As you have limited net access I took the liberty...
Chuck
Let's get some chaos into this confusion!
On Sun, 21 Oct 2001 21:16:25 +0200, "Jan Carew" <[email protected]> wrote:
>PPS Please excuse my ignorance but I still don't know what DMSO
>is............
>From DMSO.org
DMSO: Many Uses, Much Controversy
Maya Muir
Abstract
Dimethyl sulfoxide (DMSO), a by-product of the wood industry, has been in use as
a commercial solvent since 1953. It is also one of the most studied but least
understood pharmaceutical agents of our time--at least in the United States.
According to Stanley Jacob, MD, a former head of the organ transplant program at
Oregon Health Sciences University in Portland, more than 40,000 articles on its
chemistry have appeared in scientific journals, which, in conjunction with
thousands of laboratory studies, provide strong evidence of a wide variety of
properties. (See Major Properties Attributed to DMSO) Worldwide, some 11,000
articles have been written on its medical and clinical implications, and in 125
countries throughout the world, including Canada, Great Britain, Germany, and
Japan, doctors prescribe it for a variety of ailments, including pain,
inflammation, scleroderma, interstitial cystitis, and arthritis elevated
intercranial pressure.
Yet in the United States, DMSO has Food and Drug Administration (FDA) approval
only for use as a preservative of organs for transplant and for interstitial
cystitis, a bladder disease. It has fallen out of the limelight and out of the
mainstream of medical discourse, leading some to believe that it was
discredited. The truth is more complicated.
DMSO: A History of Controversy
The history of DMSO as a pharmaceutical began in 1961, when Dr. Jacob was head
of the organ transplant program at Oregon Health Sciences University. It all
started when he first picked up a bottle of the colorless liquid. While
investigating its potential as a preservative for organs, he quickly discovered
that it penetrated the skin quickly and deeply without damaging it. He was
intrigued. Thus began his lifelong investigation of the drug.
The news media soon got word of his discovery, and it was not long before
reporters, the pharmaceutical industry, and patients with a variety of medical
complaints jumped on the news. Because it was available for industrial uses,
patients could dose themselves. This early public interest interfered with the
ability of Dr. Jacob--or, later, the FDA--to see that experimentation and use
were safe and controlled and may have contributed to the souring of the
mainstream medical community on it.
Why, if DMSO possesses half the capabilities claimed by Dr. Jacob and others, is
it still on the sidelines of medicine in the United States today?
"It's a square peg being pushed into a round hole," says Dr. Jacob. "It doesn't
follow the rifle approach of one agent against one disease entity. It's the
aspirin of our era. If aspirin were to come along today, it would have the same
problem. If someone gave you a little white pill and said take this and your
headache will go away, your body temperature will go down, it will help prevent
strokes and major heart problems--what would you think?"
Others cite DMSO's principal side effect: an odd odor, akin to that of garlic,
that emanates from the mouth shortly after use, even if use is through the skin.
Certainly, this odor has made double-blinded studies difficult. Such studies are
based on the premise that no one, neither doctor nor patient, knows which
patient receives the drug and which the placebo, but this drug announces its
presence within minutes.
Others, such as Terry Bristol, a Ph.D. candidate from the University of London
and president of the Institute for Science, Engineering and Public Policy in
Portland, Oregon, who assisted Dr. Jacob with his research in the 1960s and
1970s, believe that the smell of DMSO may also have put off the drug companies,
that feared it would be hard to market. Worse, however, for the pharmaceutical
companies was the fact that no company could acquire an exclusive patent for
DMSO, a major consideration when the clinical testing required to win FDA
approval for a drug routinely runs into millions of dollars. In addition, says
Mr. Bristol, DMSO, with its wide range of attributes, would compete with many
drugs these companies already have on the market or in development.
The FDA and DMSO
In the first flush of enthusiasm over the drug, six pharmaceutical companies
embarked on clinical studies. Then, in November 1965, a woman in Ireland died of
an allergic reaction after taking DMSO and several other drugs. Although the
precise cause of the woman's death was never determined, the press reported it
to be DMSO. Two months later, the FDA closed down clinical trials in the United
States, citing the woman's death and changes in the lenses of certain laboratory
animals that had been given doses of the drug many times higher than would be
given humans.
Some 20 years and hundreds of laboratory and human studies later, no other
deaths have been reported, nor have changes in the eyes of humans been
documented or claimed. Since then, however, the FDA has refused seven
applications to conduct clinical studies, and approved only 1, for intersititial
cystitis, which subsequently was approved for prescriptive use in 1978.
Dr. Jacob believes the FDA "blackballed" DMSO, actively trying to kill interest
in a drug that could end much suffering. Jack de la Torre, MD, Ph.D., professor
of neurosurgery and physiology at the University of New Mexico Medical School in
Albuquerque, a pioneer in the use of DMSO and closed head injury, says, "Years
ago the FDA had a sort of chip on its shoulder because it thought DMSO was some
kind of snake oil medicine. There were people there who were openly biased
against the compound even though they knew very little about it. With the new
administration at that agency, it has changed a bit." The FDA recently granted
permission to conduct clinical trials in Dr. de la Torre's field of closed head
injury.
