High-carbohydrate Low-fat Diet Research Articles

The Effect of a Low-Carbohydrate High-Fat Diet on Laboratory Parameters in Women with Lipedema in Comparison to Overweight/Obese Women.

The aim of this study was to evaluate alterations in blood parameters after a low-carbohydrate high-fat (LCHF) diet in women with lipedema in comparison to overweight or obese women. A total of 115 women were classified into two groups: the lipedema group and the overweight/obesity group. Both study groups followed the caloric-restricted LCHF diet for 7 months. A total of 48 women completed the study. A reduction in body weight was observed in both study groups. A significant decrease in triglycerides and an increase in HDL-C concentrations were observed in both study groups. Despite the increase in the concentration of LDL-C observed in the lipedema group, changes in LDL-C differed between individual patients. Improvements in liver parameters, glucose tolerance, and a decrease in fasting insulin levels were observed, although they were less pronounced in the lipedema group than in the overweight/obesity group. Kidney and thyroid functions were similar before and after the LCHF diet in both groups. The LCHF diet may be a valuable nutritional strategy for lipedema and overweight/obese women, with a beneficial effect on weight, glucose profile, liver function, the concentration of triglycerides, and HDL-C and with no effect on kidney and thyroid function.

Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials

BackgroundSystematic reviews and meta-analyses of randomized clinical trials (RCTs) have reported the benefits of ketogenic diets (KD) in various participants such as patients with epilepsy and adults with overweight or obesity. Nevertheless, there has been little synthesis of the strength and quality of this evidence in aggregate.MethodsTo grade the evidence from published meta-analyses of RCTs that assessed the association of KD, ketogenic low-carbohydrate high-fat diet (K-LCHF), and very low-calorie KD (VLCKD) with health outcomes, PubMed, EMBASE, Epistemonikos, and Cochrane database of systematic reviews were searched up to February 15, 2023. Meta-analyses of RCTs of KD were included. Meta-analyses were re-performed using a random-effects model. The quality of evidence per association provided in meta-analyses was rated by the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) criteria as high, moderate, low, and very low.ResultsWe included 17 meta-analyses comprising 68 RCTs (median [interquartile range, IQR] sample size of 42 [20–104] participants and follow-up period of 13 [8–36] weeks) and 115 unique associations. There were 51 statistically significant associations (44%) of which four associations were supported by high-quality evidence (reduced triglyceride (n = 2), seizure frequency (n = 1) and increased low-density lipoprotein cholesterol (LDL-C) (n = 1)) and four associations supported by moderate-quality evidence (decrease in body weight, respiratory exchange ratio (RER), hemoglobin A1c, and increased total cholesterol). The remaining associations were supported by very low (26 associations) to low (17 associations) quality evidence. In overweight or obese adults, VLCKD was significantly associated with improvement in anthropometric and cardiometabolic outcomes without worsening muscle mass, LDL-C, and total cholesterol. K-LCHF was associated with reduced body weight and body fat percentage, but also reduced muscle mass in healthy participants.ConclusionsThis umbrella review found beneficial associations of KD supported by moderate to high-quality evidence on seizure and several cardiometabolic parameters. However, KD was associated with a clinically meaningful increase in LDL-C. Clinical trials with long-term follow-up are warranted to investigate whether the short-term effects of KD will translate to beneficial effects on clinical outcomes such as cardiovascular events and mortality.

Context-Dependent Effects of the Ketogenic Diet on Retinal Ganglion Cell Survival and Axonal Regeneration After Optic Nerve Injury.

