Anticonvulsant profile of caprylic acid, a main constituent of the medium-chain triglyceride (MCT) ketogenic diet, in mice

Właź, Piotr; Socała, Katarzyna; Nieoczym, Dorota; Łuszczki, Jarogniew J.; Żarnowska, Iwona; Żarnowski, Tomasz; Czuczwar, Stanisław J.; Gąsior, Maciej

doi:10.1016/j.neuropharm.2011.12.015

Cited by 72 publications

(61 citation statements)

References 62 publications

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“…Furthermore, this replicates the brain concentration achieved following peripheral C10 administration 9,10 . Unlabelled 3mM glucose was used in the presence of 13 C-labelled C10 and C8.…”

Section: β-Oxidation Rates Of Glucose C8 and C10 In Sh-sy5y Cellssupporting

confidence: 81%

“…These findings, coupled with the direct inhibitory effect of C10 on AMPA receptors 6 , provide mechanistic evidence whereby C10 could elicit seizure control. The anti-seizure properties of C10 are further supported by observations, in vivo, that report that mice fed with a C10-enriched chow display significantly improved seizure tolerance and brain antioxidant capacity [7][8][9][10][11] . In studies conducted by Wlaź et al, C10 levels were also determined in the brains of mice following C10-enriched feeding.…”

Section: Introductionmentioning

confidence: 73%

“…Existing data, including those generated from our own laboratory, suggest concentrations of up to 250µM C10 are required to facilitate an increase in mitochondrial biogenesis, increased antioxidant capacity and AMPA receptor inhibition 5,6,12 . However, such a concentration appears achievable, as oral administration of C10 to mice leads to brain concentrations of up to 250µM 9,10 . Medium-chain fatty acids are catabolised by β-oxidation resulting in acetyl CoA formation.…”

Section: Discussionmentioning

confidence: 99%

“…Cells were then lifted from wells with 1ml 0.25% trypsin-EDTA, suspended in 4ml culture medium and centrifuged for 4 minutes at 500xg. Supernatant was 9 removed and cells suspended in 1ml of fresh culture medium. Viability of cells was then tested using the Trypan Blue exclusion test.…”

Section: Cell Viabilitymentioning

confidence: 99%

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Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium‐chain triglyceride ketogenic diet

et al. 2017

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No. of tables: 1 2 SUMMARY Objective: The medium chain triglyceride ketogenic diet contains both octanoic (C8) and decanoic (C10) acids. The diet is an effective treatment for pharmacoresistant epilepsy. Whilst the exact mechanism for its efficacy is not known, it is emerging that C10, but not C8, interacts with targets that can explain anti-seizure effects, e.g. peroxisome proliferator-activated receptor-γ (PPARγ) (eliciting mitochondrial biogenesis and increased antioxidant status) and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. For such effects to occur, significant concentrations of C10 are likely to be required in the brain. Methods:In order to investigate how this might occur, we measured the β-oxidation rate of 13 C-labelled C8 and C10 in neuronal SH-SY5Y cells using isotope-ratio mass spectrometry. The effects of carnitine palmitoyl transferase I (CPT1) inhibition, with the CPT1 inhibitor etomoxir, on C8 and C10 β-oxidation were also investigated.Results: Both fatty acids were catabolised, as judged by 13 CO2 release. However, C10 was β-oxidised at a significantly lower rate; 20% of C8. This difference was explained by a clear dependence of C10 on CPT1 activity, which is low in neurons, whereas 66% of C8 β-oxidation was independent of CPT1. In addition, C10 β-oxidation was decreased further in the presence of C8.Significance: It is concluded that, since CPT1 is poorly expressed in the brain, C10 is relatively spared from β-oxidation and can accumulate. This is further facilitated by the presence of C8 in the MCT ketogenic diet, which has a sparing effect upon C10 β-oxidation.

