FMS & CFS – An expert patient’s view

By Robert Napier

February 2006

I have had exercise-induced pain in connective tissues since childhood and have had what is
now called Fibromyalgia Syndrome (FMS) since 85 if not earlier. This diagnosis was
formulated by the American College of Rheumatologists (ACR) five years later and I have
since then been examined by a number of consultant rheumatologists, each of whom
diagnosed FMS. A diagnosis is usually a step forward for the patient, but with this one, it
means being thrown into confusion and controversy among medical specialists while
underlying disease processes are frequently overlooked to the detriment of both patients and
the state of medical knowledge.

Not that I underestimate the difficulties. I can see how frustrating it must be to listen to
descriptions of their symptoms from patients, because the effects are both extensive and
fluctuating and most patients are themselves bewildered. All they know is that they look
normal but are trapped in a web of invisible disabilities. It is not possible to understand the
effects of FMS without having had it and wrestled with it and thought about it for many years,
but anyone who was seriously susceptible to this illness would be unlikely to survive the
years as a junior hospital doctor. So, we have patients who struggle to describe it and
consultants who struggle to make sense of it all  or give up.

Far from there being a shortage of biochemical irregularities, in fact scores of them have been
described in the literature. Each could be a cause, an effect, or an attempt by the body to
reduce problems elsewhere, in which case it might or might not be better corrected. None has
so far achieved a high enough specificity to be accepted by itself as a dependable diagnostic
marker, which is disappointing but given the variability of symptoms, perhaps not surprising.

FMS and CFS

FMS seems to have been originally thought of as a syndrome rather like what became known
as chronic fatigue syndrome (CFS) or chronic fatigue and immune dysfunction syndrome
(CFIDS), but with the addition of tender points and more emphasis on musculoskeletal pain
rather than cognitive problems. However, in formulating the diagnostic criteria for the
syndrome, the ACR found that those with the highest specificity to the selected patients (a
somewhat circular process, since changing the selection criteria changes the patient
population) were those of musculoskeletal pain and tender points. Other symptoms were not
made cardinal because the variation in them among these patients was found to lower the
specificity of the diagnosis. Because of the resulting diagnostic emphasis on pain and tender
points, many rheumatologists have come to regard FMS as basically a problem of pain
sensitisation and some now frequently refer to it simply as FM.

There is considerable symptom overlap between FMS and CFS: what we have is on the one
hand, a list of symptoms and on the other hand, individuals each of whom has a selection
from the list. The predominance of symptoms in a particular case will, I suggest, be
determined by the disease pathways, which are in turn produced by the interplay between the
subject’s genetic predispositions and exogenous factors like triggers, insults and infections.
Here, I use FMS to denote the musculoskeletal pain condition as defined by the ACR plus the
effects of neuroendocrineimmune dysfunction that are regarded as core symptoms of CFS. I
use the term CFS to comply with current usage in the literature but I accept that there is no
generally-agreed case definition and that the term is regarded by many sufferers and
researchers as unacceptably vague, with an emphasis on a symptom that is common to many
illnesses. Where I use it, I mean what used to be meant, and in some quarters still is, by the
terms myalgic encephalomyelitis (ME) or CFIDS.

Despite the symptom overlap and the existence of individuals who fulfil the diagnostic
requirements for both FMS and CFS, research has identified ways in which the biomedical
profiles can differ and FMS is classified in the ICD at M79 as a distinct entity. On 3rd June
98, Baroness Hollis from the then DSS stated in a letter to an MP; "The Government
recognises that fibromyalgia syndrome (FMS) is a condition which can cause a wide variety
of disabilities from mild to severe. In some cases, it can be a very debilitating and distressing
condition”. Thus, the existence of FMS as a separate entity, and its severity, were officially
recognised (perhaps assisted by my successful case on this diagnosis against a health insurer
heard in the High Court two years previously). The status of FMS was confirmed in a
communication from the CMO to GPs in August 03 which included an item called
"Fibromyalgia – A Medical Entity”.

Depending on how it is described, FMS can comprise, co-exist with or be secondary to a

number of medical disorders and in many cases, these may not have been properly diagnosed
– perhaps because the availability of FMS as a diagnostic label has spared clinicians the
trouble of further investigations. In any event, new descriptive labels based on disease
pathways, as these become better understood, will enable more focussed research and
treatment. This process will require a greater concentration on subsets, which in turn will
require more attention to the noting of symptoms. The complexity of FMS is formidable and
of the lengthy list of possible symptoms, two of the most prominent, pain and fatigue, pose
especially difficult conceptual problems.

Pain
Medical examinations can be a frustrating experience for both parties. The musculoskeletal
pain of FMS is produced by exercise or static stress, and will show up on examination only if
tendon insertions into muscle or bone are affected and these come under stress at the limits of
movement, as can happen at the neck or hip. Where movement is limited by joint structure,
such as at the elbow or knee, this is unlikely to happen, and problems in the muscles or fascia
are unlikely to show up at all, except by comparatively modest pain here and there on
palpation.

The activities of the patient are frequently limited by numerous sites of pain. In my case, and
that of many other gradual-onset patients that I have spoken to, each of these sites will have a
history of pain following what were, for that individual, overuse injuries. However, given the
usual brevity of the examination, this history is usually not noted and the patient’s problems
are described as generalised pain. I do not dispute that there is central pain sensitisation in
FMS, but it is, I believe, produced by extensive localised pain that leads to the whole system
of pain perception becoming hyperactive through mechanisms that are now becoming better
understood. I have numerous sites of chronic musculoskeletal pain produced by poorly-
repaired wear and tear. When I started to take the fibrinolytic enzyme nattokinase in October
02, the pain from lysing of adhesions around numerous muscles, fascia, tendons and nerves
was so great as to prevent sleep entirely on the first night.