DMSO Penetrates Membranes and Eases Pain
The first quality that struck Dr. Jacob about the drug was its ability to pass
through membranes, an ability that has been verified by numerous subsequent
researchers.1 DMSO's ability to do this varies proportionally with its
strength--up to a 90 percent solution. From 70 percent to 90 percent has been
found to be the most effective strength across the skin, and, oddly, performance
drops with concentrations higher than 90 percent. Lower concentrations are
sufficient to cross other membranes. Thus, 15 percent DMSO will easily penetrate
the bladder.2
In addition, DMSO can carry other drugs with it across membranes. It is more
successful ferrying some drugs, such as morphine sulfate, penicillin, steroids,
and cortisone, than others, such as insulin. What it will carry depends on the
molecular weight, shape, and electrochemistry of the molecules. This property
would enable DMSO to act as a new drug delivery system that would lower the risk
of infection occurring whenever skin is penetrated.
DMSO perhaps has been used most widely as a topical analgesic, in a 70 percent
DMSO, 30 percent water solution. Laboratory studies suggest that DMSO cuts pain
by blocking peripheral nerve C fibers.3 Several clinical trials have
demonstrated its effectiveness,4,5 although in one trial, no benefit was found.6
Burns, cuts, and sprains have been treated with DMSO. Relief is reported to be
almost immediate, lasting up to 6 hours. A number of sports teams and Olympic
athletes have used DMSO, although some have since moved on to other treatment
modalities. When administration ceases, so do the effects of the drug.
Dr. Jacob said at a hearing of the U.S. Senate Subcommittee on Health in 1980,
"DMSO is one of the few agents in which effectiveness can be demonstrated before
the eyes of the observers....If we have patients appear before the Committee
with edematous sprained ankles, the application of DMSO would be followed by
objective diminution of swelling within an hour. No other therapeutic modality
will do this."
Chronic pain patients often have to apply the substance for 6 weeks before a
change occurs, but many report relief to a degree they had not been able to
obtain from any other source.
DMSO and Inflammation
DMSO reduces inflammation by several mechanisms. It is an antioxidant, a
scavenger of the free radicals that gather at the site of injury. This
capability has been observed in experiments with laboratory animals7 and in 150
ulcerative colitis patients in a double-blinded randomized study in Baghdad,
Iraq.8 DMSO also stabilizes membranes and slows or stops leakage from injured
cells.
At the Cleveland Clinic Foundation in Cleveland, Ohio, in 1978, 213 patients
with inflammatory genitourinary disorders were studied. Researchers concluded
that DMSO brought significant relief to the majority of patients. They
recommended the drug for all inflammatory conditions not caused by infection or
tumor in which symptoms were severe or patients failed to respond to
conventional therapy.9
Stephen Edelson, MD, F.A.A.F.P., F.A.A.E.M., who practices medicine at the
Environmental and Preventive Health Center of Atlanta, has used DMSO extensively
for 4 years. "We use it intravenously as well as locally," he says. "We use it
for all sorts of inflammatory conditions, from people with rheumatoid arthritis
to people with chronic low back inflammatory-type symptoms, silicon immune
toxicity syndromes, any kind of autoimmune process.
"DMSO is not a cure," he continues. "It is a symptomatic approach used while you
try to figure out why the individual has the process going on. When patients
come in with rheumatoid arthritis, we put them on IV DMSO, maybe three times a
week, while we are evaluating the causes of the disease, and it is amazing how
free they get. It really is a dramatic treatment."
As for side effects, Dr. Edelson says: "Occasionally, a patient will develop a
headache from it, when used intravenously--and it is dose related." He
continues: "If you give a large dose, [the patient] will get a headache. And we
use large doses. I have used as much as 30ÝmlÝIV over a couple of hours. The
odor is a problem. Some men have to move out of the room [shared] with their
wives and into separate bedrooms. That is basically the only problem."
DMSO was the first nonsteroidal anti-inflammatory discovered since aspirin. Mr.
Bristol believes that it was that discovery that spurred pharmaceutical
companies on to the development on other varieties of nonsteroidal
anti-inflammatories. "Pharmaceutical companies were saying that if DMSO can do
this, so can other compounds," says Mr. Bristol. "The shame is that DMSO is less
toxic and has less int he way of side effects than any of them."
Collagen and Scleroderma
Scleroderma is a rare, disabling, and sometimes fatal disease, resulting form an
abnormal buildup of collagen in the body. The body swells, the
skin--particularly on hands and face--becomes dense and leathery, and calcium
deposits in joints cause difficulty of movement. Fatigue and difficulty in
breathing may ensue. Amputation of affected digits may be necessary. The cause
of scleroderma is unknown, and, until DMSO arrived, there was no known effective
treatment.
