Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats

Oliveira, Marcela de Almeida Rabello; Ataíde, Terezinha da Rocha; Oliveira, Suzana Lima de; Lucena, Ana Luíza de Melo; Lira, Carla Emmanuela Pereira Rodrigues de; Soares, Anderson Acioli; Almeida, Clarissa Beatriz Santos de; Ximenes-da-Silva, Adriana

doi:10.1016/j.neulet.2008.01.032

Cited by 61 publications

(51 citation statements)

References 33 publications

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“…Our findings support the role of KDs in migraine treatment, maybe modulated by KBs inhibitory effects on neural inflammation and cortical spreading depression [2], and enhancing brain mitochondrial metabolism [3]. Ketogenic VLCD could find a transient role in antagonize the ponderal increase, a common side effect among prophylactic migraine treatments.…”

Section: Resultssupporting

confidence: 78%

Short term improvement of migraine headaches during ketogenic diet: a prospective observational study in a dietician clinical setting

Lorenzo

Sirianni²,

Pierelli

2013

J Headache Pain

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Section: Resultssupporting

confidence: 78%

Short term improvement of migraine headaches during ketogenic diet: a prospective observational study in a dietician clinical setting

Lorenzo

Sirianni²,

Pierelli

2013

J Headache Pain

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“…The discovery of this new chemical space for compounds with antiseizure activity, comprising branched and cyclic derivatives of a medium chain fatty acid in the MCT ketogenic diet, has implications for other therapeutic areas. The MCT diet also provides a positive effect in decreasing brain excitability in young animals (De Almeida Rabello et al, 2008), as well as playing a neuroprotective role in traumatic brain injury and stroke (Gasior et al, 2006). Finally, the diet also has potential for other neurologic disorders characterized by neuronal cell death (Stafstrom and Rho, 2012), such as Alzheimer disease (Reger et al, 2004;Henderson et al, 2009) and Parkinson disease (VanItallie et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Seizure Control by Derivatives of Medium Chain Fatty Acids Associated with the Ketogenic Diet Show Novel Branching-Point Structure for Enhanced Potency

Chang

Zuckermann

Williams

et al. 2014

J Pharmacol Exp Ther

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The medium chain triglyceride (MCT) ketogenic diet is a major treatment of drug-resistant epilepsy but is problematic, particularly in adults, because of poor tolerability. Branched derivatives of octanoic acid (OA), a medium chain fat provided in the diet have been suggested as potential new treatments for drug-resistant epilepsy, but the structural basis of this functionality has not been determined. Here we investigate structural variants of branched medium chain fatty acids as new seizure-control treatments. We initially employ a series of methyl-branched OA derivatives, and using the GABA A receptor antagonist pentylenetetrazol to induce seizure-like activity in rat hippocampal slices, we show a strong, branch-point-specific activity that improves upon the related epilepsy treatment valproic acid. Using low magnesium conditions to induce glutamate excitotoxicity in rat primary hippocampal neuronal cultures for the assessment of neuroprotection, we also show a structural dependence identical to that for seizure control, suggesting a related mechanism of action for these compounds in both seizure control and neuroprotection. In contrast, the effect of these compounds on histone deacetylase (HDAC) inhibition, associated with teratogenicity, shows no correlation with therapeutic efficacy. Furthermore, small structural modifications of the starting compounds provide active compounds without HDAC inhibitory effects. Finally, using multiple in vivo seizure models, we identify potent lead candidates for the treatment of epilepsy. This study therefore identifies a novel family of fatty acids, related to the MCT ketogenic diet, that show promise as new treatments for epilepsy control and possibly other MCT ketogenic diet-responding conditions, such as Alzheimer disease.

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“…Other case reports exist but there are no large clinical series or trials. Notwithstanding this limitation, laboratory investigations have found that both short-term and long-term treatment with either MCT or long-chain triglyceride forms of the KD resulted in a significant reduction in the velocity of cortical spreading depression (CSD) velocity in immature rats (de Almeida Rabello Oliveira et al, 2008). Another intriguing aspect of this study was the observation that triheptanoin – an anaplerotic substrate that enhances tricarboxylic acid cycle function – had a notable effect in retarding CSD, consistent with a later report that triheptanoin supplementation raised pentylenetetrazol tonic seizure threshold and delayed the development of corneal kindled seizures (Willis et al, 2010).…”

Section: The Kd In Migrainementioning

confidence: 99%

The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders

Stafstrom¹,

Rho²

2012

Front. Pharmacol.

365

294

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Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat – or at least ameliorate symptoms of – these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more “natural” treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component.

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Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats

Cited by 61 publications

References 33 publications

Short term improvement of migraine headaches during ketogenic diet: a prospective observational study in a dietician clinical setting

Short term improvement of migraine headaches during ketogenic diet: a prospective observational study in a dietician clinical setting

Seizure Control by Derivatives of Medium Chain Fatty Acids Associated with the Ketogenic Diet Show Novel Branching-Point Structure for Enhanced Potency

The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders

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