The importance of general pain amplification in FMS tends to be self-reinforcing, because

that is how patient groups are selected – through the tender point test. The diagnostic tender
points can be over musculotendinous insertions or over the belly of a muscle and although
many are in sites where there are sustained stresses, it is not obvious why they are where they
are. This part of the examination has subjective elements on both sides. There is supposed to
be an evocative response of crying out or flinching (something that men, who have higher
pain thresholds anyway, are very inhibited about doing) and this response has to be judged by
the examiner to be an acceptable one. However, in the hands of a skilled rheumatologist
whose knowledge of anatomy is sure enough to allow some guile in pressing neutral points as
well as catching the examinee unawares and in unexpected postures when trying the specified
tender points, it can be a discriminating and reliable tool.

The problem with thinking of FMS as a central pain amplification problem is that it not only
ignores the local injuries that give rise to this, but also allows some rheumatologists to forget
the rest of the symptoms and all the biochemical irregularities that researchers keep finding.

They can then use the argument that pain is subjective because all that can objectively exist is
signals travelling through the nervous system: these signals do not become pain until the brain
says so, and that has to be subjective. This is like the point that children make when they ask
how we can know that we all see the same colours. The answer is that we can never be
certain, but unless there is good evidence to the contrary, we have to assume that our bodies
work in the same way. In the case of FMS, that means we have to assume that pain indicates
somatic distress and this is supported by the evidence of elevated cerebrospinal fluid levels of
the pain-transmitting substance P. Furthermore, since pain perception is something that we
share with all animals, it is going to be fairly primitive in the first instance, with the brain
acting as part of an organic continuum with the central nervous system. Only secondarily, in
terms of interpretation and response, is there going to be scope for psychological input.

People with FMS have hypersensitive nervous systems for the same reason that they generally
have hyperactive immune systems – because these systems have been repeatedly stimulated to
the point where an inflammatory cascade has been set in motion. The involvement of the
immune system is an important but often neglected part of the syndrome.

Fatigue
The body is a complex, self-managing system in which causes, effects and responses are hard
to untangle. In the absence of hard clinical evidence of what is happening, understanding the
different types of fatigue that sufferers get requires some conceptual effort.

It is first necessary to distinguish fatigue from normal tiredness, when energy levels are low
and the body is signalling a need for rest and recuperation, and from listlessness. Listlessness
is psychogenic, is produced to conserve energy and reduce frustration and is a normal
response to a situation where the realization of goals is blocked. Most people have
experienced it at some time and anyone with a chronic condition that limits activity is more
likely to experience it. Personality type plays a part too: people with FMS that I know are
notably resistant to it, being more likely to respond to adversity by pushing themselves harder,
and in fact a determination to ignore overuse pains has usually been a feature in their
histories.

The fatigue that is characteristic of FMS is much more debilitating than tiredness or
listlessness and I find it also has a woozy or drugged quality. When I get it, usually some time
after exercise or prolonged activity, it is accompanied by bronchial and nasal mucus, tinnitus
and constriction of the left sinus. This fatigue is a hall of mirrors because there are, I believe,
subtly different ways in which it arises and distinguishing between them as they fluctuate can
be very difficult. It is produced by the neuroendocrineimmune system in an attempt to
manage resources and is present in many diseases – part of an innate survival strategy
common to all higher animals and now known to be cytokine-mediated. Its severity here
should surprise only those who do not appreciate how ill patients can be.

As I see it, faced with an infection, the system has a number of options.

 It can mount a challenge.

 If this is not opportune – a fight or flee situation, for example – it can defer this and try to
limit the spread of the pathogen in the meantime.
 If the first is not possible or is failing, the second is failing too and survival is threatened,
it can attempt to eke out resources by shutting down activity.

To take an example that we are all familiar with, when we catch a cold, the usual symptoms,
like sore throat, mucus and high temperature, are produced not by the virus but by the
immune response and are accompanied by fatigue – a mild version of what sufferers here
experience – in order to discourage exertion. Although the immune challenge inevitably takes
some time to develop, it seems to be deferrable to some extent: sinuses clearing in stressful
situations has been widely observed. A bad cold frequently takes hold during periods of
activity, in crowded places when we are tired and run down, but if activity levels are
sustained, the full immune response comes when we are better nourished and resting. It has
not benefited survival to make untimely immune challenges that divert much-needed
resources, or to make unsuccessful ones that leave the pathogens free to reproduce again. An
attack that was both untimely and unsuccessful would be a double and perhaps fatal setback.

Screening of FMS and CFS patient populations for opportunistic infections usually reveals
higher levels than controls of whatever is being tested for, be it viruses, bacteria, mycoplasma
or fungi. What seems to be happening is that they contract these infections but their immune
systems are unable to mount an effective challenge, so the pathogens linger. There is also
evidence of a change in cytokine profile and a shift from cellular (Th1) to humoral (Th2 –
antibody-mediated) immunity. Th1 is downgraded and Th2 is in a chronically reactive state
where the system appears to be running hard to stand still and has no spare capacity.

Testing of immune coagulation activators has shown these present in a significant proportion
of sufferers, indicating that their immune systems are conducting a holding operation awaiting
the right conditions for eradication. If sufferers take anything, like undenatured whey, that
boosts the immune system, an immune response starts, shown by a sore throat, mucus and
perhaps swollen glands and, of course, fatigue, as the immune system tries to marshal
resources for the big push. If they exert themselves, their energy resources are depleted at the
same time as pathogens in fibrin and the lymph system are stirred up by vasodilation and
increased blood and lymph flow, mobilised into the blood stream and exposed to the immune
system. When this happens, because the immune system cannot cope, the only survival
mechanism that the body has left is to limit further activity by sharply increasing fatigue, and
this fatigue continues until the status quo has been restored.

