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Background: Malignant tumors of the breast are the most diagnosed cancers in females globally. Recent evidence suggests that carbohydrate restriction (CR), especially ketogenic diets, has become a potential treatment approach for many malignancies, including breast cancer. Tamoxifen (TAX) is a selective estrogen receptor modulator (ERM) that can reduce the risk of cancer recurrence. The current work was designed to assess the impact of CR on the proliferation of breast adenocarcinoma cells and to compare this impact with that of TAX. Study groups included: group 1: vehicle-treated mice; group 2: the Ehrlich group: injected Ehrlich ascites carcinoma (EAC) cells (2.5 × 106) in 0.25 ml isotonic saline; group 3: CR group: mice were supplied with a diet regimen of severe CR throughout the study and injected EAC at week 7; group 4: hormonal therapy (HT) group: mice in this group injected with EAC at week 7 and then received TAX at a dose of 20 mg/kg 3 times/week orally for 3 weeks; and lastly group 5: the group of combined intervention. The mice in the CR, HT, and the combined groups received Ehrlich cancer cells at the same dose and route as the Ehrlich group. Results: CR and HT groups demonstrated a significant decrease in levels of insulin-like growth factor (IGF-1), carbohydrate antigen (CA 15–3), hexokinase 2 (HK2), hypoxia-inducible factor-1 (HIF-1) α, and malondialdehyde (MDA) compared to the Ehrlich group. Additionally, the mean area % of caspase-3 was significantly increased, and the mean area % of Ki67 and estrogen receptor (ER)α was significantly decreased. Conclusions: The combined treatment demonstrated the most advantageous outcome, as evidenced by reduced CA 15–3 levels, tumor size, and the mean area % of Ki67. This suggests that the addition of severe CR to the conventional therapy of breast cancer has a beneficial effect. [ABSTRACT FROM AUTHOR]

Abstract Background Malignant tumors of the breast are the most diagnosed cancers in females globally. Recent evidence suggests that carbohydrate restriction (CR), especially ketogenic diets, has become a potential treatment approach for many malignancies, including breast cancer. Tamoxifen (TAX) is a selective estrogen receptor modulator (ERM) that can reduce the risk of cancer recurrence. The current work was designed to assess the impact of CR on the proliferation of breast adenocarcinoma cells and to compare this impact with that of TAX. Study groups included: group 1: vehicle-treated mice; group 2: the Ehrlich group: injected Ehrlich ascites carcinoma (EAC) cells (2.5 × 106) in 0.25 ml isotonic saline; group 3: CR group: mice were supplied with a diet regimen of severe CR throughout the study and injected EAC at week 7; group 4: hormonal therapy (HT) group: mice in this group injected with EAC at week 7 and then received TAX at a dose of 20 mg/kg 3 times/week orally for 3 weeks; and lastly group 5: the group of combined intervention. The mice in the CR, HT, and the combined groups received Ehrlich cancer cells at the same dose and route as the Ehrlich group. Results CR and HT groups demonstrated a significant decrease in levels of insulin-like growth factor (IGF-1), carbohydrate antigen (CA 15–3), hexokinase 2 (HK2), hypoxia-inducible factor-1 (HIF-1) α, and malondialdehyde (MDA) compared to the Ehrlich group. Additionally, the mean area % of caspase-3 was significantly increased, and the mean area % of Ki67 and estrogen receptor (ER)α was significantly decreased. Conclusions The combined treatment demonstrated the most advantageous outcome, as evidenced by reduced CA 15–3 levels, tumor size, and the mean area % of Ki67. This suggests that the addition of severe CR to the conventional therapy of breast cancer has a beneficial effect.

Ketogenic diets (KDs) are an alternative to improve strength performance and body composition in resistance training participants. The objective of this review and meta-analysis is to verify whether a ketogenic diet produces an increase in the strength of resistance-trained participants. We have evaluated the effect of the ketogenic diet in conjunction with resistance training on the strength levels in trained participants. Boolean algorithms from various databases (PubMed, Scopus, and Web of Science) were used. Meta-analyses were carried out, one on the 1-RM squat (SQ), with 106 trained participants or athletes, and another on the 1-RM on the bench press (BP), evaluating 119 participants. We did not find significant differences between the groups in the variables of SQ or BP, although the size of the effect was slightly higher in the ketogenic group. Conclusions: KDs do not appear to impair 1-RM performance; however, this test does not appear to be the most optimal tool for assessing hypertrophy-based strength session performance in resistance-trained participants. [ABSTRACT FROM AUTHOR]

Carbohydrate restriction is not typically recommended for children with type 1 diabetes mellitus (T1DM) because of concerns regarding growth retardation, ketoacidosis, severe hypoglycemia, and dyslipidemia. There is no consensus regarding the effects of carbohydrate restriction on the growth of children with T1DM. However, some previously reported cases of T1DM exhibited growth retardation during carbohydrate restriction, whereas others showed no obvious impairment. A female child with T1DM exhibited severe height growth velocity impairment during carbohydrate restriction in early childhood. Her height standard deviation score (SDS) was 1.12 at the initial T1DM diagnosis (2 yr and 11 mo of age) and -1.33 at 4 yr and 8 mo of age. Her height velocity was only 1.7 cm/yr (SDS -7.02). Discontinuing carbohydrate restriction substantially improved her height growth velocity. Implementing a carbohydrate-restricted diet in children with T1DM can negatively affect height growth velocity. [ABSTRACT FROM AUTHOR]

This study investigates the effects of a ketogenic low-carbohydrate high-fat (LCHF) diet on body composition in healthy, young, normal-weight women. With the increasing interest in ketogenic diets for their various health benefits, this research aims to understand their impact on body composition, focusing on women who are often underrepresented in such studies. Conducting a randomized controlled feeding trial with a crossover design, this study compares a ketogenic LCHF diet to a Swedish National Food Agency (NFA)-recommended control diet over four weeks. Seventeen healthy, young, normal-weight women adhered strictly to the provided diets, with ketosis confirmed through blood β-hydroxybutyrate concentrations. Dual-energy X-ray absorptiometry (DXA) was utilized for precise body composition measurements. To avoid bias, all statistical analyses were performed blind. The findings reveal that the ketogenic LCHF diet led to a significant reduction in both lean mass (−1.45 kg 95% CI: [−1.90;−1.00]; p < 0.001) and fat mass (−0.66 kg 95% CI: [−1.00;−0.32]; p < 0.001) compared to the control diet, despite similar energy intake and physical activity levels. This study concludes that while the ketogenic LCHF diet is effective for weight loss, it disproportionately reduces lean mass over fat mass, suggesting the need for concurrent strength training to mitigate muscle loss in women following this diet. [ABSTRACT FROM AUTHOR]

Metabolische Flexibilität ist die Fähigkeit des Stoffwechsels, sich effizient an das Nahrungsangebot und den Energiebedarf anzupassen. Sie wird durch gesunde Mitochondrien und ein ausgewogenes Hormonsystem gewährleistet und ist für Osteopath*innen von Bedeutung, da sie für ein gesundes Zusammenspiel der Körperfunktionen unerlässlich ist. Ein Verlust der metabolischen Flexibilität führt zu Insulinresistenz und steht in Zusammenhang mit vielen Erkrankungen, die wir in der Praxis täglich behandeln. Durch Lebensstilberatung können Osteopath*innen die Wirkung ihrer Behandlungen erhöhen. Ein angepasster Lebensstil verhindert die Zirkulation von entzündungsfördernden Zytokinen sowie von hohen Konzentrationen von Mastzellen und pathogenen Hormonen und optimiert die Selbstheilungskräfte. Anhand einer prospektiven Studie zeigen wir, dass eine Lebensstilberatung durch Osteopath*innen, die von Lifestyle-Coachs begleitet wird, positive Effekte auf die metabolische Flexibilität und damit auf die metabolische Gesundheit hat. Wir Osteopath*innen können für einen gesunden Stoffwechsel sorgen und sind gut beraten, unsere Patient*innen auf die gesundheitsfördernde Wirkung von Kohlenhydratbeschränkung und Fasten hinzuweisen. Metabolic flexibility is the ability of the metabolism to efficiently adapt to the food supply and energy requirements. It is ensured by healthy mitochondria and a balanced hormone system, and it is important for osteopaths as it is essential for the healthy interplay of bodily functions. A loss of metabolic flexibility leads to insulin resistance and is linked to many conditions that we treat in practice on a daily basis. By means of lifestyle advice, osteopaths can increase the effect of their treatments. An adapted lifestyle prevents the circulation of pro-inflammatory cytokines and obesogenic and pathogenic concentrations of certain hormones, leading to improved self-healing powers. Based on a prospective study, we show that lifestyle counseling by osteopaths, accompanied by lifestyle coaches, has positive effects on metabolic flexibility and thus on metabolic health. We osteopaths can ensure a healthy metabolism and are well advised to point out the health-promoting effects of carbohydrate restriction and fasting to our patients. [ABSTRACT FROM AUTHOR]

