Gold And Its Relationship
To Neurological/Glandular Conditions
Douglas G. Richards, Ph.D., David L. McMillin, M.A.,
Eric A. Mein, M.D., Carl D. Nelson, D.C.
Meridian Institute
International Journal of Neuroscience
2002, Volume 112, pages 31-53
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Abstract
Despite increasing sales of gold supplements, and claims of benefits
for neurological and glandular conditions, gold has received little attention
in modern medical literature except as a drug for rheumatoid arthritis.
Historically, however, gold had a reputation as a "nervine," a therapy
for nervous disorders. A review of the historical literature shows gold
in use during the 19th century for conditions including depression,
epilepsy, migraine, and glandular problems including amenorrhea and impotence.
The most notable use of gold was in a treatment for alcoholism developed
by Leslie E. Keeley, M.D. In the modern medical literature, gold-containing
medicines for rheumatoid arthritis are known to have occasional neurotoxic
adverse effects. There are also a few studies suggesting a role for gold
as a naturally occurring trace element in the reproductive glands. One
small recent study demonstrated a possible positive effect of gold on cognitive
ability. There is a need for more experimental and clinical research into
the neuropharmacology and neurochemistry of gold, and exploration of gold's
possible role as a trace element.
Gold and its Relationship to Neurological/Glandular Conditions
The modern use of gold-containing medicines focuses primarily on rheumatoid
arthritis, with some recent attention to other anti-inflammatory uses of
gold, and to new anticancer and antimicrobial gold drugs (Fricker, 1998).
Otherwise, in mainstream medicine, gold has been seen as a metal with little
biological relevance. In contrast, the benefits suggested for gold-containing
supplements, widely available in health food stores and over the Internet,
address a variety of conditions including alcoholism, depression, and gland
function (e.g., http://www.colloidalgold.com, 2001; http://www.topsilver.com,
2001). Is there any support for a neuropharmacologic effect of gold?
Although there is very little modern research on these applications
for gold, historically one notable use of gold was as a "nervine," a substance
that could revitalize people suffering from nervous conditions, what today
we would call neurological and psychiatric disorders such as epilepsy and
depression. This paper will review the historical use of gold as a healing
agent for the nervous and glandular systems, and then look at recent literature
pointing to a biological role in these systems for gold.
Goodwin and Goodwin (1984) in the Journal of the American Medical
Association, have addressed what they term the "tomato effect," rejection
of highly efficacious therapies. The analogy is with the long-held belief
that tomatoes were poisonous, despite evidence to the contrary. The tomato
effect contrasts with the placebo effect, where a positive (but spurious)
response causes therapies to be accepted which are later shown to be useless
or harmful. The Goodwins use gold as an example of the tomato effect. The
original rationale behind the use of gold for rheumatoid arthritis was
its effectiveness as an antibiotic for tuberculosis (with the assumption
that rheumatoid arthritis was a related infectious disease). When, by 1945,
the infectious theory of rheumatoid arthritis was discarded, gold therapy
fell into disfavor, despite its proven effectiveness. "Gold started to
regain its former popularity only when the medical community accepted both
the evidence of gold's efficacy and medicine's ignorance of gold's mechanism
of action. The fact that gold now has an unknown mechanism of action -
is a truly idiopathic medicine - is no longer an impediment to its use,
because rheumatoid arthritis has become an idiopathic disease" (p. 2389).
The intent of this paper is to explore a similar situation for gold
and neurological/glandular disorders. Neither the causes of the disorders
nor the mechanism of gold are known, yet there are reports pointing to
a possible involvement of naturally-occurring gold in the nervous and glandular
systems, and evidence from historical sources of a possible efficacy of
gold in therapy for neurological disorders.
Historical Review of Gold as a Nervine
Gold has a therapeutic history in both Eastern and Western traditions.
Mahdihassan (1985) has explored the historical use of gold in Eastern traditions.
The Chinese were the first to prepare and use red colloidal gold as the
alchemical drug of longevity. The word alchemy derives from two Chinese
words: Kim (gold) and Yeh (juice). Kimyeh (gold juice) entered the Arabic
language as kimiya, and with the definite article, al, the arabic word
for the red colloidal gold was alkimiya, which in the Western world, gave
the word alchemy. The procedure for the preparation of red colloidal gold
is still in use today in India, prescribed by Ayurvedic physicians for
rejuvenation and revitalization in old age under the name of Swarna Bhasma
(red gold).
There is modern scientific support for at least one effect of Eastern
gold preparations on the nervous system. Bajaj and Vohora (1998) studied
the analgesic activity of gold preparations used in Ayurveda and Unani-Tibb,
two Indian medical traditions. Two calcined gold preparations were compared
to the modern antiarthritis gold drug auranofin in rats, using four types
of noxious stimuli. Both the Indian drugs and auranofin exhibited analgesic
activity. The analgesic effects of the two Indian drugs could be partly
blocked by pretreatment with naloxone (an opiate antagonist), but not the
effects of the auranofin. The authors feel that this suggests involvement
of an opioidergic mechanism for the Indian drugs.
