Nutrients

Editorial

4 pages, 209 KiB

Open AccessEditorial

Editorial for “The Role of Ketogenic Diet in Human Health and Diseases”: The Multifaceted Impact of Ketogenic Diets on Health and Disease

by Mikiko Watanabe, Silvia Savastano, Carla Lubrano and Giovanni Spera

Nutrients 2023, 15(18), 4027; https://doi.org/10.3390/nu15184027 - 17 Sep 2023

Viewed by 3591

Abstract

The ketogenic diet (KD), characterized by a very low carbohydrate intake and variable protein, fat and calorie intake, has long been in the spotlight for its potential therapeutic applications [...] Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

Research

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10 pages, 871 KiB

Open AccessArticle

Acute Insulin Secretory Effects of a Classic Ketogenic Meal in Healthy Subjects: A Randomized Cross-Over Study

by Alberto Battezzati, Andrea Foppiani, Alessandro Leone, Ramona De Amicis, Angela Spadafranca, Andrea Mari and Simona Bertoli

Nutrients 2023, 15(5), 1119; https://doi.org/10.3390/nu15051119 - 23 Feb 2023

Cited by 6 | Viewed by 3966

Abstract

The classic ketogenic diet (KD) is a high-fat, low-carbohydrate diet that mimics a starvation state with sufficient caloric intake to sustain growth and development. KD is an established treatment for several diseases, and it is currently evaluated in the management of insulin-resistant states, [...] Read more.

The classic ketogenic diet (KD) is a high-fat, low-carbohydrate diet that mimics a starvation state with sufficient caloric intake to sustain growth and development. KD is an established treatment for several diseases, and it is currently evaluated in the management of insulin-resistant states, although insulin secretion after a classic ketogenic meal has never been investigated. We measured the insulin secretion to a ketogenic meal in 12 healthy subjects (50% females, age range 19–31 years, BMI range 19.7–24.7 kg/m²) after cross-over administrations of a Mediterranean meal and a ketogenic meal both satisfying ~40% of an individual’s total energy requirement, in random order and separated by a 7-day washout period. Venous blood was sampled at baseline and at 10, 20, 30, 45, 60, 90, 120, and 180 min to measure glucose, insulin, and C-peptide concentrations. Insulin secretion was calculated from C-peptide deconvolution and normalized to the estimated body surface area. Glucose, insulin concentrations, and insulin secretory rate were markedly reduced after the ketogenic meal with respect to the Mediterranean meal: glucose AUC in the first OGTT hour −643 mg × dL⁻¹ × min⁻¹, 95% CI −1134, −152, p = 0.015; total insulin concentration −44,943 pmol/L, 95% CI −59,181, −3706, p < 0.001; peak rate of insulin secretion −535 pmol × min⁻¹ × m⁻², 95% CI −763, −308, p < 0.001. We have shown that a ketogenic meal is disposed of with only a minimal insulin secretory response compared to a Mediterranean meal. This finding may be of interest to patients with insulin resistance and or insulin secretory defects. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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11 pages, 287 KiB

Open AccessEditor’s ChoiceArticle

The Effects of Eight Weeks’ Very Low-Calorie Ketogenic Diet (VLCKD) on Liver Health in Subjects Affected by Overweight and Obesity

by Roberta Rinaldi, Sara De Nucci, Fabio Castellana, Martina Di Chito, Vito Giannuzzi, Endrit Shahini, Roberta Zupo, Luisa Lampignano, Giuseppina Piazzolla, Vincenzo Triggiani, Raffaele Cozzolongo, Gianluigi Giannelli and Giovanni De Pergola

Nutrients 2023, 15(4), 825; https://doi.org/10.3390/nu15040825 - 6 Feb 2023

Cited by 18 | Viewed by 7675

Abstract

Very low-calorie ketogenic diets (VLCKD) are widely employed in successful weight-loss strategies. Herein, we evaluated the efficacy and safety of a VLCKD on non-alcoholic fatty liver disease (NAFLD) and parameters commonly associated with this condition in overweight and obese subjects who did not [...] Read more.