Background: Obesity and related metabolic health disorders are major clinical problems that have become increasingly prevalent worldwide. Aim: This before-after study examined the impact of therapeutic carbohydrate restriction (TCR) in managing metabolic health and promoting weight loss in a clinical setting using indirect calorimetry (IC). Setting: Data were collected from medical records obtained from a specialised allied health clinic focusing on metabolic health. Methods: The study analysed retrospective data from 202 overweight or obese participants (77% female, mean age 47.3) who received TCR as part of a behavioural modification programme involving multiple visits where their lifestyle, body composition and respiratory quotient (RQ), a key indicator of fat oxidation were recorded. Results: The study found that TCR improved fat oxidation in 84% of participants at short term visit (around 2 weeks), with an average weight loss of 1.8 kg. At medium term visit (around 12 weeks), 82% of participants maintained an increase in fat oxidation rate, with an average weight loss of 3.9 kg. In addition, among those with recorded body composition and waist circumference, 71% of weight lost was from fat, with an average reduction of 4.9 cm in waist measurements. Conclusion: This real-world study suggests that personalised TCR guided by IC can be an effective strategy for improving metabolic flexibility to help manage excess weight and related co-morbidities in a free-living population. Further research is needed to examine the long-term effects of TCR using this approach. Contribution: The utilisation of IC allows for the examination of individual shifts and improvements in metabolism among patients undergoing TCR.

Introduction: Interventions which improve the body composition and metabolic health of women with breast cancer are essential because they can improve the prognosis of this disease. Ketogenic diets have been suggested as complementary nutritional treatments for cancer patients. This systematic review was conducted with aim to determine the effect of ketogenic diets on the therapeutic and metabolic outcomes of breast cancer. Methods: In this systematic review, in order to find the related articles, Medline, Embase, Google Scholar, ScienceDirect, Magiran, SID, ISC, and Cochrane databases were searched with the keywords of low carbohydrate, carbohydrate restriction, Ketogenic diet, breast cancer, breast tumor, and breast neoplasms in English and Persian languages until November 2022. Results: Five studies were reviewed. The results showed that breast cancer patients following a ketogenic diet had significant improvements in emotional and social functions, reduced disease symptoms, and improved metabolic health biomarkers (creatinine, triglycerides, insulin and free insulin-like growth factor I). Conclusion: Long-term adherence to a ketogenic diet can lead to weight loss, tumor size reduction, improved quality of life, improved inflammatory factors, body composition, insulin resistance, and serum lipid profile disorders in breast cancer patients. Clinical trials are suggested to evaluate the effects of ketogenic diets on these metabolic factors, treatment, and quality of life in women with breast cancer.

Emerging evidence suggests that "leanness" and good metabolic health markers may predict larger increases in LDL cholesterol (LDL-C) in response to carbohydrate restriction. Specifically, a recent cohort study demonstrated an inverse association between BMI and LDL-C change among individuals on carbohydrate-restricted diets and identified a subgroup of "Lean Mass Hyper-Responders" (LMHR) who exhibit exceptional increases in LDL-C, in the context of low triglycerides and high HDL-C. We present the case of one subject, LM, who adopted a ketogenic diet for management of ulcerative colitis. He subsequently experienced an increase in LDL-C from 95 to 545 mg/dl, at peak, in association with HDL-C >100 mg/dl and triglycerides ~40 mg/dl, typical of the emergent LMHR phenotype. Assessments of LM's dietary intake, lipid panels, and BMI are consistent with prior data and suggest that the LMHR phenomenon is not dependent on saturated fat intake but inversely associates with BMI changes. Finally, computed tomography angiography conducted on LM after over 2 years of hypercholesterolemia revealed no evidence of calcified or non-calcified plaque.

When lean people adopt carbohydrate-restricted diets (CRDs), they may develop a lipid profile consisting of elevated LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) with low triglycerides (TGs). The magnitude of this lipid profile correlates with BMI such that those with lower BMI exhibit larger increases in both LDL-C and HDL-C. The inverse association between BMI and LDL-C and HDL-C change on CRD contributed to the discovery of a subset of individuals-termed Lean Mass Hyper-Responders (LMHR)-who, despite normal pre-diet LDL-C, as compared to non-LMHR (mean levels of 148 and 145 mg/dL, respectively), exhibited a pronounced hyperlipidemic response to a CRD, with mean LDL-C and HDL-C levels increasing to 320 and 99 mg/dL, respectively, in the context of mean TG of 47 mg/dL. In some LMHR, LDL-C levels may be in excess of 500 mg/dL, again, with relatively normal pre-diet LDL-C and absent of genetic findings indicative of familial hypercholesterolemia in those who have been tested. The Lipid Energy Model (LEM) attempts to explain this metabolic phenomenon by positing that, with carbohydrate restriction in lean persons, the increased dependence on fat as a metabolic substrate drives increased hepatic secretion and peripheral uptake of TG contained within very low-density lipoproteins (VLDL) by lipoprotein lipase, resulting in marked elevations of LDL-C and HDL-C, and low TG. Herein, we review the core features of the LEM. We review several existing lines of evidence supporting the model and suggest ways to test the model's predictions.

Ketogenic diets (KDs) are an alternative to improve strength performance and body composition in resistance training participants. The objective of this review and meta-analysis is to verify whether a ketogenic diet produces an increase in the strength of resistance-trained participants. We have evaluated the effect of the ketogenic diet in conjunction with resistance training on the strength levels in trained participants. Boolean algorithms from various databases (PubMed, Scopus, and Web of Science) were used. Meta-analyses were carried out, one on the 1-RM squat (SQ), with 106 trained participants or athletes, and another on the 1-RM on the bench press (BP), evaluating 119 participants. We did not find significant differences between the groups in the variables of SQ or BP, although the size of the effect was slightly higher in the ketogenic group. Conclusions: KDs do not appear to impair 1-RM performance; however, this test does not appear to be the most optimal tool for assessing hypertrophy-based strength session performance in resistance-trained participants.

Abstract Background The optimal nutritional treatment for gestational diabetes (GDM) is still a matter of debate. With increasing rates of GDM and potential negative consequences for the health of mother and child, the best treatment should be established. The Nordic diet with emphasis on plant-based protein show promising health outcomes in other populations but has yet to be investigated in GDM population. The aim of this study, which is part of the “Effect of plant-based Nordic diet versus carbohydrate-restricted diet on glucose levels in gestational diabetes” (eMOM) pilot study was to compare the short-term effects of healthy Nordic diet (HND) and the currently recommended moderate restriction of carbohydrates diet (MCRD) on glucose and lipid metabolism in women with GDM. Methods This was a randomized crossover where each of the diet interventions (HND and MCRD) were consumed for 3 days with a 3-day wash-out period in between. In total, 42 pregnant women diagnosed with GDM (

Introduction: Gestational diabetes is one of the most common pregnancy complications, which has negative consequences for both mother and fetus. A crucial treatment strategy is modifying the mother's diet. The present study was performed with aim to determine the effects of low carbohydrate (LC) diets on the outcomes of gestational diabetes. Methods: In this systematic review, search was done with the keywords including low carbohydrate diet, carbohydrate restriction, ketogenic diet, gestational diabetes, hyperglycemia, glucose intolerance, insulin resistance, and clinical trials in Persian and English languages in databases of Medline, PubMed, Embase, Science Direct, Magiran, ISD, ISC, and Cochrane until March 2023. Results: This systematic review examined seven studies. Some studies showed that carbohydrate restriction can have beneficial effects on metabolic outcomes, glycemic control, less insulin therapy needs, delivery method, and fetal weight. The LC diet did not lead to ketonemia in pregnant women. However, in other studies, adherence to the LC regimen did not reduce the number of women requiring insulin. There were no significant differences between the groups in terms of insulin dose or time of insulin treatment initiation, and both groups had similar pregnancy outcomes. Conclusion: Adherence to the low carbohydrate diet (about 40%) in pregnant mothers with gestational diabetes could have beneficial effects on some metabolic outcomes, delivery method, weight and health of the fetus. It did not lead to ketonemia in pregnant mothers. However, there are contradictions in the findings of the studies due to the amount and type of carbohydrates. It is recommended to conduct more clinical trials with different percentages of carbohydrates and a higher sample size.