Post-exertional fatigue, which has a characteristic delayed onset, can also be produced by
reactive oxygen species – a normal consequence of exercise, but too much to deal with in
those already suffering from oxidative stress. Circulating toxins, some of them free radicals,
can be elevated by the action of agents, like antioxidants, that enable activation of
detoxification pathways and I get fatigue without exercise whenever I take antioxidants that
do this (see Oxidative Stress & Toxification below). It is a mistake to suppose that anything
that reduces pain and fatigue is necessarily a good thing: any treatment that is genuinely
therapeutic will usually increase one or both until whatever progress has been enabled has run
its course.
The Psychogenic School
Having ignored the other symptoms and concentrated on the subjective aspects of pain and
fatigue, the way is clear for some specialists to try to psychologise these conditions. They
have two very great problems. First, there is a large and growing volume of research that
cannot be fitted into this model and secondly there is strong resistance from those patients
who are convinced that this approach does not adequately explain their symptoms or their
history. Ideally, practitioners would keep abreast of research, but the problem is that
physiological anomalies are so extensive and intricate that some find it easier to ignore the
studies in favour of implying, directly or indirectly, that the symptoms are the result of
somatisation. This enables them to transfer feelings of inadequacy from themselves to the
patients and preserve their status within the doctor/patient relationship.

Then there are the psychologists, who, in their efforts to gain acceptance and livelihood
within the medical profession, have always sought to extend their territory into any area
where physiological evidence is difficult or unclear, usually to move out again with ignominy
when that evidence becomes established. The better-accepted research findings of
biochemical irregularities in FMS provide more protection against this encroachment than is
enjoyed by CFS. By collaborating in the giving of a diagnosis of CFS to patients who do not
have the syndrome but whose fatigue is psychogenic, psychologists have managed to change
the make-up of patient cohorts with this diagnosis sufficiently to confuse research findings.
Syndrome patients can then no longer be properly distinguished and so they too can be
claimed for psychology. These psychologists have been aided and abetted by pharmaceutical
companies who, where they lack more specific drugs, try to push antidepressants, and by state
and private benefit providers whose strategy where possible is to re-categorise organic
illnesses into psychological ones where benefit conditions are generally less favourable to
claimants.

Non-syndrome patients are even expressly preferred for trials of CBT, for example. This
might sound outrageous, but so-called CFS studies conducted by psychologists frequently
state that long-term patients have been excluded and/or that the usual diagnostic criteria (e g
Merck 17th Ed table 287-1) for other symptoms in addition to fatigue have been disregarded.
Those who get worse and drop out are routinely excluded from the results and there are no
follow-up studies on those who say, perhaps under pressure, that they have improved.

When the authors publish, they are granted a tacit exemption by journals and reviewers from
the usual requirement to take account of other (physiological) published work in the field and
indeed without this exemption, the poor quality of the papers would be too obvious –
particularly since double blind or even single blind trials are not possible for CBT. At best,
the authors’ conclusions are based on an attempt to replace the sufferers’ subjective
descriptions of their symptoms with their subjective responses under influences such as
placebo and pressure to conform. At worst, these studies are deliberately conducted in such a
way that only one outcome is possible.

Personal Progress
My belief has always been that there are organic reasons why people develop FMS and that to
produce such widespread effects, the disease pathways must be fundamental – so fundamental
that the neuroendocrine and immune systems as well as muscles, nerves and connective
tissues can be affected. What could mine be?
When I went into Northwick Park hospital for tests in 85, I said that something was going
wrong with my tissues during exercise, so that burning, stinging pains would develop, and
that I did not seem to be maintaining or repairing connective tissues properly after exercise so
that in many areas, they were becoming increasingly painful. I also said that I was
experiencing pains and paraesthesiae along lines of nerves, fatigue, opportunistic infections
and chemical sensitivities as well as a further selection from what we now know to be the
usual list. The staff were sympathetic but had no effective treatments to offer. My condition
was getting steadily worse and the future was bleak, so I had no choice but to make what
progress I could on my own.

I had first to establish what my symptoms were, then to try to work out what might be the
underlying causes and then to try to find treatments and subject them to trials. My list of
symptoms was in effect an early draft of the fibromyalgia syndrome, which had not then been
formulated and in fact, I did not know for many years that anyone else had these problems. I
bought a standard rheumatology textbook, Arthritis and Allied Conditions, and worked
through it. The only conditions that seemed to have any kind of fit with my musculoskeletal
pains were the calcium crystal deposition diseases. This reinforced a growing suspicion that
mineral imbalances were involved, and the appearance of a hard lump on my wrist that was
swiftly dissolved by oral magnesium provided concrete evidence. I bought books on nutrition
and set about identifying what nutrients might help, then I bought them and conducted trials
to see what were the benefits, the side effects, the signs of overdose and the optimum dose.

In 85, I had been prescribed NSAIDs and after a while I started to get intrigued by the effects
they had. I read up on them and found that these drugs suppressed inflammation by
suppressing, through inhibition of cyclooxygenase, certain prostaglandins, which also
suppressed repair pathways – counter-productive for anyone trying to improve repair
metabolism. While they relieved the pain they made me inexorably worse, as they were bound
to do if I was right in thinking that my metabolism was impaired. It dawned on me that if I
found anything that improved repair, I would know it quite quickly because pain and fatigue
would increase, and this has proved to be right every time.

Of course, I have had many advantages not enjoyed by conventional researchers – a body
available 24/7 for experimental purposes, immediate approval and funding of trials, 100%
patient compliance and accurate reporting of progress (any placebo effect quickly wore off). I
have looked primarily for agents that, for sound therapeutic reasons, would produce long-term
benefits, albeit it with an initial increase in pain and fatigue. I have investigated numerous
substances, mainly minerals, vitamins, phytochemicals, essential fatty acids and enzymes,
changing one variable at a time, making close observations and keeping careful records.