Very low-calorie ketogenic diets (VLCKD) are widely employed in successful weight-loss strategies. Herein, we evaluated the efficacy and safety of a VLCKD on non-alcoholic fatty liver disease (NAFLD) and parameters commonly associated with this condition in overweight and obese subjects who did not take any drugs. This prospective, real-life study included thirty-three participants who followed a VLCKD for 8 weeks. NAFLD was diagnosed using transient elastography (FibroScan). Data on anthropometric measurements, bioimpedance analysis, and biochemical assays were gathered both before and after the dietary intervention. BMI (kg/m²) (from 33.84 ± 6.55 to 30.89 ± 6.38, p < 0.01), waist circumference (cm) (from 106.67 ± 15.51 to 98.64 ± 16.21, p < 0.01), and fat mass (Kg) (from 38.47 ± 12.59 to 30.98 ± 12.39, p < 0.01) were significantly lower after VLCKD. CAP (db/m), the FibroScan parameter quantifying fatty liver accumulation, showed a significant reduction after VLCKD (from 266.61 ± 67.96 to 223 ± 64.19, p < 0.01). After VLCKD, the fatty liver index (FLI), a benchmark of steatosis, also revealed a significant decline (from 62.82 ± 27.46 to 44.09 ± 31.24, p < 0.01). Moreover, fasting blood glucose, insulin, triglycerides, total cholesterol, LDL-cholesterol, ALT, γGT, and FT3 blood concentrations, as well as insulin resistance (quantified by HOMAIR) and systolic and diastolic blood pressure levels, were significantly lower after VLCKD (p < 0.01 for all the parameters). By contrast, HDL-cholesterol, 25 (OH) vitamin D, and FT4 blood concentrations were higher after VLCKD (p < 0.01 for all parameters). The variation (δ) of CAP after VLCKD did not show a correlation with the δ of any other parameter investigated in this study. We conclude that VLCKD is a helpful approach for NAFLD independent of changes in factors commonly associated with NAFLD (obesity, fat mass, insulin resistance, lipids, and blood pressure) as well as vitamin D and thyroid hormone levels. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

17 pages, 989 KiB

Open AccessArticle

Italian Ketogenic Mediterranean Diet in Overweight and Obese Patients with Prediabetes or Type 2 Diabetes

by Cincione Raffaele Ivan, Antonietta Messina, Giuseppe Cibelli, Giovanni Messina, Rita Polito, Francesca Losavio, Ester La Torre, Vincenzo Monda, Marcellino Monda, Stefano Quiete, Elias Casula, Nicola Napoli and Giuseppe Defeudis

Nutrients 2022, 14(20), 4361; https://doi.org/10.3390/nu14204361 - 18 Oct 2022

Cited by 13 | Viewed by 5204

Abstract

Obesity is a multifactorial disease strongly associated with insulin resistance and/or type 2 diabetes mellitus. Correct nutrition represents a valid strategy to fight these dysmetabolic pathologies responsible for numerous diseases, including inflammatory and cardiovascular ones. Medical nutrition therapy, including a Mediterranean diet (MD) [...] Read more.

Obesity is a multifactorial disease strongly associated with insulin resistance and/or type 2 diabetes mellitus. Correct nutrition represents a valid strategy to fight these dysmetabolic pathologies responsible for numerous diseases, including inflammatory and cardiovascular ones. Medical nutrition therapy, including a Mediterranean diet (MD) and a very low-calorie ketogenic diet (VLKCD), is the first-line treatment for prediabetes/diabetes and overweight/obesity. Eighty patients (forty women and forty men) affected by overweight/obesity and type 2 diabetes mellitus or impaired glucose tolerance or impaired fasting glucose (51 (ys) ± 1.75; BMI (kg/m²) 33.08 ± 1.93; HA1c (%): 6.8% ± 0.25) were enrolled at the University Service of Diet Therapy, Diabetology and Metabolic Diseases, Policlinico Riuniti Hospital of Foggia, and subjected to a very-low-calorie Mediterranean diet and a very-low-calorie ketogenic Mediterranean diet for thirty days. Both diets result in a marked decrease in body weight (kg) and BMI (kg/m²). At the same time, only the very-low-calories ketogenic Mediterranean diet reduced waist and hip circumferences. Both diets helped reduce fat mass, but a major loss was achieved in a very low-calorie ketogenic Mediterranean diet. Among gluco-metabolic parameters, only the very-low-calorie ketogenic Mediterranean diet group showed a significant decrease in fasting blood glucose and HbA1c, insulin, C-peptide total cholesterol, LDL, and triglycerides. The results of our study seem to show that the very-low-calorie ketogenic Mediterranean diet is a good strategy to improve rapidly metabolic, anthropometric, and body composition parameters in patients with prediabetes or diabetes and overweight/obesity. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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30 pages, 13588 KiB

