Brand New Update from Dr John Graham Australia

Discussion in 'Fibromyalgia Main Forum' started by metrogirl, Feb 5, 2009.

  1. metrogirl

    metrogirl New Member

    Sorry but this is very long. Dr Graham is a very respected specialist here in Adelaide, Australia who has unfortunately retired. He does however continue research into ME/CFS and this update is very extensive but very informative. Hope it helps....Lol.....metrogirl... :)
    ------ Forwarded Message
    From: john graham <>
    Date: Fri, 06 Feb 2009 10:38:32 +0000
    To: David Mitchell <>
    Subject: Updated chapter

    Dear Colleagues,
    Here is an update,



    The therapeutic task in C.F.S. is to decrease or eliminate pathogen loads, decrease environmental pollution, optimize immune function, heal any intestinal disorder, optimize nutrition, counter oxidative stress, and allow restoration of all cellular function and signaling.

    All of this is in the setting of the consciousness of the person who is intimately involved in this healing task.

    It necessarily involves ongoing conversations that allow each person in her or his own way to co-evolve the healing outcome.
    I like to call this “a dance of understanding”

    This fits with my idea that evolution whether it be in the changes in the cosmos, in biological systems, or in our thinking, never ceases.

    The healing processes could produce a change from an “ill” or “dysfunctional” state of homeostasis to an optimally functioning state.

    It should be stated from the outset that in practice this is sometimes a far from satisfactory area.

    Hypotheses need much more work on them.

    We are accessing the work of many authors, some of whom are laboratory researchers, others clinicians and yet others modelers of molecular biology. Some are readers who like to word and reword the work of others.

    How can we evaluate the merit of claims?

    Indeed is it possible at any point in time to put therapies in some sort of order?

    Which can be used together?

    Taking all these things into consideration some specific therapies have been suggested and some of these are designed to rectify chemical abnormalities and others are to protect and help the cell membrane to improve. I cite some of these therapies.

    In what follows there will be a strong emphasis on nutrition.

    The quality and nature of nutrients could provide the body with everything it needs for optimal health.

    It seems likely that not only are there nutrient deficiencies in the third world, but in the midst of plenty, Western countries have not achieved ideal nutrition. Vitamins C and D should be especially considered.

    If impaired ATP production by mitochondria is important, the Sarah Myhill plan is endorsed by cardiologists Drs Stephen Sinatra and James Roberts.

    Glyconutrients with the less common sugars, mannose, fucose, xylose, N-acetyl glucosamine, N-acetyl galactosamine, and n-acetyl neuraminic acid are crucial parts of functional glycoproteins such as immune cell receptors.

    Dr Darryl See claims that glyconutrients from some plants enhance T (NK) (TH1) cell function, (e.g. by acetyl mannans enhancing the receptor response to antigen,) but resulting in decreased viral loads, and decreasing fatigue symptoms.

    Helpful glyconutrients occur in aloe vera, garlic, and onion, yams and sweet potato, turnip, parsnip and carrot, cabbage, cauliflower, broccoli and brussel sprouts, tomato, pineapple, paw paw and rice bran. Dr See would recommend plants free from pesticide.

    This work has not been adequately evaluated, but there is no risk from these foods in moderate amounts.

    It will increasingly emerge that we will see the development of effective anti viral agents.

    I would like to emphasize that if viral infection cannot be proven, it may be sensible not to use antiviral agents, especially if they pose risks to the patients.
    1 Antiviral agents
    Herpes viruses may be decreased by acyclovir, and famciclovir (HSV1 and 2). These agents are used in acute episodes, and must be started promptly to be effective.

    Because of the widespread infection rate, the majority of people have HSV1 antibodies, (also EBV, varicella- zoster virus), but many never manifest clinical disease. It is interesting to map circumstances where these viruses reactivate.

    Acyclovir inhibits viral replication but does not eradicate virus. It is converted to active forms by phosphorylation in virus-affected cells, and host cell kinases bring the monophosphate to acyclovir triphosphate, which inhibits virus induced DNA polymerase.

    It is effective in HHV1 and 2 in terms of shortening and lessening the severity of attacks.

    Clinical trials in EBV infectious mononucleosis have not shown any advantage over placebo treatment.

    Ganciclovir is a guanosine analogue that is more active against CMV.

    It is converted in cells by a viral phosphotransferase encoded by CMV gene region UL97, and the ganciclovir triphosphate is a selective inhibitor of CMV DNA polymerase.

    Most clinical trials have occurred in patients with HIV infections or other immunocompromized states, because CMV infections in patients with AIDS are very serious.

    It is not yet clear whether there is a sub group of CFS sufferers who could benefit by IV ganciclovir, but Dr A Martin Lerner claims that there is a mild CMV related cardiomyopathy which presents as a CFS like illness, and that it responds to ganciclovir therapy. Ganciclovir does have some bone marrow toxicity, which should make us cautious in less serious situations.

    Ganciclovir has poor oral bioavailability.

    An orally available drug called valganciclovir (Valcyte) is available, but is restricted under Australia’s PBS.

    It may be the best agent for persistent CMV or HHV6A infection.

    At this time I look more closely at myocardial function in CFS sufferers, especially if they report any dyspnoea.

    Sarah Myhill certainly thinks the cardiac side of severe CFS has been neglected.

    A major advocate for anti viral therapies is Dr W John Martin from California, with unfolding evidence about “Stealth viruses”, a variety of mutated CMV. This subject again needs substantiation, but Martin claims his data includes cytopathic effects produced by CFS patient’s cells in vitro, induced illness when it is injected into cats, and also extensive PCRs confirming CMV viral sequences on the viral material.

    He has further identified a simian (green monkey) CMV in some of his CFS patients.

    These materials are infective and cause illness in cats that are injected with this material.

    Unfortunately, his work has not been verified and he is no longer working in this field.

    This is more a reminder that the persistence of viruses may turn out to be important in particular diseases.

    Foscamet has an antiviral spectrum against all of the herpes virus group, and can be active against CMV infections that are resistant to ganciclovir. It also has some antiretroviral activity, and inhibits the viral DNA polymerases from hepatitis B.