Hypofibrinolysis
Fibrin is formed in a complex process by thrombin from fibrinogen, a protein dissolved in the
plasma, the first stage being soluble fibrin monomer (SFM). It should be formed in response
to damage to the blood vessel wall and lysed by plasmin when repair is complete. Endothelial
cells on intact blood vessel walls concentrate circulating antithrombin, which neutralises
thrombin, and contain heparans that interact with it to intensify its action. They also express
thrombomodulin, which activates the anticoagulant protein C system. If the presence of
thrombin has not been adequately controlled and more SFM is being generated than can be
lysed, it will accumulate in the blood and can coat the blood vessel walls. This state is
sometimes referred to as “thrombophilia and hypofibrinolysis”.
There was a family history on both sides of thrombosis and I was experiencing intermittent
claudication in my calf muscles after 200 yards’ walking. My ESR had been measured on two
occasions at Northwick Park at 1. This extremely low figure is not consistent with elevated
levels of fibrinogen because this causes red blood cells to form rouleaux, like little stacks of
coins, which, being more massive, fall out of suspension quicker. It is, however, consistent
with a proportion of the fibrinogen being converted to SFM, which increases blood viscosity.

For these reasons and because of the predictable, localised pattern of the claudication, I
thought that fibrin in small blood vessels might be impeding blood flow and the transfer of
nutrients and toxic metabolites. In February 88, I read that researchers were using the steroid
Stanozolol as a fibrinolytic and asked my GP to prescribe a course of it. I experienced strong
tingling sensations where the claudication had been worst followed by some improvement in
walking range. This was encouraging, but the process petered out after a month or two and
there were side effects, so I resolved to find better agents.

Over the following years, I found a number of good fibrinolytics – especially nattokinase,
which became available as an extract in 02 – and platelet aggregation inhibitors. Small studies
were published in the late 90s showing that a proportion of FMS and CFS patients respond to
anticoagulant drugs. Dr David Berg, of Hemex Laboratories, says that the fibrin lining blood
vessels does not cross-link to form clots if there is insufficient thrombin present to activate
factor XIII in the coagulation cascade. He has developed a panel of blood tests called Immune
System Activation of Coagulation (ISAC) to identify the deficiencies involved. However,
treatment seems to rely mainly on heparin, a thrombin inhibitor that many patients do not do
well on and that cannot be taken orally, and a small number of other agents. This development
provided welcome theoretical support for my work, but without a better range of (preferably
oral) agents to address the specific deficiencies identified, the tests would not be of practical
value to me.

Mineral Imbalances & Adhesions

Magnesium (Mg) is critical to many cellular functions, including energy production, protein
formation and cellular replication. It participates in more than 300 enzymatic reactions in the
body, including the production of adenosine triphosphate (ATP), a compound that provides
most of the energy required by cells when it breaks down to form adenosine diphosphate
(ADP). It is also required to activate the pumps that move sodium out of and potassium into
the cells, so a deficiency will lead to an intracellular deficiency of potassium as well and
greatly disrupt cell function. Without adequate Mg levels, control of blood sugar is impaired,
since it plays a central role in the secretion and action of insulin. It blocks the entry of calcium
(Ca) into vascular smooth-muscle cells and deficiency is characteristic in patients with
peripheral vascular disease. Mg favours the deposition of calcium phosphate in the bones and
its removal from soft tissues, and is the standard treatment for calcium crystal deposition.

There are also cardiovascular effects. Although studies of its effects on the coagulation
cascade have produced conflicting results, Mg deficiency is vasoconstricting and increases
homocysteine levels because major enzymes involved in homocysteine metabolism are Mg-
dependent. Epidemiological studies have shown a strong inverse relationship between Mg
status and atherosclerosis and it is also used clinically to treat arrhythmias.

Mg is active at the mitochondrial level, where it activates numerous enzymes. It is an N-

Methyl D-Aspartate (NMDA) receptor blocker and low levels can produce nervous hyper-
responsiveness. They also increase production of catecholamines, a type of stress-response
neurotransmitters, which increase serum Mg levels by triggering its release from cells, thus
lowering intracellular levels, and then produce free radicals themselves by auto-oxidation.
Studies show that low Mg and low glutathione are frequently found in the same individuals
and the cardiovascular risks of Mg deficiency can generally be reduced by antioxidant
therapy, which indicates that Mg deficiency might be pro-oxidant apart from the
catecholamine-mediated effects in subjects with high stress levels. There is some debate on
this question but it does seem that magnesium protects antioxidants.

One can imagine a vicious circle where hypomagnesaemia for dietary and/or genetic reasons
(70% of variance in Mg red blood cell levels has been found to be familial), including
hypofibrinolysis, leads to increased coagulation, homocysteine levels and oxidative stress,
which in turn leads to oxidative microclotting (oxidation of proteins in the coagulation
cascade) and more fibrin lining blood vessels, thus further reducing the transport of Mg into
the tissues. Although this might be true in my case, there are some uncertainties regarding Mg
status generally in FMS, which seems to be about normal in serum, below normal in
erythrocytes and above normal in leukocytes, so it is hard to say how many others this might
apply to. However, trial subjects who are not classed as Mg deficient also benefit from
supplementation, so it appears that normal levels are sub-optimal. Malnutrition of
micronutrients is now so widespread that this can be true of quite a number of them. Sub-
optimal is a concept that is not generally understood within the medical profession, where an
intake that does not produce frank symptoms of clinical deficiency is regarded as adequate.
Would anyone claim that a healthy fluid intake is just enough to avoid clinical dehydration? I
hope not, but this distinction applies to all nutrients, not just water.

