Dietary Intervention Period Research Articles

Effect of weight-maintaining ketogenic diet on glycemic control and insulin sensitivity in obese T2D subjects

IntroductionLow carbohydrate ketogenic diets have received renewed interest for the treatment of obesity and type 2 diabetes. These diets promote weight loss, improve glycemic control, and reduce insulin resistance. However,...

362 Nutrikinetic evaluation and modeling of 25-hydroxyvitamin D3 in beef cattle

Abstract The objective of this study was to evaluate serum 25-hydroxyvitamin D3 [25(OH)D3] status in beef cattle when 1) fed diets with supplemental 25(OH)D3 or calcidiol (HyD, dsm-firmenich, Plainsboro, NJ), and 2.) a single dose of calcidiol was administered to cannulated heifers on nutrikinetic evaluation and predictive modeling simulations. In experiment 1, crossbred heifer calves [n = 96, initial body weight (BW) = 222 ± 12.4 kg] were assembled from auction markets near Dickson, TN and transported ~1,069 km to Manhattan, KS. Heifers (n = 12 per pen) were stratified by BW and randomly allocated to a corn-based receiving diet with one of four dietary treatments: 1) No supplemental D3 or calcidiol (CON, n = 24), 2) 3,000 IU supplemental D3·heifer⁻¹·d⁻¹ (D3, n = 24), 3.) 0.5 mg calcidiol/h/d (Hy D Low, n = 24), or 4.) 1.0 mg calcidiol·heifer⁻¹·d⁻¹ (Hy D High, n = 24) for 60 d. Blood samples were collected from each heifer prior to transport (d -1), on arrival (d 0) and on d 14, 31, and 60 of dietary treatment period. Data were analyzed using the GLIMMIX procedure of SAS using animal as experimental unit and treatment as fixed effect. HyD High calves had greater (P < 0.001) serum 25(OH)D3 concentrations than HyD Low at d 14 and 31 (Figure 1 and 2). At d 14, 31 and 60, HyD High and HyD Low calves had greater (P < 0.001) serum 25(OH)D3 concentrations than CON or D3 treatments. In experiment 2, cannulated crossbred heifers (n = 8, initial BW = 289 ± 44.9 kg were randomly assigned to one of two treatments: 1.) 3 mg/272 kg BW calcidiol, or 2.) 5 mg/272 kg BW calcidiol in a single dose administered via rumen cannula at h 0. Serial blood samples were collected at baseline out to 70 d post-dose. Serum 25(OH)D3 concentrations were analyzed via HPLC coupled with tandem MS (dsm-firmenich, Belvidere, NJ). Predictive modeling simulations of serum 25(OH)D3 concentrations used non-parametric superposition (Certara Phoenix WinNonlin 64, St. Louis, MO) from applying non-compartmental analysis with the assumptions of linearity, independent calcidiol dose response, and the rate of absorption and the average systemic clearance were consistent for each calcidiol dosing interval. The elimination half-life (t1/2) of calcidiol was determined to be an average of 7.1 d and area under change in concentration-time curve time 0 to the last time point that measured above baseline concentration post dose (AUC0-last) averaged of 32.6 d (Table 1). Non-parametric dosing simulations using nutrikinetic parameters from experiment 2 suggest that administration of two 5 mg oral doses of calcidiol with daily feeding of 1 mg would result in a rapid and sustained increase in serum 25(OH)D3. However, simulations should be confirmed in vivo before implementation.

Western diet consumption impairs memory function via dysregulated hippocampus acetylcholine signaling

Western diet (WD) consumption during early life developmental periods is associated with impaired memory function, particularly for hippocampus (HPC)-dependent processes. We developed an early life WD rodent model associated with long-lasting HPC dysfunction to investigate the neurobiological mechanisms mediating these effects. Rats received either a cafeteria-style WD (ad libitum access to various high-fat/high-sugar foods; CAF) or standard healthy chow (CTL) during the juvenile and adolescent stages (postnatal days 26–56). Behavioral and metabolic assessments were performed both before and after a healthy diet intervention period beginning at early adulthood. Results revealed HPC-dependent contextual episodic memory impairments in CAF rats that persisted despite the healthy diet intervention. Given that dysregulated HPC acetylcholine (ACh) signaling is associated with memory impairments in humans and animal models, we examined protein markers of ACh tone in the dorsal HPC (HPCd) in CAF and CTL rats. Results revealed significantly lower protein levels of vesicular ACh transporter in the HPCd of CAF vs. CTL rats, indicating chronically reduced ACh tone. Using intensity-based ACh sensing fluorescent reporter (iAChSnFr) in vivo fiber photometry targeting the HPCd, we next revealed that ACh release during object-contextual novelty recognition was highly predictive of memory performance and was disrupted in CAF vs. CTL rats. Neuropharmacological results showed that alpha 7 nicotinic ACh receptor agonist infusion in the HPCd during training rescued memory deficits in CAF rats. Overall, these findings reveal a functional connection linking early life WD intake with long-lasting dysregulation of HPC ACh signaling, thereby identifying an underlying mechanism for WD-associated memory impairments.