    Foscamet does not require activation by thymidine kinase (TK) or other kinases. (Theoretically it might be active against herpes virus mutants which are deficient in TK, and in vitro this has been demonstrated.)

    It is not an agent to be used lightly. It appears to be ineffective in HHV6 infections and reactivations.

    As mentioned above nutritional substances such as some fatty acids such as lauric, capric and caprylic acids, and derivatives such as monolaurin, milk ingredients (lactoferrin), plant antioxidants (kaempferol) and vitamin A have activity against CMV.

    It is notable that prostaglandin E2 increases CMV activity.

    Lysine at doses of 2 gms/day may enhance reduction of herpes viruses.

    St Johns Wort (hypericum) also has activity against herpes viruses, EBV and oral stomatitis virus. The Newcastle group suggest that some viruses are favoured by certain lipid profiles and one might attempt to change lipid patterns.

    It should be noted that St.John’s Wort is an inducer of the cytochrome P450 enzyme CYP3A4 and decreases the efficacy of the oral contraceptive pill.

    It can also decrease the levels and antiviral effects of HIV protease inhibitors such as indinavir, and the anti-rejection drug cyclosporin.

    This reminds us that we need to know more about interactions between drugs and herbal medicines.
    Transfer factors.
    These are peptides of some 40 amino acid lengths, which enhance antimicrobial activity and also greatly increase T natural killer cell functions. They appear to down regulate auto-immune activity.

    Bovine and human transfer factors seem to be identical.

    The natural situation leads to the offspring getting immunity to infections

    Encountered by the mother, but the pathogens of the cow differ significantly from human pathogens.

    They appear to be very safe.

    Darryl See has tested transfer factor and shows that it has a marked effect in increasing natural killer cell activity.

    He strongly favours its use in CFS.

    There is very little literature on transfer factors.

    Finally, some claim that IV vitamin C 30 Gms infusion may help to deal with any acute viral illness or flare-up. (Lack of controlled trials here!)

    I have wondered about the pretreatment of some patients before embarking on the other therapies, and this is where Sarah Myhill’s background therapies are likely to be protective.
    (a) Mycoplasma and Chlamydia.
    Mycoplasma infection can be treated acutely with tetracyclines, macrolides or ciprofloxacin.

    With chronic persistence of mycoplasmas, we are not usually able to prove whether they are pathogens or not.

    If Trevor Marshall PhD is correct then with all chronic bacterial infections we should consider that killing the organisms can result in cytokine release and in some persons this may make them feel ill. This could suggest starting with much lower doses than those mentioned below!)

    Doxycycline doses of 200 mgm/day at first (6 weeks) then 100 mgm/day (further 6 weeks). It is uncertain as to what is the optimum duration of these therapies.

    Minocycline has better intracellular penetration than doxycycline.

    Doses are possibly 50 mg alternate days, increasing as tolerated to 50 mg daily, then and 100 mg daily.

    The prescriber will need to be aware of side effects such as benign intracranial hypertension with ongoing minocycline therapy.

    If used supplements of minerals, (Fe, Ca, Mg, Mn, Mo, Se and Zn etc) should be delayed to at least 4 hours after the tetracycline dose, since these minerals may impair doxycycline bioavailability and effects.

    A difficulty exists in discerning whether resident mycoplasmas are, non pathogenic or pathogenic

    Azithromycin, clarithromycin, josamycin and also ciprofloxacin have also been used widely to eradicate mycoplasmas that are pathogens.

    The ketolide, telithromycin will emerge as useful for some of these organisms that are resistant to macrolides.

    Macrolides (except azithromycin) must not be given with statins (azithromycin is not metabolized by CYP 3A4), and the antihistamines, astemizole, terfenadine and chlorpheniramine, since they are potent inhibitors of CP450 3A4 isoforms.

    Azithromycin achieves higher tissue concentrations and intra cellular levels than other macrolides.
    (b)Rickettsiae and Coxiella
    As stated earlier in regards to Rickettsiae, Cecile Jadin recommends one week on and three weeks off with these antibiotic courses.

    It is likely that chronic infection requires more courses because the organism can persist inside cells in a dormant state. I would consider continuing these courses for many months, and possibly changing from doxycycline to either a macrolide or ciprofloxacin in resistant cases.

    Jadin suggest that in chronic rickettsial disease, the mean time to achieve recovery is about 8 months.
    There is little published data to help us here!
    Classical and established doses appear to be doxycycline 100mg bd in adults, but children where teeth and bones are still growing should avoid this.

    My previous plan was to use doxycycline 100mg twice daily for cycles of 7-10 days on 10 days off. (There may be a need to vary the cycle length)

    If the situation is of some standing, minocycline with better intracellular penetration may be preferred.

    If I use minocycline, I am wary of long courses and as mentioned, we need to consider the risk of benign intracranial hypertension as a side effect.

    I stop it if ANA levels rise.

    In the past, if 2 cycles hadn’t helped, I use clarithromycin 500mg bd for 7 days (15mg/kg/day) or azithromycin 500mg one twice per day for 2 or 3 days (10mg/kg/day) can given before the next doxycycline cycle.

    I now tend to follow Marshall’s protocol for most suitable persons, but I am very careful how I choose this, and do not let vitamin D3 levels get too low!

    This is also a situation where persons with CFS may be more prone to the reaction that Marshall thinks is a Herxheimer reaction.

    He strongly recommends much lower doses such as 250 mg every third day. He writes and lectures that each molecule entering the germ weakens it.

    Azithromycin has high intracellular concentration and a long 1/2 life.

    Ciprofloxacin 750mg bd for weekly cycles can also be considered, as can clindamycin (A lincoside) at 250 mg bd.

    Jadin has case numbers in the thousands and reports 84-96% success rates in the chronic rickettsial group.

    She needs to publish the sero-positivity rate of South Africans who are well, and co morbidity data.

    Now we can note Prof Kenny De Meir Leir’s findings and the interesting work of Trevor Marshall.

    In recent presentations (2006), Marshall reports 40/77 CFS cases and 20/34 FMS cases responding to his protocol, usually taking well over a year to achieve this!
    4 I will later address the Marshall protocol more fully!
    A task is damp down any reaction to killing bacteria, as well as to shift things to decrease microbial survival.

