabolism, inflammation and oxidative stress.     

Whey Protein Supplementation Improves the Glycemic Response and May Reduce Non-Alcoholic Fatty Liver Disease Related Biomarkers in Women with Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) increases type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) with insulin resistance. We hypothesized that a 35 g whey preload would improve insulin sensitivity and glucose handling while reducing biomarkers associated with NAFLD. Twenty-nine age-matched women (CON = 15, PCOS = 14) completed oral glycemic tolerance tests following baseline (Day 0) as well as an acute (Day 1) and short-term whey supplementation (Day 7). Whey had an interaction effect on glucose (p = 0.02) and insulin (p = 0.03), with glucose remaining stable and insulin increasing with whey supplementation. Insulin sensitivity (p < 0.01) improved with whey associated with increased glucagon secretion (p < 0.01). Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) remained unchanged, but “day” had an effect on the AST:ALT ratio (p = 0.04), whereas triglycerides and sex hormone binding globulin overall were greater in the PCOS group (p < 0.05). Total cholesterol decreased in PCOS (by 13%) and CON (by 8%) (NS). HepG2 cells treated with plasma from participants before and after whey decreased lipid accumulation in the PCOS group after whey (p < 0.05). Whey provided an insulinogenic and glycemic homeostatic effect in women with PCOS with the potential to combat NAFLD-consequences.     

Effect of Overeating Dietary Protein at Different Levels on Circulating Lipids and Liver Lipid: The PROOF Study

Background: During overeating, a low protein diet slowed the rate of weight gain and increased the energy cost of the added weight, suggesting that low protein diets reduced energy efficiency. The Protein Overfeeding (PROOF) study explored the metabolic changes to low and high protein diets, and this sub-study examined the changes in body composition and blood lipids when eating high and low protein diets during overeating. Methods: Twenty-three healthy volunteers (M = 14; F = 9) participated in an 8-week, parallel arm study where they were overfed by ~40% with diets containing 5% (LPD = low protein diet), 15% (NPD = normal protein diet), or 25% (HPD = high protein diet) protein. Dual energy X-ray absorptiometry (DXA) and computer tomography (CT) were used to quantify whole body and abdominal fat and intrahepatic lipid, respectively. Metabolites were measured by standard methods. Results: Protein intake and fat intake were inversely related since carbohydrate intake was fixed. Although overeating the LPD diet was associated with a significant increase in high density lipoprotein (HDL)-cholesterol (p < 0.001) and free fatty acids (p = 0.034), and a significant decrease in fat free mass (p < 0.0001) and liver density (p = 0.038), statistical models showed that dietary protein was the main contributor to changes in fat free mass (p = 0.0040), whereas dietary fat was the major predictor of changes in HDL-cholesterol (p = 0.014), free fatty acids (p = 0.0016), and liver fat (p = 0.0007). Conclusions: During 8 weeks of overeating, the level of dietary protein intake was positively related to the change in fat free mass, but not to the change in HDL-cholesterol, free fatty acids, and liver fat which were, in contrast, related to the intake of dietary fat.     

Independent Dose–Response Associations between Fetuin-A and Lean Nonalcoholic Fatty Liver Disease

Patients with lean NAFLD make up an increasing subset of liver disease patients. The association between lean NAFLD and feutin-A, which serves as a hepatokine and adipokine, has never been examined. Our study aimed to explore the association of serum fetuin-A among lean and non-lean patients. The study comprised 606 adults from the community, stratified into lean or non-lean (BMI </≥ 24 kg/m²) and NAFLD or non-NAFLD (scoring of ultrasonographic fatty liver indicator, US-FLI ≥ 2/< 2). Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD among the tertiles of fetuin-A after adjustment. The least square means were computed by general linear models to estimate marginal means of the serum fetuin-A concentrations in relation to the NAFLD groups. The odds ratio (OR) of having NAFLD for the highest versus the lowest tertile of fetuin-A was 2.62 (95% CI: 1.72–3.98; p for trend < 0.001). Stratifying by BMI, the OR of having lean NAFLD for the highest versus the lowest tertile of fetuin-A was 2.09 (95% CI: 1.09–3.98; p for trend 0.026), while non-lean NAFLD had no significant association with the fetuin-A gradient after adjustments. Fetuin-A was positively associated with lean NAFLD after adjusting for central obesity and insulin resistance.     

