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Ketogenic Diet and Metabolism
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Ketogenic Diet and Metabolism

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (18 February 2022) | Viewed by 55808

Special Issue Editors

Dr. Jane Shearer

E-Mail Website
Guest Editor
Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, AB, Canada
Interests: nutrition; metabolism; physical activity; women’s health; pregnancy
Special Issues, Collections and Topics in MDPI journals
Dr. Marina Mourtzakis

E-Mail Website
Co-Guest Editor
University of Waterloo, Waterloo, ON N2J 3G1, Canada
Interests: body composition; nutrition; diet; cancer; chronic disease
Dr. Matthias Klein

E-Mail Website
Co-Guest Editor
Department of Food Science and Technology, The Ohio State University, Columbus, OH 43210, USA
Interests: metabolomics; NMR; microbiome; maternity; chronic disease; type 2 diabetes; machine learning; artificial intelligence

Special Issue Information

Dear Colleagues,

The focus of this Special Issue is “Ketogenic Diet and Metabolism”. Comprising a high proportion of fat, adequate protein, and low carbohydrates, the ketogenic diet (KD) causes a drastic shift in host metabolism by mimicking the fasting state and promoting ketone body production and utilization. The impact of such a radical dietary shift affects almost all tissues in the body (neural, muscular, hepatic), as well as the gut microbiome. The all-encompassing aim of this Special Issue is to identify and characterize the effects of the ketogenic diet under varied conditions (rest, exercise) and populations. Topics ranging from cell metabolism and signalling to the whole organism and its physiological functioning in both health and disease will be considered.  Of particular interest is the use of the ketogenic diet, either as a primary or adjunct therapy in chronic metabolic disease states, including diabetes, cardiovascular disease, cancer and obesity. In addition, work relating to dietetics, diet compliance, marketing and health claims fit into this Special Issue. We encourage the submission of original research articles, reviews, and meta-analyses. 

Dr. Jane Shearer
Guest Editor
Dr. Marina Mourtzakis
Dr. Matthias Klein
Co-Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabolism
  • ketogenic diet
  • nutrition
  • diet

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Published Papers (7 papers)