Circulating MicroRNA-19 and cardiovascular risk reduction in response to weight-loss diets

MicroRNA-19 (miR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). We examined whether change in circulating miR-19 was associated with change in CVD risk during weight loss. This study included 509 participants with overweight or obesity from the 24-month weight-loss diet intervention study (the POUNDS Lost trial) and with available data on circulating miR-19a-3p and miR-19b-3p at baseline and 6 months. The primary outcome for this analysis was the change in atherosclerotic CVD (ASCVD) risk at 6 and 24 months, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the changes in ASCVD risk score components. Circulating miR-19a-3p and miR-19b-3p levels significantly decreased during the initial 6-month dietary intervention period (P=0.008, 0.0004, respectively). We found that a greater decrease in miR-19a-3p or miR-19b-3p was related to a greater reduction in ASCVD risk (β[SE]=0.33 [0.13], P=0.01 for miR-19a-3p; β[SE]=0.3 [0.12], P=0.017 for miR-19b-3p) over 6 months, independent of concurrent weight loss. Moreover, we found significant interactions between change in miR-19 and sleep disturbance on change in ASCVD risk over 24 months of intervention (P interaction=0.01 and 0.008 for miR-19a-3p and miR-19b-3p, respectively). Participants with a greater decrease in miR-19 without sleep disturbance had a greater reduction of ASCVD risk than those with slight/moderate/great amounts of sleep disturbance. In addition, change in physical activity significantly modified the associations between change in miR-19 and change in ASCVD risk over 24 months (P interaction=0.006 and 0.004 for miR-19a-3p and miR-19b-3p, respectively). A greater decrease in miR-19 was significantly associated with a greater reduction in ASCVD risk among participants with an increase in physical activity, while non-significant inverse associations were observed among those without an increase in physical activity. In conclusion, decreased circulating miR-19 levels during dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and these associations were more evident in people with no sleep disturbance or increase in physical activity. ClinicalTrials.gov NCT00072995.

A four-week dietary intervention with mycoprotein-containing food products reduces serum cholesterol concentrations in community-dwelling, overweight adults: A randomised controlled trial

BackgroundSubstituting dietary meat and fish for mycoprotein, a fungal-derived food source rich in protein and fibre, decreases circulating cholesterol concentrations in laboratory-controlled studies. However, whether these findings can be translated to a home-based setting, and to decrease cholesterol concentrations in overweight and hypercholesterolemic individuals, remains to be established. ObjectiveWe investigated whether a remotely-delivered, home-based dietary intervention of mycoprotein-containing food products would affect various circulating cholesterol moieties and other markers of cardio-metabolic health in overweight (BMI >27.5 kg·m-2) and hypercholesterolaemic (>5.0 mmol·L-1) adults. MethodsSeventy-two participants were randomized into a controlled, parallel-group trial conducted in a free-living setting, in which they received home deliveries of either meat/fish control products (CON; n=39; BMI 33±1 kg·m-2; 13 males, 26 females) or mycoprotein-containing food products (MYC; n=33; BMI 32±1 kg·m-2; 13 males, 20 females) for 4 weeks. Fingertip blood samples were collected and sent via postal service before and after the dietary intervention period and analysed for concentrations of serum lipids, blood glucose and c-peptide. ResultsSerum total cholesterol concentrations were unchanged throughout the intervention in CON, but decreased by 5±2% in MYC (from 5.4±0.2 to 5.1±0.2 mmol·L-1; P<0.05). Serum low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol concentrations were also unchanged in CON, but decreased in MYC by 10±3% and 6±2% (both by 0.3±0.1 mmol·L-1; P<0.05). Serum high-density lipoprotein cholesterol and free triglyceride concentrations were unaffected in CON or MYC. Post-intervention, MYC displayed lower mean blood glucose (3.7±0.2 versus 4.3±0.2 mmol·L-1) and c-peptide (779±76 vs. 1064±86 pmol·L-1) concentrations (P<0.05) vs. CON. ConclusionsWe show that a home-based dietary intervention of mycoprotein-containing food products effectively lowers circulating cholesterol concentrations in overweight, hypercholesterolemic adults. This demonstrates that mycoprotein consumption is a feasible and ecologically valid dietary strategy to improve markers of cardio-metabolic health in an at-risk population under free living conditions. Clinical trial registrationNCT04773483 (https://classic.clinicaltrials.gov/ct2/show/NCT04773483)