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“…Furthermore, this replicates the brain concentration achieved following peripheral C10 administration 9,10 . Unlabelled 3mM glucose was used in the presence of 13 C-labelled C10 and C8.…”

Section: β-Oxidation Rates Of Glucose C8 and C10 In Sh-sy5y Cellssupporting

confidence: 81%

Section: Introductionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Cell Viabilitymentioning

confidence: 99%

See 2 more Smart Citations

Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium‐chain triglyceride ketogenic diet

et al. 2017

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“…[10,18] Animal studies suggested both CKD and MCTKD have a positive effect in decreasing brain cerebral excitability in young animal, [19] and acute anticon- vulsant property of caprylic acid, the main constituent of the MCTKD, may benefit and add to the overall clinical efficacy for seizure control. [20] Due to lack of large systemic review or randomized study with MAD and LGIT, more studies are in progress to prove the effectiveness of MAD and LGIT.…”

Section: Efficacymentioning

confidence: 99%

Medium-chain Triglyceride Ketogenic Diet, An Effective Treatment for Drug-resistant Epilepsy and A Comparison with Other Ketogenic Diets

2013

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The ketogenic diet (KD) is one of the most effective therapies for drug-resistant epilepsy. The efficacy of the medium-chain triglyceride KD (MCTKD) is as excellent as the classic KD (CKD), which has been documented in several subsequent retrospective, prospective, and randomized studies. MCT oil is more ketogenic than long-chain triglycerides. Therefore, the MCTKD allows more carbohydrate and protein food, which makes the diet more palatable than the CKD. The MCTKD is not based on diet ratios as is the CKD, but uses a percentage of calories from MCT oil to create ketones. There has also been literature which documents the associated gastrointestinal side effects from the MCTKD, such as diarrhea, vomiting, bloating, and cramps. Therefore, the MCTKD has been an underutilized diet therapy for intractable epilepsy among children.The author has used up to >70% MCTKD diet to maximize seizure control with gastrointestinal side effects optimally controlled. As long as health care professionals carefully manage MCTKD, many more patients with epilepsy who are not appropriate for CKD or modified Atkins diet or low glycemic index treatment will benefit from this treatment. A comparison between the MCTKD and other KDs is also discussed. (Biomed J 2013;36:9-15)

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Medium‐Chain Oils

Galante¹

2020

Bailey's Industrial Oil and Fat Products

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Medium‐chain triglycerides (MCT) are glycerine esters of primarily C8:0 and C10:0 fatty acids. Since these oils first became available in the 1950s, they have been the subject of attention because of their unique properties. MCT are more easily metabolized than conventional long‐chain fats and provide a rapid, concentrated source of energy. As a result of their unique metabolic pathway, their first use was in medical foods for the critically ill and those unable to digest or metabolize conventional long‐chain fats. MCT with odd‐chain length fatty acids (especially C7:0) are also of interest for the management of certain diseases due to their ability to provide fuel for energy production. Ongoing research continues to demonstrate the potential health benefits MCT offer for a variety of conditions, especially brain health and weight management, and for individuals ranging from premature infants to aging adults. Animals including pets can also benefit from the supplementation of MCT in their diet. In addition, the physical properties of MCT are distinct from those of conventional fats and oils. This has led to the use of MCT in a number of other applications, especially in the food industry. This article provides an overview of MCT production and metabolism followed by a discussion of their use in various applications, emphasizing current research into nutritional applications. The utility of both even‐chained and odd‐chained MCT will be presented.

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Anticonvulsant profile of caprylic acid, a main constituent of the medium-chain triglyceride (MCT) ketogenic diet, in mice

Cited by 72 publications

References 62 publications

Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium‐chain triglyceride ketogenic diet

Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium‐chain triglyceride ketogenic diet

Medium-chain Triglyceride Ketogenic Diet, An Effective Treatment for Drug-resistant Epilepsy and A Comparison with Other Ketogenic Diets

Medium‐Chain Oils

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