When tested at Northwick Park in 85, my blood phosphate level was shown as 1.42 mmol/L
against a reference range of 0.75 - 1.36, though this was not commented on. (My Ca level was
shown as 2.39 mmol/L, within the reference range of 2.27 - 2.65. Mg level was not
measured.) If blood phosphate levels are too high, the body tries to lower them by depositing
calcium phosphate in soft tissues and since these deposits contain twice as much Ca as
phosphorous, blood Ca levels can be reduced. Mg, Ca, zinc, iron, copper and manganese are
said to be in opposition to phosphorous, so that if their levels are raised, phosphorous levels
will fall. Of these, Mg, zinc and manganese have proved helpful in clearing deposits from my
tissues.

Taking Mg produced repeated pains at numerous sites, mainly in those places where I had
rheumatic pains and particularly in those places which tended to run cooler and feel chilled, i
e very extensively in the lower legs from a few inches above the knee, but also the elbows,
wrists and neck. There were occasional exquisite soft crunching sounds round joints at
extremities of movement  particularly on one occasion at the back of my neck  as though
softened deposits were being crushed. The pains in the muscles behind my eyes were from
time to time very sharp and throbbing.

As crystals dissolve within their tissue matrix, there is no longer a snug fit and they become
more abrasive than before. I thought this must explain the widespread pains that I got from
magnesium supplementation until in 92 I tried a spell of, for me, high doses. I experienced
pains running right across my abdomen and on one occasion these were so severe that I was
completely immobilised for 30 minutes. When they had run their course, the pains during and
after exercise that I had experienced there for years had disappeared. However, unlike other
possible sites of crystal deposition, this one was not part of the musculoskeletal system and
was usually kept warm. A literature search revealed one only possible explanation: the
releasing of peritoneal adhesions. These normally form after surgery or similar trauma: that I
had formed them without either indicated that my susceptibility to adhesions must have been
quite exceptionally high.
From then on, I had to try to distinguish between these two possible causes of the pains that I
get from magnesium supplementation. (I was later to discover a third – the pain caused when
toxins are mobilised in tissues.) Both leave a soreness in the tissues that takes a few days to
subside. However, the hallmark of calcium crystals is their abrasiveness on exercise. When
they are dissolved, I notice increased pain only when they have been embedded in dense
tissues like tendons. Adhesions are painful on exercise when two surfaces that are supposed to
slide tug on one another, producing a sharp pain that will be more acute at certain points in
the range of motion. Releasing the adhesion always produces a sharp burning pain and with
large ones, this happens bit by bit. During this process, stresses on remaining parts of the
adhesion will increase, producing sharp pains on exercise that can last for months.

Many of the agents that I went on to try for their fibrinolytic activity produced pains that must
have been lysing of adhesions or drawing out of toxins because these agents have no known
role in dissolving crystalline deposits. In the ankles and feet there would often be a sudden
onset of pain when walking that was so sharp that I was unable to continue until it had passed,
which usually took between 10 and 20 minutes. Adhesions, like calcium crystal deposits in
soft tissues, are associated with Mg deficiency and they also are thought to be a consequence
of impaired fibrinolysis.

Oxidative Stress & Toxification

Some agents, as diverse as MSM, vitamins B12 and C and phytochemicals, would produce
eye and eyelid redness and irritation accompanied by nasal and bronchial mucus, fatigue and
mild nausea, and most of the eye and eyelid redness was being produced by the tears, which I
could feel burning my eyes and irritating my nose. Later, my urine would be dark and my
socks would have a burnt smell from substances in the sweat. There would also be skin
eruptions – tiny blisters in weals that itched and burned – especially on my lower legs, where
they appeared directly above the worst-affected areas as minute amounts of watery but highly
irritant fluid had found their way to the surface. This process was accompanied by pains in the
underlying tissues and both pains and skin eruptions would increase with each increase in
dose and then decrease over time. These tissues would also ache a lot unless they were kept
very warm. The effect of the agents was cumulative.

As time went by, I realised that these effects could not have been simply allergic reactions
because the range of agents producing them was too wide and they always diminished over
time after the introduction of a new agent or an increase in dose. Also, the skin eruptions were
directly over the areas where pains had been produced. The only thing that the agents all had
in common was that they were antioxidants, and there appear to be two main modes of action.
First, antioxidants aid detoxification, and the eye irritation and skin eruptions were most
likely due to intermediate substances, which are more irritant than the form the toxins are in
when stored. Secondly, antioxidants stimulate white blood cells, better termed leukocytes,
since most of them are actually in the lymph.

Free radicals are molecules with one or more unpaired electrons that are highly reactive
because they steal electrons from other molecules. This loss of electrons is called oxidation,
and free radicals, so called because they are free to do just this, are often referred to as
oxidising agents. A certain level of free radicals is a normal by-product of the body’s
metabolism of oxygen and they perform useful functions, such as helping the immune system,
but too many can upset the functions performed by membranes, such as regulating the
passage of calcium into and out of a cell. This is called oxidative stress and the oxidation of
critical cell components such as lipids, proteins and DNA can lead to cell death.
Oxidative stress leads to an accumulation of environmental toxins because intermediate
compounds include free radicals, and a supply of antioxidant nutrients and enzymes is
required to reduce them as they go through the various stages before they can be safely
excreted. Without these, detoxification cannot proceed, so toxins are retained within the liver
or fat tissue and in my experience in muscle and sometimes bone. Toxic overload, particularly
of aldehydes, increases sensitivity to a wide range of compounds and can result in brain fog,
as in a hangover (caused by acetaldehyde), and inflammation of blood and lymph vessels.

As I tried new agents, some would produce the effects described above and others would not.
I was therefore able to assess the effectiveness for me of the agents that I was testing without
having to wait and see to what extent my condition would eventually improve. From time to
time, I would identify a useful agent in this way and start taking it. If one of these was omitted
for a while and then reinstated, the effects described above would be strong. This also
happened if it was not taken often enough. This enabled me to establish exactly the right dose.
If something produced a strong response when I took it, I increased the dose or took it more
often until the response became more subdued. The puzzle was why I needed so many and
why the reinstatement of one of them would produce such strong effects.