Lower Energy-Dense Ready Meal Consumption Affects Self-Reported Appetite Ratings with No Effect on Subsequent Food Intake in Women

Slimming World (SW), a commercial weight management organisation, has designed a range of low energy-dense ready meals (LEDRMs) in line with their programme. This randomised crossover study compared commercially available equicaloric ready meals differing in energy density on satiety and food intake. It was hypothesised that the LEDRM would reduce energy intake (EI) whilst increasing fullness and reducing hunger compared to higher energy-dense ready meal (HEDRM, control). A total of 26 female participants (aged 18–65 years; body mass index of 28.8 ± 3.0 kg·m⁻²) attended two test days. The participants ate a standard breakfast, and four hours later, ate either a LEDRM or HEDRM at lunch. EI was measured four hours later at an ad libitum tea. Satiety measurements were recorded throughout the day using visual analogue scales and a weighed food diary was completed for the remainder of the day. The results revealed that the LEDRM reduced hunger and increased fullness (both p < 0.001). There was no difference in EI at the evening meal between the ready meals (p > 0.05), however, during the whole LEDRM testing day, the participants consumed significantly less fat (7.1%) and saturated fat (3.6%) (both p < 0.01), but significantly more carbohydrates, sugars, fibre, protein, and salt (all p < 0.01). The results indicate that the participants felt more satiated after consuming ready meals of the same energy content but larger portion size. Despite no significant difference in short-term EI between the ready meals, the results indicated that the LEDRM produced beneficial subjective satiety responses and, therefore, can help to improve the nutritional content of meals i.e., reduce saturated fat consumption.     

The Combination of Berberine,Tocotrienols and Coffee Extracts Improves Metabolic Profile and Liver Steatosis by the Modulation of Gut Microbiota and Hepatic miR-122 and miR-34a Expression in Mice

Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight (p < 0.01), amelioration of insulin-sensitivity (p = 0.021), total cholesterol (p = 0.014), low-density-lipoprotein-cholesterol (p < 0.001), alanine-aminotransferase (p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.     

Gluten-Free Diet: Nutritional Strategies to Improve Eating Habits in Children with Celiac Disease: A Prospective,Single-arm Intervention Study

Background: Elimination of gluten-containing cereals and consumption of ultra-processed gluten-free foods might cause an unbalanced diet, deficient in fiber and rich in sugar and fat, circumstances that may predispose celiac children to chronic constipation. Aim: to evaluate if counseling with a registered dietitian (RD) was capable of improving eating and bowel habits in a celiac pediatric population. Methods: Dietetic, lipid profile and stool modifications were analyzed, comparing baseline assessments with those twelve months after receiving heathy eating and nutrition education sessions. At both time points, 3-day food records, a bowel habit record and a lipid panel were conducted. Calculated relative intake of macro- and micro-nutrients were compared with current recommendations by the European Food Safety Authority (EFSA). Student’s paired t-test, McNemar test, Mandasky test and Pearson correlation tests were used. Results: Seventy-two subjects (58.3% girls) with a mean (standard deviation (SD)) age of 10.2 (3.4) years were included. Baseline diets were imbalanced in macronutrient composition. Significant improvements were observed in their compliance with dietary reference values (DRVs), where 50% of the subjects met fat requirements after the education and 67% and 49% with those of carbohydrates and fiber, respectively (p < 0.001). Celiac children decreased red meat and ultra-processed foods consumption (p < 0.001) and increased fruits and vegetables intake (p < 0.001), leading to a reduction in saturated fat (p < 0.001) and sugar intake (p < 0.001). Furthermore, 92% of the patients achieved a normal bowel habit, including absence of hard stools in 80% of children constipated at baseline (p < 0.001). Conclusions: RD-led nutrition education is able to improve eating patterns in children with celiac disease (CD).     

The Influence of Reducing Diets on Changes in Thyroid Parameters in Women Suffering from Obesity and Hashimoto’s Disease