Early- but not late-adolescent Western diet consumption programs for long-lasting memory impairments in male but not female rats

Early life Western diet (WD) consumption leads to impaired memory function, particularly for processes mediated by the hippocampus. However, the precise critical developmental window(s) during which WD exposure negatively impacts hippocampal function are unknown. Here, we exposed male and female rats to a WD model involving free access to a variety of high-fat and/or high-sugar food and drink items during either the early-adolescent period (postnatal days [PN] 26–41; WD-EA) or late-adolescent period (PN 41–56; WD-LA). Control (CTL) rats were given healthy standard chow throughout both periods. To evaluate long-lasting memory capacity well beyond the early life WD exposure periods, we performed behavioral assessments after both a short (4 weeks for WD-EA, 2 weeks for WD-LA) and long (12 weeks for WD-EA, 10 weeks for WD-LA) period of healthy diet intervention. Results revealed no differences in body weight or body composition between diet groups, regardless of sex. Following the shorter period of healthy diet intervention, both male and female WD-EA and WD-LA rats showed deficits in hippocampal-dependent memory compared to CTL rats. Following the longer healthy diet intervention period, memory impairments persisted in male WD-EA but not WD-LA rats. In contrast, in female rats the longer healthy diet intervention reversed the initial memory impairments in both WD-EA and WD-LA rats. Collectively, these findings reveal that early-adolescence is a critical period of long-lasting hippocampal vulnerability to dietary insults in male but not female rats, thus highlighting developmental- and sex-specific effects mediating the relationship between the early life nutritional environment and long-term cognitive health.

The Impact of a Short-Term Ketogenic Low-Carbohydrate High-Fat Diet on Biomarkers of Intestinal Epithelial Integrity and Gastrointestinal Symptoms.

Endurance exercise can disturb intestinal epithelial integrity, leading to increased systemic indicators of cell injury, hyperpermeability, and pathogenic translocation. However, the interaction between exercise, diet, and gastrointestinal disturbance still warrants exploration. This study examined whether a 6-day dietary intervention influenced perturbations to intestinal epithelial disruption in response to a 25-km race walk. Twenty-eight male race walkers adhered to a high carbohydrate (CHO)/energy diet (65% CHO, energy availability = 40kcal·kg FFM-1·day-1) for 6 days prior to a Baseline 25-km race walk. Athletes were then split into three subgroups: high CHO/energy diet (n = 10); low-CHO, high-fat diet (LCHF: n = 8; <50g/day CHO, energy availability = 40kcal·kg FFM-1·day-1); and low energy availability (n = 10; 65% CHO, energy availability = 15kcal·kg FFM-1·day-1) for a further 6-day dietary intervention period prior to a second 25-km race walk (Adaptation). During both trials, venous blood was collected pre-, post-, and 1hr postexercise and analyzed for markers of intestinal epithelial disruption. Intestinal fatty acid-binding protein concentration was significantly higher (twofold increase) in response to exercise during Adaptation compared to Baseline in the LCHF group (p = .001). Similar findings were observed for soluble CD14 (p < .001) and lipopolysaccharide-binding protein (p = .003), where postexercise concentrations were higher (53% and 36%, respectively) during Adaptation than Baseline in LCHF. No differences in high CHO/energy diet or low energy availability were apparent for any blood markers assessed (p > .05). A short-term LCHF diet increased intestinal epithelial cell injury in response to a 25-km race walk. No effect of low energy availability on gastrointestinal injury or symptoms was observed.