IntroductionCarbohydrate-restricted diets are one of the most effective dietary interventions for weight loss. However, the optimum carbohydrate intake for implementing the most effective weight-loss interventions is still being discussed. We aimed to determine the optimum carbohydrate intake for short- and long-term weight loss in adults with overweight and obesity.MethodsWe searched PubMed, Scopus, Web of Science, and CENTRAL from inception to May 2021 for randomized controlled trials examining the effect of a carbohydrate-restricted diet (≤45% of energy intake) as compared to a control diet (carbohydrate intake >45% of energy intake) on body weight in adults with overweight/obesity. A random-effects dose–response meta-analysis was conducted to calculate the mean difference for each 10% decrease in carbohydrate intake at the 6-month follow-up (1 to 6 months), 12-month follow-up (6 to 12 months), and follow-up longer than 12 months. The shape of the dose-dependent effects was also evaluated. The certainty of the evidence was rated using the GRADE approach. The minimal clinically important difference (MCID) threshold was defined as 5% weight loss (equal to 4.39 kg).ResultsA total of 110 trials were selected for the present meta-analysis. In the linear dose–response meta-analysis, each 10% decrease in carbohydrate intake reduced body weight by 0.64 kg (95% CI: −0.79 to −0.49; n = 101 trials with 4,135 participants, high-certainty evidence) at the 6-month follow-up and by 1.15 kg (95% CI: −1.61 to −0.69; 42 trials with 2,657 participants, moderate-certainty evidence) at the 12-month follow-up. Non-linear dose–response meta-analyses indicated a monotonic reduction in body weight with the decrease in carbohydrate intake, with the greatest reduction at 5% at the 6-month follow-up (mean difference 5%: −3.96 kg, 95% CI: −4.92 to −3.00) and 10% at the 12-month follow-up (mean difference 10%: −6.26 kg, 95% CI: −10.42 to −2.10). At follow-up longer than 12 months, dose–response analyses suggested a non-linear effect, wherein carbohydrate intakes higher than 40% and lower than 30% were not effective for weight loss.DiscussionCarbohydrate restriction is an effective dietary strategy for important weight loss in adults with overweight and obesity. At 6-month and 12-month follow-ups, body weight decreased proportionally, more than the MCID threshold, along with the decrease in carbohydrate intake. At follow-up longer than 12 months, there was a non-linear effect, with the greatest reduction at 30% carbohydrate intake.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022315042.

Introduction: Interventions which improve the body composition and metabolic health of women with breast cancer are essential because they can improve the prognosis of this disease. Ketogenic diets have been suggested as complementary nutritional treatments for cancer patients. This systematic review was conducted with aim to determine the effect of ketogenic diets on the therapeutic and metabolic outcomes of breast cancer. Methods: In this systematic review, in order to find the related articles, Medline, Embase, Google Scholar, ScienceDirect, Magiran, SID, ISC, and Cochrane databases were searched with the keywords of low carbohydrate, carbohydrate restriction, Ketogenic diet, breast cancer, breast tumor, and breast neoplasms in English and Persian languages until November 2022. Results: Five studies were reviewed. The results showed that breast cancer patients following a ketogenic diet had significant improvements in emotional and social functions, reduced disease symptoms, and improved metabolic health biomarkers (creatinine, triglycerides, insulin and free insulin-like growth factor I). Conclusion: Long-term adherence to a ketogenic diet can lead to weight loss, tumor size reduction, improved quality of life, improved inflammatory factors, body composition, insulin resistance, and serum lipid profile disorders in breast cancer patients. Clinical trials are suggested to evaluate the effects of ketogenic diets on these metabolic factors, treatment, and quality of life in women with breast cancer. [ABSTRACT FROM AUTHOR]

In glucose-deprived conditions, ketone bodies are produced by the liver mitochondria, through the catabolism of fatty acids, and are used peripherally, as an alternative energy source. Ketones are produced in the body under normal conditions, including during pregnancy and the neonatal period, when following a ketogenic diet (KD), fasting, or exercising. Additionally, ketone synthesis is also augmented under pathological conditions, including cases of diabetic ketoacidosis (DKA), alcoholism, and several metabolic disorders. Nonetheless, diet is the main regulator of total body ketone concentrations. The KDs are mimicking the fasting state, altering the default metabolism towards the use of ketones as the primary fuel source. Recently, KD has gained recognition as a medical nutrition therapy for a plethora of metabolic conditions, including obesity and diabetes mellitus (DM). The present review aims to discuss the role of ketones, KDs, ketonemia, and ketonuria in DM, presenting all the available new evidence in a comprehensive manner. [ABSTRACT FROM AUTHOR]

A pragmatic low carbohydrate diet intervention changes neither carbohydrate consumption nor glycemia in adolescents and young adults with type 1 diabetes in a randomized trial. Effects of a diet higher in carbohydrate/lower in fat versus lower in carbohydrate/higher in monounsaturated fat on post meal triglyceride concentrations and other cardiovascular risk factors in type 1 diabetes. Keywords: carbohydrate restriction; low-carbohydrate diet; meta-analysis; systematic review; type 1 diabetes EN carbohydrate restriction low-carbohydrate diet meta-analysis systematic review type 1 diabetes 2770 2773 4 08/03/23 20230901 NES 230901 BACKGROUND One of the most challenging parts in daily management of type 1 diabetes (T1D) is postprandial glucose excursions.[1] Based on the rationale that carbohydrates have the greatest impact on postprandial blood glucose, it has been suggested that decreasing carbohydrate consumption will improve postprandial glycaemic control.[1] However, the ideal dietary approach in T1D is ambiguous.[2] The American Diabetes Association suggests that medical nutrition therapy is fundamental for the management of diabetes, while arguing that there are no universal guidelines for the distribution of macronutrients for individuals with diabetes.[3] In contrast to type 2 diabetes (T2D),[4] randomized controlled trials (RCTs) assessing carbohydrate restriction in T1D have not been incorporated in a systematic review and meta-analysis. Carbohydrate restriction, low-carbohydrate diet, meta-analysis, systematic review, type 1 diabetes. [Extracted from the article]

The adoption of carbohydrate-restrictive diets to improve health is increasing in popularity, but there is a dearth of research on individuals who choose to severely restrict or entirely exclude carbohydrates. The present study investigated the beliefs and experiences of individuals following a diet that severely limits, or entirely excludes, dietary carbohydrates, colloquially known as a 'zero-carb' diet, for at least 6 months. Zero-carb dieters (n = 170) recruited via a social networking site completed an online qualitative survey prompting them to discuss their motives, rationale, and experiences of following a low-carb diet. Transcripts of participants' responses were analyzed using inductive thematic analysis. Results revealed that participants' decision to follow a zero-carb diet was driven by health concerns and benefits. Participants expressed a strong social identity and belongingness to online zero-carb communities. Participants reported strong intentions to follow the diet indefinitely. Shortcomings of the diet centered on experienced stigma; lack of support from healthcare providers and significant others; limited access to, and high cost of, foods; and limited scientific data on the diet. Further research into the benefits and shortcomings of zero-carb diets across settings and populations is warranted, and guidelines for healthcare professionals on how to support individuals following a zero-carb diet are needed.