    For the TH1 state we may have the task to decrease the high 1,25 dihydroxy D3 in the Th1 set immune set patient, but the marker may well be the 25 D3 level, as this may be a blocker on the 1,25 D3 receptor (VDR) interfering with efficiency of innate immunity.

    We are still not privy to what is happening in the intranuclear sites of the VDR or indeed on other intranuclear family receptors!

    Decreasing vitamin D3 intake along with avoiding sunlight could make sense here, but despite Marshall’s claims, we need to be wary of inducing vitamin D deficiency.

    I always follow up 25 D3 and 1,25 D3 levels at 2-3 months intervals.

    I am much stricter than Marshall in ensuring that persons do not become D deficient!!

    If low I check parathyroid hormone and calcium levels.

    Olmesartan rapidly reduces 1,25 dihydroxy D3 levels, but not to subnormal levels.

    The dose is 20- 40 mg 3-4 times per day.(titrate does to suit the person.)

    Minocycline and azithromycin are better than doxycycline, in dealing with cell wall deficient bacteria, because of better intra cellular penetration.

    In this situation dosing could follow Marshall’s recommendations, at least as far as a cautious beginning!

    A suggested dose is minocycline 12.5 - 25mg on alternate days for 30 days, then azithromycin 250mg every 3 days for 21 days.

    The dose is remarkably low, but it may need to be repeated.

    Each of these medications has capacity to decrease inflammation directly as they decrease matrix metalloproteinases such as MMP9.

    I need to state my clinical experience that many CFS and fibromyalgia patients appear to have adverse reactions when given antibiotics.

    These responses may include worsening of fatigue, aches, nausea, headache and just feeling really ill.

    My search of the literature has failed to reveal the reasons for these reactions though many explanations have been offered.

    The commonest explanations including Marshall’s ideas seem to be a “Herxheimer type reaction”, and/or release of cytokines, secondary to microbial death.

    Since I am committed to holistic approaches, I restate my use of the following supportive therapies to the above antibiotic protocols.

    It is apparent that many doctors do not pay much attention to fine tuning or ideal nutrition to each person. (This may be quite different from person A to person B.)

    (1) Fresh pineapple.

    This contains bromelain a protease which increases the absorption of any quercetin in the diet, and is 40% absorbed itself. It is fibrinolytic and the intention is to decrease fibrin deposition at vascular and other locations.

    (2) Quercetin.

    This plant flavonoid and antioxidant is an inhibitor of phospholipaseA2, and its anti-inflammatory effects include vessel protection.

    A bonus is its cancer preventing and antioxidant effect of LDL cholesterol.
    Effective doses may be 600-1,000 mg per day in divided doses.
    It may also quell some of the Herxheimer type reactions.
    Details on Quercetin.
    Glycosides are compounds that yield one or more sugars among the products of hydrolysis. Glycosides may be considered sugar ethers.

    The non-sugar component is known as the aglycone, and the sugar component is called glycone. The flavonoid glycosides and their aglycones are generally termed


    Rutin, quercitrin, and the citrus bioflavonoids, including hesperidin, hesperetin, diosmin, and naringen, are among the best known flavonoid constituents.

    Quercetin is the aglycone of quercitrin, rutin and other flavonoids.

    Quercetin (3,5,7,3’,4’-pentahydroxyflavone) may delay oxidant injury and cell death by: scavenging oxygen radicals; protecting against lipid peroxidation, and thereby terminating the chain-radical reaction; chelating metal ions, to form inert complexes that cannot take part in the conversion of superoxide radicals and hydrogen peroxide into hydroxyl radicals.

    Plants/Food Which Contain Quercetin:



    Bearberry (Arctostaphylos uva-ursi)

    Bell Peppers

    Black Catechu (Acacia catechu)

    Boneset (Eupatorium perfoliatum

    Brussel Sprouts


    Elder flowers (Sambucus canadensis)

    Eucalyptus (Eucalyptus globulus)

    Euphorbia (Euphorbis piluifera)

    Fenugreek (Trigonella foenum-graecum)

    Hydrangea (Hydrangea arborescens)


    Pale catechu (Uncaria gambir)

    Passionflower (Passiflora incarnata)


    Podophyllum (Podophyllum peltatum)


    Squill (Urginea maritima)


    Tea ( bioavailability is about half that of quercetin from onion.)

    Witch hazel (Hamamelis virginica)


    Is a potent antioxidant.

    Is a PPAR agonist, down regulating inflammatory cytokines.

    · Inhibits the following enzyme systems:

    Aldose reductase (an enzyme which promotes the synthesis and intracellular

    Accumulation of sorbitol)

    AR is a critical regulator of TNF-alpha-induced apoptotic signaling in endothelial cells.

    The inhibition of aldose reductase (AR) provides an interesting strategy to prevent the complications of chronic diabetes.

    Catechol-O-methyl transferase

    Cyclic nucleotide phosphodiesterases


    Oestrogen synthetase

    Histidine decarboxylase

    This may decrease histamine induced inflammatory injury.


    Several lipoxygenases

    Matrix metalloproteinase 9

    Phospholipase A2

    Protein kinases

    Transport ATPases

    Xanthine oxidase

    Thus effects are

    · Anti-inflammatory - prevents mast cell and basophil degranulation

    · Anti-oxidant

    · Helps reduce the formation of leukotrienes of the 4 series

    · Increases cyclic AMP

    · Inhibits phospholipase A 2

    · Inhibits platelet aggregation

    · Prevents breakdown of collagen matrix of connective tissue and ground substance

    *Protects pancreatic beta cells from damaging effects of free radicals

    *Sparing effect on epinephrine

    *Stabilizes membranes

    *Inhibits apolipoprotein B secretion by liver and intestinal cells.

    *Decreases diacylglycerol acyl transferase activity.