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Research

Jump to: Review

16 pages, 2959 KiB  
Article
Addition of Prebiotics to the Ketogenic Diet Improves Metabolic Profile but Does Not Affect Seizures in a Rodent Model of Infantile Spasms Syndrome
by Chunlong Mu, Angela Pochakom, Raylene A. Reimer, Anamika Choudhary, Melinda Wang, Jong M. Rho, Morris H. Scantlebury and Jane Shearer
Nutrients 2022, 14(11), 2210; https://doi.org/10.3390/nu14112210 - 26 May 2022
Cited by 4 | Viewed by 3598
Abstract
The ketogenic diet (KD) is an effective treatment for infantile spasms syndrome (IS). However, the KD has implications for somatic growth, development, and the gut microbiota. The impact of incorporating a prebiotic fiber (PRE, oligofructose-enriched inulin, 0.8 g/dL) into a KD diet on [...] Read more.
The ketogenic diet (KD) is an effective treatment for infantile spasms syndrome (IS). However, the KD has implications for somatic growth, development, and the gut microbiota. The impact of incorporating a prebiotic fiber (PRE, oligofructose-enriched inulin, 0.8 g/dL) into a KD diet on spasms, developmental milestones, fecal gut microbiota, metabolites, and hippocampal mitochondrial metabolism were examined. Following IS induction, animals were randomized to KD or KD + PRE diets. A third group without IS and suckled by dams was included as a normally developing reference group (R). PRE inclusion decreased ketones and increased circulating glucose levels but had no impact on spasms. In the liver, PRE increased triglyceride concentrations, decreased carnitine levels, and downregulated genes encoding enzymes responsible for ketogenesis. In the hippocampus, PRE increased glutathione levels but did not affect the maximal respiratory capacity of mitochondria. Analysis of the gut microbiota showed that KD + PRE increased microbial richness and the relative abundance of Bifidobacterium pseudolongum and Lactobacillus johnsonii. No differences in developmental milestones (i.e., surface righting, negative geotaxis, and open field behavior) were observed between KD and KD + PRE, except for ultrasonic vocalizations that were more frequent in KD + PRE. In summary, PRE did not impact spasms or developmental outcomes, but was effective in improving both metabolic parameters and gut microbiota diversity. Full article
(This article belongs to the Special Issue Ketogenic Diet and Metabolism)
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11 pages, 486 KiB  
Article
The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency
by Orna Staretz-Chacham, Ben Pode-Shakked, Eyal Kristal, Smadar Yaala Abraham, Keren Porper, Ohad Wormser, Ilan Shelef and Yair Anikster
Nutrients 2021, 13(10), 3523; https://doi.org/10.3390/nu13103523 - 7 Oct 2021
Cited by 17 | Viewed by 3357
Abstract
Background: Dihydrolipoamide dehydrogenase (DLD lipoamide dehydrogenase, the E3 subunit of the pyruvate dehydrogenase complex (PDHC)) is the third catalytic enzyme of the PDHC, which converts pyruvate to acetyl-CoA catalyzed with the introduction of acetyl-CoA to the tricyclic acid (TCA) cycle. In humans, PDHC [...] Read more.
Background: Dihydrolipoamide dehydrogenase (DLD lipoamide dehydrogenase, the E3 subunit of the pyruvate dehydrogenase complex (PDHC)) is the third catalytic enzyme of the PDHC, which converts pyruvate to acetyl-CoA catalyzed with the introduction of acetyl-CoA to the tricyclic acid (TCA) cycle. In humans, PDHC plays an important role in maintaining glycose homeostasis in an aerobic, energy-generating process. Inherited DLD-E3 deficiency, caused by the pathogenic variants in DLD, leads to variable presentations and courses of illness, ranging from myopathy, recurrent episodes of liver disease and vomiting, to Leigh disease and early death. Currently, there is no consensus on treatment guidelines, although one suggested solution is a ketogenic diet (KD). Objective: To describe the use and effects of KD in patients with DLD-E3 deficiency, compared to the standard treatment. Results: Sixteen patients were included. Of these, eight were from a historical cohort, and of the other eight, four were on a partial KD. All patients were homozygous for the D479V (or D444V, which corresponds to the mutated mature protein without the mitochondrial targeting sequence) pathogenic variant in DLD. The treatment with partial KD was found to improve patient survival. However, compared to a historical cohort, the patients’ quality of life (QOL) was not significantly improved. Conclusions: The use of KD offers an advantage regarding survival; however, there is no significant improvement in QOL. Full article
(This article belongs to the Special Issue Ketogenic Diet and Metabolism)
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8 pages, 531 KiB  
Article
Dietary-Induced Ketogenesis: Adults Are Not Children
by Keren Porper, Leor Zach, Yael Shpatz, Bruria Ben-Zeev, Michal Tzadok, Elisheva Jan, Alisa Talianski, Colin E. Champ, Zvi Symon, Yair Anikster and Yaacov R. Lawrence
Nutrients 2021, 13(9), 3093; https://doi.org/10.3390/nu13093093 - 2 Sep 2021
Cited by 6 | Viewed by 3823
Abstract
There is increasing interest in the use of a ketogenic diet for various adult disorders; however, the ability of adults to generate ketones is unknown. Our goal was to challenge the hypothesis that there would be no difference between adults and children regarding [...] Read more.
