|Guts, Brains and Gulf Veterans|
"There is an age when one teaches what one knows but there follows
2. The Gulf War
a. IN PREPARATION FOR THE WAR
b. IN THE THEATRE OF OPERATIONS.
It is apparent that a (i), (ii) and b (i-iii) are clearly a result of the preparation of troops for Operation Granby (UK) and Operation Desert Storm (USA). We exposed our own troops to major toxins. It can be argued from first hand accounts that the chemical warfare agents were largely liberated as a result of bombing of Iraqi production, distribution and storage sites for chemical and biological weapons. These exposures can be linked directly to the chronic illnesses Gulf War Veterans are experiencing. They impact on many different systems in the body causing multi-symptom, multi-organ, and multi-system adverse effects. Table 1, Hooper 2000a. For the official MoD line see their web site, http://www.mod.uk/gulfwar/. Evidence challenging the official line is available in Burton, 1997; Tucker, 1997; Thomas 1998; Hooper 2000a; and the House of Commons Select Defence Committee, 2000.
Table 1. Known Effects of the Gulf Exposures on the Different Systems of the Body
X = a known adverse effect by an agent on the system indicated.
The Gulf War has been presented as an example of a bloodless victory by the Coalition forces with very few casualties on the battlefield. The truth is rather different, Table 2.
Table 2. Numbers of Deployed, Dead, Wounded and Prisoners in Gulf War
Although battlefield casualties were few almost 15% of the USA troops have been placed on registers of official Gulf-related illnesses and a 2-3 times greater reporting of symptoms of ill-health have been reported in both the USA, Iowa study, 1997, Fukuda et al, 1998 and UK, Unwin et al, 1999, Ismail et al, 1999. Fukuda et al, 2000 Some 26% of USA troops are now in receipt of benefits for Gulf War-associated illnesses according to a spokesperson for the Veterans' Administration, VA, Nugent, 2000. Excess deaths have been reported among USA personnel, Kang and Bullman, 1996, but the increase in UK deaths was not significant, Macfarlane et al, 2000, Table 2 and 3. In both mortality studies the time frame is too short to include any excess deaths that might arise from cancers. In the UK one GWV has died every week since the end of the Gulf War.
Table 3 Registered Numbers of GWVs in Receipt of Health Care and Litigation
*32, 000 cases pending. **VA figure but many GWVs are now outside the VA system.
The symptoms reported by the GWVs are described as of 'unknown origin', Merck 1999. and overlap significantly with the symptoms associated with Myalgic Encephalomyelitis-Chronic Fatigue syndrome, ME-CFS, Nicolson, 1996, and other chronic illnesses such as fibromyalgia, FMS, Multiple Chemical Sensitivity, MCS, and even Multiple sclerosis and AIDS, Table 4.
Table 4 Common Symptoms shared by a number of Chronic Diseases.
+ Literature Reported
3. Gulf War Veterans and IAG.
The IAG test has been developed and validated in the field of autism spectrum disorders, ASD, where high levels of IAG have been found in ~80% of children and young people, Shattock et al. 1997, 1998; Whiteley et al. 1999. Independent laboratories have obtained similar results, AAL, 2000.
Figure 1. GWVS: (A) with clear and (B) doubtful IAG peak
We have now tested some 40 GWVs and found in every case but one high levels of IAG present in their urine, Figure 1. A number of children of GWVs have also been found to have high levels of IAG, Figure 2 even when the father, Figure 1B, had no clear IAG peak. We do not yet have any evidence that the children of GWVs are more susceptible to autism spectrum disorders than children born to non-deployed troops or those born to civilian parents. However it is a disturbing thought that the kinds of exposures suffered in the Gulf might lead to autistic spectrum disorders in children. There may be a parallel with the unfolding story of vaccines and the newly identified autism-associated ileo-colonic lymphoid nodular hyperplasia, Wakefield et al, 1998. Such a possibility is consistent with the identification of IAG as a major peak in chromatograms obtained from urine samples of people with ME-CFS and MCS. Both these diagnoses have been made in regard to some GWVs. Chemical and viral triggers are known to play a role in other chronic disorders, Urnovitz, 1992.