    *Has inhibitory effects on glycation of proteins

    Clinical Indications:

    · Allergies

    · Antiviral - herpes virus I, para-influenzae 3, polio virus I,

    Respiratory syncytial virus

    · Aphthous stomatitis

    · Asthma

    · Benign prostatic hypertrophy (BPH)

    · Bronchitis

    · Candidiasis

    · Cataract prevention- if diabetic

    · Crohn’s disease

    · Diabetes mellitus

    · Eczema

    · Fibrocystic breast disease

    · Fibromyalgia

    · Gout

    · Headaches

    · Haemorrhoids

    · Irritable bowel syndrome

    · Otitis media

    · Ovarian cancer - inhibition of tumour promotion (squamous cell carcinoma, ovarian carcinoma and oestrogen receptor negative breast cancer)

    · Psoriasis

    · Rheumatoid arthritis

    · Ulcerative colitis

    · Atopic dermatitis

    · Diabetic cataracts, neuropathy, retinopathy

    · Inflammatory conditions


    · 400 mg. 20 minutes before meals, TID

    5 Drug/Nutrient Interactions
    · Bromelain may enhance quercetin absorption

    Quercetin is an inhibitor of CYP450 3A4 isoforms and may increase the blood levels of 3A4 metabolized drugs and hormones.

    A major caution is interaction with common HMG CoA reductase inhibitors (except pravastatin)

    (3) Be sure that the patient is taking adequate zinc and vitamin C, and lots of coloured plant products.

    (4) Lactobacilli of the acidophilus and bifidus groups, and perhaps the yeast, Saccharomyces boulardii (these can also decrease antibiotic induced diarrhoea)

    It is very desirable to actually assess gut flora in order to find and correct any dysbiosis.
    6 In some cases the above lactobacilli should not be used!
    If irritable bowel symptoms are present, the special use of E coli Nissle and VSL#3 can be considered.

    Adequate dietary intake of fructo-oligosaccharide (inulin) as in artichoke, pear, asparagus and similar plants, supports healthy colonic flora.

    Probiotics are usually very well tolerated. (See more details below)

    (5) Other microbicidal agents.

    (a) Antimicrobial substances in colostrum and milk may emerge as having a role in dealing with some infections, while protecting normal gut flora.

    7 Lactoferrin
    This consists of a series of glycoproteins with activity against staphylococci, gut bacterial pathogens, candida, and viruses such as hepatitis C. As well it has been shown to heal experimentally induced colitis.

    Actions include depriving some bacteria of needed iron, breaking up biofilm which colonies of bacteria use to be less susceptible to body chemicals, and also enhancing of neutrophil phagocytic activity.

    There are species differences in these molecules, and most commercial products are of bovine origin.

    (b) Derivatives from coconut or coconut milk 300 ml per day.

    This contains lauric acid, which can be converted into monolaurin in the intestine, and has anti microbial actions, particularly against staphylococci (see later) but including CMV and allied viruses.

    Other fatty acids, capric acid especially as its monoglyceride, monocaprin and caprylic acid have antimicrobial activity. Monocaprin can inhibit chlamydia.

    Monolaurin can be obtained from the USA ( <> )

    This form is better tolerated than coconut milk and is probably more effective.

    I so far remain unconvinced by this work.

    Other Bacteria

    Chronic sinus, skin, respiratory and urogenital tract infections should be treated with appropriate antibiotics. At the same time attention needs to be paid to keeping the gut flora as healthy as possible. Some plants exhibit a capacity to inhibit bacterial proliferation. For example cinnamon, garlic, ginger, olive leaf, turmeric and St John’s Wort.

    The use of a nasal cream containing mupirocin, neomycin or bacitracin could kill bacteria in the anterior nares. Cleansing lotions and soaps containing chlorhexidine or similar might help cleanse the skin in general and the perineum in particular.
    I always aim to get the CRP normal.

    Dental hygiene and particularly healing gingivitis is also likely to be important.

    Herbalists may like to use locally placed and diluted tea tree oil or lavender oil as these have been shown to have anti-staphylococcal activity. Systemic antibiotic to eradicate coagulase negative staphylococci is probably not justified (or possible)

    Further research is needed in this area.

    Other antimicrobial therapies should be explored especially in the light of resistance to antibiotics.

    If studies in Hungary on olive leaf extracts are true, (Robert Lyons in Budapest) doses of 750mg (standardized to contain12.5mg oleuropein) 2-4 times per day could be tried. None of the patients that I have seen seem to respond to this.

    Olive leaf seems to be more helpful when used in combination with hops and rosemary.

    8 Gut Flora
    Newcastle research suggests that in some chronic fatigue sufferers the total count of intestinal flora is lower than normal and that there may be in particular sub normal levels of aerobes such as E coli or anaerobes such as bacteroides. (Note the previous data on bacteriophages that attack E Coli.)

    There may also be a lack of lacto bacilli. Lactobacilli of the acidophilus group appear to be protective in the upper intestine and the bifidus group protective to the lower bowel.

    In a few cases there may be an overgrowth of enterococci or alpha-haemolytic or non-haemolytic streptococci.

    These appear to make R-lactate,

    These organisms can be reduced with low doses of ampicillin, or cephalexin such as 250 mg bd for 1-2 days.

    There is a strong case to treat other all chronic fatigue sufferers with lactobacilli (acidophilus and bifidus) together with fructooligosaccharides from onion, artichoke, asparagus and pear) but this is particularly important when antibiotics are used.

    We need to evaluate which forms of probiotics are best.

    In the future we may find non-pathogenic strains of E coli can be reintroduced into the intestine in much the same way that we use lacto bacilli today.

    Recent data suggests that E coli Nissle may be helpful especially in irritable bowel syndromes. (Check through Google search)

    Also VSL#3 may be promising.

    Further research is needed on the subject of optimum probiotics in human intestinal disorders, e.g. irritable bowel syndrome and chronic fatigue.

    At present I strongly avoid the use of the drug tegaserod (Zelmac).
    Yeasts and Candida
    Anticandidal therapies and avoidance of dietary ingestion of yeasts (saccharomyces), which might have common antigens, may be one component of lessening inflammatory changes in small intestinal epithelial structures.

    Lactoferrin found in fresh milks has potent anticandidal activity; principally through it’s iron-binding effects.

    If the claims of yeast over-proliferation in the intestine are true it is astonishing that gastroenterologists doing endoscopic examinations have not identified candida more often. (These claims are common in naturopathic circles, but my perusal of the literature has failed to find support for the claims.)