One reason is that some antioxidants are more effective than others in quenching any
particular free radical. Another lies in the extraordinary interdependence of antioxidants.
When a free radical is reduced, (so called because its positive charge is reduced by the
acquisition of a negatively charged electron from an antioxidant) that antioxidant then
becomes oxidised until it can acquire an electron from another antioxidant. These electron
transport chains can be very long, with numerous antioxidants involved, and if there is a
shortage of one of them, the whole chain slows up, so that increasing the deficient antioxidant
produces a surge of activity. A major problem that industrialised societies face is that the
number of antioxidants that we require increases with the number of free radicals that our
bodies have to cope with from synthetic chemicals and their breakdown, while intensive
agriculture lowers the presence of all micronutrients in food, including antioxidants.

Homocysteine
In the early nineties, detoxification unleashed by B12 was so strong, including red eyes and
eyelids, constricted sinuses, pains in muscles, tendons and nerves, skin eruptions and –
uniquely to B12 – tiny blisters on my fingertips, that my doses were limited to 75 mcg
cyanocobalamin daily. B12 is an outstanding antioxidant and detoxifier and helps to de-
activate nitric oxide and peroxynitrite radicals. A maximum tolerance this low is unheard of
in the literature and indicates an extreme toxicity state. The only other B vitamin to provoke a
similar response was folic acid and that too at low doses: just the RDA would produce a surge
of stinging tears, red eyes and eyelids and nose irritation, plus nasal and bronchial mucus,
fatigue and nausea. Folic also is a potent antioxidant, but the overlap between their effects and
my very strong response to small doses of either suggested some more specific commonality,
most likely homocysteine, and this was confirmed years later when I tried trimethylglycine
(TMG) and experienced the same effects.

Homocysteine (Hcy), so called because it is a homologue or variant form of cysteine, is a

toxic, sulphur-containing amino acid. It is formed exclusively upon demethylation of the
essential amino acid methionine. Inadequate metabolism of Hcy, through genetic disorders or
deficiencies in vitamin co-factors, leads to elevated plasma levels, called
hyperhomocysteinemia (HHcy). In a 97 Swedish study of twelve outpatients stated to fulfil
the criteria for both FMS and CFS, blood laboratory levels were generally normal except that,
in all the patients, Hcy was elevated in the cerebrospinal fluid (CSF). There was a significant
positive correlation between CSF-Hcy levels and fatigue and an inverse relationship between
these and CSF-B12.

HHcy is implicated in a number of diseases, including immune dysfunction. The list of Hcy’s
negative cardiovascular effects is so long that there is space here to mention only a few of
them. Hcy causes platelet aggregation and inhibits the expression and activity of endothelial
cell surface thrombomodulin, the thrombin co-factor responsible for activating the major
anticoagulant pathway Protein C. Hcy reduces expression of the anticoagulant heparin
sulphate and inhibits its binding and interferes with the fibrinolytic properties of the
endothelial cells. By decreasing bioavailable nitric oxide (NO), even moderate HHcy impairs
endothelial-dependent vasodilation and inhibition of platelet adhesion and aggregation.

HHcy causes abnormal vascular responses by increasing the production of superoxide anion
(O2), which is believed to react with and further decrease the availability of endothelial NO
and yield the highly-damaging free radical peroxynitrite. Hcy is said also to promote oxidant
injury to vascular cells through auto-oxidation and several other means including protein
homocysteinylation. In the process of forming homocysteinylated proteins, further oxidative
stress develops and these proteins, in particular low-density lipoproteins (LDL), become
damaged. Research indicates that, contrary to previous belief, LDL becomes a cardiovascular
risk factor only when it is oxidised.

Hcy can be converted back to methionine by remethylation, which requires one of: 1) folic
acid as methyl donor with B12 as co-factor; 2) TMG. Both work independently, though can
be used at the same time. Hcy can also be converted to cysteine and then glutathione or
taurine by transsulphuration, which requires B6. TMG supplements frequently contain folic,
B6 and B12, to enable all three pathways. Transulphuration holds out the prospect of
converting unwanted homocysteine to highly-desirable cysteine, which is generally thought to
be the rate-limiting amino acid for the production of glutathione. A Russian study concluded
that 50% of the cysteine in glutathione is derived through this pathway, and enhancing it
would be like turning base metal into gold. However, the pathway is redox-sensitive –
antioxidants such as superoxide dismutase, catalase and water-soluble E inhibit the process
and one or two pro-oxidants enhance it, so it becomes less active as antioxidant status
improves.

Summary
I believe that I have suffered from the following. Although they might appear unrelated, th e
frequency with which they arise in FMS indicates to me that they are the effects of one or more
biochemical irregularities.

 Tissue mineral imbalances and crystalline deposits of calcium compounds.

 Accumulations of fibrin on the walls of small blood vessels, elevated plasma
homocysteine and constriction of the microcirculation (see later).
 Poorly repaired and hence cumulative injuries from exercise and static stresses, sometimes
involving adhesions, to fascia, other connective tissues and nerves.
 Oxidative stress, toxification and resulting chemical sensitivities, exacerbated in particular
by inadequate levels of magnesium, zinc and vitamins B1, B6, B12 and folic acid and the
consequent impairment of the many enzyme systems that are dependent on these.
 An inflammatory immune state involving impaired function, fluctuating immune response
and inadequately-controlled opportunistic infections.

The distribution in my body of musculoskeletal pains reflects not only the history of
mechanical stresses to muscles, fascia, muscle/tendon junctions, tendons and nerves, but also
the local reduction of blood flow and hence repair, particularly at night, through cold or
pressure. Shooting pains in my arms and legs as adhesions release closely follow the lines of
major nerves, and tethering of the left sciatic nerve has been particularly troublesome.
Previously adhered tissues have a surface of scar tissue that generates friction on exercise,
which therefore has to be limited to a level that avoids an inflammatory cascade leading to re-
adhesion.