Purpose: There is increasing interest in nonpharmacologic approaches to protect retinal ganglion cells (RGCs) after injury and enhance the efficacy of therapeutic molecules. Accumulating evidence demonstrates neuroprotection by the high-fat low-carbohydrate ketogenic diet (KD) in humans and animal models of neurologic diseases. However, no studies to date have examined whether the KD protects RGCs and promotes axonal regrowth after traumatic injury to the optic nerve (ON) or whether it increases efficacy of experimental proregenerative molecules. In this study, we investigated whether the KD promoted RGC survival and axonal regeneration after ON injury in the presence and absence of neuroprotective Wnt3a ligand. Methods: Adult mice were placed on a KD or control diet before ON crush injury and remained on the diet until the end of the experiment. Nutritional ketosis was confirmed by measuring serum beta-hydroxybutyrate levels. Mice were intravitreally injected with Wnt3a ligand or phosphate-buffered saline (PBS), and RGC survival, function, axonal regeneration, and inflammatory responses were measured. Results: Mice fed the KD showed increased RGC survival and reduced inflammatory cells in PBS-injected mice. Also, mice fed the KD had increased RGC functional responses but not increased RGC numbers in the presence of Wnt3a, indicating that the KD did not enhance the prosurvival effect of Wnt3a. The KD did not promote axonal regeneration in the presence or absence of Wnt3a. Conclusions: The KD has a complex protective effect after ON injury and cotreatment with Wnt3a. This work sets the foundation for studies identifying underlying molecular mechanisms.

LIVER METABOLIC EFFECTS OF A HIGH-FAT LOW- CARBOHYDRATE DIET IN RATS: A STUDY UNDER DIFFERENT ENERGY CONDITIONS

The beneficial effects of high-fat, low-carbohydrate (HFLC) diets on glucose metabolismhave been questioned and its effects on liver metabolism are not totally clear. This workaimed to evaluate the HFLC diet effects under different energy conditions on glucosehomeostasis, fatty liver development and hepatic gluconeogenesis using the isolated perfusedrat liver. HFLC diet (79% fat, 19% protein, and 2% carbohydrates in Kcal%) wasadministered to rats over four weeks under three conditions: hypercaloric; isocaloric andhypocaloric (energy reduction of 20%). Fasting blood glucose levels and total fat in the liverwere higher in all HFLC diet rats. Oral glucose tolerance was impaired in isocaloric andhypercaloric groups, although insulin sensitivity wasn´t altered. HFLC diet also causedmarked liver metabolic alterations: higher gluconeogenesis rate from lactate and a reducedcapacity to catabolize alanine, the latter effect more intense in the hypocaloric condition. Weconcluded that, even when HFLC diets are used for weight loss, our data imply that they canpotentially cause harmful consequences for the liver.

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2023 American College of Cardiology Conference.

To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2023 American College of Cardiology (ACC) conference. The CLEAR outcomes randomized control trial (RCT) compared bempedoic acid to placebo in patients at high-risk of cardiovascular disease (CVD) or prevalent CVD and statin intolerance for CV outcomes. The YELLOW III was a single-arm study that evaluated the effect of Evolocumab on coronary plaque characteristics in patients with stable coronary artery disease (CAD). A cohort evaluated the association between a self-reported low-carbohydrate high-fat (ketogenic) diet and serum lipid levels as compared to a standard diet. The LOADSTAR trial compared CV outcomes with targeted low-density lipoprotein cholesterol (LDL-C) approach vs. high-intensity statin in patients with CAD. The PCDS statin cluster randomized trial compared the effectiveness of an electronic reminder to the clinician on a high-intensity statin use among patients with a history of ASCVD as compared to no reminder. A prospective cohort study compared the extent of coronary atherosclerosis among lifelong endurance athletes and healthy non-athletes. A causal artificial intelligence study combined polygenic risk scores with data from large CV prevention RCTs to guide systolic blood pressure and LDL-C reduction targets to reach average CV risk. The ACCESS trial evaluated the impact of eliminating copayment for low-income older adults in Canada with chronic CV diseases on composite CV outcomes. A pooled analysis of 3 large RCTs evaluated the association between residual inflammatory risk and CV outcomes, as compared to residual elevated cholesterol risk in patients receiving statin therapy. A Phase 2B RCT compared the efficacy of an oral PCSK9i, MK-0616, in reducing LDL-C as compared to a placebo. The late-breaking clinical science presented at the 2023 conference of the ACC paves the way for an evidence-based alternative to statin therapy and provides data on several common clinical scenarios encountered in daily practice.

Habitual low carbohydrate high fat diet compared with omnivorous, vegan, and vegetarian diets.