    Even if there is no clear link between chronic fatigue syndromes and candida it is important to protect the body from any low grade inflammation in the functional inner surfaces of the intestine.

    I support the use of lactoferrin in these situations.

    Perhaps there should be more dialogue between gastroenterologists and microbiologists and those who claim that yeasts do cause other effects than those documented in medical texts.
    9 One area that needs a truly scientific study is that of “live blood analysis”
    This involves the use of very high magnification (8.000-18000x) of live blood samples, combined with the ease of changing from direct viewing to phase contrast and dark field illumination.

    This was presented at the Chicago conference about Marshall’s work.

    There is also facility to obtain photographic and video records of these views.

    It would be possible to comprehensively compare this data with the biochemical, microbiological, and immunological data that I have mentioned in this paper.

    A formal adequate study on this subject is long overdue and would include special stains, special culture media, immunofluorescent studies and PCR testing for microbial DNA.
    Amoebae are very common throughout the world. It is estimated that they are present in one third of the world’s people.

    People are vulnerable to pathogenic amoebae, especially in places that lack high quality water reticulation or sewerage.

    Dr Peter Snow in New Zealand feels that amoebae (principally Giardia Lamblia) may be important in some cases of C.F.S.

    He favours an acute amoebicidal agent (e.g. tinidazole 2 Gm) followed by some 3 weeks of daily metronidazole 400 mgm bd (or similar) to eradicate encysted forms of the protozoa.

    These agents have activity against gut anaerobes such as bacteroides.

    Herbalists use Artemisia (wormwood) and one drop of pure oil of cloves to kill intestinal parasites. (Both are given orally.)

    Artemisinin has been used in Malaria.

    We need more research on the prevalence of pathogenic amoebae in the human intestine, particularly in countries like Australia.
    It may be useful to take glyconutrients in the form of vegetables, fruits and salads on a daily basis and in some particular cases to use powdered concentrates of these substances. Helpful glyconutrients include those found in aloe vera, garlic, and onion, yams and sweet potato, turnip, parsnip and carrot, cabbage, cauliflower, broccoli and brussel sprouts, tomato, berries, pineapple, paw paw and rice bran.

    From a strictly scientific viewpoint, more evidence is needed on this subject, but these plants are good choices anyway.
    Although this summary will include recommendations by others who support these empirical nutrient trials, there is an urgent need for data collection to throw light on any of these claims.

    It is well established that many people eat inadequate diets.

    If a CFS sufferer comes to believe that food makes her or him ill, there is a serious danger that she or he may end up with mal or subnutrition.

    A recent report suggests that some of the people reporting chemical sensitivity are possessed with acute sense of smell and taste. They appear to have particular smells and tastes, which they dislike and the aversive reaction (via the limbic system.) can be strong.

    This area of human thinking connects strongly with control issues, which in turn are strongly connected with fear and experiences of guilt and anger.

    The medical professions find it extremely difficult to find ways to help the problem of the person who believes she or he has major food and chemical sensitivities.
    My thinking has paralleled writings from Dr Sarah Myhill < <> >

    She is using

    Acetyl-l carnitine 500mg 3 times per day,

    Vitamin B3 100mg 3-4 x per day,

    Co-enzyme Q10 200-300mg per day,(with piperine in black pepper to increase absorption.)

    R-alpha lipoic acid 100mg 3-4 times per day,

    D-ribose 3-5Gm /day to increase energy availability

    The D-ribose is helpful to an alternative energy pathway, as well as being a component of ATP and RNA. It helps muscles including the heart muscle, generate ATP.It is very safe.

    It is helpful in almost all heart diseases.I always give Coenzyme Q10 with persons taking statins.
    Fatty acids are carboxylic acids.

    Human fatty acids are long chain fatty acids.

    The overall intention is to minimize the production of inflammatory prostaglandins, which are metabolites of arachidonic acid.

    Inflammatory prostaglandins are of the 2 series and inflammatory leukotrienes belong to the 4 series.

    An optimum ratio of omega 3 fatty acids, omega 6 fatty acids and omega 9 fatty acids is still being debated.

    A diet that is very high in sunflower or safflower oil is very high in the omega 6 fatty acid, linoleic acid.

    While linoleic acid is essential, excessive amounts can increase the generation of arachidonic acid metabolites. For this reason some reduction of these oils is important in inflammatory states.

    There is evidence that increased secretion of insulin induced by foods with a high glycaemic index, enhances linoleic acid conversion into arachidonic acid. This suggests an advantage in avoiding more than small amounts of such foods.

    Cooking in olive oil which contains 80% omega- 9 mono unsaturated fatty acid (oleic acid) will not produce proinflammatory metabolites. It too should not be overheated!

    Pure canola oil also has quite a good ratio of omega9, 6 and 3 fatty acids

    (Also Australian canola oil has less than 1% trans fatty acids).

    Flaxseed oil has 50-60% alpha linolenic acid (an omega 3 fatty acid) and can be used to supplement olive though it should not be heated at all.

    Fish oils (omega 3 fatty acids) are likely to be helpful.

    Fish obtain fatty acids from algae and distribution happens up the food chain.

    Eicosapentaenoic acid (C20) and docosahexanoic acid (C22) have anti-inflammatory and cell membrane protective properties.

    Recent research continues to show brain protection, and even mild antidepressant effects.

    Recently Dr Bob Gibson in Adelaide has shown that supplements of flaxseed oil had little effect on EPA and DHA levels.

    This does not mean it has risks.

    He suggests that the elongases and desaturases are competed for by polyunsaturated fatty acids, leaving the conversion rate low.

    If this is the case, I favour giving both flaxseed and fish oils.

    If one gave only the EPA and DHA, one should consider giving the fatty acid transporter acetyl-l- carnitine as well. (See below)

    It is pertinent to note that labeling of edible oil products in Australia is inadequate. In Australia, only 2 manufacturers make all margarines.

    The consumer needs to know that trans fatty acids are at very low levels (<1%), and that omega 3,6, and 9 unsaturated fatty acids are balanced.

    It should state on the product container that the trans level is 0.03 G (or less)/5g serve of the product.

    A good rule is to avoid all cheap or inadequately labeled margarines.

