Dear Friends:

Here is some exciting new information, not only for those who have autism, but for those who have been vaccinated, and seem to have problems with Carbs, and PH balance, etc. This is another reason to supplement EPO and CLO. Study again the Section of "Mastering Autism".  "Managing Fatty Acids", to understand how controlling fatty acids balances the amino acid profile *and* controls the inflammation and damage spoken of here. A high carbohydrate intake is contributory to high ARA. Make sure you and your child are getting adequate protein in every meal and major snack. Bromelain is a powerful anti-inflammatory.

Dr Gordon Bell, Nutrition Group, Institute of Aqua culture, University of Stirling, Stirling FK9 4LA, Scotland.

What is a "phospholipid spectrum disorder" and why is it relevant to the complex biochemical and physiological abnormalities that occur in autism?

Phospholipids are the building blocks of all cell membranes. They provide a barrier between the outside of a cell and the inside thereby preventing mixing of intra cellular and extra-cellular components. As well as containing phospholipids cell membranes contain numerous proteins, including ion channels, receptors and enzymes, many of which have essential roles in cell-cell communication. Such functions are, of course, vital in neural tissues. The structure and function of these membrane-associated proteins can be directly affected by the nature of the phospholipids which surround them.

The phospholipids comprise two fatty acids and a polar head group, which can be an amine, amino acid or sugar, attached to a glycerol backbone (Fig. 1).

The fatty acid components have many roles in determining the structure and function of the membrane and it is the metabolism of these fatty acids which appears abnormal in autistic spectrum disorders (ASD).

Fatty acids in cell membranes are subject to natural wear and tear and the damaged ones are removed from the phospholipid by a phospholipase enzyme. The incomplete phospholipid, called a lyso-phospholipid, is damaging to the integrity of the membrane and is normally rapidly repaired by a fatty acyl transferase/ligase enzyme. Therefore, if the phospholipase is overactive, or present at abnormally high levels, and/or the fatty acyl transferase/ligase is under active, then damage to cell membranes will result making them "leaky" and affecting the function of proteins embedded in the membrane. In autism, red blood cell membrane phospholipids have been shown to be abnormally unstable upon storage suggesting that turnover of fatty acids in these membranes may be unusually high.

In Asperger's syndrome, although the cell membranes appear more stable, the fatty acid compositions show important differences in terms of their polyunsaturated fatty acid (PUFA) content. Studies in our laboratory indicate that the n-6 PUFA, arachidonic acid (ARA) is often elevated whereas the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are often depleted compared to control samples. In addition, using an assay developed by Dr David Horrobin of Laxdale Ltd. biochemists at the Victoria Hospital in Glasgow have shown an increase in the phospholipase A2 (PLA2) enzyme in blood cells from individuals with autism and Asperger's syndrome. The PLA2 releases PUFA, such as EPA, DHA and ARA, from cell membranes resulting in membrane damage and the production of highly inflammatory substances known as prostaglandins, leukotrienes and thromboxanes, known collectively as eicosanoids.

How can abnormal PLA2 and excessive eicosanoid production result in the physiological and psychological problems found in ASD? The cells of the neural system contain high levels of PUFA representing between 15-30% of neural tissue by dry weight and, of those, ARA and DHA represent 80-90% of the total. In normal synaptic function, ARA and DHA are released into the synaptic junction, by the action of PLA2, along with neurotransmitter compounds, followed by re-uptake of neurotransmitter and PUFA. If PLA2 activity is elevated, an excess of PUFA may be released from the synapse resulting in oxidation of the free PUFA.

Oxidized PUFA can set up a cascade of reactions resulting in extensive inflammatory reactions and cellular damage.

In the cells of the gut epithelium and endothelium ARA is the predominant PUFA and n-3 PUFA are only minor components. If elevated PLA2 is present in these cells, free ARA will be produced and a range of highly inflammatory eicosanoids produced. In addition lyso-phospholipids, which remain after phospholipase action, are potent cytolytic agents (that cause cell membrane breakdown) that may cause "leakiness" in gut cells.

The cells of the immune system, including lymphocytes, macrophages and eosinophils, require PLA2 to produce prostaglandins and leukotrienes essential for enabling immune cells to locate and destroy pathogenic organisms. While low levels of prostaglandins, particularly PGE2, are stimulatory to the immune system, high levels tend to reduce immune responses. Thus, increased PLA2 could result in immune suppression as well as increasing the prevalence of auto-immune disorders such as asthma, eczema, rheumatoid arthritis and diabetes.

Work in our laboratory, using red blood cells (RBC) as a model system, has suggested that PLA2 is elevated in individuals with autism and Asperger's syndrome. The RBC usually contain less EPA and DHA and, sometimes, more ARA than control subjects. In addition, the RBC membrane PUFA composition appears particularly unstable on storage at -20oC in patients with autism, compared to control subjects. This is strongly indicative of increased PLA2 in the RBC, perhaps coupled with increased oxidation of PUFA. Recently, in conjunction with the Victoria Hospital in Glasgow and Laxdale Ltd, increased PLA2 has been confirmed in a number of individuals with autism and Asperger's syndrome.

Although we have looked at relatively few (seven) individuals so far all have shown evidence of a phospholipid spectrum disorder. We hope to study these effects in a wider sample of patients with ASD in the near future.