The use of gold in Western medicine as a nervine has a long history
as well. The medieval alchemists, like their Eastern counterparts, and
probably drawing on the traditions of Eastern alchemy, sought a form of
gold that could be internally consumed, "potable gold," as the elixir of
life. Paracelsus, in the 16th century, recommended preparations
of gold in his therapy for epilepsy (Temkin, 1971). By the beginning of
the 17th century, alchemists were clearly able to produce the
soluble salt gold trichloride (Higby, 1982). By the mid 17th
century, gold was in use as a nervine:
"A gold cordial could be found in the new pharmacopoeias of the 17th
century and was advocated by Nicholas Culpepper for the treatment of ailments
caused by a decrease in the vital spirits, such as melancholy, fainting,
fevers, and falling sickness [epilepsy]" (Fricker, 1996). This is notable
because it includes a grouping of what today would be called neurological/psychiatric
disorders (e.g., depression, epilepsy).
By the beginning of the 19th century, gold had become a recognized
(although probably not very effective) treatment for syphilis, a disease
causing dementia among other serious symptoms. In 1821 the Frenchman J.
A. Chrestien published "Researches and observations on the effects of preparations
of gold in the treatment of many diseases and notably in syphilitic maladies"
(Niel & Chrestien, 1821). Chrestien was a notable physician of the
time, with a degree from the University of Montpelier, and memberships
in the Royal Academy of Paris, the Royal Academy of Medicine of Madrid,
and many other learned societies. His interest in gold came from the observation
that it had milder side effects than mercury (the common treatment for
syphilis at the time). He was also apparently the first to notice that
in occasional cases treatment with gold produced an increase in vitality
and intellectual faculties, and had a stimulating effect on the glands
and sexual functioning. Chrestien and those who followed him used gold
trichloride as their form of gold.
In 1879, James Compton Burnett published a lengthy treatise on the use
of gold in medicine. Burnett was a medical doctor, a homeopath, and a prolific
author (27 books listed in the National Library of Medicine catalog). Burnett
traced the modern use of gold back to Chrestien's first book in 1811, but
gave credit to earlier figures as well. He noted that the ingestion of
gold is mentioned in the Bible (Exodus 32:20), and that the Chinese were
using it in 2500 BC, according to Wiegleb's History of Alchemy in
1777. He traced its use in a diversity of disorders, including neurological
and glandular problems such as epilepsy, sterility, and diseases of the
uterus, to the publication of De Auri Tinctura sive Auro Potabili Vero,
etc. by Glauber in Amsterdam in 1651. He also noted that, "Hahnemann
[Samuel Hahnemann, the originator of homeopathy] mentions nearly thirty
authors (1698-1730) who praise Gold as a valuable remedy in various diseases
such as melancholia." (p. 91).
According to Burnett, Chrestien's use of gold was at first opposed by
the medical profession, which had abandoned the use of gold in medicine.
However, after Chrestien's publication, gold regained its popularity. Burnett
cites Legrand's (1828) account, the Medicinal Properties of Gold,
in which he lists 80 medical men of the time, who became known as "auralists,"
who were exploring the use of gold. Burnett says, "Gold is an excitant.The
patients feel an indescribable sense of well-being, they feel
themselves lighten (as they express it), so that we may say that Gold
possesses hilariant properties. The intellectual faculties are more
active. It has been known to produce frequent erotic salacity going
on to painful priapism. M Legrand, however, states that he has not
used it as an aphrodisiac, but it has been used as such with success" (p.
49). Burnett also says, "Some are of the opinion that Gold belongs to that
class of noble metals, such as silver and copper, which exert a powerful
influence on the nervous system. Of this opinion is Vogt (Pharmaco-dynamik)"
(p. 57).
Burnett was also well aware of the toxic effects of high doses of gold.
He identifies himself as a homeopath, but had a different philosophy than
many homeopaths. In traditional homeopathy, the remedy is an extremely
high dilution of a substance, so high that not even a single molecule remains.
It was Hahnemann's alternative to "heroic" medicine, which involved high
doses that were frequently toxic. Burnett took a middle course, resembling
the approach of 20th century medicine. He preferred low dilutions,
as opposed to high ones. Thus his recommended dosage of gold is 3/100 or
9/100 of a grain. Since a grain is 65 milligrams, this would range from
1.95 mg to 5.85 mg. This is very close to the range of daily dose of modern
antiarthritic drugs, e.g., the 6 mg per day (1.74 mg of gold, at 29% gold)
standard dose of auranofin. It seems possible, then, that Burnett did find
an effective dose of gold with relatively low toxicity.
By the end of the 19th century, and in the first half of
the 20th century, gold is listed as a treatment for nervous
disorders in sources ranging from medical texts to the first Merck manual.
In discussing the treatment of asthma, for example, Eichhorst (1886)
in his Handbook of Practical Medicine says, "In nervous individuals,
resort should be had to the nervines: bromide of potassium, valerian, arsenic,
auronatrium chloratum [gold sodium chloride], zinc, copper, and silver
preparations, etc." (p. 236) Bromide of potassium and valerian are still
used for treatment of nervous disorders, and arsenic came into use in the
early 1900s as a treatment for syphilis, which has neurological manifestations.
