Chapter 13

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 signalling.

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 which 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 a far from satisfactory area.

Hypotheses need much more work on them.

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. Vitamin D should be especially considered.

PATHOGENS
Viruses

Glyconutrtients 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, (eg 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.

Antiviral agents

Herpes viruses may be decreased by acyclovir, and famcyclovir (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 which 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.

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

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 which are injected with this material.

Foscamet has an antiviral spectrum against all of the herpes virus group, and can be active against CMV infections which 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( kaempherol ) 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.

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, 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.

Mycoplasmas

Mycoplasmas can be treated acutely with tetracyclines, macrolides or ciprafloxacin.

With chronic persistence of mycoplasmas

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.

Mino cycline has better intracellular penetration than doxycycline.

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

A difficulty exists in discerning whether mycoplasmas are resident, 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.

Rickettsiae
As stated earlier in regards to rickettsias, 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 ciprafloxacin in resistant cases.

Jadin suggest that in chronic rickettsial disease, the mean time to achieve recovery is about 8 months.

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 earlier 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)

This is more appropriate for acute disease, and may well be inadequate for chronic infections.

Minocycline has better penetration into cells, and we are trying to work out whether we should follow the Marshall plan to be very wary of Herxheimer reactions.

It ma be prudent to start courses at doses of 25mg on alternate days ,increasing to 50 mg on alternate days after a week or two.It remains unclear about the optimal duration of therapy, but it may wel be many months or more.

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

I now use azithromycin more than before and start at 250mg on alternate days for several weeks as tolerated.

If 2 cycles haven't helped, I was using clarithromycin 500mg bd for 7 days (15mg/kg/day) or azithromycin 500mg one twice per day for 2 or 3 days (10mg/kg/day) given before the next minocycline cycle.

Azithromycin has high intracellular concentration and a long 1/2 life.)and may be a better choice for chronic disease.
.
Ciprofloxacin 750mg bd for weekly cycles can also be considered.

I now think that close attention is needed in each individual case, wth most caution in persons who report side effects.

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

She needs to publish the seropositivity 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.

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 high1,25 dihydroxy D3 in the Th1 set immune set patient.

Decreasing vitamin D3 intake along with avoiding sunlight makes sense here,and olmesartan rapidly reduces 1,25 dihydroxy D3 levels.

The dose is 40 mg 3-4 times per day.

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

In this situation dosing coud follow Marshall's recommendations.

A suggested dose is minocycline12.5 - 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 matrix metalloproteinases.

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.

I restate my use of the following supportive therapies.

(1) Fresh pineapple.
This contains bromelain a protease whih increases tha 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 flavanoid and antioxidant is an inhibitor of phospholipaseA2,and its antiinflammatory 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
flavonoids.

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:

Apple
Asparagus
Bearberry (Arctostaphylos uva-ursi)
Bell Peppers
Black Catechu (Acacia catechu)
Boneset (Eupatorium perfoliatum
Brussel Sprouts
Dill
Elder flowers (Sambucus canadensis)
Eucalyptus (Eucalyptus globulus)
Euphorbia (Euphorbis piluifera)
Fenugreek (Trigonella foenum-graecum)
Hydrangea (Hydrangea arborescens)
Kale
Pale catechu (Uncaria gambir)
Passionflower (Passiflora incarnata)
Pear
Podophyllum (Podophyllum peltatum)
Onion
Squill (Urginea maritima)
Tarragon
Tea ( bioavailability is about half that of quercetin from onion.)
Witch hazel (Hamamelis virginica)

Actions:

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 signalling 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

Cyclo-oxygenase

Oestrogen synthetase

Histidine decarboxylase
This may decrease histamine induced inflammatory injury.

Hyaluronidase

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

Dosage:

* 400 mg. 20 minutes before meals, TID

Drug/Nutrient Interactions

* Bromelain may enhance quercetin absorption

Cautions
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)

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

Probiotics are 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.

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 ( www.lauricidin.com )

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, 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.

Dental hygiene and 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.

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

There is a strong case to treat 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.

Lacto bacilli are sometimes called probiotics and they may work by adherence to intestinal cells thus competing with pathogenic bacteria for attachment. In effect this inhibits some of the pathogenic component.

Benefits of probiotics.

As well they may have the following benefits.