    It is unacceptable for manufacturers to continue to leave the high trans fatty acid products on the market!

    Peanut pastes are now usually labeled in Australia.

    I believe we should continue to protest to the Government until other food labeling is adequate!

    In Australia, Flora Canola spread, Golden canola, Flora Monosun spread and Meadow Lea Canola spread appear to be safe. (There are others)

    Oxidized fatty acids, and trans fats appear to increase the risk of macular degeneration in the eyes.

    All polyunsaturate increases in diet need the use of anti-oxidants. (See below)

    Butter usually contains about 2% trans fatty acids.

    We need governments to enforce adequate food labeling about trans fatty acids.

    If inflammation is mediated through leukotrienes of the 4 series (principally LTB4) there is a case for using fatty acids from sea creatures such as the sea cucumber and the New Zealand green lipped mussel.

    The preparation called Lyprinol (Lyprinex) is a purified mixture of eicosatetraenoic acids analogous to arachidonic acid and inhibits both 5 and 12 lipoxygenases radically reducing proinflammatory leukotrienes. The dose is 5 mgm per kg of body weight per day.

    While in vitro activity has been demonstrated by Dr Henry Betts at The Queen Elizabeth Hospital in Woodville, South Australia, there is a need for proof of activity in human inflammatory states.

    Lyprinol might be indicated when neutrophils are implicated in the ongoing pathology, as LTB4 is a potent chemotactic agent for neutrophils.

    In these inflammatory states it may also emerge that there is a role for the use of cetyl myristoleate, which is an esterified form of a monounsaturated fatty acid known as myristoleic acid.

    This substance exists naturally in small quantities in some animals, (for example mice with natural levels of CMO were resistant to polyarthritis induced with Freund’s adjuvant.)

    Subsequently this has been found to apparently turn off inflammation in a range of human inflammatory conditions such as rheumatoid arthritis. The dose is 2.5 grams twice a day for a month.

    This is also work that needs validation from other researchers.

    It is disappointing that there is so little literature on this.

    Its effect seems to be enhanced by adding digestive enzymes containing lipases and by concomitant use of glucosamine and perhaps Lyprinol.

    In summary it appears that there is an optimum ratio of omega 3, omega 6 and omega 9 fatty acids, and we will integrate these with antioxidants such as mixed tocopherols, tocotrienols and coenzyme Q10 which decrease lipid peroxide levels.

    Other plant antioxidants such as quercetin also protect against lipid peroxidation.

    The full improvement of each person’s diet is the subject of my ongoing commitment to people finding health promoting and protective diets.


    Kenny De Meir Leir emphasizes the abnormalities in the gut in many forms of CFS.

    Restoration of normal gut flora and optimal health of epithelial and other gut cells might be enhanced by the following methods:

    (1) Adequate protein intake and this might well include supplements of specific amino acids such as those reported as low by the Newcastle group (eg serine). Their belief is that protein digestion is incomplete, thus many sufferers are requiring amino acids in the diet.

    Specific amino acid supplements ((glutamine, taurine, serine, glycine, glutathione, alpha keto glutarate and carnitine are suggested) and the antioxidant, alpha lipoic acid could well be important.

    This is particularly for intestinal cells but as well to be certain that all other body cells get adequate essential amino acids as well as to overcome putative metabolic blocks.

    It seems that there is no evidence that oral glutathione is effective in boosting cellular levels of glutathione.

    There is some evidence (as mentioned earlier) that whey proteins from milk may be good way to increase amino acids and increase glutathione production inside cells.

    I have not seen success with amino acid supplements, and am presently following Cheney in recommending whey protein devoid of casein and lactose.

    There is some evidence of carnitine deficiency in CFS.

    On days when meat is not consumed, take 2 grams of acetyl-L-carnitine. Vegetarians should supplement their diet with acetyl L-carnitine (best absorbed form) by taking 2 grams daily. (See Website of Dr Sarah Myhill <www.DrMyhill .com <> >

    (3) Eating evenly.

    (4) Avoid excessive intake of foods with high glycaemic index (avoiding functional hyperinsulinaemia).

    (5) Consider using D-ribose. In order to make new ATP, one needs a sugar, namely D-ribose. Normally the body can manufacture this for itself from glucose, but if energy levels are very low, then it may be unable to synthesize enough of this essential sugar. So when the CFS sufferers push themselves too much, ADP is converted into AMP, which they cannot recycle. It normally takes a few days to make new ATP from D-ribose, but the CFS sufferers (and persons with heart disease) may really struggle to make D-ribose.
    It also enhances the hexose monophosphate shunt!
    It has been reported to improve fibromyalgia.

    (6) Avoiding foods which might cause gut “sensitization”, or other injury, (e.g.dairy products, gluten). (Also excluding gluten enteropathy.)

    This aspect needs elaboration in light of the possible role of lectins in grain husks promoting some disease states.

    At least 3 weeks of exclusion and perhaps more should be considered in refractory CFS.

    (7) Adequate folate, B12, B5 and B6 and vitamin A and D.

    (8)The recent evidence of people avoiding sunlight has led to studies on levels of vitamin D in various populations. This has uncovered many people with low levels.

    A recent Australian study (Geelong, Victoria) revealed that about half of psychiatric patients had low levels of vitamin D3

    Low vitamin D in childhood gives rise to rickets, and in adulthood to osteomalacia. I check to see that PTH has not risen.

    Immune cells need 1,25 D3, but according to Trevor Marshall, D3 itself may block the action of 1,25 D3.

    I am keeping an open mind about this subject.

    Now there is further evidence of vitamin D helping immune function.

    In multiple sclerosis, rheumatoid arthritis and Sjogren’s syndrome, low vitamin D levels increase the risk of these diseases. (All of this may need re-examining in the light of Marshall’s work!)

    (9) The Newcastle researchers favour pancreatic enzyme supplements to increase the adequacy of digestive processes.

    (10) Fish and flaxseed oil also appear to be protective to the gut.

    (11) Vitamin C in small repeated doses during each day. I make the comment that whenever we cook foods and destroy vitamin C, it makes sense to take vitamin C to replace that loss.

    (12) I always favour taking it with the plants we eat.