Open AccessArticle

Ketogenic Diet Treatment of Defects in the Mitochondrial Malate Aspartate Shuttle and Pyruvate Carrier

by Bigna K. Bölsterli, Eugen Boltshauser, Luigi Palmieri, Johannes Spenger, Michaela Brunner-Krainz, Felix Distelmaier, Peter Freisinger, Tobias Geis, Andrea L. Gropman, Johannes Häberle, Julia Hentschel, Bruno Jeandidier, Daniela Karall, Boris Keren, Annick Klabunde-Cherwon, Vassiliki Konstantopoulou, Raimund Kottke, Francesco M. Lasorsa, Christine Makowski, Cyril Mignot, Ruth O’Gorman Tuura, Vito Porcelli, René Santer, Kuntal Sen, Katja Steinbrücker, Steffen Syrbe, Matias Wagner, Andreas Ziegler, Thomas Zöggeler, Johannes A. Mayr, Holger Prokisch and Saskia B. Wortmann Show full author list Hide full author list

Nutrients 2022, 14(17), 3605; https://doi.org/10.3390/nu14173605 - 31 Aug 2022

Cited by 15 | Viewed by 5392

Abstract

The mitochondrial malate aspartate shuttle system (MAS) maintains the cytosolic NAD+/NADH redox balance, thereby sustaining cytosolic redox-dependent pathways, such as glycolysis and serine biosynthesis. Human disease has been associated with defects in four MAS-proteins (encoded by MDH1, MDH2, GOT2, SLC25A12 [...] Read more.

The mitochondrial malate aspartate shuttle system (MAS) maintains the cytosolic NAD+/NADH redox balance, thereby sustaining cytosolic redox-dependent pathways, such as glycolysis and serine biosynthesis. Human disease has been associated with defects in four MAS-proteins (encoded by MDH1, MDH2, GOT2, SLC25A12) sharing a neurological/epileptic phenotype, as well as citrin deficiency (SLC25A13) with a complex hepatopathic-neuropsychiatric phenotype. Ketogenic diets (KD) are high-fat/low-carbohydrate diets, which decrease glycolysis thus bypassing the mentioned defects. The same holds for mitochondrial pyruvate carrier (MPC) 1 deficiency, which also presents neurological deficits. We here describe 40 (18 previously unreported) subjects with MAS-/MPC1-defects (32 neurological phenotypes, eight citrin deficiency), describe and discuss their phenotypes and genotypes (presenting 12 novel variants), and the efficacy of KD. Of 13 MAS/MPC1-individuals with a neurological phenotype treated with KD, 11 experienced benefits—mainly a striking effect against seizures. Two individuals with citrin deficiency deceased before the correct diagnosis was established, presumably due to high-carbohydrate treatment. Six citrin-deficient individuals received a carbohydrate-restricted/fat-enriched diet and showed normalisation of laboratory values/hepatopathy as well as age-adequate thriving. We conclude that patients with MAS-/MPC1-defects are amenable to dietary intervention and that early (genetic) diagnosis is key for initiation of proper treatment and can even be lifesaving. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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Graphical abstract

11 pages, 981 KiB

Open AccessArticle

Safety and Efficacy of Eucaloric Very Low-Carb Diet (EVLCD) in Type 1 Diabetes: A One-Year Real-Life Retrospective Experience

by Andrea Kleiner, Barbara Cum, Livia Pisciotta, Ivan Raffaele Cincione, Ludovica Cogorno, Amalia Prigione, Antonio Tramacere, Andrea Vignati, Luca Carmisciano and Samir Giuseppe Sukkar

Nutrients 2022, 14(15), 3208; https://doi.org/10.3390/nu14153208 - 5 Aug 2022

Cited by 11 | Viewed by 6098

Abstract

A eucaloric very low carbohydrate diet (EVLCD) is a diet with a daily caloric intake equal to the total daily energy expenditure (TDEE) with a carbohydrate content of <50 g/day. The literature on very low carbohydrate diets (VLCD) in type 1 diabetes (DM [...] Read more.