There is increasing interest in the use of a ketogenic diet for various adult disorders; however, the ability of adults to generate ketones is unknown. Our goal was to challenge the hypothesis that there would be no difference between adults and children regarding their ability to enter ketosis. Methods: Two populations were studied, both treated with identical very low-carbohydrate high-fat diets: a retrospective series of children with epilepsy or/and metabolic disorders (2009–2016) and a prospective clinical trial of adults with glioblastoma. Dietary intake was assessed based upon written food diaries and 24-h dietary recall. Ketogenic ratio was calculated according to [grams of fat consumed]/[grams of carbohydrate and protein consumed]. Ketone levels (β-hydroxybutyrate) were measured in blood and/or urine. Results: A total of 168 encounters amongst 28 individuals were analyzed. Amongst both children and adults, ketone levels correlated with nutritional ketogenic ratio; however, the absolute ketone levels in adults were approximately one quarter of those seen in children. This difference was highly significant in a multivariate linear regression model, p < 0.0001. Conclusions: For diets with comparable ketogenic ratios, adults have lower blood ketone levels than children; consequently, high levels of nutritional ketosis are unobtainable in adults. Full article
(This article belongs to the Special Issue Ketogenic Diet and Metabolism)
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16 pages, 3134 KiB  
Communication
Slow but Steady—The Responsiveness of Sympathoadrenal System to a Hypoglycemic Challenge in Ketogenic Diet-Fed Rats
by Polina E. Nedoboy, Myfanwy Cohen and Melissa M.-J. Farnham
Nutrients 2021, 13(8), 2627; https://doi.org/10.3390/nu13082627 - 29 Jul 2021
Cited by 4 | Viewed by 3671
Abstract
The sympathoadrenal counterregulatory response to hypoglycemia is critical for individuals with type 1 diabetes due to impaired ability to produce glucagon. Ketogenic diets (KD) are an increasingly popular diabetes management tool; however, the effects of KD on the sympathoadrenal response are largely unknown. [...] Read more.
The sympathoadrenal counterregulatory response to hypoglycemia is critical for individuals with type 1 diabetes due to impaired ability to produce glucagon. Ketogenic diets (KD) are an increasingly popular diabetes management tool; however, the effects of KD on the sympathoadrenal response are largely unknown. Here, we determined the effects of KD-induced ketosis on the sympathoadrenal response to a single insulin-induced hypoglycemic challenge. We investigated how a 3 week KD feeding regimen affected the main components of the sympathoadrenal counterregulatory response: adrenal sympathetic nerve activity (ASNA), adrenal gland activity, plasma epinephrine, and brainstem glucose-responsive C1 neuronal activation in anesthetized, nondiabetic male Sprague-Dawley rats. Rats on KD had similar blood glucose (BG) levels and elevated ketone body β-hydroxybutyrate (BHB) levels compared to the control Chow diet group. All KD rats responded to hypoglycemia with a robust increase in ASNA, which was initiated at significantly lower BG levels compared to Chow-fed rats. The delay in hypoglycemia-induced ASNA increase was concurrent with rapid disappearance of BHB from cerebral and peripheral circulation. Adrenal gland activity paralleled epinephrine and ASNA response. Overall, KD-induced ketosis was associated with initiation of the sympathoadrenal response at lower blood glucose levels; however, the magnitude of the response was not diminished. Full article
(This article belongs to the Special Issue Ketogenic Diet and Metabolism)
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15 pages, 2588 KiB  
Article
Very-Low-Calorie Ketogenic Diet as a Safe and Valuable Tool for Long-Term Glycemic Management in Patients with Obesity and Type 2 Diabetes
by Eleonora Moriconi, Elisabetta Camajani, Andrea Fabbri, Andrea Lenzi and Massimiliano Caprio
Nutrients 2021, 13(3), 758; https://doi.org/10.3390/nu13030758 - 26 Feb 2021
Cited by 66 | Viewed by 22034
Abstract
Obesity-related type 2 diabetes represents one of the most difficult challenges for the healthcare system. This retrospective study aims to determine the efficacy, safety and durability of a very-low-calorie ketogenic diet (VLCKD), compared to a standard low-calorie diet (LCD) on weight-loss, glycemic management, [...] Read more.
Obesity-related type 2 diabetes represents one of the most difficult challenges for the healthcare system. This retrospective study aims to determine the efficacy, safety and durability of a very-low-calorie ketogenic diet (VLCKD), compared to a standard low-calorie diet (LCD) on weight-loss, glycemic management, eating behavior and quality of life in patients with type 2 diabetes (T2DM) and obesity. Thirty patients with obesity and T2DM, aged between 35 and 75 years, who met the inclusion criteria and accepted to adhere to a VLCKD or a LCD nutritional program, were consecutively selected from our electronic database. Fifteen patients followed a structured VLCKD protocol, fifteen followed a classical LCD. At the beginning of the nutritional protocol, all patients were asked to stop any antidiabetic medications, with the exception of metformin. Data were collected at baseline and after 3 (T1) and 12 (T2) months. At T1 and T2, BMI was significantly reduced in the VLCKD group (p < 0.001), whereas it remained substantially unchanged in the LCD group. HbA1c was significantly reduced in the VLCKD group (p = 0.002), whereas a slight, although not significant, decrease was observed in the LCD group. Quality of life and eating behavior scores were improved in the VLCKD group, whereas no significant changes were reported in the LCD group, both at T1 and T2. At the end of the study, in the VLCKD group 26.6% of patients had stopped all antidiabetic medications, and 73.3% were taking only metformin, whereas 46.6% of LCD patients had to increase antidiabetic medications. The study confirms a valuable therapeutic effect of VLCKD in the long-term management of obesity and T2DM and its potential contribution to remission of the disease. Full article
(This article belongs to the Special Issue Ketogenic Diet and Metabolism)
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Review