Potter (1894), in his Materia Medica, based on the U.S. Pharmacopoeia
of 1890, describes the effects of small doses of gold: "The Salts of Gold
promote appetite and digestion, stimulate the cerebral functions, and produce
a marked mental exhilaration, a sense of well-being. Continued, they induce
aphrodisiac effects in both sexes, and in women an increase of the menstrual
discharge..Amenorrhea and Impotence, of the functional kind, - may be cured
by it." He is also well aware of the toxic effects of too large a dose,
resembling those of mercury, and including "nausea and vomiting, glandular
irritation.violent gastroenteritis, mental disturbance, convulsions, priapism,
trembling, paralysis." This recognition of both kinds of effects is significant,
since later in this paper the adverse effects of gold will be discussed
as a possible indicator of areas particularly sensitive to the therapeutic
effects of lower doses of gold.
The 1899 Merck's Manual lists gold under "aphrodisiacs" (p. 187).
Gold bromide is an "anti-epileptic, anodyne, nervine," used for, "epilepsy,
migraine, etc.; said to act, in small doses, quickly and continuously,
without bromism" (p. 38). Bromides, particularly potassium bromide, were
first used as nervines in the mid-19th century, to treat epilepsy,
insomnia, nervous excitement and irritability (Leake, 1975). They were
the first effective anti-seizure medicine. It is not clear exactly when
gold bromide began to be used, but it appears that it was found to be effective
in a smaller dose than potassium bromide used alone. For example, the standard
dose of gold bromide was given in Merck's Manual as 1/10 to 1/5
grain, 2 to 3 times daily. This can be contrasted with a standard dose
of potassium bromide, of 5 to 60 grains (Garber, 1942), or of sodium bromide
(10-60 grains, Garber, 1942; 5-30 grains, Dorland, 1908). Ryan and Baumann
(1999) give modern guidelines for bromide dosage in epilepsy- might gold
bromide allow a lower dose to be effective?
Hare (1912) in his Text Book of Practical Therapeutics , notes
"it [gold sodium chloride] is said to act as a powerful sexual stimulant
and to be of service in impotence dependent upon inability to obtain an
erection or when there is deficient glandular action" (p. 274). Page 900
in Hare lists a standard dose of "gold and sodium chloride" as 1/20 - 1/10
grain (3 - 6 mg), and "gold bromide" as 1/8-1/2 grain (8 - 30 mg).
Fomon (1920) in his book Medicine and the Allied Sciences, in
the section on Materia Medica and Therapeutics: Agents Producing Changes,
says gold (as chloride of gold sodium) "stimulates the nervous system,"
"stimulates the sexual organs," and is employed in therapeutics as an aphrodisiac,
an alterative in chronic diseases, and in the Keeley cure for alcoholism
and opiumism.
Even as late as 1942, Stedman's Practical Medical Dictionary
(Garber, 1942) lists gold bromide as employed in epilepsy, headache, and
as a nerve sedative. Double chloride of gold and sodium is listed as an
alterative (a medicine that produces a favorable change in the processes
of nutrition and repair, Dorland, 1908) and tonic. Finally, Stedman's notes
the Keeley cure or gold cure, "a secret method of treatment of alcoholism,
said to be by the administration of strychnine and gold chloride." Actually,
based on Keeley's own writings (Keeley, 1897), strychnine is unlikely to
be a component of Keeley's cure.
The most interesting use of gold in treatment is the gold cure of Leslie
E. Keeley, M.D. (1832-1900). Keeley's great discovery was that the chloride
of gold and sodium (prepared by mixing gold chloride and sodium chloride)
was an effective treatment for addictions, including morphine/opium and
cocaine addiction as well as alcoholism. In the 19th century,
a variety of medications were used in an effort to ease withdrawal symptoms
and cure addictions. Most, such as atropine and strychnine, were so toxic
that they were of little use. Even gold chloride was too caustic for internal
consumption. Keeley found that he had to carefully monitor patients for
toxic effects. Then, however, he discovered that mixing gold chloride with
sodium chloride and a substance which he kept secret produced a cure for
addiction that "accomplishes this quietly and mildly, without any shock
or reactive effects" (Keeley, 1897, p. 82).
Keeley was well aware of the history of gold in medicine, citing numerous
researchers who had worked with gold in the treatment of diseases including
syphilis and tuberculosis, but noting the problems with gold toxicity (that
his discovery had solved). Keeley had excellent powers of observation.
For example, in the course of treating addictions, he noted: "In opium
patients whose bodies are covered with nodulations, sores, pimples, blotches,
tumors, and ulcers, resulting from the poison of the "drug," remarkable
effects have been produced by the use of gold. The sores rapidly heal up
and pass away, even without the use of any liniment or local application
whatever" (p. 84). Gold medications are now a recognized replacement for
steroids in treating serious skin conditions (Thomas, 1987).