Background: The optimal nutritional treatment for gestational diabetes (GDM) is still a matter of debate. With increasing rates of GDM and potential negative consequences for the health of mother and child, the best treatment should be established. The Nordic diet with emphasis on plant-based protein show promising health outcomes in other populations but has yet to be investigated in GDM population. The aim of this study, which is part of the "Effect of plant-based Nordic diet versus carbohydrate-restricted diet on glucose levels in gestational diabetes" (eMOM) pilot study was to compare the short-term effects of healthy Nordic diet (HND) and the currently recommended moderate restriction of carbohydrates diet (MCRD) on glucose and lipid metabolism in women with GDM. Methods: This was a randomized crossover where each of the diet interventions (HND and MCRD) were consumed for 3 days with a 3-day wash-out period in between. In total, 42 pregnant women diagnosed with GDM (< 29 + 0 gestational week) were randomized. Glucose data was collected by continuous glucose monitors (CGM, Freestyle Libre®, Abbott, USA) worn for 14 days, and participants gave blood samples before and after diet interventions. The primary outcome was time spent in glucose target range (TIR, < 7.8 mmol/L). TIR, 3-day mean tissue glucose as well as changes in fasting glucose, homeostatic model of insulin resistance (HOMA-IR) and blood lipids were analyzed with paired samples statistical analyses. Results: Thirty-six women with complete 14 days CGM data were analyzed. Both diet interventions produced a high degree of TIR (99% SD 1.8), without a difference between the diets (p = 0.727). The 3-day mean glucose was significantly lower in HND than in MCRD (p = 0,049). Fasting insulin (p = 0,034), insulin resistance (p = 0,030), total and LDL cholesterol (p = 0,023 and 0,008) reduced more in the MCRD diet than the HND. NS differences in any other measure of CGM or blood tests. Conclusions: HND and MCRD did not differ in terms of their short-term effect on TIR. A larger study with sufficient power is needed to confirm the differences in short-term mean glucose, insulin resistance and lipid metabolism. Trial registration: Registered in clinicaltrials.gov (21/09/2018, NCT03681054). [ABSTRACT FROM AUTHOR]

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Although these diets may be viewed as an easy shortcut to lose weight rapidly and easily, subjects often use these diets without any medical counselling or nutritional rehabilitation for the long-term management of weight maintenance, which should represent the most important and ambitious goal of VLCKD nutritional therapy. Keywords: carbohydrate restriction; cardiometabolic risk; metabolic rehabilitation; precision nutrition; weight cycling; weight loss EN carbohydrate restriction cardiometabolic risk metabolic rehabilitation precision nutrition weight cycling weight loss 1 3 3 11/06/23 20231101 NES 231101 Very low-calorie ketogenic diets (VLCKDs) are nowadays considered a notable example of a dietary-based treatment with proven efficacy against a variety of conditions. Diets for weight management in adults with type 2 diabetes: an umbrella review of published meta-analyses and systematic review of trials of diets for diabetes remission. [Extracted from the article]

A fully provided, hypocaloric, carbohydrate-reduced high-protein (CRHP) diet compared to a hypocaloric conventional diabetes (CD) diet for 6 weeks improved glycemic control to a greater extent in face of an intended 6% weight loss in individuals with type 2 diabetes mellitus (T2DM). The present 24-week extension of that study reports on the efficacy of CRHP and CD diets in a real-life setting. Sixty-five individuals with T2DM who completed the initial 6-week fully provided diet period (% energy from carbohydrate, protein, and fat was 30/30/40 in CRHP, and 50/17/33 in CD) continued a free-living, dietician guided 24-week period of which 59 individuals completed. The CRHP compared to CD group reported a 4% lower carbohydrate intake and had higher urea excretion by 22% (both p ≤ 0.05) at week 30, suggesting less difference in carbohydrate and protein intake between groups during the 24-week extension compared to week 6. The loss of body weight during the initial 6 weeks was maintained in both groups during the 24-week extension (−5.5 ± 4.5 and −4.6 ± 4.8 kg) as well as HbA1c (−8.4 ± 6.2 and −8.4 ± 6.9 mmol/mol) with no significant differences between groups. The additional benefits on glucoregulation harnessed by carbohydrate restriction under full diet provision for 6 weeks combined with titrated weight loss could not be maintained in a real-life setting of self-prepared diet aiming on similar diets for 6 months. [ABSTRACT FROM AUTHOR]

In glucose-deprived conditions, ketone bodies are produced by the liver mitochondria, through the catabolism of fatty acids, and are used peripherally, as an alternative energy source. Ketones are produced in the body under normal conditions, including during pregnancy and the neonatal period, when following a ketogenic diet (KD), fasting, or exercising. Additionally, ketone synthesis is also augmented under pathological conditions, including cases of diabetic ketoacidosis (DKA), alcoholism, and several metabolic disorders. Nonetheless, diet is the main regulator of total body ketone concentrations. The KDs are mimicking the fasting state, altering the default metabolism towards the use of ketones as the primary fuel source. Recently, KD has gained recognition as a medical nutrition therapy for a plethora of metabolic conditions, including obesity and diabetes mellitus (DM). The present review aims to discuss the role of ketones, KDs, ketonemia, and ketonuria in DM, presenting all the available new evidence in a comprehensive manner.

• Lean mass hyper-responders exhibit extreme increases in LDL-c on ketogenic diets. • LDL-c increases in LMHRs are dependent on carbohydrate restriction. • Other cardiometabolic risk factors are normal to optimal in LMHRs. • A prudent clinical approach is required for managing LDL-c in LMHR patients. • Research is warranted to assess mechanisms and cardiovascular risk of this trait. [ABSTRACT FROM AUTHOR]

Objective: The cardio‐renal benefits of sodium glucose‐like transporter 2 inhibitor (SGLT2i) therapies have been demonstrated in patients with and without type 2 diabetes. However, no studies have explored the long‐term metabolic effects of SGLT2i, combined with dietary carbohydrate restriction. Our primary objective was to describe long‐term changes in weight, energy expenditure, appetite and body composition after 12 months of Dapagliflozin therapy, with carbohydrate restriction, in people with type 2 diabetes and obesity. Our secondary objective was to assess changes in adiponectin and leptin. Method: This was a 12‐month cohort study in a secondary care setting. Participants (n = 18) with type 2 diabetes (T2D) and class 3 obesity underwent baseline indirect calorimetry for determination of 24‐h energy expenditure, body composition, fasting serum leptin and adiponectin levels, and appetitive assessments. Following initiation of Dapagliflozin (and dietary carbohydrate restriction), measurements were repeated at monthly intervals up to 12 months. Results: Mean starting weight of participants was 129.4 kg (SD 25.9), mean BMI 46.1 kg/m2 (SD 8.3) and mean HbA1c 53.9 mmol/mol (14.1). Seventeen participants completed the study; after 12 months of Dapagliflozin and dietary carbohydrate restriction, mean weight loss was 8.1 kg (SD 11.3 kg; p =.009). This was mediated by reduced fat mass (mean loss, 9.9 kg; SD 10.4 kg; p =.002) associated with reduced serum leptin at 12 months (mean reduction 11,254 pg/ml; SD 16,075; p =.011). There were no significant changes in self‐reported appetite, 24‐h energy expenditure or serum adiponectin during follow‐up. Conclusion: In this study, combined Dapagliflozin therapy and carbohydrate restriction in patients with T2D and obesity resulted in a significant reduction of body weight and fat mass at 12 months without any discernible changes in energy expenditure or appetite. These results offer a scientific and clinical rationale to conduct an exploratory trial investigating the effects of a low carbohydrate diet combined with SGLT2 inhibitors in patients with T2D. [ABSTRACT FROM AUTHOR]

Purpose of Review: Very-low-carbohydrate (VLC) and ketogenic diets (KDs) have been used for weight loss and more recently in patients with insulin resistance and type 2 diabetes. The impact of VLC and KDs on lipids/lipoproteins is a concern. The purpose of this review is to discuss the impact of KDs on body weight and lipids/lipoproteins. Recent Findings: VLC/KDs contribute to greater weight loss in the short term (< 6 months) compared to higher carbohydrate diets, but there is typically no difference between the diets by 12 months. Triglyceride and high-density lipoprotein cholesterol levels generally improve, but there is a variable response in low-density lipoprotein cholesterol levels, with some individuals experiencing a dramatic increase, particularly those with latent genetic dyslipidemias. Summary: Healthcare professionals should educate patients on the risks and benefits of following VLC/KDs and encourage the consumption of carbohydrate-rich foods associated with positive health outcomes. [ABSTRACT FROM AUTHOR]

