What is a ketogenic diet and how does it affect the use of medicines?

McArtney, Rowena; Bailey, Alexandra S.; Champion, H.

doi:10.1136/archdischild-2014-307000

Cited by 9 publications

(8 citation statements)

References 17 publications

(39 reference statements)

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“…A ketogenic diet (KD) consists of low carbohydrate, high fat and adequate protein. This diet was designed to simulate the biochemical effects of fasting, which is used for the treatment of drug-refractory seizures (1,2). By limiting the intake of carbohydrates, it forces the body to switch to fatty acid oxidation as an energy source, leading to a ketogenic state.…”

Section: Introductionmentioning

confidence: 99%

Bone loss and biomechanical reduction of appendicular and axial bones under ketogenic diet in rats

Ding

et al. 2019

Exp Ther Med

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A ketogenic diet (KD) is composed of low-carbohydrate, high-fat and adequate levels of protein. It has been used for decades as a method to treat pediatric refractory epilepsy. However, recently, its side effects on the bones have received increasing attention. In order to comprehensively evaluate the effect of KD on the microstructures and mechanical properties of the skeleton, 14 male Sprague-Dawley rats were equally divided into two groups and fed with a KD (ratio of fat to carbohydrate and protein, 3:1) or a standard diet for 12 weeks. Body weight, as well as blood ketone and glucose levels, were monitored during the experiment. Bone morphometric analyses via micro-computerized tomography were performed on cortical and trabecular bone at the middle L4 vertebral body, the proximal humerus and tibia. The compressive stiffness and strength of scanned skeletal areas were calculated using micro-finite element analysis. The KD led to higher ketone levels and lower glucose levels, with reduced body weight and total bone mineral density (TBMD). After 12 weeks, the diet reduced the bone volume fraction, the trabecular number of cancellous bone, cortical thickness, total cross-sectional area inside the periosteal envelope and the bone area of cortical bone in the tibia and humerus, while increasing trabecular separation. However, KD may not affect the L4 vertebral body. The serum calcium or phosphate concentrations in the blood remained unchanged. In addition, bone stiffness and strength were clearly decreased by the KD, and significantly correlated with the BMD and bone area at all scanned sites. In conclusion, KD led to significant bone loss and reduced biomechanical function in appendicular bones, with a lesser impact on axial bones.

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Section: Introductionmentioning

confidence: 99%

Bone loss and biomechanical reduction of appendicular and axial bones under ketogenic diet in rats

Ding

et al. 2019

Exp Ther Med

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“…As KD can be effective in difficult‐to‐treat seizures, including SCN2A associated self‐limited formerly benign neonatal seizures, neonatal infantile seizures and epileptic encephalopathies, 9–13 potential interactions between AEDs and KD have to be considered. KD can result in delayed drug absorption through delayed gastric emptying, enhanced absorption of lipophilic drugs, stimulation of bile secretion and intestinal lymph drug absorption, inhibition of epithelial transporters, alteration of protein‐binding (increased free drug fraction due to changed protein intake, or binding competition with high amounts of free fatty acid 23 ), and gastrointestinal tract irritations resulting in reduced absorption 24–26 . Data addressing CBZ concentration during KD or Atkins diet are scarce.…”

Section: Discussionmentioning

confidence: 99%

Drug–drug and drug–food interactions in an infant with early‐onset SCN2A epilepsy treated with carbamazepine, phenytoin and a ketogenic diet

Welzel

Ziesenitz

Weber

et al. 2020

Brit J Clinical Pharma

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Sodium channel 2 subunit α (SCN2A) mutations cause difficult‐to‐treat early‐onset epilepsy. Effective treatment includes high‐dose phenytoin or carbamazepine ± ketogenic diet (KD). We describe an infant with early‐onset SCN2A‐epilepsy with subtherapeutic carbamazepine concentration during transition from phenytoin treatment to avoid long‐term neurotoxicity. The transition from high‐dose phenytoin (20 mg kg−1 d−1, concentration: ≥20 mg/L) with KD, to carbamazepine (50–75 mg kg−1 d−1, concentration: 9–12 mg/L) lasted 85 days, which we suspected was due to significant drug–drug and/or drug–food interactions. Model‐based analysis of carbamazepine pharmacokinetics quantified significant time‐ and dose‐dependent phenytoin‐mediated CYP3A4 induction and carbamazepine concentration‐dependent auto‐induction (apparent clearance increased up to 2.5/3‐fold). Lower carbamazepine concentrations under KD were modelled as decreased relative bioavailability (44%), potentially related to decreased fraction absorbed (unexpected for this lipophilic drug), increased intestinal/hepatic metabolism and/or decreased protein‐binding with KD. This suggests importance of carbamazepine‐concentration monitoring during KD‐introduction/removal and necessity of high carbamazepine doses to achieve therapeutic concentrations, especially in infants treated with high‐dose phenytoin.