Included in Keeley's book is a copy of an editorial from the Chicago
Tribune, February 13, 1894. The editorial discusses Keeley's remarkable
record, citing a recent summary of 1000 cases, of which over 90% seemed
to have achieved a long-term cure of their addictions. Other evidence of
the efficacy of Keeley's gold therapy includes the testimonial of Clark
(1893), who wrote a detailed description of his own experiences in Keeley's
program, and a historical discussion of the Keeley League by Barclay (1964).
Higby (1982) cites an estimate as high as 100,000 patients treated with
gold by Keeley, and notes that by the mid-1890s, over 30,000 former Keeley
patients joined clubs, "dedicated to the twin goals of mutual support and
spreading the gospel of Dr. Keeley's marvelous gold treatment" (p. 138).
Unfortunately, Keeley's exact formula was kept a closely guarded secret,
and the use of gold in treatment of alcoholism at Keeley Institutes ceased
with Keeley's death. Higby calls for more historical research on the Keeley
gold cure, since Keeley probably administered more medicinal gold than
anyone before or since. Despite the absence of formal scientific study,
Keeley's success in treating addictions such as alcohol and morphine is
impressive historical evidence of the potential of gold as a nervine, given
that these problems are still very difficult to treat.
The use of gold as a therapy not only for alcoholism, but for a variety
of neurological and glandular disorders, continued into the 1940s in the
work of Edgar Cayce. Callan (1979) in the first editorial addressing holistic
medicine in the Journal of the American Medical Association, credits
Cayce with the origin of holistic medicine in America. Cayce followed the
philosophy evident in Barnett: very small doses ( < 1 mg) of gold chloride
taken orally. The gold was buffered with either sodium bicarbonate or sodium
bromide, presumably to reduce toxicity. Although there were testimonials
to the efficacy of Cayce's treatments (Cayce, 1993), no controlled studies
of the use of gold were conducted in his time.
Nineteenth century microscopists also discovered an application for
gold in exploration of the nervous system. Gold salts have been employed
in neurological staining for light microscopy since Cohnheim in 1866 (Clark,
1983). Ramon y Cajal (1995) notes that Gerlach in 1871 stained with gold
chloride and was able to enhance the distinction between white and gray
matter in sections, and to obtain an unprecedented degree of contrast.
Gurr (1962) lists several stains in modern use containing gold chloride,
for neuroglia fibers, astrocytes, nerve fibers, sheaths and cells, and
even for nerve fibers of planarians.
The affinity of gold for the nervous system and the implications of
this for the treatment of nervous disorders was remarked on by Keeley (1897):
"The use of gold by the histologist to develop microscopical nerves may,
perhaps, be said to indicate that nerve fibre has a peculiar affinity for
that metal. The application of it in solution brings out nerves which otherwise
would be invisible. When the fact is recognized that absorption by lifeless
fibre is quite unlike assimilation or reconstruction of that which is vitalized,
then the development of lifeless microscopic nerves by a solution of gold
may be in part owing to some of the recondite forces which cause the gold,
taken into circulation, to reconstruct living ones" (p. 82).
A similar approach to drug discovery was held by Paul Ehrlich (1854-1915).
"Ehrlich's earliest observations dealt with the staining of tissues for
microscopic examination, and so with the processes by which particular
dyestuffs combined with and were fixed to specific components of the tissues.
Ehrlich supposed that the action of drugs in bodily organs was likely to
involve similar fixation. As an early test of this thesis, he treated a
small number of malarial patients with the dye methylene blue, which was
known to stain (that is, be fixed by) the malaria parasite, and he showed
that it had a modest therapeutic effect" (Weatherall, 1993, p. 925).
Taylor (1985), in a review of therapeutic uses of trace elements in
neurological/psychiatric disorders, notes that while metal compounds have
been administered for several centuries, the scientific basis for treatment
with trace elements began with the use of gold compounds, initially in
patients with tuberculosis and later those with rheumatoid arthritis. He
points out the other important uses of trace elements, including "the central
nervous system where the use of lithium has provided spectacular results
in the treatment of affective and other disorders." Lithium carbonate is
a simple metal salt with major effects; the same may be possible for gold
salts. It is interesting that the first use of lithium in medicine was
lithium bromide in the 19th century (Scott, 1992); gold bromide
was also used, for epilepsy.
To summarize the relevance of the historical uses of gold, it is clear
that there is a long tradition of gold as a nervine. But there were no
multicenter clinical trials; that is a modern phenomenon. There were only
observations and reports of individual cases. Keeley's work stands out
in this regard, but there is no other scientific support for his claims;
as with most of 19th century medicine, there are only testimonials.
Yet this work can be seen as a source of hypotheses for testing with present
day methods.
As 20th century medicine developed, gold disappeared from
the pharmacopoeias, except in the case of rheumatoid arthritis. Forestier
(1935) demonstrated its effectiveness in arthritis, although the popularity
of gold and belief in its effectiveness has waxed and waned (Goodwin &
Goodwin, 1984). Yet there appears to be no early 20th century
literature on the efficacy of gold for neurological and glandular conditions,
either pro or con. And the possible biological role of gold as a naturally-occurring
trace element was not explored at all until recently.