A eucaloric very low carbohydrate diet (EVLCD) is a diet with a daily caloric intake equal to the total daily energy expenditure (TDEE) with a carbohydrate content of <50 g/day. The literature on very low carbohydrate diets (VLCD) in type 1 diabetes (DM 1) is limited, although recently published scientific studies have highlighted their safety and efficacy in managing DM 1. In this retrospective analysis, we report the clinical data of 33 patients affected by DM 1 carrying out insulin therapy who switched voluntarily from their usual diet (high carb, low fat) to an EVLCD. Our aim is to evaluate the glycemic control, the amount of insulin needed in order to maintain glycemic control and safety of EVLCD. The switch improved glycemic control (mean glycated hemoglobin decreased from 8.3% to 6.8% (p < 0.01). The number of patients who reached a glycated hemoglobin value of <7% increased statistically from 12% to 57% (p < 0.01), and there was a statistically significant decrease (p < 0.01) in the units of daily insulin (from 36.7± 14.9 IU to 28.9 ±9.1 IU) A reduction from 54% to 24% in clinical level 2 hypoglycemia episodes was reported. No cases of severe hypoglycemia or ketoacidosis were observed. The results of the study support that EVLCD in DM 1 seems safe and effective when adopted under tight medical supervision. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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11 pages, 1385 KiB

Open AccessArticle

Beneficial Effects of the Very-Low-Calorie Ketogenic Diet on the Symptoms of Male Accessory Gland Inflammation

by Rosita A. Condorelli, Antonio Aversa, Livia Basile, Rossella Cannarella, Laura M. Mongioì, Laura Cimino, Sarah Perelli, Massimiliano Caprio, Sebastiano Cimino, Aldo E. Calogero and Sandro La Vignera

Nutrients 2022, 14(5), 1081; https://doi.org/10.3390/nu14051081 - 4 Mar 2022

Cited by 3 | Viewed by 4755

Abstract

Introduction. Obesity exposes individuals to the risk of chronic inflammation of the prostate gland. Aim and design of the study. A longitudinal clinical study was conducted on selected overweight/obese patients with male accessory gland inflammation (MAGI) to evaluate the effects of body weight [...] Read more.

Introduction. Obesity exposes individuals to the risk of chronic inflammation of the prostate gland. Aim and design of the study. A longitudinal clinical study was conducted on selected overweight/obese patients with male accessory gland inflammation (MAGI) to evaluate the effects of body weight loss on their urogenital symptoms. Materials and methods. One hundred patients were selected and assigned to two groups undergoing two different nutritional programs. The first group (n = 50) started a Mediterranean diet (MedDiet) and the second (n = 50) a very-low-calorie ketogenic diet (VLCKD). Before and after three months on the diet, each patient was evaluated for body weight, waist circumference, and MAGI symptoms. The MAGI was assessed using the Structured Interview about MAGI (SI-MAGI), a questionnaire previously designed to assess the symptoms of MAGI. The questionnaire explores four domains, including urinary symptoms, ejaculatory pain or discomfort, sexual dysfunction, and impaired quality of life. Finally, in the two groups, the frequency of an α-blocker used to treat urinary tract symptoms was also evaluated. Results. Patients on MedDiet experienced significant amelioration in urinary symptoms and quality of life. Patients under VLCKD reported not only significant improvement of the same parameters, but also in ejaculatory pain/discomfort and sexual dysfunction. Finally, the percentage of patients on VLCKD taking the α-blocker decreased significantly. Moreover, patients under VLCKD showed a greater loss of body weight than those following the MedDiet. Discussion. The results of this study support the effectiveness of VLCKD in improving the symptoms of patients with MAGI. This improvement involved all of the domains of the SI-MAGI questionnaire and became manifest in a relatively short time. We suggest that a ketogenic nutritional approach can be used in overweight/obese patients with MAGI. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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12 pages, 952 KiB

Open AccessArticle

Randomized Clinical Trial to Evaluate the Morphological Changes in the Adventitial Vasa Vasorum Density and Biological Markers of Endothelial Dysfunction in Subjects with Moderate Obesity Undergoing a Very Low-Calorie Ketogenic Diet

by Enric Sánchez, Maria-Dolores Santos, Maitane Nuñez-Garcia, Marta Bueno, Ignacio Sajoux, Andree Yeramian and Albert Lecube

Nutrients 2022, 14(1), 33; https://doi.org/10.3390/nu14010033 - 23 Dec 2021

Cited by 9 | Viewed by 4566

Abstract

Weight loss after bariatric surgery decreases the earlier expansion of the adventitial vasa vasorum (VV), a biomarker of early atheromatous disease. However, no data are available regarding weight loss achieved by very low calorie ketogenic diets (VLCKD) on VV and lipid-based atherogenic indices. [...] Read more.