Efficacy of convenience meal-type foods designed for diabetes in the management of metabolic syndrome based on a 3-week trial

ObjectivesThis study aimed to assess the effect of meal-type food for diabetes on improving metabolic syndrome risk factors in adults. MethodsThe participants were adult men and women aged 40–55 y with 1 or more risk factors for metabolic syndrome. They were provided with a diabetic diet (a meal-type food) and general diet in the form of home meal replacement for 3 wk. The current research used a crossover design. All participants had iso-caloric meal replacement per day, and there was a 2-wk washout period between each diet. The nutritional standards of a diabetic diet were based on the guidelines of the Ministry of Food and Drug Safety, which are: <50% carbohydrates, <10% sugars, <7% saturated fat, and >10 g dietary fiber. The average caloric content was 489.1 ± 45.0 kcal. The composition of the general diet was similar to that of the diabetic diet; however, there were differences in sugar content. In total, 15 participants were included in the research, and there was no significant difference between the 2 groups in terms of nutrient intake during the intervention period. ResultsBody weight (P = 0.001), body mass index (P = 0.004), waist circumference (P = 0.030), triacylglycerol (P = 0.002), total cholesterol (P = 0.001), and low-density lipoprotein cholesterol (P = 0.008) levels were significantly lower in the diabetic diet intervention period than before and after 3 wk of the intervention. In addition, reduction in body weight (P = 0.001), body mass index (P = 0.006), waist circumference (P = 0.032), and triacylglycerol (P = 0.036) and total cholesterol (P = 0.007) levels in the diabetic diet intervention period significantly differed compared with those in the general diet intervention period. ConclusionsReplacing 1 meal per day with meal-type food for diabetes improved body composition and blood lipid levels in adults with metabolic syndrome risk factors.

Associations of circulating proteins with lipoprotein profiles: proteomic analyses from the OmniHeart randomized trial and the Atherosclerosis Risk in Communities (ARIC) Study

BackgroundWithin healthy dietary patterns, manipulation of the proportion of macronutrient can reduce CVD risk. However, the biological pathways underlying healthy diet-disease associations are poorly understood. Using an untargeted, large-scale proteomic profiling, we aimed to (1) identify proteins mediating the association between healthy dietary patterns varying in the proportion of macronutrient and lipoproteins, and (2) validate the associations between diet-related proteins and lipoproteins in the Atherosclerosis Risk in Communities (ARIC) Study.MethodsIn 140 adults from the OmniHeart trial, a randomized, cross-over, controlled feeding study with 3 intervention periods (carbohydrate-rich; protein-rich; unsaturated fat-rich dietary patterns), 4,958 proteins were quantified at the end of each diet intervention period using an aptamer assay (SomaLogic). We assessed differences in log2-transformed proteins in 3 between-diet comparisons using paired t-tests, examined the associations between diet-related proteins and lipoproteins using linear regression, and identified proteins mediating these associations using a causal mediation analysis. Levels of diet-related proteins and lipoprotein associations were validated in the ARIC study (n = 11,201) using multivariable linear regression models, adjusting for important confounders.ResultsThree between-diet comparisons identified 497 significantly different proteins (protein-rich vs. carbohydrate-rich = 18; unsaturated fat-rich vs. carbohydrate-rich = 335; protein-rich vs. unsaturated fat-rich dietary patterns = 398). Of these, 9 proteins [apolipoprotein M, afamin, collagen alpha-3(VI) chain, chitinase-3-like protein 1, inhibin beta A chain, palmitoleoyl-protein carboxylesterase NOTUM, cathelicidin antimicrobial peptide, guanylate-binding protein 2, COP9 signalosome complex subunit 7b] were positively associated with lipoproteins [high-density lipoprotein (HDL)-cholesterol (C) = 2; triglyceride = 5; non-HDL-C = 3; total cholesterol to HDL-C ratio = 1]. Another protein, sodium-coupled monocarboxylate transporter 1, was inversely associated with HDL-C and positively associated with total cholesterol to HDL-C ratio. The proportion of the association between diet and lipoproteins mediated by these 10 proteins ranged from 21 to 98%. All of the associations between diet-related proteins and lipoproteins were significant in the ARIC study, except for afamin.ConclusionsWe identified proteins that mediate the association between healthy dietary patterns varying in macronutrients and lipoproteins in a randomized feeding study and an observational study.Trial registrationNCT00051350 at clinicaltrials.gov.