Having identified increased PLA2 and membrane PUFA loss what steps can we take to alleviate the damage and so improve the well being of individuals with ASD? In schizophrenic patients, where a similar phospholipid disorder has been identified, considerable success has been achieved by supplementation with omega-3 (n-3) PUFA, particularly EPA.

EPA is an inhibitor of PLA2 activity and probably helps to stabilize cell membranes and reduce inflammatory reactions by competing with ARA and modulating the effects of ARA-derived eicosanoids. Although no clinical trials of EPA-rich oils and concentrates have been performed in patients with autism to date, a number of positive reports have been received from parents supplementing their children with EPA preparations. Improvements include improved eye contact and sociability, improved spontaneous speech and improved gut function as well as reduced fluid intake and urination.

An EPA intake of around 1-2 g per day seems to be appropriate as provided by concentrates such as KirunalT and Eye QT. It is hoped that a clinical trial of the 97% EPA concentrate produced by Laxdale Ltd., presently being investigated with schizophrenic patients, will be conducted with ASD patients in the near future.

This additional information from Dr. Pat Kane and Dr. Klinghardt.

The Phospholipase 2 (PLA2) destroys essential fatty acids. Therefore PLA2 stimulants should be avoided.

Insulin is a PLA2-stimulator. So the patients should have a diet with low carbohydrates, a maximum of 6 bread exchange units per day.

Dr. Klinghardt adds: Avoid all grain, including rice. No bread! In the future- Eat  vegetables with eggs.

With increased PLA2 the following happens:
- membrane lipids are lost
- prostaglandins synthesis is disturbed
- the membrane permeability is disturbed
- the homeostasis is disturbed.

The therapeutic goal at brain diseases is to break down long chained fatty acids. So you should avoid peanut oil, rape-seed oil (canola oil)  and mustard, because they contain long chained fatty acids. E.g. at autistic children we work with evening primrose oil and electrolytes.

Lipid infusion or ingestion of a high-fat diet results in insulin resistance, but the mechanism underlying this phenomenon remains unclear.

Here we show that, in rats fed a high-fat diet, whole-animal, muscle and liver insulin resistance is ameliorated following hepatic overexpression of malonyl-coenzyme A (CoA) decarboxylase (MCD), an enzyme that affects lipid partitioning. MCD overexpression decreased circulating free fatty acid (FFA) and liver triglyceride content. In skeletal muscle, levels of triglyceride and long-chain acyl-CoA (LC-CoA)-two candidate mediators of insulin resistance-were either increased or unchanged. Metabolic profiling of 36 acylcarnitine species by tandem mass spectrometry revealed a unique decrease in the concentration of one lipid-derived metabolite, -OH-butyrate, in muscle of MCD-overexpressing animals. The best explanation for our findings is that hepatic expression of MCD lowered circulating FFA levels, which led to lowering of muscle -OH-butyrate levels and improvement of insulin sensitivity.

Journal of Lipid Research, Vol. 45, 1500-1509, August 2004

Phosphatidylcholine deficiency upregulates enzymes of triacylglycerol metabolism in CHO cells

J. Matías Caviglia*, I. Nelva T. de Gómez Dumm*, Rosalind A. Coleman and R. Ariel Igal1,*
* Instituto de Investigaciones Bioquímicas de La Plata, Universidad Nacional de La Plata, 1900-La Plata, Argentina

* Departments of Nutrition and Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

Treatment with dipalmitoylphosphatidylcholine normalized both the PC and TAG levels. Despite low TAG levels, the incorporation of [14C]oleate into TAG was increased in CHO MT58 cells. The in vitro de novo synthesis of TAG and the activity of diacylglycerol acyltransferase were 90% and 34% higher, respectively. Two other key enzyme activities in TAG synthesis, acyl-CoA synthetase and mitochondrial glycerol-3-phosphate acyltransferase (GPAT), increased by 48% and 2-fold, respectively, and mitochondrial GPAT mRNA increased by 4-fold. Additionally, TAG hydrolysis was accelerated in CHO MT58 cells, and in vitro lipolytic activity increased by 68%.

These studies suggest that a homeostatic mechanism increases TAG synthesis and recycling in response to PC deficiency. TAG recycling produces diacylglycerol and fatty acids that can be substrates for de novo PC synthesis and for lysophosphatidylcholine (lysoPC) acylation. In CHO MT58 cells, in which de novo PC synthesis is blocked, lysoPC acylation with fatty acid originating from TAG may represent the main pathway for generating PC.

Abbreviations: ACS, acyl-CoA synthetase; CT, CTP:phosphocholine cytidylyltransferase; DAG, diacylglycerol; DGAT, diacylglycerol O-acyltransferase; DPH, 1,6-diphenyl 1,3,5-hexatriene; DPPC, dipalmitoyl-phosphatidylcholine; GPAT, glycerol-3-phosphate acyltransferase; lysoPC, lysophosphatidylcholine; PC, phosphatidylcholine; TAG, triacylglycerol

Supplementary key words: phosphatidylcholine metabolism .  triacylglycerol synthesis . lipolysis . diacylglycerol acyltransferase . lipase

This VERY IMPORTANT concept is also presented in David Horrobin's excellent work.
Read:  "Phospholipid Spectrum Disorder in Psychistry"  Marius Press
Author David Horrobin , Malcolm Peet