The Biological Role of Naturally Occurring Gold
There is a continuum of effects with increasing concentration in the
biological activity of elements, from beneficial physiological effects
as trace elements, to pharmacological effects, to toxic effects at high
doses (Mertz, 1998). As described above, the pharmacological and toxic
effects of gold were well known historically, although the pharmacological
application is more limited today. But very few studies of trace elements
in the body have included gold. However, those few studies have shown that
naturally occurring gold is found concentrated in glandular and reproductive
tissues, and, in the female, its concentration cycles with the reproductive
cycle.
Alexiou, Grimanis, Grimani, Papaevangelou, Koumantakis, and Papadatos
(1977) measured trace elements, including gold, in human placenta and newborn
liver at birth. They found gold in significantly higher concentrations
(3-fold higher) in placenta than liver tissue. Because some essential trace
elements (Zinc, Cobalt and Selenium) were found in higher concentrations
in the liver tissue, Alexiou et al. conclude that gold is a non-essential
trace element. An alternative may be that gold is specifically involved
in reproductive glandular activity, as discussed below.
Hagenfeldt, Landgren, Plantin, and Diczfaluzy (1977) measured trace
elements, including gold, in the human endometrium and decidua, looking
for cyclic variations, including those during pregnancy. It had been previously
established that there are significant cyclic variations in major elements
with known importance, such as sodium, potassium, and copper. Using uteri
from women undergoing hysterectomy, they found that the levels of gold
were similar in the endometrium and the decidua. There were cyclic variations
in gold (as well as a number of other elements), which were significant
at the p<0.05 level. They reported that the levels of gold were slightly
lower around midcycle than at other stages of the cycle, but the physiological
significance of these changes is unknown.
In the male reproductive system, Skandhan and Abraham (1984) measured
gold in semen, and noted that, "this is the richest source of gold reported
in biological materials" (p. 587). They also speculated that, since gold
was not seen in one pathological sample with asthenozoospermia, that may
be an indication that reduction of this trace element led to this pathology.
Kauf, Wiesner, Niese, and Plenert (1984) measured the amounts of a number
of trace elements in the hair of newborn infants. They noted, "The investigation
of trace elements in the hair of babies resulted in the remarkable observation
that in the first three months of life zinc, copper and gold contents shows
a considerable increase to multiple levels of the birth values, followed
by a decrease.It must be emphasized that gold, although classified as a
non-essential trace element, behaves in the hair of infants just like the
physiologically important essential trace elements zinc and copper" (p.
299).
One major source on trace elements in neurological disease is the work
of Gooddy, Williams, and Nicholas (1974). The 1974 study, which summarizes
the results of several studies by previous researchers, does not give values
for gold. They do, however, point out the importance of many trace elements
in enzyme systems. The discovery of the biological activity of these elements
has largely depended on development of technology for measuring them at
very low levels. They point out the great metabolic importance of copper,
and note that the vertical neighbors of copper (in the periodic table of
elements indicating some similar properties), silver and gold, "are known
medically almost as curiosities, with some rare therapeutic and toxic properties"
(p. 330). Given this observation, it is not clear why they failed to measure
these elements in their study.
El-Yazigi, Al-Saleh, and Al-Mefty (1984) looked at both silver and gold,
as well as a variety of other trace elements, in cerebrospinal fluid (CSF)
of patients with cerebral neoplasms (brain tumors). The concentration of
silver was markedly increased in patients with malignant tumors; the malignant
tumor/control patient concentration ratio was 2.31. They state that the
biochemical mechanism of this increased concentration is unknown. Interestingly,
though there was no consistent relationship between gold and tumor vs.
control subjects, for the single patient with pinealblastoma the
concentration of gold was about twice the concentration for the
controls or other tumor types.
El-Yazigi, Kanaan, Martin, and Siquiera (1990) also looked at other
trace elements in the CSF, in particular platinum. They note that there
are no previous values in the literature for platinum in the CSF. They
found that platinum, in the opposite direction from silver, is depleted
in patients with tumors. Platinum is known to react with DNA, and has treatment
uses in cancer, as well as mutagenic properties. Platinum is also adjacent
to gold in the periodic table of elements (the highly neurotoxic mercury
is on the other side of gold, and toxic lead is close by). The platinum
concentrations in the control group were 11.4 (SD 1.7) micrograms/liter.
This is about 1/3 of the concentration of gold from the other study. In
patients with tumors, the platinum concentration is about half this level.
Are there dietary sources of this gold? This can be an important issue,
since dietary factors may be responsible for many of the reported inconsistent
and divergent findings in trace element research (Nielsen, 1985). Warren
(1989) looked at potential sources of gold in the diet. He noted that in
1981 gold was found in honey bee pollen in amounts as high as 0.9 ppm (dry
weight). He found two plants (in British Columbia, Canada) that conceivably
could provide gold in the diet, either to honeybees or perhaps directly
- Phacelia sericea and Dryas drummondi - which carry 25-50
times as much gold as any other plants with which they are associated.