Weight loss after bariatric surgery decreases the earlier expansion of the adventitial vasa vasorum (VV), a biomarker of early atheromatous disease. However, no data are available regarding weight loss achieved by very low calorie ketogenic diets (VLCKD) on VV and lipid-based atherogenic indices. A randomized clinical trial was performed to examine changes in adventitial VV density in 20 patients with moderate obesity who underwent a 6-month very low calorie ketogenic diet (VLCKD, 600–800 kcal/day), and 10 participants with hypocaloric diet based on the Mediterranean Diet (MedDiet, estimated reduction of 500 kcal on the usual intake). Contrast-enhanced carotid ultrasound was used to assess the VV. Body composition analysis was also used. The atherogenic index of plasma (log (triglycerides to high-density lipoprotein cholesterol ratio)) and the triglyceride-glucose index were calculated. Serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. The impact of weight on quality of life-lite (IWQOL-Lite) questionnaire was administered. Participants of intervention groups displayed a similar VV values. Significant improvements of BMI (−5.3 [−6.9 to −3.6] kg/m², p < 0.001), total body fat (−7.0 [−10.7 to −3.3] %, p = 0.003), and IWQOL-Lite score (−41.4 [−75.2 to −7.6], p = 0.027) were observed in VLCKD group in comparison with MedDiet group. Although after a 6-months follow-up period VV density (mean, right and left sides) did not change significantly in any group, participants in the VLCKD exhibited a significantly decrease both in their atherogenic index of plasma and serum concentration of sICAM-1. A 6-month intervention with VLCKD do not impact in the density of the adventitial VV in subjects with moderate obesity, but induces significant changes in markers of endothelial dysfunction and CV risk. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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Review

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10 pages, 295 KiB

Open AccessReview

Ketogenic Diets in the Management of Lennox-Gastaut Syndrome—Review of Literature

by Urszula Skrobas, Piotr Duda, Łukasz Bryliński, Paulina Drożak, Magdalena Pelczar and Konrad Rejdak

Nutrients 2022, 14(23), 4977; https://doi.org/10.3390/nu14234977 - 23 Nov 2022

Cited by 6 | Viewed by 2874

Abstract

Epilepsy is an important medical problem with approximately 50 million patients globally. No more than 70% of epileptic patients will achieve seizure control after antiepileptic drugs, and several epileptic syndromes, including Lennox-Gastaut syndrome (LGS), are predisposed to more frequent pharmacoresistance. Ketogenic dietary therapies [...] Read more.

Epilepsy is an important medical problem with approximately 50 million patients globally. No more than 70% of epileptic patients will achieve seizure control after antiepileptic drugs, and several epileptic syndromes, including Lennox-Gastaut syndrome (LGS), are predisposed to more frequent pharmacoresistance. Ketogenic dietary therapies (KDTs) are a form of non-pharmacological treatments used in attempts to provide seizure control for LGS patients who experience pharmacoresistance. Our review aimed to evaluate the efficacy and practicalities concerning the use of KDTs in LGS. In general, KDTs are diets rich in fat and low in carbohydrates that put the organism into the state of ketosis. A classic ketogenic diet (cKD) is the best-evaluated KDT, while alternative KDTs, such as the medium-chain triglyceride diet (MCT), modified Atkins diet (MAD), and low glycemic index treatment (LGIT) present several advantages due to their better tolerability and easier administration. The literature reports regarding LGS suggest that KDTs can provide ≥50% seizure reduction and seizure-free status in a considerable percentage of the patients. The most commonly reported adverse effects are constipation, diarrhea, and vomiting, while severe adverse effects such as nephrolithiasis or osteopenia are rarely reported. The literature review suggests that KDTs can be applied safely and are effective in LGS treatment. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

16 pages, 745 KiB

Open AccessEditor’s ChoiceReview

The Therapeutic Role of Short-Chain Fatty Acids Mediated Very Low-Calorie Ketogenic Diet–Gut Microbiota Relationships in Paediatric Inflammatory Bowel Diseases

by Naser A. Alsharairi

Nutrients 2022, 14(19), 4113; https://doi.org/10.3390/nu14194113 - 3 Oct 2022

Cited by 19 | Viewed by 4684

Abstract

The very low-calorie ketogenic diet (VLCKD) has been recognized as a promising dietary regimen for the treatment of several diseases. Short-chain fatty acids (SCFAs) produced by anaerobic bacterial fermentation of indigestible dietary fibre in the gut have potential value for their underlying epigenetic [...] Read more.

