R. Paul St. Amand, M.D.
4560 Admiralty Way, Suite #355
Marina del Rey, Ca. 90292
The Use of Uricosuric Agents in Fibromyalgia
This is a
our paper written for patients with fibromyalgia that describes the
and our method of treatment. The following is a more technical paper
for medical personnel. It includes a theory that might explain the
involved in the disease and our therapeutic results. A knowledge of the
entity is presumed.
of affected tissues determines the presenting, chief complaint.
include a preponderance of musculoskeletal symptoms; "brain" symptoms
irritability, depression, apathy, nervousness, difficulty with memory
concentration) or the irritable bowel syndrome (gas, bloating, cramps,
constipation alternating with diarrhea). Initial symptoms of widely
cycles are often forgotten by patients who present later in their
We do not find tender "points" but distinct, swollen lesions in varied
distributions. Involved areas are sites of total or partial tendinous,
ligamentous, fascial and muscular swellings or contractions. We "map"
lesions on a preprinted body caricature that shows the induration,
shape and location of each (see illustration) There are usually many
than the accepted "eleven out of eighteen." Lesions may not correspond
to sites of patient complaints, but are objectively felt and recorded
future comparison. These steadily "working" structures, augmented by
of multiple organs, readily induce pain and fatigue.
The symptoms and maps of patients with the "chronic fatigue syndrome" identify them as fibromyalgics. Because of higher pain thresholds, they are most aware of fatigue and cognitive difficulties. We have not seen the myofascial pain syndrome or systemic candidiasis as separate entities. Therefore we treat all as the same disease, in the same manner.
we found uricosuric medications helped patients with an ill-defined,
illness that later became known as "fibromyalgia." Two gout
probenecid and sulfinpyrazone proved effective and, because we had no
treatment, were godsends. We tailored the dosage raising it
until cyclic reversal of the illness began. In less responsive
titration took considerable time. Some patients were allergic to
(probenecid) and suffered hyperacidity with sulfinpyrazone (AnturaneTM).
We had no alternate treatment.
A few years ago
the expectorant, guaifenesin, is weakly uricosuric.1 It is
sufficiently potent to treat gout, but has proven invaluable in our
for fibromyalgia. Analysis of two hundred sixty-four consecutive
showed cumulative success: 300 mg. bid was effective for 20% of
600 mg. bid, for 70%; 1800 mg. per day, for 90%. Some 10% have required
2400 mg. or more daily. Guaifenesin is distinctly more effective than
previous medications and has no listed side effects. Only rarely has a
patient had slight nausea, hyperacidity, or rash. It must be dispensed
without other ingredients that do cause complaints. There is no patent
on guaifenesin and it is inexpensive. Though serum serotonin levels of
patients on guaifenesin have not been investigated, its metabolite, 5
(5-hydroxyindoleacetic acid), is increased in the urine.1
often markedly, which signals the onset of disease reversal. This is a
crucial time for patients who can require much encouragement during
intense cycling. I encourage them to record periods of intensification
or improvement. Remapping on subsequent visits reveals, at a glance,
of partial or total clearing to confirm adequacy of dosage. Newly
areas reverse sooner than older ones. Regression with guaifenesin
at a rate of about one year for every two months of treatment. The
dosage patients (300 mg. bid) show their responsiveness by greatly
this process. Improvement is sustained initially for only a few hours,
later for days and eventually, weeks. Duration of illness and
to the medication determine recovery time.
is inherited. Usually there is a family history of similar symptoms or
of osteoarthritis that also "maps" with the same muscular, tendinous
ligamentous lesions as in fibromyalgia. It is tempting to conclude from
our spectrum of patients (onset ages four to seventy-four) that
today is the prelude to osteoarthritis tomorrow. The age spread
multiple gene involvement. The four to one ratio, women to men,
at least one of these should lie on the X chromosome. Symptoms are
in adolescence or earlier if both parents are afflicted. A history of
pains" is common. We have treated five four year-olds, all girls, one
whom complained of pains at age two. She frequently awakened at night
required hot baths and massage.
I feel fibromyalgia is a retention disease like most cases of gout but with more varied tissue dispersion. Though patients respond to uricosuric agents, urates are not involved. The ubiquitous symptoms, number of organs and systems affected, point to a metabolic misadventure induced by the accumulation of a different anion. This putative ion wreaks havoc throughout many systems and yet evokes no inflammatory response. It is obviously perceived as a normal tissue constituent. For several reasons I suspect a partial role for inorganic phosphate (Pi). This is supported by some observations. Patients note cyclic chipping or peeling fingernails (calcium phosphate). Dental calculus, tartar, (calcium phosphate) often breaks off and, sometimes, no longer forms during treatment. Calcium added to meals allowed lower dosages of medication (phosphate binding and fecal elimination). Twenty-four hour urine examinations upon beginning guaifenesin showed large increases in phosphate excretion and, in lesser amounts, calcium and oxalate. Though other anions might be involved, the preceding suggest a primary defect in phosphate (and possibly pyrophosphate) metabolism. If so, the following formula would account for depressed mitochondrial ATP generation:
G= ATP (Pi=
ADP+Pi (G=energy change)
biopsied fibromyalgic, trapezial lesions and reported a roughly 20%
in ATP despite specimen dilution with normal tissue.2 They
noted a similar decrease in phosphocreatine, the high energy reservoir.