    (13) In true vitamin D deficiency, cholecholecalciferol (vitamin D3) can be added as 4,000IU/day until levels are 80-100 nmol/L (Daylight skin exposure is also needed.)

    (13) Mineral support

    Magnesium in a highly bioavailable form up to 300 -500 mgm elemental Mg/day can correct any chronic magnesium deficiency, and perhaps act as a functional calcium channel blocker. Magnesium may enhance sleep, decrease irritability, and diminish central nervous system NMDA activation.

    Serum magnesium levels are not a good guide to cellular magnesium levels and red cell magnesium is a better measure.

    Potassium supplementation (or use of spironolactone or amiloride) could increase total body potassium and this is being studied further by Dr R Burnet, as it appears to only apply to the low potassium group.

    I prefer the potassium supplements if I can establish potassium deficiency.

    (The potassium and above drugs should not be used with ACE inhibitors or angiotensin 2 receptor blockers.)

    It is important for people to be replete in chromium, manganese, molybdenum, selenium and zinc, so that metallo-enzymes using these elements can function optimally.

    Molybdenum is only added if hair analysis shows low levels. It is usually adequate in leafy vegetables and legumes.

    Suggested daily allowances would be –

    Zinc (elemental) 15 mg

    Manganese (“) 2.5 mg

    Molybdenum (“) 50-100mcg

    Chromium (“) 200 -600mcg

    Selenium (“) 200 mcg

    Further research is needed to appraise cations in people who have a high urinary citric acid level.

    The subject of mineral ratios is another area that is being explored in human and veterinary medicine.

    We probably need to rethink the subject of the correct balance of minerals if further research supports Mark Purdey’s evidence that high manganese and low copper in environments, and in animal and human brains increases the emergence of abnormal prions as in Creutzfeld-Jacob disease and bovine spongiform encephalopathy.

    Aside from the ignorance and arrogance, which led to people feeding herbivores with products from animals, and transferring prions in this way, we can have more vigilance about the interplay of causative factors

    Possibly exposure to organo-phosphorus pesticides is another risk factor.

    I mention this in order to remind ourselves of the need to evaluate care of the environments in which we live.
    10 Persons from rural locations and users of these chemicals are the main ones at risk!
    Mineral contamination of human food may include excessive mercury, aluminium, copper, lead, nickel and cadmium.

    High mercury can come from fish high up in the food chain.

    Some of the metals can be used by gut flora, but with permeable gut disorders may harm human health.

    Kenny de Meirleir has a special interest in this area.

    Some protective chelation can be given through coriander, chlorella and free-range organic eggs.
    Drs Ian Brighthope, Robert Buist, Paul Cheney, Henry Osiecki, Jeffrey Bland and Martin Pall are all in favour of multiple anti oxidants to cover a wider range of sites and oxidant situations.

    Oxidation involves electron donation, and antioxidants are electron donors.

    It follows logically that when antioxidants mop up free radicals, they are themselves oxidized.

    The net outcome of this depends on how much the products can still cause cell membrane or other cellular injury.

    Some evidence is emerging that single antioxidants such as vitamin C or E are not particularly protective and may even become pro-oxidant.

    For example, pure D alpha tocopherol can mop up a free radical and become a free radical itself.

    e.g. EH + R’ -> R’H + E’ E’ is a free radical

    Co enzyme Q10 has been shown to quench the vitamin E free radical and is also better at reducing oxidized LDL cholesterol, than is vitamin E.

    A number of trials with pure D-a(RRR-a) tocopherol have failed to produce evidence of protection against cardiovascular disease. It is known that gamma tocopherol can mop up the E free radical.

    The Heart Protection Study (HPS) is a recent example of 8 years of D-alpha tocopherol 500IU, vitamin C 500 mg and beta-carotene in combination failing to alter outcomes in people with heart disease.

    We need trials of mixed tocopherols (a,b,gandd,) and tocotrienols (a,b,g, andd, particularly because nature tends to have these antioxidants together.

    The richest sources of these substances are edible vegetable oils.

    D a tocopherol is high in wheat germ oil,

    g tocopherol is high in soybean and corn oil.

    Palm oil is high in a and g tocopherols and a and g tocotrienols.

    Thus antioxidant therapy would include:

    1. D alpha tocopherol succinate 500IU orally daily (needs another substance to deal with the generated vitamin E free radicals. (e.g mixed tocopherols, gamma tocopherol, tocotrienols, vitamin C, R-alpha lipoic acid, and coenzyme Q10 could each carry out this function.) (See below)

    2. Co enzyme Q10 100-300 mgm daily (paper in coenzymeQ10 conference, Boston1998) (enhances mitochondrial energetics and mitochondrial DNA repair, and mops up oxidized vitamin E)

    3. Plant flavonoids from many coloured vegetables, salads and fruits (especially beneficial)


    anthocyanosides (bilberry)
    mixed carotenes (carrots, yellow and orange vegetables),

    lutein and zeaxanthin(egg yolks, spinach),

    lycopenes (tomatoes),

    proanthocyanidins (grape seed and pine bark)

    quercetin ( apples, brussel sprouts, ginkgo biloba, onions, pears)

    resveratrol (grapes and peanuts)

    A minimum of seven different vegetables per day is recommended (pesticide free) specifically ensuring many different anti oxidants.

    Specific herbal agents are now being tested for anti-inflammatory actions and I note that

    (1) Humulones from hops, and curcumin from turmeric are PPAR agonists

    (2) Nettle stops activation of NF kappa beta by TNF alpha and peroxynitrite.

    (3) Boswellic acids from frankincense (boswellia) are potent elastase inhibitors.

    (4) Curcumin (from turmeric) is a good elastase inhibitor, but it also needs piperine from black pepper to improve absorption.

    (The drug Kenny De Meir Leir uses is cefoperazone)

    This is the herb that Kenny De Meir Leir uses in cases with abnormal RNAse-L.

    Now evidence is emerging that curcuminoids are neuroprotective.

    They may also have useful anti-inflammatory actions.

    In time, ginger, turmeric, cinnamon and other spices will be further explored for anti-inflammatory actions.

    Feverfew has anti-migraine and anti-inflammatory actions and may also be protective to bone.