Chronic diet-related metabolic diseases, including diabetes and obesity, impose enormous burdens on patient wellness, healthcare costs, and worker productivity. Given the interdependent nature of the human and economic costs of metabolic disease, companies should be incentivized to invest in the health of their workforce. We report data from an ongoing pilot program in which employees of a manufacturing company with obesity, prediabetes, or diabetes are being treated by a metabolic health clinic using a carbohydrate restriction, community-orientated telemedicine approach. 10 patients completed the first 6 months of the program, and all lost weight, with a mean weight reduction of 38.4 lbs (17.4 kg). Improvements in HbA1c, fasting glucose, HOMA-IR, triglycerides, C-reactive protein, and systolic blood pressure were also observed across the group. Furthermore, the 10-year risk of having a major cardiovascular event, as calculated by the American Heart Association risk calculator, decreased from a mean of 9.22 to 5.18%, representing a 44% relative risk reduction. As a result of improvements in their metabolic health, patients were able to discontinue medications, leading to an estimated annualized cost savings of USD 45,171.70. These preliminary data provide proof-of-principle that when companies invest in the metabolic health of their workers, both parties stand to gain. [ABSTRACT FROM AUTHOR]

Background: Restricted carbohydrate diets remain among the most popular for weight loss and general health improvement. Recent evidence demonstrates that carbohydrate restricted diets are low in overall diet quality, yet their association with micronutrient inadequacy has not been well characterized at a population-level in adults in the United States., Objective: 1) To evaluate the prevalence of not meeting daily micronutrient recommendations in US adults that met the Acceptable Macronutrient Distribution Ranges (AMDRs) and those who restricted carbohydrate to <45% energy, and 2) examine the effect of total fat and fat class on these results for the restricted carbohydrate group., Design: This study utilized 24-hour recall data on food and nutrient intake from respondents in the National Health and Nutrition Examination Survey (NHANES) 2007-2018., Participants/setting: This study included 15,029 respondents who were ≥20 y, had complete and reliable nutrient intake data, and were not pregnant or breastfeeding., Main Outcome Measures: The main outcome was the prevalence of not meeting daily micronutrient recommendations based on Dietary Reference Intakes (DRIs)., Statistical Analyses Performed: The National Cancer Institute's usual intake methodology was used to estimate usual dietary intake and the prevalence of the US adult population not meeting the DRIs., Results: Compared to participants that met the AMDRs, those that consumed restricted carbohydrate diets had greater prevalence of inadequacy (%

Abstract Objective The cardio‐renal benefits of sodium glucose‐like transporter 2 inhibitor (SGLT2i) therapies have been demonstrated in patients with and without type 2 diabetes. However, no studies have explored the long‐term metabolic effects of SGLT2i, combined with dietary carbohydrate restriction. Our primary objective was to describe long‐term changes in weight, energy expenditure, appetite and body composition after 12 months of Dapagliflozin therapy, with carbohydrate restriction, in people with type 2 diabetes and obesity. Our secondary objective was to assess changes in adiponectin and leptin. Method This was a 12‐month cohort study in a secondary care setting. Participants (n = 18) with type 2 diabetes (T2D) and class 3 obesity underwent baseline indirect calorimetry for determination of 24‐h energy expenditure, body composition, fasting serum leptin and adiponectin levels, and appetitive assessments. Following initiation of Dapagliflozin (and dietary carbohydrate restriction), measurements were repeated at monthly intervals up to 12 months. Results Mean starting weight of participants was 129.4 kg (SD 25.9), mean BMI 46.1 kg/m2 (SD 8.3) and mean HbA1c 53.9 mmol/mol (14.1). Seventeen participants completed the study; after 12 months of Dapagliflozin and dietary carbohydrate restriction, mean weight loss was 8.1 kg (SD 11.3 kg; p = .009). This was mediated by reduced fat mass (mean loss, 9.9 kg; SD 10.4 kg; p = .002) associated with reduced serum leptin at 12 months (mean reduction 11,254 pg/ml; SD 16,075; p = .011). There were no significant changes in self‐reported appetite, 24‐h energy expenditure or serum adiponectin during follow‐up. Conclusion In this study, combined Dapagliflozin therapy and carbohydrate restriction in patients with T2D and obesity resulted in a significant reduction of body weight and fat mass at 12 months without any discernible changes in energy expenditure or appetite. These results offer a scientific and clinical rationale to conduct an exploratory trial investigating the effects of a low carbohydrate diet combined with SGLT2 inhibitors in patients with T2D.

We evaluated the effect of weight loss induced by dietary carbohydrate restriction on health-related quality of life (HRQoL) and cognition in type 2 diabetes (T2D). In this randomised parallel trial, 72 adults with T2D and overweight/obesity (mean ± SD, HbA 1c : 57 ± 8 mmol/mol and BMI: 33 ± 5 kg/m2) were randomly assigned to a carbohydrate-reduced high-protein diet (CRHP: C30E%-P30E%-F40E%) or conventional diabetes diet (CD: C50E%-P17E%-F33E%) for 6 weeks, targeting a 6% weight loss. HRQoL was assessed from the short form 36 (SF-36) questionnaire, including physical and mental component summary (PCS and MCS) scores; global cognition, verbal memory, attention and psychomotor speed, and executive function were assessed from a neuropsychological test battery. Both diet groups achieved a 5.8 kg weight loss and improved PCS (median [25th;75th percentiles], CD: 2.7 [1.1; 4.2] vs. CRHP: 2.1 [0.7; 3.7]), with no difference between diets. The CRHP diet resulted in a clinically relevant improvement of MCS, albeit non-significantly different compared with the change after the CD diet (2.0 [-0.7; 4.8], p = 0.15). Global cognition, attention, and verbal memory were unaffected by the CRHP diet, which selectively worsened the Symbol Digit Modality Test assessing psychomotor speed when compared with the CD diet (−4.1 [-7.2;-1.1], p < 0.01). Physical health improved by weight loss independently of macronutrient distribution, while mental health and cognition may be affected by the amount of carbohydrate, protein and fat in the diet. Collectively, our data suggest that weight loss through moderate carbohydrate restriction has no clinically important impact on HRQoL and global cognition in patients with T2D. Registered under ClinicalTrials.gov Identifier no. NCT03814694. [ABSTRACT FROM AUTHOR]

Background Carbohydrate restriction is effective for type 2 diabetes management. Objectives We aimed to evaluate the dose-dependent effect of carbohydrate restriction in patients with type 2 diabetes. Methods We systematically searched PubMed, Scopus, and Web of Science to May 2021 for randomized controlled trials evaluating the effect of a carbohydrate-restricted diet (≤45% total calories) in patients with type 2 diabetes. The primary outcome was glycated hemoglobin (HbA1c). Secondary outcomes included fasting plasma glucose (FPG); body weight; serum total, LDL, and HDL cholesterol; triglyceride (TG); and systolic blood pressure (SBP). We performed random-effects dose-response meta-analyses to estimate mean differences (MDs) for a 10% decrease in carbohydrate intake. Results Fifty trials with 4291 patients were identified. At 6 months, compared with a carbohydrate intake between 55%–65% and through a maximum reduction down to 10%, each 10% reduction in carbohydrate intake reduced HbA1c (MD, −0.20%; 95% CI, −0.27% to −0.13%), FPG (MD, −0.34 mmol/L; 95% CI, −0.56 to −0.12 mmol/L), and body weight (MD, −1.44 kg; 95% CI, −1.82 to −1.06 kg). There were also reductions in total cholesterol, LDL cholesterol, TG, and SBP. Levels of HbA1c, FPG, body weight, TG, and SBP decreased linearly with the decrease in carbohydrate intake from 65% to 10%. A U-shaped effect was seen for total cholesterol and LDL cholesterol, with the greatest reduction at 40%. At 12 months, a linear reduction was seen for HbA1c and TG. A U-shaped effect was seen for body weight, with the greatest reduction at 35%. Conclusions Carbohydrate restriction can exert a significant and important reduction on levels of cardiometabolic risk factors in patients with type 2 diabetes. Levels of most cardiometabolic outcomes decreased linearly with the decrease in carbohydrate intake. U-shaped effects were seen for total cholesterol and LDL cholesterol at 6 months and for body weight at 12 months. [ABSTRACT FROM AUTHOR]