" Producing natural antimicrobial agents such as hydrogen peroxide, lactic, formic and acetic acids.
" Diminishing some toxicity from ammonia, free ammonia nitrogens, free serum phenols, indole, and indican.
" Assist in the production of lactase.
" Assist absorption of nutrients.
" Specifically decrease activity of Helico bacter Pylori and Candida Albicans.
" Protect against enteric rotavirus.
" Protect excessive cell division in colonic crypts.
" Relieve constipation and diarrhoea and also inhibit specifically Salmonella, Shigella, Pseudomonas, Staphylococcus and Klebsiella.
" Improve acne.
" Lessen procarcinogens.

We need to evaluate which forms of probiotics are best.
Bioceuticals "Symbiotique" is showing some promise.
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.
Further research is needed on the subject of optimum probiotics in human intestinal disorders, eg 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.

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 tesing for microbial DNA.

Protozoa
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 which 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 (eg 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 artemesia (wormwood) and one drop of pure oil of cloves to kill intestinal parasites. (Both are given orally.)

We need more research on the prevalence of pathogenic amoebae in the human intestine, particularly in countries like Australia.

GLYCONUTRIENTS
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.

 

NUTRITIONAL REPAIR

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.

FATTY ACID CHOICES

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

Inflammatory prostaglandins are of the 2 series and inflammatory leucotrienes 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 which 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.

Pure canola oil also has quite a good ratio of omega9, 6 and 3 fatty acids
( also Australian canola oil has less than1% 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.

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 antiinflammatory and cell membrane protective properties.

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

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 carnitine as well.

It is pertinent to note that labelling of edible oil products in Australia is inadequate.

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.

A good rule is to avoid all cheap margarines.

In Australia, Flora Canola spread, Monosun spread and Meadow Lea Canola spread appear to be safe.

Oxidized fatty acids 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 labelling about trans fatty acids.

If inflammation is mediated through leucotrienes 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 leucotrienes. 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.

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 rest of each person's diet is the subject of my ongoing commitment to people finding health promoting and protective diets.

 

 

GUT (and OTHER CELLS)

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) and the antioxidant, alpha lipoic acid.
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.

(2) Eating evenly.

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

(4) 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 promoting some disease states.
At least 3 weeks of exclusion and perhaps more should be considered in refractory CFS.

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

(6) 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.
Low vitamin D in childhood gives rise to rickets, and in adulthood to osteomalacia.

Now we have to explore the possibility that there is a subpoulation of persons who overconvert 25 D3 into 1,25 D3!

(7) Now there is further evidence of vitamin D helping immune function, but a subgroup who for a time need ways to modify D3.

In multiple sclerosis, rheumatoid arthritis and Sjogren's syndrome,does low vitamin D levels increase the risk of these diseases?

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

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

(10) 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 Vit C to replace that loss.

(11) In true vitamin D deficiency,Vitamin D can be added as1,000IU/day until levels are 80-100nmol/L (Daylight skin exposure is also needed.)

(12) 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.

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.
(These should not be used with ACE inhibitors or angiotensin 2 receptor blockers.)
It is important for people to be replete in zinc, manganese, chromium and selenium, so that metallo-enzymes using these elements can function optimally.

Suggested daily allowances would be -

zinc(elemental) 15 mg
manganese(") 2.5 mg
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 which 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 organophosphorus 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.

Mineral contamination of human food may include excessive mercury, aluminium, copper, lead, nickel and cadmium.
Some of the metals can be used by gut flora, but with permeable gut disorders may harm human health.

ANTIOXIDANTS

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 membane 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.

eg 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- (RRR- ) 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, vit C 500mg and betacarotene in combination failing to alter outcomes in people with heart disease.

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

The richest sources of these substances are edible vegetable oils.
D tocopherol is high in wheat germ oil,
tocopherol is high in soybean and corn oil.

Palm oil is high in and tocopherols and and 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, alpha lipoic acid, and co 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)
eg B carotenes (carrots),
lycopenes (tomatoes),
quercetin ( apples, brussel sprouts, ginkgo biloba, onions, pears)
anthocyanosides (bilberry)
proanthocyanidins (grape seed and pine bark)
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 actios and I note that

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

(2) nettle stops activation of Nfkappa beta by TNF alpha and peroxynitrite.

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

Kenny De MeirLeir says that they do not inhibit peripheral monocyte elastases in CFS. They may still 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.

Human beings lack an enzyme needed to synthesize vitamin C.

In other animals which 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.
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 this, particularly in any one getting an acute infection.

5. 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.

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 have not found 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.