No such changes were present in unaffected muscle. A decrease in red
cell ATP has also been documented. An energy deficit in affected cells
would explain the entire syndrome: all symptoms and the multiple
abnormalities of fibromyalgia.
Eighty to 90
ingested phosphate is absorbed. We depend on proximal renal tubular
for coordinating its retention or excretion according to need. We
an enzyme, receptor or pump defect that leads to systemic accumulation.
Phosphates readily enter cells and maintain equilibrium with those in
outer mitochondrial chamber. Excess H+ (phosphoric acid in
with phosphate) in this organelle would seriously blunt the ion's
from the matrix to the outer chamber. Electron generation and transport
for ATP formation depend on reversal of H+ direction back to
the matrix. Even a minor inborn error anywhere in the chemiosmotic
including ATP synthase would increase susceptibility to blockade. The
plausible theory of fibromyalgia is that of defective ATP generation
a fully operational citric acid (Krebs') cycle that produces heat
name "energy deprivation syndrome" rather than "fibromyalgia," which
only pain in muscles and fibers. Such change would more accurately
the metabolic error resulting in symptoms and findings of this illness.
Some, such as decreased growth hormone, IGF-1, serotonin, free ionic Ca2+,
free urinary cortisol, certain amino acids; increased serum prolactin,
substance P and angiotensin converting enzyme, make it obvious this is
a widespread, fundamental disease. Other highly phosphorylated systems
(ITP3, GTP3 etc.) would share in this dynamic,
chemistry that fails to provide energy for needs in an ever-changing,
milieu. The cycling fibomyalgic at times almost meets full energy
on occasion barely, often, not at all. Moments of energy availability
some bursts of effort but expenditures from activating any system
deplete the marginal energy bank. Thus, an accident, emotional stress,
infection or surgery sometimes seem to have initiated the first attack
of fibromyalgia. It is difficult to postulate a less basic cause of the
Whatever anion is
its entry into any cell requires cation buffering. Sodium would allow
retention that occurs during attacks. Only free, cytosolic Ca2+
can sustain the palpable, muscular contractions. ATP controlled pumps
responsible for returning calcium to the endoplasmic reticulum to clear
the sarcoplasm and permit relaxation. As in muscle, the ion must be
from the cytosol to allow cessation of activities peculiar to any cell.
Failure forces an attempt to continue reactions that lead to eventual
"fatigue" and malfunction. Even small, localized, calcium sparks from
endoplasmic reticulum can trigger equally-selective, cellular
Small, site-specific ATP action exists to control or modify the effects
of these bursts. Muscular contractions of rigor mortis are an extreme
of this process as ATP formation ceases and calcium accumulates freely
in the sarcoplasm of the dying structure.
on urinalysis may be the concentrated precipitates of our putative
In concentration, these can abrade the distal bladder and urethra
denuded surfaces and dysuria. Vaginal and vulval involvement leads to
and further trauma with intercourse in many patients. Frequent bouts of
cystitis (superficial or interstitial), vaginitis, urethritis and
candidiasis, are the sequelae. These occurrences and the frequent
of eye irritation; scalded or metallic oral sensations; pruritus;
rashes; faulty hair texture and growth; fingernail defects, all
our belief in a generalized abnormality affecting not only the brain,
and intestinal systems but is also reflected in body fluids and the
The multiple, overstimulated areas of fibromyalgia burn fuel steadily. This results in sugar craving in a futile attempt to create energy. Increasing carbohydrate intake yields little due to the impediment to ATP formation. Sugars and starches induce repetitive insulin surges that, in susceptible individuals, initiate the "hypoglycemia" syndrome. Over 50% of fibromyalgics suffer frontal headaches, tremulousness, sweats, heart palpitations or pounding, often with tachycardia and the sudden feeling of anxiety. Symptoms last approximately twenty to thirty minutes and occur a few hours postprandially, often nocturnally. Genter and Ipp reported on the release of counter-regulatory hormones during glucose tolerance tests on normal individuals.3 Blood samples taken every few minutes showed an epinephrine rise fully ten minutes before the nadir of the blood sugar. One-half of these young, healthy subjects became maximally symptomatic as epinephrine neared its peak, some at perfectly normal glucose levels. Obviously, each of us has an individual, brain set point for glucose below which threshold, glucopenia is signaled and well-defined, corrective measures are induced. Epinephrine is the trigger for the preceding symptoms, which when most intense, are labeled "panic attacks."