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“…Sometimes during KD implementation, the concentration of drugs in the blood temporarily increases compared to previous levels (changes in pH, decreased protein intake, decreased urinary excretion) -in the case of PB even up to 100%. Besides that, during treatment with the KD no significant differences in the concentration of AEDs compared to the pre-diet period have been noted (Zupec-Kania et al, 2013;McArtney et al, 2017). Despite many years of combined use of AEDs and the KD, there are only a few reports available on their pharmacodynamic interaction (McArtney et al, 2017).…”

Section: The Kd and Aedsmentioning

confidence: 99%

“…After this period, if the KD is effective, it is possible to discontinue or reduce AEDs, but there is no numerical data available. Weaning off PB and benzodiazepines is more likely to cause seizure aggravation compared to other medicines McArtney et al, 2017).…”

Section: The Kd and Aedsmentioning

confidence: 99%

“…It should be noted that, drugs that are carbonic anhydrase inhibitors (TPM, ZNS), as well as the KD (especially in the early phase of treatment), predispose patients to metabolic acidosis (a lowered blood concentration of bicarbonates) and also to kidney stones. Therefore, if they are used simultaneously with the KD, it is recommended to monitor the level of bicarbonates and consider their possible supplementation (Takeoka et al, 2002;Zupec-Kania et al, 2013;McArtney et al, 2017).…”

Section: The Kd and Aedsmentioning

confidence: 99%

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Ketogenic diet in epilepsy: an updated review

Dudzińska¹

2018

Journal of Epileptology

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Introduction. Finding an effective epilepsy treatment has been a challenge in medicine for centuries. It is especially difficult to treat drug-resistant epilepsy, which accounts for 20-30% of epilepsy cases, even after the introduction of numerous new anti-epileptic drugs (AEDs). This gives an incentive to search for therapies other than pharmacotherapy, e.g. the ketogenic diet (KD). Aim. The present review paper aims to present the current state of knowledge regarding the effectiveness of the KD, its mechanism of action, indications, method of treatment and potential adverse effects. Material and method. The review covers relevant most recent (up to March 2018) papers using PubMed and Medline databases. Results and discussion. The history of the KD dates back to ancient times. It was believed to be very promising at the beginning of the last century, but then was temporarily 'forgotten' and has been undergoing a second renaissance since around 1990. It is currently recognised in most countries. The KD is administered mainly to children but over the last few years there have been attempts to use it in adults as well. The theoretical basis of the diet consists in the fact that it 'mimics' the metabolic state of an organism subject to fasting by replacing the basic source of energy for the brain, that is glucose, with ketone bodies, which are a product of fat breakdown. In spite of scientific progress, the exact mechanism underlying the KD is still not known. Its effectiveness, at first mainly as an add-on therapy, and in some cases as the first-line monotherapy, is rated quite highly (> 50% seizure reduction in > 50% patients; of which in 20-30% of patients seizures are reduced by > 90%). It can be used to treat all types of epileptic seizures after excluding contraindications. The KD, like any medical therapy for serious illnesses, may cause adverse effects. Most of them are mild, can be prevented, and if they occur, can be fairly easily treated Conclusion. The KD as add-on therapy or as monotherapy is a medical treatment of epilepsy administered under medical supervision.

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What is a ketogenic diet and how does it affect the use of medicines?

Cited by 9 publications

References 17 publications

Bone loss and biomechanical reduction of appendicular and axial bones under ketogenic diet in rats

Bone loss and biomechanical reduction of appendicular and axial bones under ketogenic diet in rats

Drug–drug and drug–food interactions in an infant with early‐onset SCN2A epilepsy treated with carbamazepine, phenytoin and a ketogenic diet

Ketogenic diet in epilepsy: an updated review

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