OTHER SPECIAL ASPECTS
ADDRESSING THE ORGANIC ACID CHANGES

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

Perhaps extra vitamin B12 increases succinyl CoA levels enhancing succinic acid levels.

LOW BLOOD PRESSURE, POSTURAL HYPOTENSION AND DIZZINESS.

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.

DHEA

It is possible that a sub group of CFS sufferers are low in blood levels of dehydroepiandrosterone (DHEA). This may relate to low cholesterol levels.

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

By contrast adding DHEA can reduce inflammatory cytokines such as TNF . (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.

ELECTROMAGNETIC FIELDS

There is a Swedish interest group concerned with the increasing use of equipment and lines which 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 protection.

The medical profession at large has not accepted hypersensitivity to these fields as proven, but Don Maisch in Tasmania has visited homes of people with severe chronic fatigue and established that fields from two to ten milligauss are able to produce symptoms. When a person was removed, for example, from sleeping on an electric blanket or their bed was moved so that the pillow was no longer next to the refrigerator motor on the other side of the wall, the patient became normal in four to six weeks.

We are in a strong position to say that people with chronic fatigue syndrome should do their utmost to avoid significant EMF fields and if in doubt they may need to contact experts in the field to test particular locations.

MIND AND BRAIN FOG

If specific eradication of pathogens is achieved there is often a return of normal clear thinking.

Treating rickettsias adequately seems to clear this mind fog.

Dr Ian Brighthope points out that in chronic fatigue in at least one major subcategory particularly where there are CNS type disabilities ordinary B12, in the form of cyanocobalamin or hydroxy cobalamin do not cross the blood brain barrier. For this reason he believes it is necessary to use methyl cobalamin 1 mgm by injection daily for about a week and thereafter weekly.

Normally there should be no difficulty in converting hydroxy cobalamin into methyl cobalamin or S-adenosyl cobalamin, and this too needs some scientific validation.

Methyl cobalamin is unstable in solution, and needs to be shipped from the manufacturer in a frozen form and thawed overnight in the refrigerator for injection the next morning. Dr Brighthope suggests that this can greatly improve mind or brain fog. It is stable in powder form.

I have tried a product called Methylguard, which contains methyl cobalamin400mcg, folinic acid 400mcg, pyridoxal -5-phosphate 6.8mg and trimethylglycine, 600mg. This would enhance methylation and hopefully enhance brain function in this group of people. It would also increase formation of S -adenosyl methionine.

Methyl cobalamin as oral 1mg lozenges is also available.
S-adenosyl methionine is claimed to be a natural antidepressant and may have a place in treating depression or brain fog in CFS.
It is crucial that people get adequate folic acid which should be redefined to at least 400 mcg per day (E coli in the gut may contribute a substantial amount of folic acid in the normal person).
More (up to 1mg) is needed in people who have elevated levels of homocysteine. This subgroup has now been characterized. (Modern Nutrition Textbook)

About 10% of Caucasians have a point mutation in the gene which is responsible for the enzyme 5,10 methylene tetrahydrofolate reductase which converts homocysteine into methionine by adding a methyl group. These individuals have about 50% of the enzyme activity of the normal population

It is suggested that folate is given in increasing doses until the homocysteine drops well into the normal range. I suggest a target of 7-8 micromols/L.

Trimethylglycine can be added if this is not successful.

Dr Brighthope is a strong supporter of high amounts of vitamin C spread out over the day (equivalent 2-10 Gms) and niacin (mixture of nicotinic acid and nicotinamide) to a total of at least 500 mgm a day (a supraphysiological dose), in this" brain fog" group.

All of this makes sense since NIACIN is also a precursor to the NAD/NADH reactions. NADH can be purchased in the USA, and there are claims that it helps in CFS.
Tim Roberts also mentions amino acids as being helpful in this group.
.

OTHER ACTIONS OF SOME ANTIBIOTICS.

Tetracyclines inhibit intracellular protein synthesis in organisms, but also inhibit mammalian proteins such as metallo-proteinases including collagenases and elastases.
This may be important in inflammations such as gingivitis, synovitis and arthropathies.

These agents also affect T cells and cytokines.

Azithromycin also inhibits MMP9.

Clarithromycin has been shown to modify T cells and cytokines in many situations. It can inhibit Tcytotoxic cells and decrease TNF .

NEW ASPECTS OF INFLAMMATION

Peroxisome proliferator activated receptors (PPAR)

These were mentioned in Chapter 4(on receptors.)

