Autoimmune Thyroid Disease

An Unfortunate and Lengthy Adventure in Misdiagnosis

What ketosis does to the brain

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And why it’s relevant to failsafers!

Our objective was to study brain amino acid metabolism in response to ketosis. The underlying hypothesis is that ketosis is associated with a fundamental change of brain amino acid handling and that this alteration is a factor in the anti-epileptic effect of the ketogenic diet. Specifically, we hypothesize that brain converts ketone bodies to acetyl-CoA and that this results in increased flux through the citrate synthetase reaction. As a result, oxaloacetate is consumed and is less available to the aspartate aminotransferase reaction; therefore, less glutamate is converted to aspartate and relatively more glutamate becomes available to the glutamine synthetase and glutamate decarboxylase reactions. We found in a mouse model of ketosis that the concentration of forebrain aspartate was diminished but the concentration of acetyl-CoA was increased. Studies of the incorporation of 13C into glutamate and glutamine with either [1-(13)C]glucose or [2-(13)C]acetate as precursor showed that ketotic brain metabolized relatively less glucose and relatively more acetate. When the ketotic mice were administered both acetate and a nitrogen donor, such as alanine or leucine, they manifested an increased forebrain concentration of glutamine and GABA. These findings supported the hypothesis that in ketosis there is greater production of acetyl-CoA and a consequent alteration in the equilibrium of the aspartate aminotransferase reaction that results in diminished aspartate production and potentially enhanced synthesis of glutamine and GABA. Response of brain amino acid metabolism to ketosis

There are a number of different studies by Daikhin and Yudkoff that have confirmed the above hypothesis in different ways. They can be found in pubmed. I won’t repeat them all here.

Here is a study that found other differences:

The ketogenic diet (KD) is an established treatment for medically refractory pediatric epilepsy. Its anticonvulsant mechanism is still unclear. We examined the influence of the KD on the CSF levels of excitatory and inhibitory amino acids in 26 children (mean age 6.1 years) with refractory epilepsy. Seventeen amino acids were determined before and at a mean of 4 months after the start of the KD. Seizures were quantified. Highly significant changes were found in eight amino acids: increases in GABA, taurine, serine, and glycine and decreases in asparagine, alanine, tyrosine and phenylalanine. However, aspartate, glutamate, arginine, threonine, citrulline, leucine, isoleucine and valine/methionine remained unchanged. A significant correlation with seizure response was found for threonine (P=0.016). The GABA levels were higher in responders (>50% seizure reduction) than in nonresponders during the diet (P=0.041). In the very good responders (>90% seizure reduction), the GABA levels were significantly higher at baseline as well as during the diet. Age differences were found with significantly larger decreases in glutamate and increases in GABA in connection with the diet in younger children. Our results indicate that the KD significantly alters the levels of several CSF amino acids that may be involved in its mechanism of action and the increase in GABA is of particular interest. The ketogenic diet influences the levels of excitatory and inhibitory amino acids in the CSF in children with refractory epilepsy

Glutamate and aspartate are both ‘bad’ neurotransmitters for people with food chemical intolerance (aspartate is involved in salicylate reactions on NMDA receptors). Ketosis appears to reduce aspartate levels by moving glutamate production away from aspartate and towards GABA and glutamine. Other glutamate-opposing amino acids like taurine, serine and glycine are raised too. GABA and glutamine are both ‘good’, calming neurotransmitters for failsafers.

The ketogenic diet has been studied for many years in relation to intractable epilepsy in children. It has also been hypothesised to help bipolar disorder:

The ketogenic diet, originally introduced in the 1920s, has been undergoing a recent resurgence as an adjunctive treatment for refractory epilepsy, particularly in children. In this difficult-to-treat population, the diet exhibits remarkable efficacy with two-thirds showing significant reduction in seizure frequency and one-third becoming nearly seizure-free. There are several reasons to suspect that the ketogenic diet may also have utility as a mood stabilizer in bipolar illness. These include the observation that several anticonvulsant interventions may improve outcome in mood disorders. Furthermore, beneficial changes in brain-energy profile are noted in subjects on the ketogenic diet. This is important since global cerebral hypometabolism is a characteristic of the brains of depressed or manic individuals. Finally, the extracellular changes that occur in ketosis would be expected to decrease intracellular sodium concentrations, a common property of all effective mood stabilizers. Trials of the ketogenic diet in relapse prevention of bipolar mood episodes are warranted. The ketogenic diet may have mood-stabilizing properties

When the researchers say that anticonvulsant interventions help bipolar disorder, one example is the prescribing of sodium valproate for people who have bipolar disorder. I have a close friend with epilepsy who is familiar with both valproate and ketosis. Valproate is an acetone mimic that produces effects on the brain that are identical to ketosis. The difference is that valproate comes with a range of side effects that a ketogenic diet doesn’t have.

If valproate is used for bipolar disorder it naturally follows that ketosis would help too.

Unfortunately no studies have yet been conducted to back up the use of a ketogenic diet for bipolar disorder. Which is a dreadful shame. It has helped (as in ‘effectively cured whilst diet is maintained’) three members of my family who have bipolar tendencies but are just short of official diagnosis – something that Prozac didn’t do for their depression.

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Written by alienrobotgirl

13 May, 2008 at 6:47 pm

Posted in Low Carbohydrate Diets

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