Hashimoto’s disease is listed among the most common endocrine causes of obesity. As treatment of obesity in women with Hashimoto’s disease is frequently unsuccessful, the aim of this study was to evaluate the effectiveness of two different reducing diets and their influence on changes in thyroid parameters in female patients. A six-month observational/interventional study was performed on 100 women aged 18–65 years, previously diagnosed with Hashimoto’s disease and obesity and receiving L-thyroxine. The women were randomly assigned to the test group (group A, n = 50) following elimination/reducing diets, and the control group (group B, n = 50) following reducing diets with the same caloric content (without elimination). Anthropometric and thyroid parameters were evaluated at the beginning, after 3 months and after 6 months of treatment. In both groups a significant decrease in BMI and body fat percentage was achieved, but in test group A the decrease in BMI and body fat percentage was significantly greater than in control group B (p < 0.002 and p = 0.026, respectively). Serum TSH (thyroid stimulating hormon) levels decreased significantly more in group A than in group B (p < 0.001). Group A exhibited significantly greater increases in fT4 and fT3 levels than the control group (p < 0.001) as well as significantly greater decreases in the levels anti-TPO (thyroid peroxidase) (p < 0.001) and anti-TG (thyreoglobulin) antibodies (p = 0.048). The application of reducing diets with product elimination was found to be a more beneficial tool for changing anthropometric and thyroid parameters in women suffering from obesity and Hashimoto’s disease than classic reducing diets with the same energy values and macronutrient content.     

Elective Surgery in Adult Patients with Excess Weight: Can Preoperative Dietary Interventions Improve Surgical Outcomes? A Systematic Review

This systematic review summarises the literature regarding the impact of preoperative dietary interventions on non-bariatric surgery outcomes for patients with excess weight/obesity, a known risk factor for poor surgical outcomes. Four electronic databases were searched for non-bariatric surgery studies that evaluated the surgical outcomes of a preoperative diet that focused on weight/fat loss or improvement of liver steatosis. Meta-analysis was unfeasible due to the extreme heterogeneity of variables. Fourteen studies, including five randomised controlled trials, were selected. Laparoscopic cholecystectomy, hernia repair, and liver resection were most studied. Diet-induced weight loss ranged from 1.4 kg to 25 kg. Preoperative very low calorie diet (≤800 kcal) or low calorie diet (≤900 kcal) for one to three weeks resulted in: reduction in blood loss for two liver resection and one gastrectomy study (−27 to −411 mL, p < 0.05), and for laparoscopic cholecystectomy, reduction of six minutes in operating time (p < 0.05) and reduced difficulty of aspects of procedure (p < 0.05). There was no difference in length of stay (n = 7 studies). Preoperative ≤ 900 kcal diets for one to three weeks could improve surgical outcomes for laparoscopic cholecystectomy, liver resection, and gastrectomy. Multiple randomised controlled trials with common surgical outcomes are required to establish impact on other surgeries.     

Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disorders ranging from simple steatosis (non-alcoholic fatty liver, NAFL) to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFL increases the risk of liver fibrosis. If the liver is fatty due to causes of insulin resistance such as obesity and physical inactivity, it overproduces glucose and triglycerides leading to hyperinsulinemia and a low high-density lipoprotein (HDL) cholesterol concentration. The latter features predispose to type 2 diabetes and cardiovascular disease (CVD). Understanding the impact of nutritional modulation of liver fat content and insulin resistance is therefore of interest for prevention and treatment of NAFLD. Hypocaloric, especially low carbohydrate ketogenic diets rapidly decrease liver fat content and associated metabolic abnormalities. However, any type of caloric restriction seems effective long-term. Isocaloric diets containing 16%–23% fat and 57%–65% carbohydrate lower liver fat compared to diets with 43%–55% fat and 27%–38% carbohydrate. Diets rich in saturated (SFA) as compared to monounsaturated (MUFA) or polyunsaturated (PUFA) fatty acids appear particularly harmful as they increase both liver fat and insulin resistance. Overfeeding either saturated fat or carbohydrate increases liver fat content. Vitamin E supplementation decreases liver fat content as well as fibrosis but has no effect on features of insulin resistance.     

Whole and Isolated Protein Fractions Differentially Affect Gastrointestinal Integrity Markers in C57Bl/6 Mice Fed Diets with a Moderate-Fat Content

