There is well-established evidence for low-carbohydrate, high-fat (LCHF) diets in the management of chronic health conditions in adults. The natural next step is to understand the potential risks and benefits of LCHF diets for children, where they may have useful applications for general health and a variety of chronic health conditions. It is vital that any diet delivers sufficient micronutrients and energy to ensure health, wellbeing, and growth. This descriptive study assesses the nutrient and energy status of LCHF sample meal plans for children. We designed four meal plans for hypothetical weight-stable male and female children (11 years) and adolescents (16 years). Carbohydrates were limited to ≤80 g, protein was set at 15-25% of the total energy, and fat supplied the remaining calories. Using FoodWorks dietary analysis software, data were assessed against the national Australian/New Zealand nutrient reference value (NRV) thresholds for children and adolescents. All meal plans exceeded the minimum NRV thresholds for all micronutrients; protein slightly exceeded the AMDR recommendations by up to three percentage points. This study demonstrates that LCHF meal plans can be energy-, protein-, and micronutrient-replete for children and adolescents. As with any dietary approach, well-formulated meals and careful planning are key to achieving the optimal nutrient status.

Gut microbes are considered as major factors contributing to human health. Nowadays, the vast majority of the data available in the literature are mostly exhibiting negative or positive correlations between specific bacteria and metabolic parameters. From these observations, putative detrimental or beneficial effects are then inferred. Akkermansia muciniphila is one of the unique examples for which the correlations with health benefits have been causally validated in vivo in rodents and humans. In this study, based on available metagenomic data in overweight/obese population and clinical variables that we obtained from two cohorts of individuals (n = 108) we identified several metagenomic species (MGS) strongly associated with A. muciniphila with one standing out: Subdoligranulum. By analyzing both qPCR and shotgun metagenomic data, we discovered that the abundance of Subdoligranulum was correlated positively with microbial richness and HDL-cholesterol levels and negatively correlated with fat mass, adipocyte diameter, insulin resistance, levels of leptin, insulin, CRP, and IL6 in humans. Therefore, to further explore whether these strong correlations could be translated into causation, we investigated the effects of the unique cultivated strain of Subdoligranulum (Subdoligranulum variabile DSM 15176 T) in obese and diabetic mice as a proof-of-concept. Strikingly, there were no significant difference in any of the hallmarks of obesity and diabetes measured (e.g., body weight gain, fat mass gain, glucose tolerance, liver weight, plasma lipids) at the end of the 8 weeks of treatment. Therefore, the absence of effect following the supplementation with S. variabile indicates that increasing the intestinal abundance of this bacterium is not translated into beneficial effects in mice. In conclusion, we demonstrated that despite the fact that numerous strong correlations exist between a given bacteria and health, proof-of-concept experiments are required to be further validated or not in vivo. Hence, an urgent need for causality studies is warranted to move from human observations to preclinical validations.

Food-drug interaction is an infrequently considered aspect in clinical practice. Usually, drugs are taken together with meals and what follows may adversely affect pharmacokinetic and pharmacodynamic properties, and hence, the therapeutic effects. In this study, a computational protocol was proposed to explain the different assimilations of two µ-receptors agonists, eluxadoline and loperamide, with a peculiar pharmacokinetic profile. Compared to loperamide, eluxadoline is absorbed less after the intake of a fatty meal, and the LogP values do not explain this event. Firstly, keeping in mind the different pH in the intestinal tract, the protonation states of both compounds were calculated. Then, all structures were subjected to a conformational search by using MonteCarlo and Molecular Dynamics methods, with solvation terms mimicking the water and weak polar solvent (octanol). Both computational results showed that eluxadoline has less conformational freedom in octanol, unlike loperamide, which exhibits constant behavior in both solvents. Therefore, we hypothesize that fatty meal causes the \"closure\" of the eluxadoline molecule to prevent the exposure of the polar groups and their interaction with water, necessary for the drug absorption. Based on our results, this work could be a reasonable \"case study\", useful for future investigation of the drug pharmacokinetic profile.