    4. Vitamin C in doses of up to 500 mgm 5-6 times per day.

    I rate this as extremely important.

    Human beings lack an enzyme needed to synthesize vitamin C.

    In other animals that cannot make vitamin C (primates, fruit eating bats, and guinea pigs), there is a turnover equivalent to many grams/day (as much as 10-20 gm/day in a creature weighing 60-70 kg).

    It is largely because we cook our food that human beings eat so much less.

    Since nature provides antioxidants in combination rather than in isolation, there is a pattern for maximum mopping up of free radicals with less residual damaging products.

    Thus I eat a plant with colour with each dose of vitamin C.
    I make up fruit and vegetable drinks rather like those made by Dr Mehmet Oz (cardiovascular surgeon NY)

    It is worth considering infusions of vitamin C in people who do not eat well or have gut abnormalities.

    The Australian College of Nutritional and Environmental Medicine teach practitioners of the value of IV vitamin C, particularly in any one getting an acute infection and as an adjunct to cases not responding to appropriate antibiotic regimes.

    5. R-Alpha lipoic acid 200 mgm twice a day can be used to quench peroxynitrite anions (ONOO-) and gamma tocopherol 300 mgm a day does the same thing.

    Alpha lipoic acid (ALA) converts into dihydrolipoic acid (DHLA) but both are capable of quenching free radicals covering antioxidant effects in both water and fat soluble domains.

    DHLA thus neutralises reactive oxygen species such as super oxide radicals, peroxyl and singlet oxygen and is a co factor in acyl transfer reactions regenerating reduced glutathione and ascorbic acid and maybe indirectly helping the recycling of vitamin E.

    As lipoamide, ALA/DHLA function as a co factor in oxidative decarboxylation reactions of pyruvate, alpha keto glutarate and branched change keto acids. Both also have metal chelating activity.

    It is emerging as one of the best neuro-protectors currently available.

    6. Gamma tocopherol has more immediate activity than d alpha tocopherol in dealing with already present free radicals and in any event probably needs to be present at above 20% of total tocopherols to lessen damage to the D alpha tocopherol.

    7. Hydrogen atoms with an extra electron loosely attached (negative hydrogen ions) are present in glacial water in mountains in the north of Pakistan (Hunzaland) and it is claimed by Dr Patrick Flanagan that this results in water with low surface tension, and effective electron donation with potent antioxidant effects. Flanagan microclusters are tiny mineral clusters which

    act as transport vehicles delivering nutrients into cells.

    They have a very high negative electrical charge and Flanagan claims that they enhance removal of metabolic products from cells.

    They are marketed as MICROHYDRIN.

    Electron loss is part of all oxidations and electron donation is part of all antioxidant effect.

    Flanagan says that plants produce negative hydrogen in fresh ripened fruit ,but the negative hydrogen is lost in cooking or canning.

    I cannot find independent validation of Flanagan’s claims.

    Claims about colloidal minerals are also worth scientific exploration.

    I cannot find a sound basis for these substances, but suspect that they have not been adequately tested.

    It may be worth giving supplements of glutathione (e.g. in undenatured whey protein), or glycine, serine, glutamine and cysteine. Dr Paul Cheney favours using oxygen in some of these situations.

    Dr Robert Buist claims his ”Isowhey” preparation is ideal for this purpose!

    Perhaps extra vitamin B12 increases succinyl CoA levels enhancing succinic acid levels. It certainly increases delivery to the brain if it is methyl cobalamin.

    Some clinicians have recommended extra alpha keto glutaric acid.
    Increased intake of salt and fluids are recommended.

    Drs Richard Burnet and Peter Rowe (Johns Hopkins) did add fludrocortisone perhaps with potassium supplements if the above failed, and postural hypotension is confirmed. Electrolytes should be monitored if fludrocortisone or liquorice is used.

    In a recent article in the Journal of the American Medical Association, the John Hopkins group found that a trial of fludrocortisone was not superior to placebo in this type of CFS.

    In the laboratory situation most of these postural changes do not seem to be of significance, and my emphasis is simply that of maintaining adequate blood volume.

    I do not support the use of fludrocortisone. I do not use fludrocortisone!
    It is possible that a sub group of CFS sufferers are low in blood levels of dehydroepiandrosterone (DHEAS). This may relate to low cholesterol levels.

    In chronic disease, DHEAS levels may be low, and levels decrease with aging.

    By contrast adding DHEA can reduce inflammatory cytokines such as TNFa. (This latter occurs at supraphysiological levels.

    Studies continue on its role in immune regulation.

    There is some use of this by some doctors, but in general endocrinologists do not support its use in CFS. There are anecdotal examples of improvements in some cases.

    I now support its use if blood levels are low.
    There is a Swedish interest group concerned with the increasing use of equipment and lines that generate electromagnetic fields.

    It is now clear that by measurement there are many potential areas of human exposure to these significant fields.

    It is estimated that 10% of workers are presently exposed to such fields with significant adverse effects in health.

    Computers, copying machines, printers, mobile telephones, electric motors, electric blankets, fluorescent lighting and coils of cable all generate electric and magnetic fields.

    It seems likely that some people are much more sensitive to these effects and in particular sufferers of chronic fatigue give many accounts of such sensitivities.

    One sub group may be getting adverse effects from chemicals sprayed on new electronic circuits for flame resistant prot
  2. Mikie

    Mikie Moderator

    For this info. I have gone from bedridden most of the time to being able to work part time. It took a very comprehensive treatment regimen over eight years to get to where I am. I am not well--yet. I still have to monitor my energy levels and watch out for viral and mycoplasma reactivations. I may have to do this the rest of my life.

    One thing not mentioned is what Dr. Cheney calls the seizure activity many of us suffer. He recommends Klonopin. I take it so that I can sleep. It has been a God send for me. One does develop physical dependence on it and if one wants to stop taking it, one has to very, very slowly wean off of it. I've tried to wean off twice but had to go back to it. Cheney believes when one achieves a high level of healing, it is easier to wean off. Without the Klonopin, I do not get quality sleep and that is key to my well-being.

    Again, thank you for sharing this info with us.

    Love, Mikie