My priorities are as follows.

 Correct mineral imbalances and minimise crystal deposition in soft tissues.

 Minimise fibrin, homocysteine and adhesions, which tend to re-form when conditions
permit.
 Encourage repair of damage to the musculoskeletal and nervous systems by optimising
nutrition and tissue perfusion.
 Reduce oxidative stress and remove accumulated toxins.
 Optimise immune response, which requires good perfusion through all tissues, including
glands.

Every one of the supplements that I take has produced positive, repeatable, therapeutic
effects. Many agents have activities that bring more than one benefit. For example,
tocotrienols reduce oxidative damage to membranes and soften scar tissue; nattokinase
removes fibrin from the circulatory system and lyses adhesions, in which fibrin plays an
important part. Antioxidant herbs frequently have other useful functions, like helping to
release adhesions or eliminate toxins, and some are immune enhancers, in which case,
rotating them will minimise adaptation by the body or pathogens in favour of restoring the
status quo. All doses are regularly tested and re-optimised, since my needs change as my
condition improves.

These supplements are: minerals; antioxidants; antithrombins, fibrinolytics, platelet

aggregation inhibitors, homocysteine metabolisers and immune enhancers. The most useful
have been (in no particular order): calcium, copper, magnesium, manganese, selenium and
zinc; MSM and TMG; vitamins A, B1, B6, B12, folic acid, C, D and E; R-lipoic acid and co-
enzyme Q10; nattokinase; astaxanthin, lycopene and lutein; allicin (patented form), citrus
flavonoids, hydroxytyrosol and extracts of bilberry, echinacea, ginkgo biloba and grape seed.

People with FMS or CFS are more than usually sensitive to nutritional inputs. The only way
forward is to change one variable at a time, keep a careful note of the responses and
remember that everything is connected to everything else. To take the example of zinc, in the
picolinate form, which is among the most highly bioavailable, my optimum dose is 11 mg
daily. Many people think that the optimum dose is a generous one but it is not that simple.
Too much zinc will displace iron and copper, so in order to avoid deficiency problems, these
might have to be supplemented too. But iron feeds bacteria and too much iron and copper can
increase oxidative stress. So the potential problems are multiplying. The whole field is far
more complicated and interdependent than most people allow for.

Studies into central pain sensitisation have provided one explanation for the inability of
sufferers to reverse the pain aspects of FMS. However, in my experience, neuralgia,
especially involving sensitivity to cold and particularly common with the trigeminal nerve, for
example, because the face is hard to keep warm, can be a prominent feature and I think real
progress will require an understanding of local pain conditions like myofascial pain and
repetition strain injuries. “Widespread” the pain may be, but in my case it is not “diffuse”, as
introductions to studies usually recite. There is a persisting pattern of local distribution and
each of the many sites of pain has a history of development following overuse. Nor does the
pain migrate: rather, one site can become less painful and another more so.

In many parts of my body, physical activity that others might regard as light and even
therapeutic will soon produce pain in the connective tissues, especially in the fascia and in the
musculotendinous insertions. If I persist in the activity, pain levels will rise sharply and
remain high for about five days afterwards. There is a complication here, too. The fatigue
means that in order to do demanding tasks, FMS sufferers have first to get their systems
aroused by working up high levels of determination. That, plus the neuroendocrine instability
that increases the production of hormones and neurotransmitters, then increases the tendency
to push through the (temporarily suppressed) pain and cause further injury. Sufferers are
caught in a downward spiral that is not helped by general advice to take more exercise.

Although I take all the exercise I can sustain, I have learned that I have to stay below the pain
threshold. I still overdo it sometimes, but usually because circumstances have forced me into
it  for example if I walk, I have to get back to where I started. I have tried on numerous
occasions over the years to follow the medical advice to push my exercise levels up and trust
that I will sooner or later come through the pain, but the pattern is always the same. For the
first few days the improved circulation plus the adrenalin and endorphins lower pain levels,
then they start to increase again and continue to do so until I am forced to stop. If a part of my
body improves it is invariably while exercise levels are low, not while they are high.

Since the medical profession were unable to help, from 85 onwards, I struggled to work out
what the underlying physiological problems might be that could explain my symptoms and
link them together and to explore possible ways of testing my hypotheses and developing
treatments. In three important areas, namely fibrinolysis and magnesium and antioxidant
therapies, I have been several years ahead of anyone else and in many ways still am. For
example, as far as I am aware, no one else has yet managed to make antioxidant therapy really
work. The key was realising that most people’s approach to treatment is fundamentally
flawed. Doctors look for what will ease the symptoms and sufferers frequently report on
discussion groups that they tried x but stopped because they felt worse. Well, there are good
reasons and bad reasons for feeling worse and it pays to distinguish between them.

Anyone who has had a serious organic disorder for many years will probably have a huge
backlog of healing and repair. In the late eighties, my walking was limited to 300 yards a day
and I used to say that the most remarkable aspect was how low pain levels were in my legs
when I was resting. Anyone whose repair metabolism was working normally and whose legs
were that bad would be in a lot of pain, especially at night. The problem was that my body did
not have what it needed for repair. I used to say that if I could provide what was needed, I
would know it because the pain would increase, and I was right. There are many paradoxes in
these conditions – what I call the hall of mirrors. In as much as I have succeeded, it is because
I have understood those paradoxes better than anyone else.

The severity of my illness made this sustained level of application very hard but also meant that
my body would respond very clearly to therapeutic inputs. In particular, my levels of
environmental and metabolic toxins were so high that any improvement in antioxidant stat us or
tissue perfusion would bring the very strong reaction that I have described as soon as the agent(s)
reached the tissues. Similar reactions, though not necessarily as strong, have been reported by
numerous people with FMS taking guaifenesin, undenatured whey, MSM, ALA, NAC and other
detoxifying agents.