Dietary patterns which exclude whole food groups, such as vegetarian, vegan and low carbohydrate high fat diet (LCHF), are increasingly popular in general public. When carefully planned, all these diets have some known benefits for health, but concerns are also raised in particular for LCHF. The quality of LCHF diet which individuals follow in real life without supervision is not known. One hundred thirty healthy individuals with stable body mass following LCHF, vegan, vegetarian and omnivorous diet for at least six months, were compared in a cross-sectional study. Diet was analyzed through 3-day food records and FFQ, anthropometric measurements were performed and serum metabolic biomarkers determined from fasting blood. Participants on LCHF diet had the intakes of micronutrients comparable to other groups, while the intakes of macronutrients differed in line with the definition of each diet. The intakes of saturated fats, cholesterol and animal proteins were significantly higher and the intakes of sugars and dietary fibers were lower compared to other groups. Healthy eating index 2015 in this group was the lowest. There were no differences in the levels of glucose, triacylglycerols and CRP among groups. Total and LDL cholesterol levels were significantly higher in LCHF group, in particular in participants with higher ketogenic ratio. Fatty acids intakes and intakes of cholesterol, dietary fibers and animal proteins explained 40% of variance in total cholesterol level, with saturated fatty acids being the strongest positive predictor and monounsaturated fatty acids a negative predictor. None of the self-advised diets provided all the necessary nutrients in optimal levels. Due to the detected increased levels of serum cholesterols, selection of healthy fat sources, higher intake of dietary fibers and partial replacing of animal sources with plant sources of foods should be recommended to the individuals selecting LCFH dietary pattern.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04347213.

Abstract 1162: Ketogenic diet promotes tumor ferroptosis but induces relative corticosterone deficiency that accelerates cachexia

Abstract The dependency of cancer cells on glucose can be targeted with high-fat low-carbohydrate ketogenic diet (KD). However, hepatic ketogenesis is suppressed in IL-6 producing cancers, which prevents the utilization of this nutrient source as energy for the organism. In two IL-6 associated murine models of cancer cachexia we describe delayed tumor growth but accelerated onset of cancer cachexia and shortened survival when mice are fed KD. Mechanistically, we find this uncoupling is a consequence of the biochemical interaction of two simultaneously occurring NADPH-dependent pathways. Within the tumor, increased production of lipid peroxidation products (LPPs) and, consequently, saturation of the glutathione (GSH) system leads to ferroptotic death of cancer cells. Systemically, redox imbalance and NADPH depletion impairs the biosynthesis of corticosterone, the main regulator of metabolic stress, in the adrenal glands. Administration of dexamethasone, a potent glucocorticoid, improves food intake, normalizes glucose homeostasis and utilization of nutritional substrates, delays onset of cancer cachexia and extends survival of tumor-bearing mice fed KD, while preserving reduced tumor growth. Our study highlights that the outcome of systemic interventions cannot necessarily be extrapolated from the effect on the tumor alone, but that they have to be investigated for anti-cancer and host effects. These findings may be relevant to clinical research efforts that investigate nutritional interventions such as KD in patients with cancer. Citation Format: Miriam Ferrer, Nicholas Mourikis, Emma E. Davidson, Sam O. Kleeman, Marta Zaccaria, Jill Habel, Rachel Rubino, Thomas R. Flint, Claire M. Connell, Michael J. Lukey, Eileen P. White, Anthony P. Coll, Ashok R. Venkitaraman, Tobias Janowitz. Ketogenic diet promotes tumor ferroptosis but induces relative corticosterone deficiency that accelerates cachexia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1162.