Nuclear peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily. As transcription factors, PPARs regulate the expression of numerous genes and affect glycaemic control, lipid metabolism, vascular tone and inflammation.

This subfamily consists of three isotypes, alpha (NR1C1), gamma (NR1C3), and beta/delta (NRC1C2) with a differential tissue distribution.

PPARalpha is expressed primarily in tissues with a high level of fatty acid catabolism such as liver, brown fat, kidney, heart and skeletal muscle.

PPARbeta is ubiquitously expressed.

PPARgamma has a restricted pattern of expression, mainly in white and brown adipose tissues, whereas other tissues such as skeletal muscle and heart contain limited amounts.

Activation of the subtype PPAR-gamma improves insulin sensitivity.

Furthermore, PPARalpha and gamma isotypes are expressed in vascular cells including endothelial and smooth muscle cells and macrophages/foam cells.

PPARs are activated by ligands, such as naturally occurring fatty acids, which are activators of all three PPAR isotypes.

In addition to fatty acids, humolones from hops (agonists for and ), several synthetic compounds, such as fibrates(alpha), one angiotensin receptor blocker(telmisartan(( ), and thiazolidinediones (rosiglitazone and pioglitazone), bind and activate PPAR alpha and PPAR gamma.

Rosiglitazone which acts on the alpha receptor has some adverse effects on lipids, but pioglitazone, which acts on the gamma receptors does not adversely effect lipids.

Telmisartan has about 1/3 the PPAR agonist effect of pioglitazone.

As well, apigenin, chrysin, and kaempferol significantly stimulated PPAR gamma transcriptional activity in a transient reporter assay. In addition, these three flavonoids strongly enhanced the inhibition of inducible cyclooxygenase and inducible nitric oxide synthase promoter activities in lipopolysaccharide-activated macrophages which contain the PPAR gamma expression plasmids.

There are also PPAR agonist actions with curcumin.

In order to be transcriptionally active, PPARs need to heterodimerize with the retinoid-X-receptor (RXR).

Upon activation, PPAR-RXR heterodimers bind to DNA specific sequences called peroxisome proliferator-response elements (PPRE) and stimulate transcription of target genes. PPARs play a critical role in lipid and glucose homeostasis, but lately they have been implicated as regulators of inflammatory responses.

A role for PPARgamma in inflammation has also been reported in monocyte/macrophages, where ligands of this receptor inhibited the activation of macrophages and the production of inflammatory cytokines (TNFalpha, interleukin 6 and 1beta), although part of the anti-inflammatory effects of these ligands seems to be mediated by a mechanism not involving PPARgamma.

All these findings suggest a role of PPARs in the control of the inflammatory response with potential therapeutic applications in inflammation-related diseases.

Actions of PPAR agonists will probably play important roles in many inflammatory diseases.

Protection from hepatic fibrosis is another recent hope.as Xu,Fu and Chen demonstrated, for the first time, that curcumin dramatically induced the gene expression of PPAR-gamma and activated PPAR-gamma in activated HSC. Blocking its trans-activating activity by a PPAR-gamma antagonist markedly abrogated the effects of curcumin on inhibition of cell proliferation.

Orphan nuclear receptors belong to this gene super-family but their target genes and physiological function are still being studied.
The orphans belonging to the PPAR, LXR and FXR family function as lipid and bile-acid sensors while PXR and CAR function as xenobiotic sensors.

Small-molecule modulators of LXR and FXR control key genes involved in cholesterol and lipid metabolism. PXR is a highly promiscuous xenosensor that responds to xenobiotic ligands (antibiotics, statins, glucocorticoids) and induces the Cyp3A gene, thereby playing a role in hepatoprotection and bile acid metabolism.

A related receptor from the gene subfamily, CAR, displays high ligand selectivity and modulation of its activity in humans may significantly alter metabolism of drugs and other xenobiotics.

The role of the ER relatives, the ERRs will become more apparent as ligands are identified and linked to target genes and physiological function. These targets offer multiple opportunities for therapeutic intervention with small-molecule drugs, in diseases related to neuronal function, inflammation, lipid homeostasis, metabolic function and cancer.

Homocysteine (Hcy) induces nuclear factor-B (NF-B) . On the other hand, a negative correlation between high levels of Hcy and peroxisome proliferator-activated receptor (PPAR) expression has been demonstrated

Also, PPAR agonists inhibit the metalloproteinase activation in macrophages.