Various proteins or protein fractions reportedly positively affect gastrointestinal integrity and inflammation in diets providing >45% energy as fat. This study tested whether benefits were seen in diets providing 30% of energy as fat. Purified diets (PD) with isolated soy protein (ISP), dried whole milk powder (DWMP), milk fat globule membrane (MFGM), or milk protein concentrate (MPC) as protein sources were fed to C57BL/6J mice (n = 15/diet group) for 13 weeks. MFGM-fed mice were heaviest (p < 0.005) but remained within breeder norms. Growth rates and gut motility were similar for all PD-fed mice. FITC-dextran assessed gut permeability was lowest in DWMP and MFGM (p = 0.054); overall, plasma endotoxin and unprovoked circulating cytokines indicated a non-inflammatory state for all PD-fed mice. Despite differences in cecal butyrate and intestinal gene expression, all PDs supported gastrointestinal health. Whole milk provided more positive effects compared to its fractions. However, ISP-fed mice showed a >370%, (p < 0.006) increase in colonic myeloperoxidase activity indicative of tissue neutrophil infiltration. Surprisingly, FITC-dextran and endotoxin outcomes were many folds better in PD-fed mice than mice (strain, vendor, age and sex matched) fed a “chow-type” nutritionally adequate non-PD. Additional variables within a diet’s matrix appear to affect routine indicators or gastrointestinal health.     

High Intakes of [6S]-5-Methyltetrahydrofolic Acid Compared with Folic Acid during Pregnancy Programs Central and Peripheral Mechanisms Favouring Increased Food Intake and Body Weight of Mature Female Offspring

Supplementation with [6S]-5-methyltetrahydrofolic acid (MTHF) is recommended as an alternative to folic acid (FA) in prenatal supplements. This study compared equimolar gestational FA and MTHF diets on energy regulation of female offspring. Wistar rats were fed an AIN-93G diet with recommended (2 mg/kg diet) or 5-fold (5X) intakes of MTHF or FA. At weaning, female offspring were fed a 45% fat diet until 19 weeks. The 5X-MTHF offspring had higher body weight (>15%), food intake (8%), light-cycle energy expenditure, and lower activity compared to 5X-FA offspring (p < 0.05). Both the 5X offspring had higher plasma levels of the anorectic hormone leptin at birth (60%) and at 19 weeks (40%), and lower liver weight and total liver lipids compared to the 1X offspring (p < 0.05). Hypothalamic mRNA expression of leptin receptor (ObRb) was lower, and of suppressor of cytokine signaling-3 (Socs3) was higher in the 5X-MTHF offspring (p < 0.05), suggesting central leptin dysregulation. In contrast, the 5X-FA offspring had higher expression of genes encoding for dopamine and GABA- neurotransmitter receptors (p < 0.01), consistent with their phenotype and reduced food intake. When fed folate diets at the requirement level, no differences were found due to form in the offspring. We conclude that MTHF compared to FA consumed at high levels in the gestational diets program central and peripheral mechanisms to favour increased weight gain in the offspring. These pre-clinical findings caution against high gestational intakes of folates of either form and encourage clinical trials examining their long-term health effects when consumed during pregnancy.     

Association Between Low Muscle Mass and Non-alcoholic Fatty Liver Disease Diagnosed Using Ultrasonography,Magnetic Resonance Imaging Derived Proton Density Fat Fraction,and Comprehensive NAFLD Score in Korea

ObjectivesNon-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent metabolic disease. Muscle is known to influence NAFLD development. Therefore, this study aimed to determine the relationships among low muscle mass, NAFLD, and hepatic fibrosis using various definitions of low muscle mass and NAFLD diagnostic methods, including magnetic resonance imaging-based proton density fat fraction (MRI-PDFF).MethodsThis cross-sectional study included 320 participants (107 males, 213 females) from the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population cohort. Muscle mass was assessed using whole-body dual-energy X-ray absorptiometry and adjusted for the height squared, body weight, and body mass index (BMI). NAFLD was diagnosed using ultrasonography (US), MRI-PDFF, and the comprehensive NAFLD score (CNS). Hepatic fibrosis was assessed using magnetic resonance elastography. Multivariable logistic and linear regression analyses were performed to determine the aforementioned associations.ResultsAccording to US, 183 participants (57.2%) had NAFLD. Muscle mass adjusted for body weight was associated with NAFLD diagnosed using US (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.70 to 5.31), MRI-PDFF (OR, 2.00; 95% CI, 1.13 to 3.53), and CNS (OR, 3.39; 95% CI, 1.73 to 6.65) and hepatic fibrosis (males: β=-0.070, p<0.01; females: β=-0.037, p<0.04). Muscle mass adjusted for BMI was associated with NAFLD diagnosed by US (OR, 1.71; 95% CI, 1.02 to 2.86) and CNS (OR, 1.95; 95% CI, 1.04 to 3.65), whereas muscle mass adjusted for height was not associated with NAFLD.ConclusionsLow muscle mass was associated with NAFLD and liver fibrosis; therefore, maintaining sufficient muscle mass is important to prevent NAFLD. A prospective study and additional consideration of muscle quality are needed to strengthen the findings regarding this association.     