Mahler, Scott, Walsh, and Haynie (1970), in a study of trace metals, including
gold, in fingernails and hair, note the importance of differences in environmental
sources of gold in different areas. Anderson, Brooks, Stewart, and Simcock
(1998) have shown that "hyperaccumulator" plants, such as Indian mustard
(Brassica juncea) can uptake and store large amounts of gold, up
to 100 times that found in most plants. Any study of naturally occurring
gold needs to address dietary sources.
These few reports show that naturally occurring gold is found in nervous
and glandular tissue, behaves in some cases like an essential trace element,
and may change in concentration in correlation with certain diseases.
Therapeutic Gold and the Nervous/Glandular Systems
Adverse effects of drugs can be an indicator of related therapeutic
effects at lower dosages. The therapeutic and adverse effects of gold in
living organisms are varied and paradoxical. Several different gold salts
are currently in use: gold sodium thiomalate and gold thioglucose, both
administered by injection, and auranofin, a complex organic gold salt taken
orally. The primary therapeutic use of gold is in the treatment of rheumatoid
arthritis (Kean, Forestier, Buchanan, & Rooney, 1985), but there are
many other less common uses, e.g., as a steroid replacement in asthma and
skin disorders, and as an anti-cancer substance (Fricker, 1996). The primary
adverse effects include skin and gastrointestinal reactions (Locke &
Smith, 1985). Yet gold-containing drugs have numerous rarer side effects,
and can cause or exacerbate the same disorders for which they are effective
in therapy. Gold-containing drugs have been used in place of steroids in
therapy for asthma (Bernstein, Bernstein, Dubb, Faiferman, & Wallin,
1996; Nierop, Gijzel, Bel, Zwinderman, & Dijkman, 1992), but in other
cases have been responsible for respiratory disorders and even death (Blackwell
& Gossage, 1995; Blancas, Morena, Martin, de la Casa, Onoro, &
Gomez, 1998). Similarly, gold is used in dermatological therapy (e.g.,
for pemphigus) (Thomas, 1987), yet skin disorders are a common side effect
of gold medicines, and gold has also been found to cause pemphigus
(Usuba, Aiba, Hashimoto, Tanita, & Sakai, 1989). As another example,
gold may be useful in treating lupus erythematosus (Weisman, Albert, Mueller,
Zvaifler, Hesketh, & Shragg, 1983; Dalziel, Going, Cartwright, Marks,
Beveridge, & Rowell, 1986), yet gold may also induce lupus (Korholz,
Nuenberger, Gobel, & Wahn, 1988). The mechanism of action for these
effects is not known (Liebfarth & Persellin, 1981).
Neurological adverse effects of gold-containing drugs are rare, but
diverse.
They include both peripheral and central nervous system effects. At
first one might think that toxic side effects are evidence against
the utility of gold as a nervine. However, there is a therapeutic-toxic
continuum with all drugs; this was clearly recognized in the 19th
century by such gold therapists as Burnett (1879) and Keeley (1897). The
effects may be related to specific gold compounds, dosage, mode of administration
(oral, parenteral), and individual idiosyncratic responses. Toxicity can
often be a pointer to a therapeutic use at a lower dose.
Three forms of gold-induced neurological side effects have been recognized:
(1) painful neuropathy, sometimes accompanied by insomnia and anxiety,
(2) peripheral motor neuropathy, and (3) encephalopathy with symptoms including
depression, delirium, and exogenous psychoses (Schlumpf, Meyer, Ulrich,
& Friede, 1983). Some of the case studies are mentioned below; they
contain references to many other cases.
The variety of peripheral neuropathies includes various forms of polyradiculoneuropathy,
a general term referring to peripheral disorders involving multiple nerve
roots. These can include both sensory and motor symptoms, with both overactivity
and paralysis. They include Morvan's fibrillary chorea, a form of spontaneous
muscular activity (e.g., Vernay, Dubost, Thevenet, Sauvezie, & Rampon,
1986), and a Guillain-Barre-like syndrome with weakness and paralysis (e.g.,
Schlumpf et al., 1983). Some of the reports of adverse effects of gold
are simply reported as peripheral neuropathy. Weiss, Thompson, & Lazaro
(1982) report a case which was characterized by weakness and numbness of
the hands and feet in association with hyperalgesia of the palmar surface
of the hands. With cessation of gold therapy (aurothioglucose), recovery
was slow but complete. In general, patients typically recover, but slowly,
from gold-induced neuropathy.
Microscopic descriptions of peripheral neuropathy include marked loss
of myelinated nerve fibers. In one patient, a nerve biopsy revealed, "a
chronic polyneuropathy with predominant features of regeneration. Such
features are clustering of myelinated fibers and the onion bulb-like arrangement
of Schwann cells around and within such clusters" (Schlumpf et al., 1983).
This observation is especially interesting, since one of the claims for
gold as a nervine is for the regeneration of nerves.