Figure 2A. Children of GWV A Figure 2B. Children of GWV B
4. Origins and Actions of IAG.
A second metabolic pathway for the tryptophan involves opening of the indole ring by tryptophan and indole dioxygenases, TDO/IDO, and catabolism via the kynurenine pathway which leads to compounds with pro- and anti-convulsant properties, Munoz-Hoyos et al., 1997. This pathway is widely used to regulate the levels of free tryptophan which is the only essential amino acid with immunoregulatory properties. High levels of tryptophan are needed for T-cell cloning which is responsible for combating infection and destroying cancer cells. However, persistent and excessive stimulation of this pathway may be important in the development of autoimmune diseases. Similarly lack of free tryptophan can lead to increased susceptibility to infection and malignant diseases, Mellor and Munn, 1999. 5-Hydroxytryptophan, 5-HT, (serotonin) is the potent neurotransmitter molecule which is formed by the action of tryptophan hydroxylase, TrpOHase, on tryptophan. Although only about 1% of tryptophan is utilised in this pathway any disturbance of this enzyme would have major consequences for the brain, the gut and other key organs, Rang and Dale, 1991. 5-HT and drugs influencing its release have been studied in ASD with some limited success.
On theoretical grounds IAcrA would be expected to disrupt membrane structures; planar geometry would distort the regular arrangement of fatty acid residues in membranes. Preliminary studies have shown this is the case, Bell 1999. A further possibility is that IAcrA might also serve as an irreversible inhibitor of key enzymes such as 5-hydroxytryptophan hydroxylase. Molecular modelling provides some support for this, Anderson, 2000. Enzymes with an active serine or cysteine moiety in their active site might also be inhibited by IAcrA, eg. chymotrypsin and trypsin major digestive enzymes in the gut.
Scheme 1. IAG-ORIGINS?
5. IAG and Opioids.
6. Disordered Sulphate Metabolism.
i. Sulphation of glycosylaminoglycans, GAGs, is crucial for the integrity of mucous membranes, Owens, 1998, such as those lining the gut.
7. IAG, Peptide hormones and the Gut-Brain Axis.
Figure 3. Bidirectional signalling between the Gut and the Brain.
Table 5. The site of the first identification of Peptide Hormones Common to the Gut and the Brain
Sub P = Substance P; TRH = thyroid releasing hormone; ENK = enkephalins; CGRP = calcitonin gene-related peptide; CRH = corticotrophin-releasing hormone; CCK = cholecystokinin; VIP = vasoactive intestinal polypeptide; PHI = peptide histidine leucine; PYY = peptide YY; NPY = neuropeptide Y; GRH = gastrin-releasing hormone; PP = pancreatic polypeptide.
In addition the gut and brain both use the established chemical transmitters, acetylcholine, noradrenaline, dopamine, 5-HT (serotonin), and histamine. These shared neurotransmitters, endocrine, paracrine and autocrine hormones, particularly the peptides, affect perception, cognition, behaviour, mood, emotions and brain development. They also interact with the immune system, see below. Note the presence of secretin, a pancreatic hormone, in the brain. Although its function has not yet been identified it is noteworthy that injections of secretin have proved helpful in treating some ASDs. The most widely abundant peptide in the brain is CCK which acts differentially at two different receptors, CCK1 and CCK2. Low levels of this peptide are associated with anxiety, panic attacks and schizophrenia whilst high levels are associated with depression and attenuation of memory and learning, free recall, and attenuated recognition. Opioid peptides modulate the effects of CCK, Figure 4, Noble et al., 1999.
Figure 4. Modulation of CCK Activity by Opioids
8. The Gut and the Immune System.
9. Natural Gut Microflora and Fauna.
Table 6. Predominant Bacteria of the Intestinal Microflora.
It is important to recognise that other micro-organisms play a part in the normal functioning of the gut and some of these can give rise to serious disease, eg E. coli and Candida spp. The bacterial population can be considerably influenced by food and the following chart summarises an in vitro study which shows the varying proportion of different bacteria at different levels in the gut and how they change with the introduction of different carbohydrate sources, Table 7. Of particular note is the considerable increase in the proportion of lactobacilli and decrease in clostridia spp. when rice is the carbohydrate source rather than wheat or oats.
Table 7. Variations in Percentage of Gut Bacteria Populations with Different Food Sources.
These figures are from a model of one particular part of the bowel. Somewhat different figures have been obtained for conditions modelled for other parts of the bowel, Anon 2000. Note the dramatic changes in the lactobacillus levels when the diet is changed from wheat to rice. A gluten free diet would lead to increases in the lactobacillus population and a reduction in the clostridia population.
The Neuroendocrineimmune Paradigm.
Figure 5. Bidirectional signalling between the Nerve Tissue, N, the immune system, I, and the Endocrine System
Figure 6. Challenge and Homeostasis in the NeuroendocrineImmune systems.
OPs = Opioid Peptide transmitter molecules.
A new and important region of challenge is by odours which are transported intraneuronally within the olfactory tract which enter the limbic system of the brain directly since the tract penetrates the blood-brain barrier. This mechanism is of great importance in MCS, Ashford and Miller, 1998.
11. Multiple Overlapping Syndromes.
Figure 7. Overlapping Syndromes with Common Biochemical Disturbances.