Dietary metabolome profiles of a Healthy Australian Diet and a Typical Australian Diet: protocol for a randomised cross-over feeding study in Australian adults

IntroductionTraditional dietary assessment methods such as 24-hour recalls and food frequency questionnaires rely on self-reported data and are prone to error, bias and inaccuracy. Identification of dietary metabolites associated with...

Effects of a wholegrain-rich diet on markers of colonic fermentation and bowel function and their associations with the gut microbiome: a randomised controlled cross-over trial.

Diets rich in whole grains are associated with health benefits. Yet, it remains unclear whether the benefits are mediated by changes in gut function and fermentation. We explored the effects of whole-grain vs. refined-grain diets on markers of colonic fermentation and bowel function, as well as their associations with the gut microbiome. Fifty overweight individuals with increased metabolic risk and a high habitual intake of whole grains (~69 g/day) completed a randomised cross-over trial with two 8-week dietary intervention periods comprising a whole-grain diet (≥75 g/day) and a refined-grain diet (<10 g/day), separated by a washout period of ≥6 weeks. A range of markers of colonic fermentation and bowel function were assessed before and after each intervention. The whole-grain diet increased the levels of faecal butyrate (p = 0.015) and caproate (p = 0.013) compared to the refined-grain diet. No changes in other faecal SCFA, BCFA or urinary levels of microbial-derived proteolytic markers between the two interventions were observed. Similarly, faecal pH remained unchanged. Faecal pH did however increase (p = 0.030) after the refined-grain diet compared to the baseline. Stool frequency was lower at the end of the refined-grain period compared to the end of the whole-grain diet (p = 0.001). No difference in faecal water content was observed between the intervention periods, however, faecal water content increased following the whole-grain period compared to the baseline (p = 0.007). Dry stool energy density was unaffected by the dietary interventions. Nevertheless, it explained 4.7% of the gut microbiome variation at the end of the refined-grain diet, while faecal pH and colonic transit time explained 4.3 and 5%, respectively. Several butyrate-producers (e.g., Faecalibacterium, Roseburia, Butyriciococcus) were inversely associated with colonic transit time and/or faecal pH, while the mucin-degraders Akkermansia and Ruminococcaceae showed the opposite association. Compared with the refined-grain diet, the whole-grain diet increased faecal butyrate and caproate concentrations as well as stool frequency, emphasising that differences between whole and refined grains affect both colonic fermentation and bowel habits.

Abstract P338: Circulating microRNA-19 and Cardiovascular Risk Reduction in Response to Weight-Loss Diets: The Preventing Overweight Using Novel Dietary Strategies (Pounds Lost) Trial

Introduction: MicroRNA-19 (MiR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). Hypothesis: We assessed the hypothesis that change in circulating miR-19 would be associated with changes in 10-year atherosclerotic CVD (ASCVD) risk and individual cardiovascular risk factors in a dietary weight-loss intervention. Methods: This study included 509 participants with overweight or obesity from the 2-year weight-loss diet intervention study (the POUNDS LOST trial) and with available data on circulating miR-19a/b-3p at baseline and 6 months. The primary outcome was the 6-month change in the ASCVD risk score, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the change in each ASCVD component including blood pressure, lipid profiles, insulin resistance, glucose metabolism, and adiposity measures. Change in habitual physical activity and sleep disturbance were assessed from baseline to 6 months. Results: Circulating miR-19a/b-3p levels significantly decreased during the initial 6-month dietary intervention period (P=0.008, 0.0004, respectively). We found that greater decreases in log-transformed miR-19a/b-3p were related to a greater reduction in ASCVD risk (β[SE]=0.35 [0.13], P=0.01 for miR-19a-3p; β[SE]=0.33 [0.13], P=0.01 for miR-19b-3p) over 6 months. Similar positive associations were observed for changes in diastolic blood pressure with miR-19a/b-3p. Moreover, we found that sleep disturbance was significantly associated with reductions in miR-19a/b-3p from baseline to 6 months (P trend &lt;0.05). There were significant interactions between changes in miR-19a/b-3p and sleep disturbance for changes in ASCVD risk (P interaction&lt;0.005). Participants with greater decreases in miR-19a/b-3p with no/slight amount of sleep disturbance had a greater reduction of ASCVD risk from baseline to 6 months than those with moderate/great amount of sleep disturbance. In addition, changes in physical activity modified the associations between changes in miR-19a-3p and ASCVD risk. A greater decrease in miR-19a-3p was significantly associated with a greater reduction in ASCVD among participants with an increase in physical activity from baseline to 6 months. These positive associations were reversed and not significant among participants with no change/decrease in physical activity and moderate/great amount of sleep disturbance. Conclusions: In conclusion, decreased circulating miR-19 levels induced by dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and such associations were more evident in people with no/slight amount of sleep disturbance and an increase in physical activity.