Encephalopathy is the general term used for damage to the brain, as
opposed to the peripheral nerves. Gulliford, Archard, & van't Hoff
(1985) report a case of gold-induced encephalopathy, as do McAuley, Lecky,
& Earl (1977) and Perry and Jacobsen (1984). Fam, Gordon, Sarkosi,
Blair, Cooper, Harth, & Lewis (1984) describe a case of gold-induced
encephalopathy with cerebral and cerebellar white matter lesions, reversible
on withdrawal of gold therapy. Erhardt, Fischer, Fischer, & Kern (1978)
report a case of cerebro-organic syndrome related to gold therapy, consisting
of delirium, dementia, and amnestic and cognitive disorders.
Schlumpf et al. (1983) note that it is not surprising that neurologic
complications can be caused by gold because experimental work in animals
has shown that gold localizes in nervous system tissue. Gold thioglucose,
the medicine Solganol used for rheumatoid arthritis, is a well-known neurotoxin
in rodents, used in studies of obesity to destroy the ventromedial hypothalamus,
the part responsible for control of eating behavior and metabolism. In
addition to obesity, it appears to become concentrated in other glandular
tissue such as the pancreas (Blech, Bierwolf, Weiss, & Ziegler, 1986),
and the thymus and adrenals (Atkins, Lambrecht, Wolf, Ansari, & Guillaume,
1975). It can also cause generalized hypothalamic lesions in the chicken
and duck (Hopper & Satterlee, 1984). In humans it is interesting that
people who develop neurological adverse effects from gold sodium thiomalate
can be successfully changed to gold thioglucose for rheumatoid arthritis
therapy (Hill, Pile, Henderson, & Kirkham, 1995). Clearly there are
species differences in response to gold compounds, as well as pronounced
individual differences and dose-related effects.
The question of whether gold affects glandular function in humans is
still an open one. Chipman, boyar, & Fink (1982) tested the hypothesis
that gold therapy enhances endogenous cortisol secretion, using juvenile
rheumatoid arthritis patients. Their preliminary data suggested stimulation
of cortisol secretion. But the results of the more complete study were
ambiguous. Cortisol secretion was significantly greater in gold treated
patients than in similar patients not receiving gold. However, when untreated
patients were restudied after initiation of gold therapy, there was no
significant change in cortisol secretion. Gold therapy also did not significantly
alter secretion of the peptide hormones or DHEA-S. Their conclusion is
that gold does not appear to influence endogenous adrenal hormone secretion.
In summary, there are diverse neurological and glandular side effects
occasionally observed in response to gold-containing medications. These
effects are further evidence suggesting that gold may play a role in these
systems.
How Much Gold is Necessary for a Pharmacological Effect?
Conventional gold therapy uses rather large doses, typically more than
1 mg per day. But there is some evidence that very low doses of gold can
have pharmacological effects.
The gold drugs used in rheumatoid arthritis are typically administered
in very large doses. Yet the relationship between dosage and response is
not simple. Speight and Holford (1997) say, "Dosages as low as 10 mg/week
appear to be no different from 50 mg/week, which in turn is as effective
as 150 mg/week" (p. 1129). Given that toxicity is often seen at high doses,
how little gold can still produce a therapeutic effect?
Effects have occasionally been seen with very low doses of gold. Mulherin,
Struthers, & Situnayake (1997) examined the hypothesis that gold rings
might protect against erosion of the finger joints in rheumatoid arthritis.
They found that there is less articular erosion at the left hand ring finger
joints, and perhaps adjacent joints. Their hypothesis is that gold could
pass from a gold ring through the skin and local lymphatics to nearby joints
in sufficient quantities to delay articular erosion. Since metallic gold
has been seen as virtually inert in biological systems, especially when
present only at the skin surface, a therapeutic effect is surprising. But
there is some historical support for this notion. In 14th century
England, "cramp rings" were used to relieve muscular pains or spasms, and
particularly epilepsy. Gold coins were placed by the king on a church altar,
removed, and made into rings (Bloch, 1961). We have no reliable information
concerning their effectiveness.
Belt and Kaarela (1998) and Bolosiu (1998) have expressed skepticism
of the low-dose gold hypothesis. But gold has been measured in significantly
greater concentrations in fingernails nearer gold rings by Kanabrocki,
Case, Graham, Fields, Oester, & Kaplan (1968), a fact apparently unknown
either to Mulherin et al., or to Bolosiu and Belt and Kaarela. Kanabrocki
et al. noted, "Only speculation can be made on the mode of transport of
gold from wedding bands to the fingernail," a situation that is still the
case.
Klinkhoff and Teufel (1995), in an article entitled, "How low can you
go?" explored the minimum effective dose of gold for rheumatoid arthritis.
They identified a group of patients with sensitivity to both the beneficial
effects and the side effects of gold. They found that doses as low as 2
mg every 4 weeks could result in major improvement, and concluded that
the minimum effective dose is not known. (This contrasts with the standard
daily dose of 10 to 50 mg/week for parenteral gold, and of 6 mg/day for
oral gold (Goodman, Rall, Nies, & Taylor, 1990)). This is still far
more than the dose of gold available from a gold ring, but is further evidence
that physiological effects do not require large doses of gold. Interestingly,
it is similar to the amount of gold in prescriptions for neurological and
other disorders by Cayce in the early-20th century (Cayce, 1993).