Effective suppression of myocardial glucose uptake using predesigned low-carbohydrate boxed meals

BackgroundDietary preparation protocols are an effective means to suppress physiological myocardial 18F-fluorodeoxyglucose (FDG) uptake. This study aimed to investigate the efficacy of various carbohydrate-restricted diets using predesigned boxed meals. MethodsThe patients were divided into four groups to undergo different preparatory protocols as follows: a minimum 15-hour fast alone, two meals of high-fat, low-carbohydrate diet (HFLCD), two meals of high-animal-protein, low-carbohydrate diet (HAPLCD), and two meals of high-plant-based-protein, low-carbohydrate diet (HPPLCD). Boxed meals were prepared to meet the required carbohydrate restrictions. Myocardial SUVmax and SUVmean were measured and the suppression rate was analyzed. ResultsThe average myocardial SUVmax of fast alone, HFLCD, HAPLCD, and HPPLCD were 8.26 ± 5.85, 2.21 ± 1.50, 2.34 ± 1.88, and 4.10 ± 3.61, respectively, and the suppression rates were 36.6%, 93.3%, 93.3%, and 70%, respectively. The effectiveness of HFLCD, HAPLCD, and HPPLCD was all statistically superior to that of a 15-hour fast alone. SUVmax of HFLCD and HAPLCD showed no significant differences (p = 1), whereas HFLCD and HPPLCD had significant differences (p = .046). ConclusionsUsing the predesigned boxed meals based on carbohydrate restriction, HFLCD, HAPLCD, and HPPLCD can be administered to patients with different dietary needs while providing a substantial reduction in physiological myocardial FDG uptake.

Low carbohydrate high fat ketogenic diets on the exercise crossover point and glucose homeostasis.

In exercise science, the crossover effect denotes that fat oxidation is the primary fuel at rest and during low-intensity exercise with a shift towards an increased reliance on carbohydrate oxidation at moderate to high exercise intensities. This model makes four predictions: First, >50% of energy comes from carbohydrate oxidation at ≥60% of maximum oxygen consumption (VO2max), termed the crossover point. Second, each individual has a maximum fat oxidation capacity (FATMAX) at an exercise intensity lower than the crossover point. FATMAX values are typically 0.3-0.6g/min. Third, fat oxidation is minimized during exercise ≥85%VO2max, making carbohydrates the predominant energetic substrate during high-intensity exercise, especially at >85%VO2max. Fourth, high-carbohydrate low-fat (HCLF) diets will produce superior exercise performances via maximizing pre-exercise storage of this predominant exercise substrate. In a series of recent publications evaluating the metabolic and performance effects of low-carbohydrate high-fat (LCHF/ketogenic) diet adaptations during exercise of different intensities, we provide findings that challenge this model and these four predictions. First, we show that adaptation to the LCHF diet shifts the crossover point to a higher %VO2max (>80%VO2max) than previously reported. Second, substantially higher FATMAX values (>1.5g/min) can be measured in athletes adapted to the LCHF diet. Third, endurance athletes exercising at >85%VO2max, whilst performing 6 × 800m running intervals, measured the highest rates of fat oxidation yet reported in humans. Peak fat oxidation rates measured at 86.4 ± 6.2%VO2max were 1.58 ± 0.33g/min with 30% of subjects achieving >1.85g/min. These studies challenge the prevailing doctrine that carbohydrates are the predominant oxidized fuel during high-intensity exercise. We recently found that 30% of middle-aged competitive athletes presented with pre-diabetic glycemic values while on an HCLF diet, which was reversed on LCHF. We speculate that these rapid changes between diet, insulin, glucose homeostasis, and fat oxidation might be linked by diet-induced changes in mitochondrial function and insulin action. Together, we demonstrate evidence that challenges the current crossover concept and demonstrate evidence that a LCHF diet may also reverse features of pre-diabetes and future metabolic disease risk, demonstrating the impact of dietary choice has extended beyond physical performance even in athletic populations.

