Neuroactive Peptides as Putative Mediators of Antiepileptic Ketogenic Diets

Background: The prevention and treatment of obesity and its cardio-metabolic complications are relevant issues worldwide. Among lifestyle approaches, very low-calorie ketogenic diets (VLCKD) have been shown to lead to rapid initial weight loss, resulting in better long-term weight loss maintenance. As no information on VLCKD studies carried on in a real-world setting are available, we conducted this multi-centre study in a real-world setting, aiming at assessing the efficacy and the safety of a specific multiphasic VLCKD program in women with overweight or obesity. Methods: A multi-center, prospective, uncontrolled trial was conducted in 33 outpatient women (age range 27–60 y) with overweight or obesity (BMI: 30.9 ± 2.7 kg/m2; waist circumference: 96.0 ± 9.4 cm) who started a VLCKD dietary program (duration: 24 weeks), divided into four phases. The efficacy of VLCKD was assessed by evaluating anthropometric measures and cardiometabolic markers; liver and kidney function biomarkers were assessed as safety parameters. Results: The VLCKD program resulted in a significant decrease of body weight and BMI (−14.6%) and waist circumference (−12.4%). At the end of the protocol, 33.3% of the participants reached a normal weight and the subjects in the obesity range were reduced from 70% to 16.7%. HOMA-IR was markedly reduced from 3.17 ± 2.67 to 1.73 ± 1.23 already after phase 2 and was unchanged thereafter. Systolic blood pressure decreased after phase 1 (−3.5 mmHg) and remained unchanged until the end of the program. Total and LDL cholesterol and triglycerides were significantly reduced by VLCKD along with a significant HDL cholesterol increase. Liver, kidney and thyroid function markers did not change and remained within the reference range. Conclusions: The findings of a multi-center VLCKD program conducted in a real-world setting in a cohort of overweight/obese women indicate that it is safe and effective, as it results in a major improvement of cardiometabolic parameters, thus leading to benefits that span well beyond the mere body weight/adiposity reduction.

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Applications of Ketogenic Diets in Patients with Headache: Clinical Recommendations

Nutrients ◽

10.3390/nu13072307 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2307

Author(s):

Cherubino Di Lorenzo ◽

Giovanna Ballerini ◽

Piero Barbanti ◽

Andrea Bernardini ◽

Giacomo D’Arrigo ◽

...

Keyword(s):

Neurological Disorders ◽

Unmet Needs ◽

Therapeutic Option ◽

Drug Resistant ◽

Pharmacological Treatments ◽

Ketogenic Diets ◽

Neurologic Disorders ◽

Clinical Recommendation ◽

Potential Benefits ◽

Drug Resistant Epilepsy

Headaches are among the most prevalent and disabling neurologic disorders and there are several unmet needs as current pharmacological options are inadequate in treating patients with chronic headache, and a growing interest focuses on nutritional approaches as non-pharmacological treatments. Among these, the largest body of evidence supports the use of the ketogenic diet (KD). Exactly 100 years ago, KD was first used to treat drug-resistant epilepsy, but subsequent applications of this diet also involved other neurological disorders. Evidence of KD effectiveness in migraine emerged in 1928, but in the last several year’s different groups of researchers and clinicians began utilizing this therapeutic option to treat patients with drug-resistant migraine, cluster headache, and/or headache comorbid with metabolic syndrome. Here we describe the existing evidence supporting the potential benefits of KDs in the management of headaches, explore the potential mechanisms of action involved in the efficacy in-depth, and synthesize results of working meetings of an Italian panel of experts on this topic. The aim of the working group was to create a clinical recommendation on indications and optimal clinical practice to treat patients with headaches using KDs. The results we present here are designed to advance the knowledge and application of KDs in the treatment of headaches.

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A 1-Month Ketogenic Diet Increased Mitochondrial Mass in Red Gastrocnemius Muscle, but not in the Brain or Liver of Middle-Aged Mice

Nutrients ◽

10.3390/nu13082533 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2533

Author(s):

Zeyu Zhou ◽

Jocelyn Vidales ◽

José A González-Reyes ◽

Bradley Shibata ◽

Keith Baar ◽

...

Keyword(s):

Prefrontal Cortex ◽

Gastrocnemius Muscle ◽

Left Lobe ◽

Middle Aged ◽

Mitochondrial Content ◽

Mitochondrial Mass ◽

Aged Mice ◽

Fractional Area ◽

Ketogenic Diets ◽

The Impact

Alterations in markers of mitochondrial content with ketogenic diets (KD) have been reported in tissues of rodents, but morphological quantification of mitochondrial mass using transmission electron microscopy (TEM), the gold standard for mitochondrial quantification, is needed to further validate these findings and look at specific regions of interest within a tissue. In this study, red gastrocnemius muscle, the prefrontal cortex, the hippocampus, and the liver left lobe were used to investigate the impact of a 1-month KD on mitochondrial content in healthy middle-aged mice. The results showed that in red gastrocnemius muscle, the fractional area of both subsarcolemmal (SSM) and intermyofibrillar (IMM) mitochondria was increased, and this was driven by an increase in the number of mitochondria. Mitochondrial fractional area or number was not altered in the liver, prefrontal cortex, or hippocampus following 1 month of a KD. These results demonstrate tissue-specific changes in mitochondrial mass with a short-term KD and highlight the need to study different muscle groups or tissue regions with TEM to thoroughly determine the effects of a KD on mitochondrial mass.