The Modern Use of Colloidal Gold as a Nervine in Alternative
Medicine
Although gold is not in use as a nervine at present in mainstream medicine,
its use has recently been explored in alternative medicine. Instead of
the modern gold-containing drugs, or the gold chloride used historically,
colloidal gold has become popular. Colloidal gold is very fine particles
of metallic gold (from 2 nm to 150 nm), suspended in water. As discussed
earlier in the historical section, colloidal gold may have been the first
form used as a nervine, as far back as the ancient Chinese and Indian alchemists
(Mahdihassan, 1985). According to Abraham (1996) it is not toxic, but little
is known about its physiological effects. In mainstream medicine, colloidal
gold is generally thought to be biologically inert, and is used in electron
microscopy studies for that reason. By attaching it to macromolecules such
as antibodies, these molecules can be tracked to the locations where they
are active without affecting their functions (Polak & Varndell, 1984)
note, "Fortunately, upon adsorption, full biological activity of the macromolecules
is preserved." Yet Abraham reports that colloidal gold can have significant
biological effects.
Abraham and Himmel (1997) used colloidal gold to treat rheumatoid arthritis.
They studied 10 severe cases, orally administering 30 mg of colloidal gold
per day. There was no clinical evidence or laboratory evidence of toxicity
in any of the patients. The effects of the gold on the tenderness and swelling
of joints were rapid and dramatic. Evaluated individually, nine of the
10 patients improved markedly after 24 weeks of colloidal gold.
Abraham, McReynolds, and Dill (1998) explored the potential of colloidal
gold as a nervine. Encouraged by pilot work suggesting improved cognition
and well-being (Abraham, 1996), they conducted a study to see if gold could
improve cognitive functioning. They tested cognitive ability using the
Wechsler Intelligence Scales (WAIS-R) before and after four weeks on colloidal
gold at 30 mg/day. After four weeks on colloidal gold, there was a 20%
increase in IQ scores. The effect of the colloidal gold persisted in three
subjects after one to two months off gold, whereas in two subjects who
took the test three months after stopping the gold, IQ scores were down
to baseline levels. While a study of this small size is very preliminary,
it is encouraging evidence of the potential of gold as a nervine, and as
a demonstration of a non-toxic preparation.
Directions for Future Research
Future research could focus on two aspects of gold: exploring the effects
of gold supplementation on neurological conditions, and establishing whether
naturally occurring gold is an essential trace element.
Two approaches might be taken in exploring the effects of gold supplementation.
The first consists of attending to the side effects of gold medications
in cases where there is co-morbidity of rheumatoid arthritis and a neurological,
psychiatric, or glandular disorder. For example, one could ask, do patients
with epilepsy, depression, or adrenal insufficiency who may be receiving
gold for arthritis show any improvement in neurological/glandular symptoms?
Although neurological adverse effects are rare, beneficial side effects
might be found.
The second approach is to administer gold with the intention of affecting
a neurological or glandular condition. This is more challenging, since
little is known about effective or toxic doses. The bioavailability of
different gold compounds is an important consideration in exploring the
effects of gold supplementation. There are substantial differences in the
efficacy and side effects of the organic gold salts used for rheumatoid
arthritis, and individual idiosyncrasies in response. As noted previously,
it has been difficult to establish a dose-response relationship for gold
(Speight & Holford, 1997). Gold chloride, a favorite in the 19th
century, is now used primarily as a test for allergic skin reactions, not
internally, so nothing is known about its metabolism. And colloidal gold,
as noted above, should have very little physiological interaction at all,
although Abraham and Himmel (1997) present evidence to the contrary. An
advantage to using colloidal gold is that is has no known adverse effects.
Animal studies with gold chloride as well as the current gold medications
might also be productive.
Establishing gold as an essential trace element is another challenging
task. The few studies cited here are encouraging. A systematic exploration
of the concentrations of gold in cerebrospinal fluid, blood, and neurological
and glandular tissue could be performed. The results would be interesting
in neurological disorders and tumors (e.g., El-Yazigi et al., 1984), glandular
disorders (e.g., Skandhan & Abraham, 1984) and developing infants (e.g.,
Kauf et al., 1984). But much further research will be needed to confirm
these observations and determine gold's biological role. There are thousands
of studies on such elements as chromium and boron, which have only recently
been suggested as essential nutrients (Nielsen, 1990). It takes on the
average about 30-40 years for the general acceptance and application of
the discovery of a new essential trace element (Mertz, 1998). Studies in
both animals and humans will need to address specific physiological roles,
effects from deficiencies, and interactions with metabolic stressors.
This research has the potential for re-establishing gold as a significant
therapeutic agent in a much wider range of disorders than those for which
it is currently used. And it could help in sorting out valid from invalid
claims of benefits from supplementation.
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