Low carbohydrate high fat-diet in real life assessed by diet history interviews

BackgroundLow carbohydrate high fat (LCHF) diet has been a popular low carbohydrate diet in Sweden for 15 years. Many people choose LCHF to lose weight or control diabetes, but there are concerns about the effect on long-term cardiovascular risks. There is little data on how a LCHF diet is composed in real-life. The aim of this study was to evaluate the dietary intake in a population with self-reported adherence to a LCHF diet.MethodsA cross-sectional study of 100 volunteers that considered themselves eating LCHF was conducted. Diet history interviews (DHIs) and physical activity monitoring for validation of the DHIs were performed.ResultsThe validation shows acceptable agreement of measured energy expenditure and reported energy intake. Median carbohydrate intake was 8.7 E% and 63% reported carbohydrate intake at potentially ketogenic levels. Median protein intake was 16.9 E%. The main source of energy was dietary fats (72.0 E%). Intake of saturated fat was 32 E% and cholesterol was 700 mg per day, both of which exceeded the recommended upper limits according to nutritional guidelines. Intake of dietary fiber was very low in our population. The use of dietary supplements was high, and it was more common to exceed the recommended upper limits of micronutrients than to have an intake below the lower limits.ConclusionsOur study indicates that in a well-motivated population, a diet with very low carbohydrate intake can be sustained over time and without apparent risk of deficiencies. High intake of saturated fats and cholesterol as well as low intake of dietary fiber remains a concern.

Hepatic oleate regulates one-carbon metabolism during high carbohydrate feeding

Obesity is a major risk factor for type 2 diabetes, coronary heart disease, and strok. These diseases are associated with profound alterations in gene expression in metabolic tissues. Epigenetic-mediated regulation of gene expression is one mechanism through which environmental factors, such as diet, modify gene expression and disease predisposition. However, epigenetic control of gene expression in obesity and insulin resistance is not fully characterized. We discovered that liver-specific stearoyl-CoA desaturase-1 (Scd1) knockout mice (LKO) fed a high-carbohydrate low-fat diet exhibit dramatic changes in hepatic gene expression and metabolites of the folate cycle and one-carbon metabolism respectively for the synthesis of S-adenosylmethionine (SAM). LKO mice show an increased ratio of S-adenosylmethionine to S-adenosylhomocysteine, a marker for increased cellular methylation capacity. Furthermore, expression of DNA and histone methyltransferase genes is up-regulated while the mRNA and protein levels of the non-DNA methyltransferases including phosphatidylethanolamine methyltransferase (PEMT), Betaine homocysteine methyltransferase (Bhmt), and the SAM-utilizing enzymes such as glycine-N-methyltransferase (Gnmt) and guanidinoacetate methyltransferase (Gamt) are generally down-regulated. Feeding LKO mice a high carbohydrate diet supplemented with triolein, but not tristearin, and increased endogenous hepatic synthesis of oleate but not palmitoleate in Scd1 global knockout mice normalized one carbon gene expression and metabolite levels. Additionally, changes in one carbon gene expression are independent of the PGC-1α-mediated ER stress response previously reported in the LKO mice. Together, these results highlight the important role of oleate in maintaining one-carbon cycle homeostasis and point to observed changes in one-carbon metabolism as a novel mediator of the Scd1 deficiency-induced liver phenotype.

Macronutrient composition and its effect on body composition changes during weight loss therapy in patients with non-alcoholic fatty liver disease: Secondary analysis of a randomized controlled trial

ObjectivesDietary composition may affect body composition during weight loss therapy. We tested the hypothesis of whether dietary macronutrient composition influences the reduction of total abdominal adipose tissue, subcutaneous adipose tissue (SAT), or visceral adipose tissue (VAT) during weight loss. MethodsDietary macronutrient composition and body composition were analyzed as a secondary outcome of a randomized controlled trial of 62 participants with non-alcoholic fatty liver disease. Patients were randomly assigned to a calorie-restricted intermittent fasting (5:2), calorie-restricted low-carbohydrate high-fat (LCHF), or healthy lifestyle advice (standard-of-care) diet in a 12-wk intervention phase. Dietary intake was assessed by self-reported 3-d food diaries and by characterization of total plasma fatty acid profile. Percentage of energy intake (E%) from different macronutrients was calculated. Body composition was assessed by magnetic resonance imaging and anthropometric measurements. ResultsThe macronutrient composition differed significantly between the 5:2 (fat 36 E% and carbohydrates 43 E%) and the LCHF (fat 69 E% and carbohydrates 9 E%) groups (P < 0.001). Weight loss was similar in the 5:2 and LCHF groups (–7.2 [SD = 3.4] kg versus 8.0 [SD = 4.8] kg; P = 0.44) and significantly larger than for standard of care (–2.5 kg [SD = 2.3]; P < 0.001). The volume of total abdominal fat, adjusted for height, decreased on average by 4.7% (standard of care), 14.3% (5:2), and 17.7% (LCHF), with no significant differences between the 5:2 and LHCF groups (P = 0.32). VAT and SAT, adjusted for height, decreased on average by 17.1% and 12.7% for 5:2, respectively, and by 21.2% and 17.9% for LCHF, with no significant group differences (VAT [P = 0.16] and SAT [P = 0.10]). VAT was mobilized to a greater extent than SAT in all diets. ConclusionsThe 5:2 and LCHF diets had similar effects on changes in intraabdominal fat mass and anthropometrics during weight loss. This might indicate that overall weight loss is more important than diet composition to achieve changes in total abdominal adipose tissue, VAT, or SAT. The results of the present study suggest that there is a need for further studies on the effect of diet composition on body composition changes during weight loss therapy.