Effects of a Short-Term “Fat Adaptation with Carbohydrate Restoration” Diet on Metabolic Responses and Exercise Performance in Well-Trained Runners

Periodized carbohydrate availability can enhance exercise capacity, but the effects of short-term fat adaptation carbohydrate restoration (FACR) diets on metabolic responses and exercise performance in endurance athletes have not been conclusively determined. This study aimed to investigate the effect of a FACR diet on measures of resting metabolism, exercise metabolism, and exercise performance. Well-trained male runners (n = 8) completed a FACR dietary intervention (five days’ carbohydrate < 20% and fat > 60% energy, plus one-day carbohydrate ≥ 70% energy), and a control high-carbohydrate (HCHO) diet for six days (carbohydrate > 60% energy; fat < 20% energy) in a randomized crossover design. Pre- and post-intervention metabolic measures included resting metabolic rate (RMR), respiratory quotient (RQ), maximum fat oxidation rate during exercise (MFO), and maximum fat oxidation intensity (FATmax). Measures of exercise performance included maximal oxygen uptake (VO₂max), running economy (RE), and 5 km running time trial (5 km-TT). In FACR compared with HCHO, there were significant improvements in FATmax (p = 0.006) and RE (p = 0.048). There were no significant differences (p > 0.05) between FACR and HCHO in RMR, RQ, VO₂max, or 5 km-TT. Findings suggest that a short-term (six days) FACR diet may facilitate increased fat oxidation and submaximal exercise economy but does not improve 5 km-TT performance.     

The Effect of Probiotics (MCP® BCMC® Strains) on Hepatic Steatosis,Small Intestinal Mucosal Immune Function,and Intestinal Barrier in Patients with Non-Alcoholic Fatty Liver Disease

Treatment for non-alcoholic fatty liver disease (NAFLD) currently consists of lifestyle modifications such as a low-fat diet, weight loss, and exercise. The gut microbiota forms part of the gut–liver axis and serves as a potential target for NAFLD treatment. We investigated the effect of probiotics on hepatic steatosis, fibrosis, and biochemical blood tests in patients with NAFLD. At the small intestinal mucosal level, we examined the effect of probiotics on the expression of CD4+ and CD8+ T lymphocytes, as well as the tight junction protein zona occluden-1 (ZO-1). This was a randomized, double-blind, placebo-controlled trial involving ultrasound-diagnosed NAFLD patients (n = 39) who were supplemented with either a probiotics sachet (MCP^® BCMC^® strains) or a placebo for a total of 6 months. Multi-strain probiotics (MCP^® BCMC^® strains) containing six different Lactobacillus and Bifidobacterium species at a concentration of 30 billion CFU were used. There were no significant changes at the end of the study in terms of hepatic steatosis (probiotics: −21.70 ± 42.6 dB/m, p = 0.052 vs. placebo: −10.72 ± 46.6 dB/m, p = 0.29) and fibrosis levels (probiotics: −0.25 ± 1.77 kPa, p = 0.55 vs. placebo: −0.62 ± 2.37 kPa, p = 0.23) as measured by transient elastography. Likewise, no significant changes were found for both groups for the following parameters: LiverFAST analysis (steatosis, fibrosis and inflammation scores), alanine aminotransferase, total cholesterol, triglycerides, and fasting glucose. In the immunohistochemistry (IHC) analysis, no significant expression changes were seen for CD4+ T lymphocytes in either group (probiotics: −0.33 ± 1.67, p = 0.35 vs. placebo: 0.35 ± 3.25, p = 0.63). However, significant reductions in the expression of CD8+ T lymphocytes (−7.0 ± 13.73, p = 0.04) and ZO-1 (Z-score = −2.86, p = 0.04) were found in the placebo group, but no significant changes in the probiotics group. In this pilot study, the use of probiotics did not result in any significant clinical improvement in NAFLD patients. However, at the microenvironment level (i.e., the small intestinal mucosa), probiotics seemed to be able to stabilize the mucosal immune function and to protect NAFLD patients against increased intestinal permeability. Therefore, probiotics might have a complementary role in treating NAFLD. Further studies with larger sample sizes, a longer duration, and different probiotic strains are needed to evaluate the real benefit of probiotics in NAFLD.