There is even evidence that intestinal flora influence PPAR expression in intestinal locations.

I have restated this to illustrate that there are c complex aspects of the use of specific substances in therapy.

With the discovery of significant under perfused medial temporal regions of the brain by Casse and colleagues, vasodilators are being considered to improve this blood flow.
.
Angiotensin inhibitors could vasodilate the brain areas shown on the SPECT scans (R Casse, R Kwiatek et al), but telmisartan also PPAR agonists and down regulate inflammatory cytokines!

Olmesartan has been used by clinicians working with Dr Trevor Marshall in both sarcoidosis and CFS, with claims of success.

Olmesartan does not appear to have significant PPAR agonist activity.

There is now evidence that angiotensin can be pro-inflammatory in some situations, and that A2 R blockade is anti-inflammatory in its own right.

Marshall suggests that inflammation may change the A2R configuration and other evidence suggests that the activation of the receptor evokes activation of nuclear factor kappa beta.(NF )

Marshall is emphatic in maintaining that olmesartan is best in the Th1 set forms of CFS.
He writes that it rapidly decreases elevated levels of 1,25 dihydroxy D3.

At this early stage of research, I use telmisartan instead of olmesartan, and quercitone as my preferred form of quercetin, but I encourage doctors to watch closely for more research in this field.

Because telmisartan has been used extensively in hypertension, we have good data on its safety.

It binds firmly to the receptor and has a long duration of action.

Clearly if people have low blood pressure as part of CFS, caution is needed, but so far this is rarely a problem.

How do we choose what to use in particular people as we draw from this enormous range of options?

I try to discover the particular differences that the history and tests reveal and design treatment plans to fit with these patterns.

I also check carefully to avoid drug-drug, herb-drug, and herb-herb interactions.

DEPRESSION

Clearly there is much yet to be worked out about the mechanisms of chronic fatigue but I think the evidence now is in that we should regard it as an organic disease where the degree of the symptoms can provoke secondary depression.

It is important to be very aware of all the varieties of depression, since very effective therapies are available in major depressions and bipolar disorders.
Competent health professionals need to explore this area in depth in order to be clear about each form of depression.

Some people will have both CFS and depression.

Since depression is also common in the community, we can't exclude that some cases of depression can feel fatigued, but I think the degree of fatigue is seldom this great and it is still a bit unclear as to which case with chronic fatigue can be helped by the various anti depressants. Moclobemide is said to be helpful in some cases.

Many people with CFS seem to get side effects from specific serotonin reuptake inhibitor (SSRI) type medications. All of us sometime find someone who improves markedly on SSRIs, even in some one who did not regard himself or herself depressed.

I personally think these agents are overused.

The careful exploration of what the person means by fatigue is central to this area of clinical work.

STRESS AND PSYCHOLOGICAL ISSUES

In old paradigms people often thought "EITHER/OR", that is problems were either in the mind or in the body.

It is not possible for us not to be physical beings and we must necessarily feel our symptoms in our bodies.

As a whole person physician I am extremely interested in all levels and dimensions of what it is to be human. If you don't pay attention to each of these levels you cannot really respond to them all.

In particular all symptoms such as anxiety, depression, anger, frustration and grief have a context.
It is always relevant to be vigilant about depression in these conditions.

When people are distressed this reflects difficulties in the processes of living.

In a real sense what is within a person can be described as "conserved in our manner of living and experience". This is always to be respected.

When we feel ill, for whatever reason, it is impossible for there to be no psychological component.

Chronic fatigue sufferers are often despairing, frustrated and depressed and in the whole management of a life there are many things that people can do to better cope with their symptoms. Many health professionals may have a part to play in the support of fatigue sufferers and many forms of self help are really worthwhile.

The model is that of co-evolving solutions.

Updating our information in all fields of biology has never been so important.

You can ask your health professional to go beyond conventional practices as well as checking for yourself just what research is displayed on internet sites such as Medline. (pubmed)

<www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?CMD=Text&DB=PubMed>

Health professionals now can raise their own awareness about staying up to date, and appreciate how exciting it feels to commit to this lifetime of expanding our personal knowledge.

It is my hope that people who have chronic fatigue syndromes will reappraise the journey of life that they and others experience, holding on to a belief in their inner strengths, and being open to the many old and new insights that will be available the more we search.

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john.graham@flinders.edu.au

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