We no longer perform glucose tolerance tests since symptoms suffice for diagnosis. It must be noted, however, that the central nervous system becomes inured to repetitive hypoglycemic attacks and, as a result mounts no neurohormonal, counter-regulatory response. Epinephrine symptoms cease but cognitive disorders continue.4 This situation can only be surmised by the past history. Within two weeks of proper carbohydrate restriction epinephrine signaling of dietary indiscretion is restored..
is too often inappropriate. It would be better named "carbohydrate
syndrome" and treated accordingly. Our companion paper, "Hypoglycemia,"
written for patients, describes the entity and outlines the appropriate
diet. This syndrome overlaps strikingly with fibromyalgia but is
mainly by the epinephrine symptoms. Patients with the dual afflictions
do not feel better without dietary control, although examination
the anticipated, cyclic resolution of guaifenesin-treated fibromyalgia
Therefore, despite improved physical findings documented on mapping,
would be no change in the standard, patient wellness
considerable weight. Arguably, this is due to diminished activity
by the disease. Those with carbohydrate craving, whether intolerant,
an added factor. One paper has shown an increase in serum pyruvate, but
normal or low serum lactate in some fibromyalgics.5 The
of lactate accumulation points to intact aerobic metabolism. There is
pyruvate for acetyl CoA formation within the mitochondrial matrix. One
would expect normal citrate formation and the full, sequential
of the Krebs' cycle to continue. When this chemical cascade does not
ATP normally, energy is dissipated as heat. Increased citrate, a
signal of energy abundance, would strongly stimulate acetyl CoA
and therefore malonyl CoA and fatty acid formation. This could be the
for the hot flushes, sweats, and weight gain. Insulin causes increased
reabsorption of phosphates and sodium in proximal renal tubules--a
effect of that hormone. Thus, the more patients yield to sugar craving,
the more confusing and intense is the interplay of hypoglycemia and
there are facts in this paper. Guaifenesin has proven our most
medication to date. Any source of salicylate will block its benefit at
a renal, tubular level as it does in gout. Salicylates are readily
through skin. Even small amounts in cosmetics and other topicals will
or slow the effects of all agents we have used. All plants make varying
amounts of salicylate. We have many maps made during treatment that
lesions becoming static or worsening in previously improving patients
unwittingly, began using such preparations. Individuals once warned,
that over one-half of their usual skin preparations could have been
Susceptibility to blockade seems genetically determined and highly
Some are blocked by tiny amounts of offending agents yet others improve
despite moderate usage. Many patients are carbohydrate intolerant and
also be treated dietarily. These statements are factual and must be
or there will be no improvement.
of guaifenesin versus placebo was completed at the University of Oregon
in June 1995 by Doctor Robert Bennett. Both groups improved equally
the course of this one year study, a finding that suggested placebo
Three months into the study, I first observed blockade from Ben Gay and
Myoflex. In the seventh month I saw the same effect from oral, herbal
and suspected a defect in the study at least for the earliest patients.
Although Doctor Bennett was warned of this problem on a timely basis,
was not until six weeks after the study was completed that I learned of
the widespread, and increased presence of plant extracts or salicylates
in cosmetics and lotions. It is more astounding how thoroughly, small
of these additives can block the medication a fact not known to me or
Bennett. Hypoglycemics were not systematically excluded and would have
confounded the patient wellness questionnaires. As consultant with the
only experience in this treatment, I accept full responsibility but I
the study was doomed for lack of knowledge of these pitfalls. The
may take this as a lame excuse for failure, or accept my disclaimer. In
our hands and those of other physicians nationwide, results from
have been too obvious to dispute.
My sole purpose
this paper is to promote, among patients and physicians, an effective
for fibromyalgia where there is none. I seek to replace the dismal set
of medications currently in use, with a simple, non-toxic one that
at some very fundamental level. I am pleased to help any physician who
is interested in using this approach. I have no vested interests in a
without patent made generically by several companies. I do however have
a moral obligation to pursue dissemination of this information and
R. Paul St. Amand, M.D.
Assistant Clinical Professor Medicine
1. PDR, 1996.
"Humibid" p. 463. "Drug/laboratories test interactions."
2. Bengtsson, A.
K. G.: The Journal of Rheumatology, Vol 16:supplement 19, Nov.1989 pp
3. Genter, P. and
E.: Metabolism, Vol. 43, No. 1 (January), 1994, pp 98-103.
4. Hvidberg, A.
Diabetes, Vol. 45, No. 8, 1996. Impact of Recent Antecedent
on Hypoglycemic Cognitive Dysfunction in
5. Eisinger, J.;
A.; Ayavou, T, Journal of The American College of Nutrition. 13(2)
6. Delaney, T.P. et al ; Science, Vol. 266, Nov. 18, 1994. A Central Role of Salicylic Acid in Plant Disease Resistance.
Copyright ©1997, Miryam Ehrlich Williamson - ALL RIGHTS RESERVED