Protocol for the Use of the Ketogenic Diet in Preclinical and Clinical Practice

Kraeuter, Ann Katrin; Guest, Paul C.; Sarnyai, Zoltán

doi:10.1007/978-1-0716-0471-7_4

Cited by 14 publications

(10 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…KB include acetylacetate (H3C-CO-CH2-COO-), β-D-hydroxybutyrate (H3C-CHOH-CH2-COO-) and volatile acetone (H3C-CO-CH3). KD are high-fat, moderate-protein and lowcarbohydrate (usually less than 40 g/day) diets 18 , and induce a surge in KB, in particular 3hydroxybutyrate (3HB). This increase in 3HB also occurs after fasting, favoring mitochondrial respiration rather than glycolysis for energy metabolism.…”

Section: Introductionmentioning

confidence: 99%

Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade

Ferrere¹,

Alou²,

et al. 2021

View full text Add to dashboard Cite

Limited experimental evidence bridges nutrition and cancer immunosurveillance. Here, we show that ketogenic diet (KD) — or its principal ketone body, 3-hydroxybutyrate (3HB), most specifically in intermittent scheduling — induced T cell–dependent tumor growth retardation of aggressive tumor models. In conditions in which anti–PD-1 alone or in combination with anti–CTLA-4 failed to reduce tumor growth in mice receiving a standard diet, KD, or oral supplementation of 3HB reestablished therapeutic responses. Supplementation of KD with sucrose (which breaks ketogenesis, abolishing 3HB production) or with a pharmacological antagonist of the 3HB receptor GPR109A abolished the antitumor effects. Mechanistically, 3HB prevented the immune checkpoint blockade–linked upregulation of PD-L1 on myeloid cells, while favoring the expansion of CXCR3 + T cells. KD induced compositional changes of the gut microbiota, with distinct species such as Eisenbergiella massiliensis commonly emerging in mice and humans subjected to carbohydrate-low diet interventions and highly correlating with serum concentrations of 3HB. Altogether, these results demonstrate that KD induces a 3HB-mediated antineoplastic effect that relies on T cell–mediated cancer immunosurveillance.

show abstract

Section: Introductionmentioning

confidence: 99%

Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade

Ferrere¹,

Alou²,

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Diese positiven metabolischen Effekte auf hormoneller Ebene bei Mäusen scheinen bei Tumorpatienten ähnlich zu sein Dies führt zu einem Anstieg der Ketonkörper, insbesondere von 3-Hydroxybutyrat (3HB). Dieser Zustand des Metabolismus wird als Ketose bezeichnet [68]. Ein Anstieg von 3HB kann auch während des Fastens beobachtet werden.…”

Section: Intermittierendes Fastenunclassified

Diätetische Ansätze in der Tumortherapie

Leven,

Eisenburger,

Espelage

et al. 2023

Aktuelle Dermatologie

View full text Add to dashboard Cite

ZusammenfassungIm Zuge der personalisierten Medizin gewinnen bei Tumorerkrankungen patientenindividuelle Faktoren wie persönliche Ernährungsmuster, der Lebensstil, das intestinale Mikrobiom oder das Geschlecht immer mehr an Bedeutung. Neben anderen Tumorentitäten erlangt auch beim malignen Melanom die Ernährung einen zunehmenden Stellenwert. Durch die Einführung der immun- und zielgerichteten Therapien konnte die Mortalität zwar deutlich gesenkt werden, jedoch zeigt sich ein sehr heterogenes Therapieansprechen. Folglich ist das Bestreben groß, alternative oder unterstützende Faktoren für ein besseres Therapieansprechen zu identifizieren. Präklinische Studien konnten bereits positive Effekte diätetischer Interventionen auf eine Immuntherapie und in der Folge auf das Therapieansprechen zeigen. Z.T. konnte das Ansprechen auf eine Immuntherapie sogar wiederhergestellt werden. Dabei wird angenommen, dass der Zellmetabolismus durch eine bestimmte Nährstoffaufnahme „umprogrammiert“ werden kann. Um diese präklinischen Daten auf die Klinik zu transferieren, werden im Rahmen von klinischen Studien diätetische Interventionen in Kombination mit etablierten Tumortherapien untersucht und dabei deren Auswirkungen auf den Metabolismus der Tumor- und Immunzellen analysiert.

show abstract

“…Despite its clinical use for nearly 100 years, how the KD controls seizures remains unknown [12]. KD was used to regulate energy metabolism in order to manage epilepsy [13], beta-hydroxybutyrate is the major bioactive metabolite [14,15]. In this study, we are aimed to explore the role of LRP1 in Epilepsy and whether KD can treat epilepsy caused by LRP1 knockdown by using betahydroxybutyrate.…”

Section: Introductionmentioning

confidence: 99%

Ketone Body Rescued Seizure Behavior Of LRP1 Deficiency By Modulating Glutamate Transport

Zhang

Chen

et al. 2022

Preprint

View full text Add to dashboard Cite

LRP1, the low-density lipoprotein receptor 1, would be a novel candidate epilepsy gene according to our bioinformatic results and the animal study. In this study, we explored the role of LRP1 in Epilepsy and whether Beta-hydroxybutyrate, the principal ketone body of the ketogenic diet can treat epilepsy caused by LRP1 deficiency. UAS/GAL4 system was used to establish different genotype models. Flies were given Standard, High-sucrose, and ketone body food randomly. The bang-sensitive test was performed on flies and seizure-like behavior was assessed. Morphologic alteration of LRP1 defect in the brain was detected under GPF expression flies. We established global, astrocytic, and neuronal LRP1 knockdown flies. Whole body and glia LRP1 defect flies had a higher seizure rate compared to the control group in the behavior test. Ketone body decreased the seizure rate in behavior test in all LRP1 defect flies, compared to Standard and High sucrose diet. In morphologic experiments, we found that LRP1 deficiency caused partial loss of the ellipsoidal body and partial destruction of the fan-shaped body. Overexpression of glutamate transporter gene Eaat1 could mimic the ketone body effect on LRP1 deficiency flies. This study demonstrated that LRP1 defect globally or in astrocytes or neurons could induce epilepsy. The ketone body efficaciously rescued epilepsy caused by LRP1 knockdown. The results support screening for LRP1 mutations as discriminating conduct for individuals who require clinical attention and further clarify the mechanism of the ketogenic diet in Epilepsy, which could help Epilepsy patients making a precise treatment case by case.

show abstract

Protocol for the Use of the Ketogenic Diet in Preclinical and Clinical Practice

Cited by 14 publications

References 69 publications

Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade

Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade

Diätetische Ansätze in der Tumortherapie

Ketone Body Rescued Seizure Behavior Of LRP1 Deficiency By Modulating Glutamate Transport

Contact Info

Product

Resources

About