Infant nutrition affects the microbiota-gut-brain axis: Comparison of human milk vs. infant formula feeding in the piglet model.

Early nutrition plays a dominant role in infant development and health. It is now understood that the infant diet impacts the gut microbiota and its relationship with gut function and brain development. However, its impact on the microbiota-gut-brain axis has not been studied in an integrative way. The objective here was to evaluate the effects of human milk (HM) or cow’s milk based infant formula (IF) on the relationships between gut microbiota and the collective host intestinal-brain axis. Eighteen 10-day-old Yucatan mini-piglets were fed with HM or IF. Intestinal and fecal microbiota composition, intestinal phenotypic parameters, and the expression of genes involved in several gut and brain functions were determined. Unidimensional analyses were performed, followed by multifactorial analyses to evaluate the relationships among all the variables across the microbiota-gut-brain axis. Compared to IF, HM decreased the α-diversity of colonic and fecal microbiota and modified their composition. Piglets fed HM had a significantly higher ileal and colonic paracellular permeability assessed by ex vivo analysis, a lower expression of genes encoding tight junction proteins, and a higher expression of genes encoding pro-inflammatory and anti-inflammatory immune activity. In addition, the expression of genes involved in endocrine function, tryptophan metabolism and nutrient transport was modified mostly in the colon. These diet-induced intestinal modifications were associated with changes in the brain tissue expression of genes encoding the blood-brain barrier, endocrine function and short chain fatty acid receptors, mostly in hypothalamic and striatal areas. The integrative approach underlined specific groups of bacteria (Veillonellaceae, Enterobacteriaceae, Lachnospiraceae, Rikenellaceae, and Prevotellaceae) associated with changes in the gut-brain axis. There is a clear influence of the infant diet, even over a short dietary intervention period, on establishment of the microbiota-gut-brain axis.

Oxidative stress and inflammatory response to high dietary fat and carbonated soda intake in male and female Wistar rats

ObjectiveAn increasing population in many countries consume diets high in fat and refined sugars (often in carbonated soda). Although high-fat diets have been extensively studied, less attention has been paid to carbonated soda. The aim of this study was to investigate the combined effects of a high-fat diet and soda consumption on oxidative stress and inflammation in Wistar rats. MethodsThirty-two male and female Wistar rats were equally divided into four dietary groups as follows: control, soda only, high fat (HFD), and high fat and carbonated soda (HFD/soda) and were placed on the dietary treatment for 14 wk, after acclimatization. At the end of the dietary treatment period, anthropometrics, lipid profile, lipid peroxidation, antioxidant activity, and inflammatory markers were assessed. ResultsAnthropometric variables and lipid peroxidation were increased in animals fed the high fat and soda diet. There was a decrease in antioxidant levels. ConclusionThe results from this study demonstrated that a HFD in combination with soda increased the effects of oxidative stress and inflammation in Wistar rats.

Calorie restriction and calorie dilution have different impacts on body fat, metabolism, behavior, and hypothalamic gene expression.

Caloric restriction is a robust intervention to increase lifespan. Giving less food (calorie restriction [CR]) or allowing free access to a diluted diet with indigestible components (calorie dilution [CD]) are two methods to impose restriction. CD does not generate the same lifespan effect as CR. We compare responses of C57BL/6 mice with equivalent levels of CR and CD. The two groups have different responses in fat loss, circulating hormones, and metabolic rate. CR mice are hungrier, as assessed by behavioral assays. Although gene expression of Npy, Agrp, and Pomc do not differ between CR and CD groups, CR mice had a distinctive hypothalamic gene-expression profile with many genes related to starvation upregulated relative to CD. While both result in lower calorie intake, CR and CD are not equivalent procedures. Increased hunger under CR supports the hypothesis that hunger signaling is a key process mediating the benefits of CR.