Effect of aerobic exercise and low-carbohydrate high-fat diet on glucose tolerance and android/gynoid fat in overweight/obese women: A randomized controlled trial.

The study was designed to compare the effects of weight loss induced by a low-carbohydrate-high-fat diet or a normal diet, with and without exercise, on glucose tolerance measured as area under the curve (AUC), and android (A) and gynoid (G) fat distribution. The study was registered at clinicaltrials.gov; NCT04100356. In total, 57 women classified as overweight or obese (age 40 ± 3.5years, body mass index 31.1 ± 2.6kg/m2) were randomly assigned and completed a 10-week intervention using a low-carbohydrate high-fat diet or a normal diet, with or without aerobic interval exercise. An equal deficit of 700kcal/day was prescribed, either restricting the diet only, or moderately restricting diet and including three 50-min high-intensity bicycle sessions per week. There were thus four groups: normal diet (NORM); low-carbohydrate-high-fat diet (LCHF); normal diet with exercise (NORM-EX); and low-carbohydrate-high-fat diet with exercise (LCHF-EX). Linear mixed models was used to assess differences between groups. With all groups pooled, the intervention resulted in a weight loss of 6.7 ± 2.5% (p < 0.001). The intervention did not result in differences between groups in AUC glucose, nor in fasting glucose or indicis for insulin resistance such as Homeostatic Model Assessment, Matsuda Insulin Sensitivity Index, insulinogenic index and disposition index. Post-intervention android fat was lower in LCHF than NORM (3,223 ± 727 vs. 2,533 ± 535g, p = 0.041). LCHF reached a lower A/G ratio than NORM (0.94 ± 0.12 vs. 1.04 ± 0.09, p = 0.011) and LCHF-EX (0.94 ± 0.12 vs. 1.09 ± 0.09, p < 0.001) after the intervention. LCHF resulted in lower android fat mass compared to NORM and the lowest A/G ratio compared to the other matched groups, but with no accompanying improvement in AUC glucose. In conclusion, although all groups achieved improvements in glucose tolerance, no superior effect was observed with the LCHF diet, neither with nor without exercise.

Diets Differently Regulate Tumorigenesis in Young E0771 Syngeneic Breast Cancer Mouse Model.

Breast cancer (BC) is the most diagnosed cancer type, accounting for one in eight cancer diagnoses worldwide. Epidemiological studies have shown that obesity is associated with increased risk of BC in post-menopausal women, whereas adiposity reduces the risk of BC in premenopausal women. The mechanistic link between obesity and BC has been examined by combining murine BC models with high-fat diet (HFD) induced obesity. However, the effect of adiposity (not obesity) induced by a short period of HFD consumption on BC pathogenesis is not well understood. In the current study, we examined the effects of different diet compositions on BC pathogenesis using a young E0771 syngeneic BC mouse model fed on either an HFD or regular diet (RD: a low-fat high-carbohydrate diet) for a short period (4 weeks) before implanting mammary tumors in mice. We analyzed the effect of diet composition on the onset of tumor growth, metastasis, and metabolic and immune status in the tumor microenvironment (TME) using various methods including in vivo bioluminescence imaging and immunoblotting analyses. We showed for the first time that a short-term HFD delays the onset of tumorigenesis by altering the immune and metabolic signaling and energy mechanism in the TME. However, RD may increase the risk of tumorigenesis and metastasis by increasing pro-inflammatory factors in the TME in young mice. Our data suggest that diet composition, adipogenesis, and loss of body fat likely regulate the pathogenesis of BC in a manner that differs between young and post-menopausal subjects.