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9 pages, 610 KiB  
Review
Ketogenic Diet and Cardiac Substrate Metabolism
by Thien Vinh Luong, Caroline Bruun Abild, Maj Bangshaab, Lars Christian Gormsen and Esben Søndergaard
Nutrients 2022, 14(7), 1322; https://doi.org/10.3390/nu14071322 - 22 Mar 2022
Cited by 23 | Viewed by 7387
Abstract
The ketogenic diet (KD) entails a high intake of fat, moderate intake of protein, and a very limited intake of carbohydrates. Ketogenic dieting has been proposed as an effective intervention for type 2 diabetes and obesity since glycemic control is improved and sustained [...] Read more.
The ketogenic diet (KD) entails a high intake of fat, moderate intake of protein, and a very limited intake of carbohydrates. Ketogenic dieting has been proposed as an effective intervention for type 2 diabetes and obesity since glycemic control is improved and sustained weight loss can be achieved. Interestingly, hyperketonemia is also associated with beneficial cardiovascular effects, possibly caused by improved cardiac energetics and reduced oxygen use. Therefore, the KD has the potential to both treat and prevent cardiovascular disease. However, the KD has some adverse effects that could counteract the beneficial cardiovascular properties. Of these, hyperlipidemia with elevation of triglycerides and LDL cholesterol levels are the most important. In addition, poor diet adherence and lack of knowledge regarding long-term effects may also reduce the broader applicability of the KD. The objective of this narrative review is to provide insights into the KD and its effects on myocardial ketone body utilization and, consequently, cardiovascular health. Full article
(This article belongs to the Special Issue Ketogenic Diet and Metabolism)
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12 pages, 539 KiB  
Review
The Role of the Gut Microbiota on the Beneficial Effects of Ketogenic Diets
by Ilias Attaye, Sophie van Oppenraaij, Moritz V. Warmbrunn and Max Nieuwdorp
Nutrients 2022, 14(1), 191; https://doi.org/10.3390/nu14010191 - 31 Dec 2021
Cited by 42 | Viewed by 9065
Abstract
The ketogenic diet is a dietary regime focused on strongly reducing carbohydrate intake and increasing fat intake; leading to a state of ketosis. The ketogenic diet has gained much popularity over the years due to its effects on promoting weight loss, increasing insulin [...] Read more.
The ketogenic diet is a dietary regime focused on strongly reducing carbohydrate intake and increasing fat intake; leading to a state of ketosis. The ketogenic diet has gained much popularity over the years due to its effects on promoting weight loss, increasing insulin sensitivity and reducing dyslipidaemia. All these factors play a crucial role in the development of cardio-metabolic diseases; one of the greatest health challenges of the time. Moreover, the ketogenic diet has been known to reduce (epileptic) seizure activity. It is still poorly understood how following a ketogenic diet can lead to these beneficial metabolic effects. However, in recent years it has become clear that diet and the gut microbiota interact with one another and thus influence host health. The goal of this review is to summarize the current state of knowledge regarding the beneficial metabolic effects of the ketogenic diet and the role of gut microbiota in these effects. Full article
(This article belongs to the Special Issue Ketogenic Diet and Metabolism)
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