Key -see main text OCs, organochlorine pesticides; ??? other related conditions; OPs = organophosphate pesticides; GWS = Gulf War Syndrome; FMS = Fibromyalgia syndrome; ME-CFS = Myalgic encephalomyelitis; MCS = Multiple Chemical Sensitivity; HPA = hypothalamic-pituitary-adrenal stress axis.
If IAG, Sulpite, or sulphate/cysteine ratios, and RBC shape and lipid structure form a common core of shared biochemistry it is important that more specific tests associated with the individual syndromes are identified. In the case of pesticide poisoning specific identification of the pesticide will characterise the syndrome/illness. Fibromyalgia and ME-CFS commonly exist together, White et al, 2000, but there are well established clinical tests that are used to diagnose fibromyalgia. Very recently a specific test for ME-CFS has been reported that distinguishes ME-CFS from fibromyalgia, Spence et al, 2000. MCS is generally characterised by sensitivities to a wide group of chemicals at very low concentrations, Ashford and Miller, 1998. Richardson, 2000, has described the use of choline citrate and ascorbic acid to effectively treat organochlorine poisoning in patients presenting with a diagnosis of ME-CFS.
12. Treatment and the Sunderland Protocol [View ' The Sunderland Protocol' here].
1. Remove the 'bullets'. These are the opioid peptides routinely available in the diet. Essentially this means removing milk and then gluten sources from the diet. The effects of removing milk are most rapidly seen, usually within 3 weeks. If no advantage is gained then it can be restored to the diet. Next take out the gluten- the response here is much slower and takes up to 3 months to become apparent. Children may respond more quickly. Almost always the effect is to make the patient feel worse, at first. A useful analogy is with opiate withdrawal symptoms.
2. Restore sulphate levels and the sulphur cycle (this also includes the methionine cycle). Sulphate can be provided by Epsom salt baths or with small oral doses. Other sulphur supplements are MSM (methylsulphonylmethane). Garlic and onions are good sources of sulphur compounds. Vitamin B6 and B12 are essential in the methionine cycle. Assess Glutathione levels and glutathione sulphur transferase function and activity.
3. Look at antioxidant status, Vitamin C, E, selenium and zinc and possibly copper and iron.
4. Look at lipid metabolism and the use of essential fatty acids of the n-3 and n-6 classes- fish oils and evening primrose oils etc.
5. Look at energy metabolism, succinate, NADH, Enzyme Co-Q, etc.
6. Take steps to restore gut function with probiotics, glutamine, enzyme supplements such as papain, 'Seren-aid', etc.
Re-testing can be done to measure changes in the different marker molecules and improvement assessed by clinical tests.
The stepwise approach offers a helpful way of identifying those things that are effective in ameliorating the syndrome/illness and avoids the confusion and expense that is commonplace when people who are desperately ill try almost anything in a random fashion.
Figure 10 The Sunderland Protocol-Slightly modified to cover all Overlapping Syndromes.
[Figure not included in webpage version but see 'The Sunderland Protocol']
It is becoming increasingly clear that additives, sweeteners, colouring agents and other ingredients in 'junk' foods which form an growing part of the diet of many people, particularly the young, can have destructive social and behavioural effects on children especially, Winder, 2000, Lewis, 1998; Werbach, 2000; Anthony et al.,1997. Very significant improvements in behaviour and educational achievements followed the strict withdrawal of such components from the diet of school children, Winder 2000.
Also of concern are the growing amounts of pesticides and preservatives that are routinely consumed in food. The more complete the food the greater the quantities of such materials that are consumed. For example, eating whole meal bread will ensure the intake of essential vitamins and roughage but will at the same time increase the intake of pesticides and preservatives many of which are known to have adverse effects on many systems in the body, eg. organophosphates which are present in flour damage the nervous system, are mutagenic and carcinogenic, induce asthmatic reactions, and slow heart rate sometimes initiating a rebound tachycardia and hypertension. There is growing concern about these components in all our foods. the association of these toxins with the increasing numbers of ASDs, ME-CFS, asthma cases, etc., requires much more investigation. The increased emissions from road traffic, especially the particulates in the PM range of <2.5 microns, are thought to play an important part in the massive increase in childhood asthma.
Nevertheless, at the present time our growing understanding of chronic overlapping syndromes offers new ways of understanding and ameliorating the common symptoms of many of these disorders. The suffering and struggle of those involved with these syndromes is beginning to bear healing in this neglected and controversial area of sickness. The Sunderland Protocol is part of this hopeful development. I thank all who have borne the problems, difficulties and joys of ASDs for this gift to Gulf War Veterans, OP poisoned farmers, and others who share this disordered biochemistry.
|Last Updated on Thursday, 17 March 2011 12:11|