BackgroundCarbohydrate restriction may benefit β-cell function and glucose metabolism in type 2 diabetes (T2D) but also leads to weight loss which in itself is beneficial.MethodsIn order to determine the additional effect of carbohydrate restriction in addition to a fixed body weight loss, we randomly assigned 72 adults with T2D and obesity (mean ± SD HbA1c 7.4 ± 0.7%, BMI 33 ± 5 kg/m2) to a carbohydrate-reduced high-protein diet (CRHP; energy percent from carbohydrate/protein/fat: 30/30/40) or an isocaloric conventional diabetes diet (CD; 50/17/33) for 6 weeks. All foods were provided free of charge and total energy intake was tailored individually, so both groups lost 6% of baseline body weight.ResultsDespite significantly greater reductions in HbA1c (mean [95% CI] −1.9 [−3.5, −0.3] mmol/mol) after 6 weeks, the CRHP diet neither improved glucose tolerance, β-cell response to glucose, insulin sensitivity, during a 4-h oral glucose tolerance test, nor basal proinsulin secretion when compared to the CD diet, but increased C-peptide concentration and insulin secretion rate (area under the curve [AUC] and peak) significantly more (~10%, P ≤ 0.03 for all). Furthermore, compared with the CD diet, the CRHP diet borderline increased basal glucagon concentration (16 [−0.1, 34]%, P = 0.05), but decreased glucagon net AUC (−2.0 [−3.4, −0.6] mmol/L ×240 min, P < 0.01), decreased basal triglyceride and total AUC (~20%, P < 0.01 for both), and increased gastric inhibitory polypeptide total AUC (14%, P = 0.01).ConclusionA moderately carbohydrate-restricted diet for 6 weeks decreased HbA1c but did not improve β-cell function or glucose tolerance beyond the effects of weight loss when compared with a conventional diabetes diet in people with T2D.Clinical trials registrationwww.Clinicaltrials.gov, Identifier: NCT02472951.

We aimed to assess the association of a low carbohydrate diet score (LCD) with the incidence of type 2 diabetes (T2D) using Melbourne Collaborative Cohort Study (MCCS) data. Between 1990 and 1994, the MCCS recruited 41,513 people aged 40–69 years. The first and second follow-ups were conducted in 1995–1998 and 2003–2007, respectively. We analyzed data from 39,185 participants. LCD score was calculated at baseline as the percentage of energy from carbohydrate, fat, and protein. The higher the score the less percentage of carbohydrates contributed to energy intake. The association of LCD quintiles with the incidence of diabetes was assessed using modified Poisson regression, adjusted for lifestyle, obesity, socioeconomic and other confounders. Mediation of the association by adiposity (BMI) was assessed. LCD was positively associated with diabetes risk. Higher LCD score (p for trend = 0.001) was associated with increased risk of T2D. Quintile 5 (38 % energy from carbohydrates) versus quintile 1 (55 % energy from carbohydrates) showed a 20 % increased diabetes risk (incidence risk ratio (IRR) = 1.20 (95 % CI: 1.05–1.37)). A further adjustment for BMI (Body Mass Index) and WHR (Waist-to-Hip-Ratio) eliminated the association. Mediation analysis demonstrated that BMI mediated 76 % of the LCD & diabetes association. Consuming a low carbohydrate diet, reflected as a high LCD score, may increase the risk of T2D which is largely explained by obesity. Results highlight the need for further studies, including clinical trials investigating the effects of a low carbohydrate diet in T2D. • Little is known about the long-term effects of a low carbohydrate diet on the risk of diabetes. • When compared with Quintile 1, Quintile 5 low carbohydrate diet showed a 20 % increased diabetes risk. • BMI mediated 76 % of the low carbohydrate diet & diabetes association. [ABSTRACT FROM AUTHOR]

In sarcopenic obese subjects it is essential to reduce body weight and preserve lean mass, in order to avoid a worsening of muscle function. Several studies have shown that leucine supplementation can be useful to improve skeletal muscle mass in sarcopenic patients. The aim of our study was to evaluate the effectiveness of a short-term low-calorie diet (LCD) combined with supplementation with whey protein and leucine on weight loss, lean mass and muscle strength in sarcopenic, obese, hyperinsulinemic and post-menopausal women. Sixteen females with a mean age of 60 years (range: 50–70 years), BMI 37.6 kg/m2 (range: 31.7–44.1 Kg/m2), HOMA-index ≥ 2.5 (range: 2.9–12) were assigned to an LCD regimen (1000 kcal/day) with supplementation of 18 g whey proteins which 4.1 g of leucine for 45 days. Anthropometric indexes, blood and urine chemistry, body composition by DEXA, muscle strength by handgrip test and Short Physical Performance Battery (SPPB) were assessed at baseline and at the end of the treatment. A significant reduction in BMI (37.6 vs. 35.7 Kg/m2), waist circumference (107 vs. 102.4 cm), HOMA index (4.8 vs. 2.3) and fasting insulin (17.4 vs. 10.4 μIU/mL) was observed in all patients. Women preserved total lean body mass (55 vs. 5%) and significantly improved their muscle strength, as measured by handgrip (15.3 vs. 20.1 Kg), and their muscle function, as measured by SPPB (7.5 vs. 8.9). A significant increase in BUN was also observed (36.1 vs. 46.3). We conclude that LCD with adequate protein intake and supplementation with whey protein and leucine should be promoted to maintain muscle mass and improve muscle strength in post-menopausal women with sarcopenic obesity. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that "leanness" and good metabolic health markers may predict larger increases in LDL cholesterol (LDL-C) in response to carbohydrate restriction. Specifically, a recent cohort study demonstrated an inverse association between BMI and LDL-C change among individuals on carbohydrate-restricted diets and identified a subgroup of "Lean Mass Hyper-Responders" (LMHR) who exhibit exceptional increases in LDL-C, in the context of low triglycerides and high HDL-C. We present the case of one subject, LM, who adopted a ketogenic diet for management of ulcerative colitis. He subsequently experienced an increase in LDL-C from 95 to 545 mg/dl, at peak, in association with HDL-C >100 mg/dl and triglycerides ~40 mg/dl, typical of the emergent LMHR phenotype. Assessments of LM's dietary intake, lipid panels, and BMI are consistent with prior data and suggest that the LMHR phenomenon is not dependent on saturated fat intake but inversely associates with BMI changes. Finally, computed tomography angiography conducted on LM after over 2 years of hypercholesterolemia revealed no evidence of calcified or non-calcified plaque. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Lifestyle modification and weight loss are cornerstones of type 2 diabetes management. However, carbohydrate restriction may have weight-independent beneficial effects on glycaemic control. This has been difficult to demonstrate because low-carbohydrate diets readily decrease body weight. We hypothesised that carbohydrate restriction enhances the beneficial metabolic effects of weight loss in type 2 diabetes. Methods: This open-label, parallel RCT included adults with type 2 diabetes, HbA1c 48–97 mmol/mol (6.5–11%), BMI >25 kg/m2, eGFR >30 ml min−1 [1.73 m]−2 and glucose-lowering therapy restricted to metformin or dipeptidyl peptidase-4 inhibitors. Participants were randomised by a third party and assigned to 6 weeks of energy restriction (all foods were provided) aiming at ~6% weight loss with either a carbohydrate-reduced high-protein diet (CRHP, percentage of total energy intake [E%]: CH30/P30/F40) or a conventional diabetes diet (CD, E%: CH50/P17/F33). Fasting blood samples, continuous glucose monitoring and magnetic resonance spectroscopy were used to assess glycaemic control, lipid metabolism and intrahepatic fat. Change in HbA1c was the primary outcome; changes in circulating and intrahepatic triacylglycerol were secondary outcomes. Data were collected at Copenhagen University Hospital (Bispebjerg and Herlev). Results: Seventy-two adults (CD 36, CRHP 36, all white, 38 male sex) with type 2 diabetes (mean duration 8 years, mean HbA1c 57 mmol/mol [7.4%]) and mean BMI of 33 kg/m2 were enrolled, of which 67 (CD 33, CRHP 34) completed the study. Body weight decreased by 5.8 kg (5.9%) in both groups after 6 weeks. Compared with the CD diet, the CRHP diet further reduced HbA1c (mean [95% CI] −1.9 [−3.5, −0.3] mmol/mol [−0.18 (−0.32, −0.03)%], p = 0.018) and diurnal mean glucose (mean [95% CI] −0.8 [−1.2, −0.4] mmol/l, p < 0.001), stabilised glucose excursions by reducing glucose CV (mean [95% CI] −4.1 [−5.9, −2.2]%, p < 0.001), and augmented the reductions in fasting triacylglycerol concentration (by mean [95% CI] −18 [−29, −6]%, p < 0.01) and liver fat content (by mean [95% CI] −26 [−45, 0]%, p = 0.051). However, pancreatic fat content was decreased to a lesser extent by the CRHP than the CD diet (mean [95% CI] 33 [7, 65]%, p = 0.010). Fasting glucose, insulin, HOMA2-IR and cholesterol concentrations (total, LDL and HDL) were reduced significantly and similarly by both diets. Conclusions/interpretation: Moderate carbohydrate restriction for 6 weeks modestly improved glycaemic control, and decreased circulating and intrahepatic triacylglycerol levels beyond the effects of weight loss itself compared with a CD diet in individuals with type 2 diabetes. Concurrent differences in protein and fat intakes, and the quality of dietary macronutrients, may have contributed to these results and should be explored in future studies. Trial registration: ClinicalTrials.gov NCT03814694. Funding: The study was funded by Arla Foods amba, The Danish Dairy Research Foundation, and Copenhagen University Hospital Bispebjerg Frederiksberg. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that “leanness” and good metabolic health markers may predict larger increases in LDL cholesterol (LDL-C) in response to carbohydrate restriction. Specifically, a recent cohort study demonstrated an inverse association between BMI and LDL-C change among individuals on carbohydrate-restricted diets and identified a subgroup of “Lean Mass Hyper-Responders” (LMHR) who exhibit exceptional increases in LDL-C, in the context of low triglycerides and high HDL-C. We present the case of one subject, LM, who adopted a ketogenic diet for management of ulcerative colitis. He subsequently experienced an increase in LDL-C from 95 to 545 mg/dl, at peak, in association with HDL-C >100 mg/dl and triglycerides ~40 mg/dl, typical of the emergent LMHR phenotype. Assessments of LM’s dietary intake, lipid panels, and BMI are consistent with prior data and suggest that the LMHR phenomenon is not dependent on saturated fat intake but inversely associates with BMI changes. Finally, computed tomography angiography conducted on LM after over 2 years of hypercholesterolemia revealed no evidence of calcified or non-calcified plaque.