Increased Consumption of Unsaturated Fatty Acids Improves Body Composition in a Hypercholesterolemic Chinese Population.

While an increase in fat intake and the resulting excess calorie intake are implicated in weight gain, different fat types exert variable effects on body composition, with unsaturated fats showing favorable effects on body composition in Western population. Whether and to what extent these associations apply to Asian population have not been established. We investigated the effects of two separate Asian-based oil blends, rich in unsaturated fats, made from refined rice bran, sesame, and flaxseed oils, in comparison with refined olive oil, on body composition using dual-energy X-ray absorptiometry (DXA), from an 8-week, parallel design, randomized trial in 66 men (58.7 ± 5.71 years old, 23.0 ± 2.38 kg/m2) and 69 postmenopausal women (59.1 ± 5.34 years old, 21.7 ± 2.52 kg/m2), with borderline hypercholesterolemia. Despite increases in mean daily intakes of total energy (approximately +400 kcal/day, female, and approximately +240 kcal/day, male), as well as increases in percentage of calories from fats and proteins and decreases in percentage of calories from carbohydrates during the dietary intervention period, there were no significant changes in total body fat mass in both genders and also in all treatment groups. While total body weight increased slightly (0.36 ± 0.12 kg, p = 0.005) in women during intervention, this was mainly due to gain in lean mass (0.38 ± 0.081 kg, p < 0.0001). Correspondingly, there were reductions in total body fat (%), android fat (%), and gynoid fat (%) in women. No significant differences between the 3 intervention oil types were found in any of the measured parameters in either gender. Increasing relative intakes of unsaturated fats may prevent fat mass gain and circumvent muscle mass loss associated with menopause in older Asian women. Long-term studies are needed to confirm findings. This study had been registered on clinicaltrials.gov (Identifier No.: NCT03964857, https://www.clinicaltrials.gov/ct2/show/NCT03964857).

Can Ketogenic Diet Therapy Improve Migraine Frequency, Severity and Duration?

Migraine is the third most common condition worldwide and is responsible for a major clinical and economic burden. The current pilot trial investigated whether ketogenic diet therapy (KDT) is superior to an evidence-informed healthy “anti-headache” dietary pattern (AHD) in improving migraine frequency, severity and duration. A 12-week randomised controlled crossover trial consisting of the two dietary intervention periods was undertaken. Eligible participants were those with a history of migraines and who had regularly experienced episodes of moderate or mildly intense headache in the previous 4 weeks. Migraine frequency, duration and severity were assessed via self-report in the Migraine Buddy© app. Participants were asked to measure urinary ketones and side effects throughout the KDT. Twenty-six participants were enrolled, and 16 participants completed all sessions. Eleven participants completed a symptom checklist; all reported side-effects during KDT, with the most frequently reported side effect being fatigue (n = 11). All completers experienced migraine during AHD, with 14/16 experiencing migraine during KDT. Differences in migraine frequency, severity or duration between dietary intervention groups were not statistically significant. However, a clinically important trend toward lower migraine duration on KDT was noted. Further research in this area is warranted, with strategies to lower participant burden and promote adherence and retention.

Changes in physical activity during a one-year weight loss trial with liraglutide in participants with knee osteoarthritis: secondary analyses of a randomised trial

Changes in physical activity during a one-year weight loss trial with liraglutide in participants with knee osteoarthritis: secondary analyses of a randomised trial

Understanding the effects of nutrition and post-exercise nutrition on skeletal muscle protein turnover: Insights from stable isotope studies

Understanding the effects of nutrition and post-exercise nutrition on skeletal muscle protein turnover: Insights from stable isotope studies

Liraglutide after diet-induced weight loss for pain and weight control in knee osteoarthritis: a randomized controlled trial

Weight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA). To determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA. The trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2).Patients underwent a pre-random assignment diet intervention (week -8 to 0). At week 0, patients having lost >5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52. In total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre-random assignment dietary intervention period (week -8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: -2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: -6.9, -1.0; P=0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and -0.6 points, respectively; group difference, 0.9 points; 95% CI: -3.9, 5.7; P=0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively. In patients with KOA and overweight/obesity liraglutide added after an 8-wk pre-random assignment diet induced a significant weight loss at >52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.