The very low-calorie ketogenic diet (VLCKD) has been recognized as a promising dietary regimen for the treatment of several diseases. Short-chain fatty acids (SCFAs) produced by anaerobic bacterial fermentation of indigestible dietary fibre in the gut have potential value for their underlying epigenetic role in the treatment of obesity and asthma-related inflammation through mediating the relationships between VLCKD and the infant gut microbiota. However, it is still unclear how VLCKD might influence gut microbiota composition in children, and how SCFAs could play a role in the treatment of inflammatory bowel disease (IBD). To overcome this knowledge gap, this review aims to investigate the role of SCFAs as key epigenetic metabolites that mediate VLCKD–gut microbiota relationships in children, and their therapeutic potential in IBD. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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18 pages, 2727 KiB

Open AccessReview

Ketogenic Diet in the Treatment of Gliomas and Glioblastomas

by Simone Dal Bello, Francesca Valdemarin, Deborah Martinuzzi, Francesca Filippi, Gian Luigi Gigli and Mariarosaria Valente

Nutrients 2022, 14(18), 3851; https://doi.org/10.3390/nu14183851 - 17 Sep 2022

Cited by 26 | Viewed by 7227

Abstract

In recent years, scientific interest in the use of the ketogenic diet (KD) as a complementary approach to the standard cancer therapy has grown, in particular against those of the central nervous system (CNS). In metabolic terms, there are the following differences between [...] Read more.

In recent years, scientific interest in the use of the ketogenic diet (KD) as a complementary approach to the standard cancer therapy has grown, in particular against those of the central nervous system (CNS). In metabolic terms, there are the following differences between healthy and neoplastic cells: neoplastic cells divert their metabolism to anaerobic glycolysis (Warburg effect), they alter the normal mitochondrial functioning, and they use mainly certain amino acids for their own metabolic needs, to gain an advantage over healthy cells and to lead to a pro-oncogenetic effect. Several works in literature speculate which are the molecular targets of KD used against cancer. The following different mechanisms of action will be explored in this review: metabolic, inflammatory, oncogenic and oncosuppressive, ROS, and epigenetic modulation. Preclinical and clinical studies on the use of KD in CNS tumors have also increased in recent years. An interesting hypothesis emerged from the studies about the possible use of a ketogenic diet as a combination therapy along with chemotherapy (CT) and radiotherapy (RT) for the treatment of cancer. Currently, however, clinical data are still very limited but encouraging, so we need further studies to definitively validate or disprove the role of KD in fighting against cancer. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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22 pages, 969 KiB

Open AccessReview

The Effect of Ketogenic Diet on Shared Risk Factors of Cardiovascular Disease and Cancer

by Noushin Mohammadifard, Fahimeh Haghighatdoost, Mehran Rahimlou, Ana Paula Santos Rodrigues, Mohammadamin Khajavi Gaskarei, Paria Okhovat, Cesar de Oliveira, Erika Aparecida Silveira and Nizal Sarrafzadegan

Nutrients 2022, 14(17), 3499; https://doi.org/10.3390/nu14173499 - 25 Aug 2022

Cited by 39 | Viewed by 13193

Abstract

Cardiovascular disease (CVD) and cancer are the first and second leading causes of death worldwide, respectively. Epidemiological evidence has demonstrated that the incidence of cancer is elevated in patients with CVD and vice versa. However, these conditions are usually regarded as separate events [...] Read more.

Cardiovascular disease (CVD) and cancer are the first and second leading causes of death worldwide, respectively. Epidemiological evidence has demonstrated that the incidence of cancer is elevated in patients with CVD and vice versa. However, these conditions are usually regarded as separate events despite the presence of shared risk factors between both conditions, such as metabolic abnormalities and lifestyle. Cohort studies suggested that controlling for CVD risk factors may have an impact on cancer incidence. Therefore, it could be concluded that interventions that improve CVD and cancer shared risk factors may potentially be effective in preventing and treating both diseases. The ketogenic diet (KD), a low-carbohydrate and high-fat diet, has been widely prescribed in weight loss programs for metabolic abnormalities. Furthermore, recent research has investigated the effects of KD on the treatment of numerous diseases, including CVD and cancer, due to its role in promoting ketolysis, ketogenesis, and modifying many other metabolic pathways with potential favorable health effects. However, there is still great debate regarding prescribing KD in patients either with CVD or cancer. Considering the number of studies on this topic, there is a clear need to summarize potential mechanisms through which KD can improve cardiovascular health and control cell proliferation. In this review, we explained the history of KD, its types, and physiological effects and discussed how it could play a role in CVD and cancer treatment and prevention. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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18 pages, 1011 KiB