I was an excellent guinea pig and I used this fact to test and make thorough notes on over 200
agents and then test them in combination to establish optimum doses for each of those that
proved worth taking. Given the millions of different combinations, it would take an eternity to
do this by conventional blinded trials, which is why no one has done it or ever will. Our
hunter-gatherer ancestors, collecting handfuls of wild leaves, berries and roots, would have
consumed numerous phytochemical antioxidants that are largely absent from a modern diet.
Trials of just a few major antioxidants are doomed to failure because a much larger number is
required to get the electron transport chain humming. The doses are usually far too high as
well, which means that first, the many redox-sensitive metabolic processes that go on in the
body can be seriously disrupted and secondly, without suitable reducing agents, some of the
antioxidants can become pro-oxidant.

Interestingly, it was the antioxidants that enabled me to optimise the fibrinolytics and
homocysteine metabolisers. Reducing the coating of fibrin on my blood vessel walls would
increase tissue perfusion and the transport of antioxidants in and toxins out, thus producing a
detoxification surge. Reducing homocysteine would counter the pro-oxidant environment that
Hcy produces, thus enabling the antioxidants to work, and also counter vasoconstriction, thus
again increasing tissue perfusion. The strong reaction that was so reliable an indicator was
produced by intermediate toxins as detoxification pathways were activated. Further, by using
observable signs such as redness of eyes and eyelids and the skin eruptions that are produced
when toxins are being released from tissues faster than they can be removed by the
bloodstream, I could make the process more objective and not dependent on my subjective
impressions.

Wider Implications
Research into FMS and CFS has already provided valuable insights and we need much more
of it but I think understanding the illness(es) as a whole has proved so difficult for researchers
because of the limitations of the scientific method, which works well when a problem can be
broken down into small enough pieces but not when a large number of variables are
interconnected and many areas of complexity remain poorly understood.

However, if my investigations have provided valuable information that could not have been
arrived at by the scientific method, it has itself one obvious limitation. I always stress that
these illnesses are multifactorial, but even those cases primarily due to hypercoagulation and
toxification will differ because of the individual variations in biochemistries and other genetic
susceptibilities, nutritional needs and actual dietary intakes, and exposure to toxins and other
stressors. This means that if others wish to follow my regime, as a number have now usefully
done, they will have to adapt it to their own needs using methods similar to mine.

As to who might be good candidates, sufferers with a family history of coagulative or

atherosclerotic cardiovascular disease and/or a low ESR would be likely to benefit from
improving fibrinolysis and reducing homocysteine, though there are different kinds of
coagulation defects and no one should simply assume that he or she has a particular
irregularity without seeking medical advice. One further vascular problem that I have been
well aware of for many years is that of vasomotor insufficiency. In order to maintain normal
tissue housekeeping in my legs, and hence mobility, I have to provoke each day a period –
maybe an hour – of vasodilation, which I can do either by applying heat or by consuming
alcohol. Constriction of the microcirculation has slowly become more widely recognised as a
feature of FMS and I suspect might in many cases be one of the root causes. I hope to see
more research into it and more treatment options: alcohol has its drawbacks and will increase
the need for vitamin B1 to counter the deficiency that is frequently associated with FMS.
Antioxidant therapy and detoxification are now receiving clinical attention with several
studies published that confirm my own findings of their importance in these syndromes. It
would be impossible to live anywhere today without encountering environmental toxins, and
as industrialisation increases the problem far beyond what humans have evolved to deal with,
it is only to be expected that more and more people will find their bodies cannot cope. Indeed,
it could well be that the reasons for the female preponderance among sufferers include a much
higher exposure to synthetic compounds in household chemicals and cosmetics. Certainly,
anyone who is sensitive to cigarette smoke, vehicle exhaust fumes, alcohol or formaldehyde
outgassing is a good candidate for antioxidant therapy. Not everyone will benefit as much as I
have, but unlike many other therapeutic approaches, the worst that taking modest doses of a
broad spread of antioxidants can lead to is that the individual’s general health will improve.

I should stress that I have not found a cure. If these illnesses persist for more than maybe two
years, changes become established in the immune and autonomic nervous systems and, in the
case of FMS, nociceptors that no one at present knows how to reverse. Many of these are
adaptive changes to enable survival in the face of fundamental organic problems that the body
is unable to correct. It is a holding operation waiting for a cavalry that never comes. One of
the leading CFS specialists, Paul Cheney, talks of a phase three of the illness where sufferers
say that their symptoms flare up only if they attempt to do the sort of things that they used to
be able to do. In other words, survival has required a considerable and permanent reduction in
their activity levels. That is where I am and the treatments that I describe here have been and
still are a vital part of my survival.

One thing that would help us all is a paradigm shift in our health services. Pharmaceutical
companies have little interest in curing anyone: to them, a cured customer is a lost customer.
Their big earners are designed to help patients “manage their illnesses” by long-term
dependence on prescription drugs, which frequently creates further medical problems for
which additional drugs can then be prescribed. As long as we allow drug manufacturers to
determine our priorities, the number of chronically sick people will increase. The way
forward is much more emphasis on orthomolecular medicine, defined by Stedman’s medical
dictionary as “a therapeutic approach designed to provide an optimum molecular environment
for body functions, with particular reference to the optimum concentrations of substances
normally present in the body”. It goes without saying that great attention should be paid to
reducing as far as possible substances not normally present, like synthetic compounds and
environmental toxins.

Apart from those nutrients where my levels have been sub-optimal and my need for them
probably increased by illness, I had for over thirty years most of the clinical deficiency
symptoms for magnesium and vitamin B1, yet this possibility did not occur to a single one of
the six GPs and eight rheumatologists who examined me during that time. It is no criticism of
them as individuals to say that had their medical training been different, my economic
contribution to the country, and doubtless that of many others, might have lasted longer.

Robert Napier February 06