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Ketogenic diets inhibit mitochondrial biogenesis and induce cardiac fibrosis

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00411-4 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Sha Xu ◽

Hui Tao ◽

Wei Cao ◽

Li Cao ◽

Yan Lin ◽

...

Keyword(s):

Mitochondrial Biogenesis ◽

Ketone Body ◽

Cardiac Fibrosis ◽

Cardiomyocyte Apoptosis ◽

Healthy Individuals ◽

Cell Respiration ◽

Ketogenic Diets ◽

Mitochondrial Ribosome ◽

Encoding Genes ◽

Human Atrial Fibrillation

AbstractIn addition to their use in relieving the symptoms of various diseases, ketogenic diets (KDs) have also been adopted by healthy individuals to prevent being overweight. Herein, we reported that prolonged KD exposure induced cardiac fibrosis. In rats, KD or frequent deep fasting decreased mitochondrial biogenesis, reduced cell respiration, and increased cardiomyocyte apoptosis and cardiac fibrosis. Mechanistically, increased levels of the ketone body β-hydroxybutyrate (β-OHB), an HDAC2 inhibitor, promoted histone acetylation of the Sirt7 promoter and activated Sirt7 transcription. This in turn inhibited the transcription of mitochondrial ribosome-encoding genes and mitochondrial biogenesis, leading to cardiomyocyte apoptosis and cardiac fibrosis. Exogenous β-OHB administration mimicked the effects of a KD in rats. Notably, increased β-OHB levels and SIRT7 expression, decreased mitochondrial biogenesis, and increased cardiac fibrosis were detected in human atrial fibrillation heart tissues. Our results highlighted the unknown detrimental effects of KDs and provided insights into strategies for preventing cardiac fibrosis in patients for whom KDs are medically necessary.

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Medical management of children with type 1 diabetes on low‐carbohydrate or ketogenic diets

Pediatric Diabetes ◽

10.1111/pedi.13179 ◽

2021 ◽

Author(s):

Amy A. Rydin ◽

Gail Spiegel ◽

Brigitte I. Frohnert ◽

Anne Kaess ◽

Lauren Oswald ◽

...

Keyword(s):

Type 1 Diabetes ◽

Medical Management ◽

Ketogenic Diets ◽

Low Carbohydrate

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Body composition changes in physically active individuals consuming ketogenic diets: a systematic review

Journal of the International Society of Sports Nutrition ◽

10.1186/s12970-021-00440-6 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Julie L. Coleman ◽

Christopher T. Carrigan ◽

Lee M. Margolis

Keyword(s):

Systematic Review ◽

Body Composition ◽

Body Mass ◽

Risk Of Bias ◽

Fat Free Mass ◽

Cochrane Library ◽

Ideal Strength ◽

Physically Active ◽

Ketogenic Diets ◽

Study Intervention

Abstract Background To achieve ideal strength/power to mass ratio, athletes may attempt to lower body mass through reductions in fat mass (FM), while maintaining or increasing fat-free mass (FFM) by manipulating their training regimens and diets. Emerging evidence suggests that consumption of high-fat, ketogenic diets (KD) may be advantageous for reducing body mass and FM, while retaining FFM. Methods A systematic review of the literature was conducted using PubMed and Cochrane Library databases to compare the effects of KD versus control diets (CON) on body mass and composition in physically active populations. Randomized and non-randomized studies were included if participants were healthy (free of chronic disease), physically active men or women age ≥ 18 years consuming KD (< 50 g carbohydrate/d or serum or whole blood β-hydroxybutyrate (βhb) > 0.5 mmol/L) for ≥14 days. Results Thirteen studies (9 parallel and 4 crossover/longitudinal) that met the inclusion criteria were identified. Aggregated results from the 13 identified studies show body mass decreased 2.7 kg in KD and increased 0.3 kg in CON. FM decreased by 2.3 kg in KD and 0.3 kg in CON. FFM decreased by 0.3 kg in KD and increased 0.7 kg in CON. Estimated energy balance based on changes in body composition was − 339 kcal/d in KD and 5 kcal/d in CON. Risk of bias identified some concern of bias primarily due to studies which allowed participants to self-select diet intervention groups, as well as inability to blind participants to the study intervention, and/or longitudinal study design. Conclusion KD can promote mobilization of fat stores to reduce FM while retaining FFM. However, there is variance in results of FFM across studies and some risk-of-bias in the current literature that is discussed in this systematic review.

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Incidence and Characteristics of Kidney Stones in Patients on Ketogenic Diet: A Systematic Review and Meta-Analysis

Diseases ◽

10.3390/diseases9020039 ◽

2021 ◽

Vol 9 (2) ◽

pp. 39

Author(s):

Prakrati Acharya ◽

Chirag Acharya ◽

Charat Thongprayoon ◽

Panupong Hansrivijit ◽

Swetha R. Kanduri ◽

...