Open AccessReview

Ketone Bodies and SIRT1, Synergic Epigenetic Regulators for Metabolic Health: A Narrative Review

by Rossella Tozzi, Fiammetta Cipriani, Davide Masi, Sabrina Basciani, Mikiko Watanabe, Carla Lubrano, Lucio Gnessi and Stefania Mariani

Nutrients 2022, 14(15), 3145; https://doi.org/10.3390/nu14153145 - 30 Jul 2022

Cited by 21 | Viewed by 6076

Abstract

Ketone bodies (KBs) and Sirtuin-1 (SIRT1) have received increasing attention over the past two decades given their pivotal function in a variety of biological contexts, including transcriptional regulation, cell cycle progression, inflammation, metabolism, neurological and cardiovascular physiology, and cancer. As a consequence, the [...] Read more.

Ketone bodies (KBs) and Sirtuin-1 (SIRT1) have received increasing attention over the past two decades given their pivotal function in a variety of biological contexts, including transcriptional regulation, cell cycle progression, inflammation, metabolism, neurological and cardiovascular physiology, and cancer. As a consequence, the modulation of KBs and SIRT1 is considered a promising therapeutic option for many diseases. The direct regulation of gene expression can occur in vivo through histone modifications mediated by both SIRT1 and KBs during fasting or low-carbohydrate diets, and dietary metabolites may contribute to epigenetic regulation, leading to greater genomic plasticity. In this review, we provide an updated overview of the epigenetic interactions between KBs and SIRT1, with a particular glance at their central, synergistic roles for metabolic health. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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9 pages, 953 KiB

Open AccessEditor’s ChoiceReview

Ketogenic Diet and Weight Loss: Is There an Effect on Energy Expenditure?

by Alessio Basolo, Silvia Magno, Ferruccio Santini and Giovanni Ceccarini

Nutrients 2022, 14(9), 1814; https://doi.org/10.3390/nu14091814 - 26 Apr 2022

Cited by 24 | Viewed by 11796

Abstract

A dysregulation between energy intake (EI) and energy expenditure (EE), the two components of the energy balance equation, is one of the mechanisms responsible for the development of obesity. Conservation of energy equilibrium is deemed a dynamic process and alterations of one component [...] Read more.

A dysregulation between energy intake (EI) and energy expenditure (EE), the two components of the energy balance equation, is one of the mechanisms responsible for the development of obesity. Conservation of energy equilibrium is deemed a dynamic process and alterations of one component (energy intake or energy expenditure) lead to biological and/or behavioral compensatory changes in the counterpart. The interplay between energy demand and caloric intake appears designed to guarantee an adequate fuel supply in variable life contexts. In the past decades, researchers focused their attention on finding efficient strategies to fight the obesity pandemic. The ketogenic or “keto” diet (KD) gained substantial consideration as a potential weight-loss strategy, whereby the concentration of blood ketones (acetoacetate, 3-β-hydroxybutyrate, and acetone) increases as a result of increased fatty acid breakdown and the activity of ketogenic enzymes. It has been hypothesized that during the first phase of KDs when glucose utilization is still prevalent, an increase in EE may occur, due to increased hepatic oxygen consumption for gluconeogenesis and for triglyceride-fatty acid recycling. Later, a decrease in 24-h EE may ensue due to the slowing of gluconeogenesis and increase in fatty acid oxidation, with a reduction of the respiratory quotient and possibly the direct action of additional hormonal signals. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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19 pages, 665 KiB

Open AccessReview

The Influence of Ketone Bodies on Circadian Processes Regarding Appetite, Sleep and Hormone Release: A Systematic Review of the Literature

by Davide Masi, Maria Elena Spoltore, Rebecca Rossetti, Mikiko Watanabe, Rossella Tozzi, Alessandra Caputi, Renata Risi, Angela Balena, Orietta Gandini, Stefania Mariani, Giovanni Spera, Lucio Gnessi and Carla Lubrano

Nutrients 2022, 14(7), 1410; https://doi.org/10.3390/nu14071410 - 28 Mar 2022

Cited by 23 | Viewed by 8743

Abstract

Chrononutrition is an emerging branch of chronobiology focusing on the profound interactions between biological rhythms and metabolism. This framework suggests that, just like all biological processes, even nutrition follows a circadian pattern. Recent findings elucidated the metabolic roles of circadian clocks in the [...] Read more.