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Coronary heart disease (CHD) is a chronic complex disease caused by a combination of factors such as lifestyle behaviors and environmental and genetic factors. We conducted this study to evaluate the risk factors affecting the development of CHD in Xinjiang, and to obtain valuable information for formulating appropriate local public health policies.
We conducted a nested case-control study with 277 confirmed CHD cases and 554 matched controls. The association of the risk factors with the risk of CHD was assessed using the multivariate Cox proportional hazard model. Multiplicative interactions were evaluated by entering interaction terms in the Cox proportional hazard model. The additive interactions among the risk factors were assessed by the index of additive interaction.
The risk of CHD increased with frequent high-fat food consumption, dyslipidemia, obesity, and family history of CHD after adjustment for drinking, smoking status, hypertension, diabetes, family history of hypertension, and family history of diabetes. We noted consistent interactions between family history of CHD and frequent high-fat food consumption, family history of CHD and obesity, frequent high-fat food consumption and obesity, frequent high-fat food consumption and dyslipidemia, and obesity and dyslipidemia. The risk of CHD events increased with the presence of the aforementioned interactions.
Frequent high-fat food consumption, family history of CHD, dyslipidemia and obesity were independent risk factors for CHD, and their interactions are important for public health interventions in patients with CHD in Xinjiang.

We have previously found that infants with complex congenital heart disease (CHD) experience growth failure despite high-energy dietary supplementation. This is a follow-up and comparison with healthy controls at 9 years of age regarding body composition and macronutrient intake, especially in relationship to the diet provided during infancy.
Anthropometric changes in 10 children with CHD at 12 months and at 4 and 9 years of age were analysed as Z-scores. To assess body composition and food intake at 9 years of age, a dual-energy X-ray absorptiometry scan and a 3-day food diary were completed and compared with age- and gender-matched controls using Wilcoxon\'s signed-rank test for matched pairs.
Growth changes from 12 months to 9 years, converted to Z-scores for weight for height and height for age, were significantly different within the group of children with complex CHD, although no growth differences were seen in comparison with healthy controls at 9 years of age. However, the children with CHD had statistically higher abdominal fat mass index and higher daily intake of fat, particularly from saturated fatty acid in g kg-1 compared to controls.
At 9 years of age, children with complex CHD with growth failure and high fat intake in infancy have normalised growth but increased abdominal fat mass and higher intake of saturated fatty acid compared to their peers. Nutritional monitoring in early childhood may detect unhealthy diet quality and prevent later health risks in this group.

Anacetrapib is an inhibitor of cholesteryl ester transfer protein (CETP) previously under development as a lipid-modifying agent that reduces LDL-cholesterol and increases HDL-cholesterol in hypercholesterolemic patients. Anacetrapib demonstrates a long terminal half-life and accumulates in adipose tissue, which contributes to a long residence time of anacetrapib. Given our previous report that anacetrapib distributes into the lipid droplet of adipose tissue, we sought to understand whether anacetrapib affected adipose function, using a diet-induced obese (DIO) mouse model. Following 20 weeks of treatment with anacetrapib (100 mg/kg/day), levels of the drug increased to approximately 0.6 mmol/L in white adipose tissue. This level of anacetrapib was not associated with any impairment in adipose functionality as evidenced by a lack of any reduction in biomarkers of adipose functionality (plasma adiponectin, leptin, insulin; adipose adiponectin, leptin mRNA). In DIO wild-type (WT) mice treated with anacetrapib for 2 weeks and then subjected to 30% food restriction during washout to induce weight loss (18%) and fat mass loss (7%), levels of anacetrapib in adipose and plasma were not different between food restricted and ad lib-fed mice. These data indicate that despite deposition and long-term residence of ~0.6 mmol/L levels of anacetrapib in adipose tissue, adipose tissue function appears to be unaffected in mice. In addition, these data also indicate that even with severe caloric restriction and acute loss of fat mass, anacetrapib does not appear to be mobilized from the fat depot, thereby solidifying the role of adipose as a long-term storage site of anacetrapib.