Christopher C Webster, Tamzyn E Murphy, Kate M Larmuth, Timothy D Noakes, James A Smith Division of Exercise Science and Sports Medicine, University of Cape Town, Cape Town, South AfricaCorrespondence: Christopher C WebsterDivision of Exercise Science and Sports Medicine, University of Cape Town, Sports Science Institute of South Africa, Newlands, Cape Town 7700, South AfricaEmail wbschr002@myuct.ac.zaBackground: Low carbohydrate high fat (LCHF) diets are increasing in popularity amongst patients with type 2 diabetes (T2D), however it is unclear what constitutes a sustainable LCHF diet in a real-world setting.Methods: This descriptive multi-method study characterized the diets, T2D status, and personal experiences of individuals with T2D who claimed to have followed an LCHF diet for at least 6 months. Participants completed a medications history, mixed-method dietary assessment, provided a blood sample, and were interviewed in-depth about their experiences with the diet (First-Assessment). Past medical records were obtained corresponding to T2D diagnosis and prior to starting their LCHF diets. Additionally, participants were followed up 15 months later to assess T2D remission (Follow-Up).Results: Twenty-eight participants completed First-Assessment and 24 completed Follow-Up. Habitual carbohydrate intake was 20 to 50 g/d for 10 participants and 50 to 115 g/d for 17 participants. Commonly reported foods were full-fat dairy, non-starchy vegetables, coconut oil, eggs, nuts, olives and avocados, olive oil, and red meat and poultry with fat. Median (interquartile range) for HbA1c was 7.5 (6.5–9.5) % prior to starting their diets, 5.8 (5.4–6.2) % at First-Assessment and 5.9 (5.3–6.6) % at Follow-Up. Reported body weight and glucose-lowering medication requirements were considerably lower at both assessments than when starting the diet. At Follow-Up, 24 participants had been following their LCHF diets for 35 (26–53) months, the majority of which were in full or partial T2D remission. Participants perceived reduced hunger and cravings as one of the most important aspects of their diets. Of concern, many participants felt unsupported by their doctors.Conclusion: This study described the foods and characteristics of an LCHF “lifestyle” that was sustainable and effective for certain T2D patients in a real-world setting.Keywords: carbohydrate restriction, diabetes remission, ketogenic diet, LCHF, nutritional therapy, food addiction

A fully provided, hypocaloric, carbohydrate-reduced high-protein (CRHP) diet compared to a hypocaloric conventional diabetes (CD) diet for 6 weeks improved glycemic control to a greater extent in face of an intended 6% weight loss in individuals with type 2 diabetes mellitus (T2DM). The present 24-week extension of that study reports on the efficacy of CRHP and CD diets in a real-life setting. Sixty-five individuals with T2DM who completed the initial 6-week fully provided diet period (% energy from carbohydrate, protein, and fat was 30/30/40 in CRHP, and 50/17/33 in CD) continued a free-living, dietician guided 24-week period of which 59 individuals completed. The CRHP compared to CD group reported a 4% lower carbohydrate intake and had higher urea excretion by 22% (both p ≤ 0.05) at week 30, suggesting less difference in carbohydrate and protein intake between groups during the 24-week extension compared to week 6. The loss of body weight during the initial 6 weeks was maintained in both groups during the 24-week extension (−5.5 ± 4.5 and −4.6 ± 4.8 kg) as well as HbA1c (−8.4 ± 6.2 and −8.4 ± 6.9 mmol/mol) with no significant differences between groups. The additional benefits on glucoregulation harnessed by carbohydrate restriction under full diet provision for 6 weeks combined with titrated weight loss could not be maintained in a real-life setting of self-prepared diet aiming on similar diets for 6 months.

This study investigates the effects of a ketogenic low-carbohydrate high-fat (LCHF) diet on body composition in healthy, young, normal-weight women. With the increasing interest in ketogenic diets for their various health benefits, this research aims to understand their impact on body composition, focusing on women who are often underrepresented in such studies. Conducting a randomized controlled feeding trial with a crossover design, this study compares a ketogenic LCHF diet to a Swedish National Food Agency (NFA)-recommended control diet over four weeks. Seventeen healthy, young, normal-weight women adhered strictly to the provided diets, with ketosis confirmed through blood β-hydroxybutyrate concentrations. Dual-energy X-ray absorptiometry (DXA) was utilized for precise body composition measurements. To avoid bias, all statistical analyses were performed blind. The findings reveal that the ketogenic LCHF diet led to a significant reduction in both lean mass (-1.45 kg 95% CI: [-1.90;-1.00]; p < 0.001) and fat mass (-0.66 kg 95% CI: [-1.00;-0.32]; p < 0.001) compared to the control diet, despite similar energy intake and physical activity levels. This study concludes that while the ketogenic LCHF diet is effective for weight loss, it disproportionately reduces lean mass over fat mass, suggesting the need for concurrent strength training to mitigate muscle loss in women following this diet., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of this study, the collection, analyses, or interpretation of the data, the writing of the manuscript, or the decision to publish the results.