The role of low-carbohydrate diets in the intensive care unit.

Low-carbohydrate, high-fat (LCHF) nutrition therapy is characterized by carbohydrates comprising <26% of the daily caloric intake and a higher proportion of fat. LCHF therapies reduce exogenous glucose load, improve glycemic control, decrease inflammation, and improve clinical outcomes such as respiratory function. Given the altered metabolism in critically ill patients, LCHF nutrition therapy may be especially beneficial as it enables the conservation of protein and glucose for metabolic roles beyond energy use. In critical illness, LCHF diets have the potential to reduce hyperglycemia, improve ventilation, decrease hospital length of stay and reduce hospital costs. The purpose of this commentary piece is to describe LCHF nutrition therapy, summarize its impact on health outcomes, and discuss its role in the intensive care unit (ICU). Additional research on the effects of LCHF nutrition therapy on critically ill patients is warranted, including a focus on COVID-19.

High fat diet improves metabolic flexibility during progressive exercise to exhaustion (VO2max testing) and during 5 km running time trials.

Recently we reported similar performances in both progressive tests to exhaustion (VO2max) and 5km running time trials (5KTT) after consuming low-carbohydrate, high-fat (LCHF) or high-carbohydrate, low-fat (HCLF) diets. Accordingly, we tested the null hypothesis that the metabolic responses during both tests would be similar across diets. In a randomized, counterbalanced, cross-over design, seven male athletes (VO2max: 61.9 ± 6.1 mL/kg/min; age: 35.6 ± 8.4 years; height: 178.7 ± 4.1 cm; mass: 68.6 ± 1.6 kg; body fat: 5.0 ± 1.3%) completed six weeks of LCHF (6/69/25% energy carbohydrate/fat/protein) and HCLF (57/28/15% energy carbohydrate/fat/protein) diets, separated by a two-week washout. Substrate utilization and energy expenditure were measured during VO2max tests and 5KTTs. The LCHF diet markedly increased fat oxidation and reduced carbohydrate oxidation, with no associated impairment in either the VO2max tests or the 5KTTs. Following the LCHF diet, athletes generated 50% or more of their energy requirements from fat at exercise intensities up to 90% VO2max and reached the crossover point for substrate utilization at ~85% VO2max. In contrast, following the HCLF diet, carbohydrate provided more than 50% of the total energy consumption at all exercise intensities. During the 5KTT, ~56% of energy was derived from fat following the LCHF diet whereas more than 93% of the energy came from carbohydrate following the HCLF diet. This study provides evidence of greater metabolic flexibility following LCHF eating and challenges the popular doctrines of "carbohydrate dependence" for high intensity exercise and the role dietary macronutrients play in human performance.

The effect of a low carbohydrate high fat diet on lipid and lipoprotein metabolism: insight from a RCT

The effect of a low carbohydrate high fat diet on lipid and lipoprotein metabolism: insight from a RCT

Relationship between Ketones, Ghrelin, and, Appetite on Isocaloric Diets with Varying Carbohydrate Quality and Amount: Results from a Randomized Controlled Trial in People with Obesity (CARBFUNC)