The aim of this case study was to report on the performance outcomes and subjective assessments of long-term low-carbohydrate, high-fat (LCHF) diet in a world-class long-distance triathlete who had been suffering from gastrointestinal distress in Ironman competition. The lacto-ovo vegetarian athlete (age = 39 years; height = 179 cm; usual racing body mass = 75 kg; sum of seven skinfolds = 36 mm) changed his usual high carbohydrate (CHO) availability diet to an LCHF diet for 32 weeks (∼95% compliance). He participated in three professional races while on the LCHF diet, but acutely restored CHO availability by consuming CHO in the preevent meals and during the race as advised. The athlete had his worst-ever half-Ironman performance after 21 weeks on the LCHF diet (18th). After 24 weeks on LCHF, he had his second worst-ever Ironman performance (14th) and suffered his usual gastrointestinal symptoms. He did not finish his third race after 32 weeks on LCHF. He regained his usual performance level within 5 weeks back on a high CHO diet, finishing second and fourth in two Ironman events separated by just 3 weeks. Subjective psychological well-being was very negative while on the LCHF diet, with feelings of depression, irritability, and bad mood. In conclusion, this long-term (32 weeks) LCHF intervention did not solve the gastrointestinal problems that the athlete had been experiencing, it was associated with negative performance outcomes in both the half-Ironman and Ironman competitions, and it had a negative impact on the athlete\'s subjective well-being.

The low-carbohydrate, high-fat (LCHF) diet is becoming increasingly employed in clinical dietetic practice as a means to manage many health-related conditions. Yet, it continues to remain contentious in nutrition circles due to a belief that the diet is devoid of nutrients and concern around its saturated fat content. This work aimed to assess the micronutrient intake of the LCHF diet under two conditions of saturated fat thresholds.
In this descriptive study, two LCHF meal plans were designed for two hypothetical cases representing the average Australian male and female weight-stable adult. National documented heights, a body mass index of 22.5 to establish weight and a 1.6 activity factor were used to estimate total energy intake using the Schofield equation. Carbohydrate was limited to <130 g, protein was set at 15%-25% of total energy and fat supplied the remaining calories. One version of the diet aligned with the national saturated fat guideline threshold of <10% of total energy and the other included saturated fat ad libitum.
The primary outcomes included all micronutrients, which were assessed using FoodWorks dietary analysis software against national Australian/New Zealand nutrient reference value (NRV) thresholds.
All of the meal plans exceeded the minimum NRV thresholds, apart from iron in the female meal plans, which achieved 86%-98% of the threshold. Saturated fat intake was logistically unable to be reduced below the 10% threshold for the male plan but exceeded the threshold by 2 g (0.6%).
Despite macronutrient proportions not aligning with current national dietary guidelines, a well-planned LCHF meal plan can be considered micronutrient replete. This is an important finding for health professionals, consumers and critics of LCHF nutrition, as it dispels the myth that these diets are suboptimal in their micronutrient supply. As with any diet, for optimal nutrient achievement, meals need to be well formulated.

Detailed protocols and recommendations for the assessment of energy balance have been provided to address the problems associated with different body mass and body composition as apparent for mouse models in obesity research. Here, we applied these guidelines to investigate energy balance in two inbred mouse strains with contrasting susceptibilities for diet-induced obesity (DIO). Mice of the AKR/J strain are highly susceptible, whereas the SWR/J mice are almost completely resistant. The proximate mechanisms responsible for this striking phenotypic difference are only partially understood.
Body mass and body composition, metabolizable energy, energy expenditure (EE), body temperature and spontaneous physical activity behavior were first assessed in a cohort of male AKR/J (N=29) and SWR/J (N=30) mice fed on a low-fat control diet (CD) to identify metabolic adaptations determining resistance to DIO. Thereafter, the immediate metabolic responses to high-fat diet (HFD) feeding for 3 days were investigated. Groups of weight-matched AKR/J (N=8) and SWR/J (N=8) mice were selected from the initial cohort for this intervention.
Strain differences in body mass, fat mass and lean mass were adjusted by body mass as this was the only covariate significantly correlated with metabolizable energy and EE. On the CD, EE and fat oxidation was higher in SWR/J than in AKR/J mice, whereas no difference was found for metabolizable energy. In response to HFD feeding, both strains increased metabolizable energy intake, but also increased EE, body temperature, and fat oxidation. The catabolic adaptations to HFD feeding opposed the development of positive energy balance. Increased EE was not due to increased spontaneous physical activity. A significant strain difference was found when balancing metabolizable energy and daily energy expenditure (DEE).
The guidelines were applicable with some limitations related to the adjustment of differences in body composition. Metabolic phenotyping revealed that metabolizable energy, DEE and metabolic fuel selection all contribute to the development of DIO. Therefore, assessing both sides of the energy balance equation is essential to identify the proximate mechanisms.