Keyword(s):

Uric Acid ◽

Kidney Stones ◽

Observational Studies ◽

Meta Analysis ◽

Random Effects Model ◽

Ketogenic Diets ◽

Cochrane Database ◽

Uric Acid Stones ◽

Low Carbohydrate

Very-low-carbohydrate diets or ketogenic diets are frequently used for weight loss in adults and as a therapy for epilepsy in children. The incidence and characteristics of kidney stones in patients on ketogenic diets are not well studied. Methods: A systematic literature search was performed, using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from the databases’ inception through April 2020. Observational studies or clinical trials that provide data on the incidence and/or types of kidney stones in patients on ketogenic diets were included. We applied a random-effects model to estimate the incidence of kidney stones. Results: A total of 36 studies with 2795 patients on ketogenic diets were enrolled. The estimated pooled incidence of kidney stones was 5.9% (95% CI, 4.6–7.6%, I2 = 47%) in patients on ketogenic diets at a mean follow-up time of 3.7 +/− 2.9 years. Subgroup analyses demonstrated the estimated pooled incidence of kidney stones of 5.8% (95% CI, 4.4–7.5%, I2 = 49%) in children and 7.9% (95% CI, 2.8–20.1%, I2 = 29%) in adults, respectively. Within reported studies, 48.7% (95% CI, 33.2–64.6%) of kidney stones were uric stones, 36.5% (95% CI, 10.6–73.6%) were calcium-based (CaOx/CaP) stones, and 27.8% (95% CI, 12.1–51.9%) were mixed uric acid and calcium-based stones, respectively. Conclusions: The estimated incidence of kidney stones in patients on ketogenic diets is 5.9%. Its incidence is approximately 5.8% in children and 7.9% in adults. Uric acid stones are the most prevalent kidney stones in patients on ketogenic diets followed by calcium-based stones. These findings may impact the prevention and clinical management of kidney stones in patients on ketogenic diets.

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Low-Carb and Ketogenic Diets in Type 1 and Type 2 Diabetes

Nutrients ◽

10.3390/nu11050962 ◽

2019 ◽

Vol 11 (5) ◽

pp. 962 ◽

Cited By ~ 27

Author(s):

Bolla ◽

Caretto ◽

Laurenzi ◽

Scavini ◽

Piemonti

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Dietary Interventions ◽

Ketogenic Diets ◽

Patients With Diabetes ◽

Intrinsic Complexity ◽

Few Data ◽

Reducing Carbohydrates

Low-carb and ketogenic diets are popular among clinicians and patients, but the appropriateness of reducing carbohydrates intake in obese patients and in patients with diabetes is still debated. Studies in the literature are indeed controversial, possibly because these diets are generally poorly defined; this, together with the intrinsic complexity of dietary interventions, makes it difficult to compare results from different studies. Despite the evidence that reducing carbohydrates intake lowers body weight and, in patients with type 2 diabetes, improves glucose control, few data are available about sustainability, safety and efficacy in the long-term. In this review we explored the possible role of low-carb and ketogenic diets in the pathogenesis and management of type 2 diabetes and obesity. Furthermore, we also reviewed evidence of carbohydrates restriction in both pathogenesis of type 1 diabetes, through gut microbiota modification, and treatment of type 1 diabetes, addressing the legitimate concerns about the use of such diets in patients who are ketosis-prone and often have not completed their growth.

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A Calorie-Restricted Ketogenic Diet Reduces Cerebral Cortex Vascularization in Prepubertal Rats

Nutrients ◽

10.3390/nu11112681 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2681

Author(s):

Viggiano ◽

Meccariello ◽

Santoro ◽

Secondulfo ◽

Operto ◽

...

Keyword(s):

Cerebral Cortex ◽

Substantia Nigra ◽

Ketogenic Diet ◽

Capillary Density ◽

Diet Group ◽

Cerebral White Matter ◽

Control Group ◽

Standard Diet ◽

Ketogenic Diets ◽

Prepubertal Rats

The antiepileptic effect of ketogenic diets is acknowledged but its mechanism of action is poorly understood. The present work aimed to evaluate possible effects of a calorie-restricted ketogenic diet (CRKD) on brain growth and angiogenesis in normal prepubertal rats. Two groups of prepubertal rats were fed with a standard diet (group 1) or a CRKD (group 2) for ten weeks. Then, rats were sacrificed and the thickness for the following structures was evaluated by histology: (1) cerebral cortex, (2) deep cerebral white matter, and (3) substantia nigra. The capillary density was also evaluated within: (1) cerebral cortex, (2) dentate gyrus of the hippocampus, (3) periaqueductal grey matter, and (4) substantia nigra. The results showed a smaller thickness of all the areas examined and a reduced capillary density within the cerebral cortex in the CRKD-treated group compared to the control group. These findings suggest an association between reduced angiogenesis within the cerebral cortex and the antiepileptic effects of CRKD.

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