BackgroundLow-carbohydrate high-fat (LCHF) diets may suppress the increase in appetite otherwise seen after diet-induced fat loss. However, studies of diets without severe energy restriction are lacking, and the effects of carbohydrate quality relative to quantity have not been directly compared. ObjectivesTo evaluated short- (3 mo) and long-term (12 mo) changes in fasting plasma concentrations of total ghrelin, β-hydroxybutyrate (βHB), and subjective feelings of appetite on 3 isocaloric eating patterns within a moderate caloric range (2000–2500 kcal/d) and with varying carbohydrate quality or quantity. MethodsWe performed a randomized controlled trial of 193 adults with obesity, comparing eating patterns based on “acellular” carbohydrate sources (e.g., flour-based whole-grain products; comparator arm), “cellular” carbohydrate sources (minimally processed foods with intact cellular structures), or LCHF principles. Outcomes were compared by an intention-to-treat analysis using constrained linear mixed modeling. This trial was registered at clinicaltrials.gov as NCT03401970. ResultsOf the 193 adults, 118 (61%) and 57 (30%) completed 3 and 12 mo of follow-up. Throughout the intervention, intakes of protein and energy were similar with all 3 eating patterns, with comparable reductions in body weight (5%−7%) and visceral fat volume (12%−17%) after 12 mo. After 3 mo, ghrelin increased significantly with the acellular (mean: 46 pg/mL; 95% CI: 11, 81) and cellular (mean: 54 pg/mL; 95% CI: 21, 88) diets but not with the LCHF diet (mean: 11 pg/mL; 95% CI: −16, 38). Although βHB increased significantly more with the LCHF diet than with the acellular diet after 3 m (mean: 0.16 mmol/L; 95% CI: 0.09, 0.24), this did not correspond to a significant group difference in ghrelin (unless the 2 high-carbohydrate groups were combined [mean: −39.6 pg/mL; 95% CI: −76, −3.3]). No significant between-group differences were seen in feelings of hunger. ConclusionsModestly energy-restricted isocaloric diets differing in carbohydrate cellularity and amount showed no significant differences in fasting total ghrelin or subjective hunger feelings. An increase in ketones with the LCHF diet to 0.3–0.4 mmol/L was insufficient to substantially curb increases in fasting ghrelin during fat loss.

Community Assessment for a Low-Carbohydrate Nutrition Education Program in South Africa

Eat Better South Africa (EBSA) is an organization that provides low-carbohydrate, high-fat (LCHF) nutrition and health education programs for women from under-resourced South African communities. Community assessments are essential to explore participants' potential facilitators and challenges of adhering to new dietary behaviours and should be implemented before any dietary interventions. This study is a qualitative community assessment to enable the EBSA program to better meet potential participants' needs and explore their willingness to enrol in the EBSA program. Sixty women from two communities in the Western Cape were interviewed through six focus group discussions. A thematic analysis was conducted using NVivo 12 software, and four themes were developed around the women's (1) role within the households; (2) dietary behaviour; (3) health perceptions; and (4) willingness to participate in an LCHF program. Women mentioned that they were responsible for cooking and shopping for their households. They expressed their understanding of healthy and unhealthy behaviours and their dietary patterns. Some women showed concerns about LCHF diets, but others wanted to learn more due to their knowledge of other people's positive experiences with the diet. There was a general desire to become healthy. However, the women anticipated dietary behaviour change to be challenging. Those challenges mostly revolved around their socioeconomic environments. The findings are intended to inform EBSA (or other nutrition interventions) on what to consider when implementing their interventions in these communities.

Hepatic Oleate Regulates Insulin-like Growth Factor-Binding Protein 1 Partially through the mTORC1-FGF21 Axis during High-Carbohydrate Feeding.

Stearoyl-CoA desaturase-1 (SCD1) catalyzes the rate-liming step of monounsaturated fatty acid biosynthesis and is a key regulator of systemic glucose metabolism. Mice harboring either a global (GKO) or liver-specific deletion (LKO) of Scd1 display enhanced insulin signaling and whole-body glucose uptake. Additionally, GKO and LKO mice are protected from high-carbohydrate diet-induced obesity. Given that high-carbohydrate diets can lead to chronic metabolic diseases such as obesity, diabetes, and hepatic steatosis, it is critical to understand how Scd1 deficiency confers metabolically beneficial phenotypes. Here we show that insulin-like growth factor-binding protein 1 (IGFBP1), a hepatokine that has been reported to enhance insulin signaling, is significantly elevated in the liver and plasma of GKO and LKO mice fed a low-fat high-carbohydrate diet. We also observed that the expression of hepatic Igfbp1 is regulated by oleic acid (18:1n9), a product of SCD1, through the mTORC1-FGF21 axis both in vivo and in vitro.