Low carbohydrate diets have a promising mechanistic rationale in the treatment of cancer with favorable preclinical data. The strongest data suggest synergistic effects of dietary interventions with traditional cancer therapies. Recent prospective clinical trials suggest that low carbohydrate diets are safely and feasibly added within a busy oncology clinic, with hopeful additive effects in treatment enhancement.

Chronic diet-related metabolic diseases, including diabetes and obesity, impose enormous burdens on patient wellness, healthcare costs, and worker productivity. Given the interdependent nature of the human and economic costs of metabolic disease, companies should be incentivized to invest in the health of their workforce. We report data from an ongoing pilot program in which employees of a manufacturing company with obesity, prediabetes, or diabetes are being treated by a metabolic health clinic using a carbohydrate restriction, community-orientated telemedicine approach. 10 patients completed the first 6 months of the program, and all lost weight, with a mean weight reduction of 38.4 lbs (17.4 kg). Improvements in HbA1c, fasting glucose, HOMA-IR, triglycerides, C-reactive protein, and systolic blood pressure were also observed across the group. Furthermore, the 10-year risk of having a major cardiovascular event, as calculated by the American Heart Association risk calculator, decreased from a mean of 9.22 to 5.18%, representing a 44% relative risk reduction. As a result of improvements in their metabolic health, patients were able to discontinue medications, leading to an estimated annualized cost savings of USD 45,171.70. These preliminary data provide proof-of-principle that when companies invest in the metabolic health of their workers, both parties stand to gain.

Although carbohydrate restriction is not a new approach for the management of Type 2 diabetes, interest in its safety and efficacy has increased significantly in recent years. The purpose of the current narrative review is to summarise the key relevant research and practical considerations in this area, as well as to explore some of the common concerns expressed in relation to the use of such approaches. There is a strong physiological rationale supporting the role of carbohydrate restriction for the management of Type 2 diabetes, and available evidence suggests that low carbohydrate dietary approaches (LCDs) are as effective as, or superior to, other dietary approaches for its management. Importantly, LCDs appear to be more effective than other dietary approaches for facilitating a reduction in the requirement for certain medications, which leads to their effects on other health markers being underestimated. LCDs have also been demonstrated to be an effective method for achieving remission of Type 2 diabetes for some people. The available evidence does not support concerns that LCDs increase the risk of cardiovascular disease, that such approaches increase the risk of nutrient deficiencies, or that they are more difficult to adhere to than other dietary approaches. A growing number of organisations support the use of LCDs as a suitable choice for individuals with Type 2 diabetes.

Evidence suggests that low carbohydrate eating patterns are effective for rapid weight loss 1, however, little is known about their long-term effects on the risk of chronic diseases. We assessed the association of a low carbohydrate diet score (LCD) with the incidence of type 2 diabetes using Melbourne Collaborative Cohort Study (MCCS) data. Between 1990 and 1994, the MCCS recruited 41,513 people aged 40 to 69 years. The first and second follow-ups were conducted in 1994-1998 and 2003-2007, respectively2. We analysed data from 39,185 participants. LCD at baseline was calculated as the percentage of energy from carbohydrate, fat, and protein. The higher the score the less carbohydrate contributed to energy intake. The association of LCD quintiles with the incidence of diabetes was assessed using modified Poisson regression, adjusted for lifestyle, obesity, socioeconomic and other confounders. LCD was positively associated with diabetes risk. Higher LCD score (p for trend = 0.001) was associated with increased risk of type 2 diabetes. Quintile 5 (38% energy from carbohydrates) versus quintile 1 (55% energy from carbohydrates) showed a 20% increased diabetes risk (incidence risk ratio (IRR) = 1.20 (95% CI: 1.05-1.37)). A further adjustment for BMI and WHR eliminated the association. Mediation analysis demonstrated that BMI attributed 76% of the LCD & diabetes association. Consuming a low carbohydrate diet, reflected as a high LCD score, may increase the risk of type 2 diabetes which is largely explained by obesity. Results imply the need for further studies, including clinical trials investigating the effects of a low carbohydrate diet in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Glucose hypometabolism and insulin resistance increase risk for and accelerate progression in Parkinson's disease and neurocognitive disorders. We conducted a proof of concept trial to determine whether ketogenesis, a metabolic adaptation induced by dietary carbohydrate restriction, can improve cognitive performance in Parkinson's disease patients with mild cognitive impairment. Methods: We enrolled patients with mild cognitive impairment associated with Parkinson's disease in an eight-week nutritional intervention with random assignment to either high-carbohydrate consumption typical of the Western dietary pattern (n = 7) or to a low-carbohydrate, ketogenic regimen (n = 7). We assessed changes in cognitive performance as well as motor function, anthropometrics, and metabolic parameters. Results: Relative to the high-carbohydrate group, the low-carbohydrate group demonstrated improvements in lexical access (p = 0.02, Cohen's f effect size = 0.76) and memory (p = 0.01, f = 0.87) and as well as a trend for reduced interference in memory (p = 0.06, f = 0.60). The low-carbohydrate group also exhibited reduced body weight (p

When lean people adopt carbohydrate-restricted diets (CRDs), they may develop a lipid profile consisting of elevated LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) with low triglycerides (TGs). The magnitude of this lipid profile correlates with BMI such that those with lower BMI exhibit larger increases in both LDL-C and HDL-C. The inverse association between BMI and LDL-C and HDL-C change on CRD contributed to the discovery of a subset of individuals—termed Lean Mass Hyper-Responders (LMHR)—who, despite normal pre-diet LDL-C, as compared to non-LMHR (mean levels of 148 and 145 mg/dL, respectively), exhibited a pronounced hyperlipidemic response to a CRD, with mean LDL-C and HDL-C levels increasing to 320 and 99 mg/dL, respectively, in the context of mean TG of 47 mg/dL. In some LMHR, LDL-C levels may be in excess of 500 mg/dL, again, with relatively normal pre-diet LDL-C and absent of genetic findings indicative of familial hypercholesterolemia in those who have been tested. The Lipid Energy Model (LEM) attempts to explain this metabolic phenomenon by positing that, with carbohydrate restriction in lean persons, the increased dependence on fat as a metabolic substrate drives increased hepatic secretion and peripheral uptake of TG contained within very low-density lipoproteins (VLDL) by lipoprotein lipase, resulting in marked elevations of LDL-C and HDL-C, and low TG. Herein, we review the core features of the LEM. We review several existing lines of evidence supporting the model and suggest ways to test the model’s predictions.

In sarcopenic obese subjects it is essential to reduce body weight and preserve lean mass, in order to avoid a worsening of muscle function. Several studies have shown that leucine supplementation can be useful to improve skeletal muscle mass in sarcopenic patients. The aim of our study was to evaluate the effectiveness of a short-term low-calorie diet (LCD) combined with supplementation with whey protein and leucine on weight loss, lean mass and muscle strength in sarcopenic, obese, hyperinsulinemic and post-menopausal women. Sixteen females with a mean age of 60 years (range: 50–70 years), BMI 37.6 kg/m2 (range: 31.7–44.1 Kg/m2), HOMA-index ≥ 2.5 (range: 2.9–12) were assigned to an LCD regimen (1000 kcal/day) with supplementation of 18 g whey proteins which 4.1 g of leucine for 45 days. Anthropometric indexes, blood and urine chemistry, body composition by DEXA, muscle strength by handgrip test and Short Physical Performance Battery (SPPB) were assessed at baseline and at the end of the treatment. A significant reduction in BMI (37.6 vs. 35.7 Kg/m2), waist circumference (107 vs. 102.4 cm), HOMA index (4.8 vs. 2.3) and fasting insulin (17.4 vs. 10.4 μIU/mL) was observed in all patients. Women preserved total lean body mass (55 vs. 5%) and significantly improved their muscle strength, as measured by handgrip (15.3 vs. 20.1 Kg), and their muscle function, as measured by SPPB (7.5 vs. 8.9). A significant increase in BUN was also observed (36.1 vs. 46.3). We conclude that LCD with adequate protein intake and supplementation with whey protein and leucine should be promoted to maintain muscle mass and improve muscle strength in post-menopausal women with sarcopenic obesity.