Schizophrenia Diet

What is a proper schizophrenia diet. A lot has been written about this topic for many decades

There has been lot of research implicating disturbed glutamate metabolism as involved in the core schizophrenia symptoms. The theory points to the hypofunctioning of the N-methyl D-aspartate receptor (NMDA) receptor, which is a type of glutamate receptor. Glutamate is one of the neurotransmittors in the brain (A neurotransmittor is as a chemical signal between neurons - released from one neuron and taken up by another neuron.) The most compelling evidence is derived from the ability of NMDA receptor antagonists (blockers), like phenylcycline and ketamine, being able to produce schizophrenia-like symptoms in healthy individuals and exacerbate symptoms in schizophrenia patients. It is thus thought that overcoming the hypofunctioning of the NMDA receptor is the key to reversing some of the symptoms of schizophrenia.

Glutamate and other direct-acting NMDA receptor agents are however toxic to the brain. Experiments over the last decade have been directed at the glycine-receptor site of the NMDA receptor. Experiments have relied on agents such as glycine, D-serine, D-alanine, D-cycloserine and sarcosine.

With illnesses such as schizophrenia which can be quite devastating, patients, their families, loved ones, and other advocates become desparate for a cure or even just an improvement in the symptoms. The search for an effective treatment can lead to much confusion and conflicting advice. I'll be presenting the latest research findings on a range of compounds which have been proclaimed as curing schizophrenia.

Glycine is an organic compound, the smallest of the amino acids, and is one of the basic building blocks of protein. Glycine is used in animal feeds, food supplements, protein drinks and as sweetener. It is also used in some drugs to improve absorption, such as analgesics and antacids. In the brain, glycine acts as an activator at the NMDA receptor which has an excitatory function. Of all the ammino acids, glycine transfer into the brain is the lowest and high oral doses of glycine are therefore needed to achieve significant increases in the central nervous system.

Serine also potentiates the NMDA receptor acting at the glycine site. In schizophrenia, levels of serine have been found to be low, suggesting a poosible reduction in serine activity. Serine is also more permeable and able to cross into the brain easier compared to glycine, thus requiring a smaller amount per dose.

D-cycloserine is an analogue of serine and freely available to enter the brain and acts as a partial agonist at the glycine site on the NMDA receptor. It has a narrow therapeutic range however, acting as a blocker at high doses.

High doses of glycine up to 30g have been shown to reduce negative symptoms of schizophrenia, such as emotional flatness, apathy and social withdrawal. Another study with doses up to 60g per day (0.8g/kg) could be administered without any adverse effects. These improvements have been accompanied by an increase in the CSF level of glycine.

A recent review and meta-analyses of 18 short-term trials looked at using glycine, D-serine or D-cycloserine to increase antipsychotic action. The results supported glycine and D-serine moderately reducing negative symptoms of schizophrenia. D-cycloserine had less effect on negative sympotms. These early studies therefore suggested that glycine,D-serine and D-cycloserine had beneficial effects in schizophrenia, especially in negative symptoms.

The argument against these earlier results is that these studies were in relatively small sample populations. A larger study the 'CONSIST' study did not find significant benfit of additional glycine or D-cycloserine. The result suggested that glycine was not beneficial in reducing negative symptoms in shizophrenia. Later analyses however showed that the few patients receiving typical antipsychotics had a greater decrease (though not statistically significant, in the negative symptoms ratings, compared to those taking placebo. Glycine and D-cycloserine both resulted in greater reductions in scores for negative and cognitive symptoms in in-patients, but not in out-patients. Results are therefore not conclusive. This does not mean that it will not be effective in some individuals.

Sarcosine is a naturally occurring compound which is synthesised in the liver from glycine. It is classed as a glycine transport inhibitor which regulates the glycine level at the neurone. As a result, glycine transport inhibitors may be more effective increasing the synaptic glycine levels and potentiating NMDR function. There are numerous compounds in preclinical testing. Clinical findigs are still limited to sarcosine. Previous studies have found that doses up to 2gram per day are safe and have improved schizophrenia symptoms in individuals on all antipsychotics except clozapine.

Trials of these glycinergic drugs with clozapine seem to have had no effect or have made symptoms worse. They seem to interfere with the action of clozapine.

At present, increasing synaptic glycine through the inhibition of glycine transporters seems to be one of the more attractive targets for the development of novel drugs for the treatment of schizophrenia. Evidence does seem to suggest that these compounds can benefit some individuals with resistant symptoms. Again, discuss these options with your psychiatrist before experimenting, or at least get a psychiatrist that is open-minded.

References
Schiz Res 2005,72:225-234
Braz J Med Biol Res Nov 2009,42(11)1002-1014




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