Chrononutrition is an emerging branch of chronobiology focusing on the profound interactions between biological rhythms and metabolism. This framework suggests that, just like all biological processes, even nutrition follows a circadian pattern. Recent findings elucidated the metabolic roles of circadian clocks in the regulation of both hormone release and the daily feeding–fasting cycle. Apart from serving as energy fuel, ketone bodies play pivotal roles as signaling mediators and drivers of gene transcription, promoting food anticipation and loss of appetite. Herein we provide a comprehensive review of the literature on the effects of the ketogenic diets on biological processes that follow circadian rhythms, among them appetite, sleep, and endocrine function. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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10 pages, 278 KiB

Open AccessReview

The Ketogenic Diet: Is It an Answer for Sarcopenic Obesity?

by Zahra Ilyas, Simone Perna, Tariq A. Alalwan, Muhammad Nauman Zahid, Daniele Spadaccini, Clara Gasparri, Gabriella Peroni, Alessandro Faragli, Alessio Alogna, Edoardo La Porta, Ali Ali Redha, Massimo Negro, Giuseppe Cerullo, Giuseppe D’Antona and Mariangela Rondanelli

Nutrients 2022, 14(3), 620; https://doi.org/10.3390/nu14030620 - 30 Jan 2022

Cited by 12 | Viewed by 7043

Abstract

This review aims to define the effectiveness of the ketogenic diet (KD) for the management of sarcopenic obesity. As the combination of sarcopenia and obesity appears to have multiple negative metabolic effects, this narrative review discusses the effects of the ketogenic diet as [...] Read more.

This review aims to define the effectiveness of the ketogenic diet (KD) for the management of sarcopenic obesity. As the combination of sarcopenia and obesity appears to have multiple negative metabolic effects, this narrative review discusses the effects of the ketogenic diet as a possible synergic intervention to decrease visceral adipose tissue (VAT) and fatty infiltration of the liver as well as modulate and improve the gut microbiota, inflammation and body composition. The results of this review support the evidence that the KD improves metabolic health and expands adipose tissue γδ T cells that are important for glycaemia control during obesity. The KD is also a therapeutic option for individuals with sarcopenic obesity due to its positive effect on VAT, adipose tissue, cytokines such as blood biochemistry, gut microbiota, and body composition. However, the long-term effect of a KD on these outcomes requires further investigations before general recommendations can be made. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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19 pages, 706 KiB

Open AccessReview

The Role of Short-Chain Fatty Acids in Mediating Very Low-Calorie Ketogenic Diet-Infant Gut Microbiota Relationships and Its Therapeutic Potential in Obesity

by Naser A. Alsharairi

Nutrients 2021, 13(11), 3702; https://doi.org/10.3390/nu13113702 - 21 Oct 2021

Cited by 30 | Viewed by 7379

Abstract

As the very low-calorie ketogenic diet (VLCKD) gains increased interest as a therapeutic approach for many diseases, little is known about its therapeutic use in childhood obesity. Indeed, the role of VLCKD during pregnancy and lactation in influencing short chain fatty acid (SCFA)-producing [...] Read more.

As the very low-calorie ketogenic diet (VLCKD) gains increased interest as a therapeutic approach for many diseases, little is known about its therapeutic use in childhood obesity. Indeed, the role of VLCKD during pregnancy and lactation in influencing short chain fatty acid (SCFA)-producing bacteria and the potential mechanisms involved in the protective effects on obesity are still unclear. Infants are characterized by a diverse gut microbiota composition with higher abundance of SCFA-producing bacteria. Maternal VLCKD during pregnancy and lactation stimulates the growth of diverse species of SCFA-producing bacteria, which may induce epigenetic changes in infant obese gene expression and modulate adipose tissue inflammation in obesity. Therefore, this review aims to determine the mechanistic role of SCFAs in mediating VLCKD-infant gut microbiota relationships and its protective effects on obesity. Full article

(This article belongs to the Special Issue The Role of Ketogenic Diet in Human Health and Diseases)

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