Arthur Scherbel, MD, of the department of rheumatic diseases and pathology at
the Cleveland Clinic Foundation, conducted a study using DMSO with 42
scleroderma patients who had already exhausted all other possible therapies
without relief. Dr. Scherbel and his coworkers concluded 26 of the 42 showed
good or excellent improvement. Histotoxic changes were observed together with
healing of ischemic ulcers on fingertips, relief from pain and stiffness, and an
increase in strength. The investigators noted, "It should be emphasized that
these have never been observed with any other mode of therapy."10 Researchers in
other studies have since come to similar conclusions.11
Does DMSO Help Arthritis?
It was inevitable that DMSO, with its pain-relieving, collagen-softening, and
anti-inflammatory characteristics, would be employed against arthritis, and its
use has been linked to arthritis as much as to any condition. Yet the FDA has
never given approval for this indication and has, in fact, turned down three
Investigational New Drug (IND) applications to conduct extensive clinical
trials.
Moreover, its use for arthritis remains controversial. Robert Bennett, MD,
F.R.C.P., F.A.C.R., F.A.C.P., professor of medicine and chief, division of
arthritis and rheumatic disease at Oregon Health Sciences University (Dr.
Jacob's university), says other drugs work better. Dava Sobel and Arthur Klein
conducted their own informal study of 47 arthritis patients using DMSO in
preparation for writing their book, Arthritis: What Works, and came to the same
conclusion.12
Yet laboratory studies have indicated that DMSO's capacity as a free-radical
scavenger suggests an important role for it in arthritis.13 The Committee of
Clinical Drug Trials of the Japanese Rheumatism Association conducted a trial
with 318 patients at several clinics using 90 percent DMSO and concluded that
DMSO relieved joint pain and increased range of joint motion and grip strength,
although performing better in more recent cases of the disease.14 It is employed
widely in the former Soviet Union for all the different types of arthritis, as
it is in other countries around the world.
Dr. Jacob remains convinced that it can play a significant role in the treatment
of arthritis. "You talk to veterinarians associated with any race track, and
you'll find there's hardly an animal there that hasn't been treated with DMSO.
No veterinarian is going to give his patient something that does not work.
There's no placebo effect on a horse."
DMSO and Central Nervous System Trauma
Since 1971, Dr. de la Torre, then at the University of Chicago, has experimented
using DMSO with injury to the central nervous system. Working with laboratory
animals, he discovered that DMSO lowered intracranial pressure faster and more
effectively than any other drug. DMSO also stabilized blood pressure, improved
respiration, and increased urine output by five times and increased blood flow
through the spinal cord to areas of injury.15-17 Since then, DMSO has been
employed with human patients suffering severe head trauma, initially those whose
intracranial pressure remained high despite the administration of mannitol,
steroids, and barbiturates. In humans, as well as animals, it has proven the
first drug to significantly lower intracranial pressure, the number one problem
with severe head trauma.
"We believe that DMSO may be a very good product for stroke," says Dr. de la
Torre, "and that is a devastating illness which affects many more people than
head injury. We have done some preliminary clinical trials, and there's a lot of
animal data showing that it is a very good agent in dissolving clots."
Other Possible Applications for DMSO
Many other uses for DMSO have been hypothesized from its known qualities hand
have been tested in the laboratory or in small clinical trials. Mr. Bristol
speaks with frustration about important findings that have never been followed
up on because of the difficulty in finding funding and because "to have on your
resume these days that you've worked on DMSO is the kiss of death." It is simply
too controversial. A sampling of some other possible applications for this drug
follows.
DMSO as long been used to promote healing. People who have it on hand often use
it for minor cuts and burns and report that recovery is speedy. Several studies
have documented DMSO use with soft tissue damage, local tissue death, skin
ulcers, and burns.18-21
In relation to cancer, several properties of DMSO have gained attention. In one
study with rats, DMSO was found to delay the spread of one cancer and prolong
survival rates with another.22 In other studies, it has been found to protect
noncancer cells while potentiating the chemotherapeutic agent.
Much has been written recently about the worldwide crisis in antibiotic
resistance among bacteria (see Alternative & Complementary Therapies, Volume 2,
Number 3, 1996, pages 140-144) Here, too, DMSO may be able to play a role.
Researcher as early as 1975 discovered that it could break down the resistance
certain bacteria have developed.23
In addition to its ability to lower intracranial pressure following closed head
injury, Dr. de la Torre's work suggests that the drug may actually have the
ability to prevent paralysis, given its ability to speedily clean out cellular
debris and stop the inflammation that prevents blood from reaching muscle,
leading to the death of muscle tissue.
With its great antioxidant powers, DMSO could be used to mitigate some of the
effects of aging, but little work has been done to investigate this possibility.
Toxic shock, radiation sickness, and septicemia have all been postulated as
responsive to DMSO, as have other conditions too numerous to mention here.
DMSO in the Future
Will DMSO ever sit on the shelves of pharmacies in this country as a legal
prescriptive for many of the conditions it may be able to address? Will the
studies we need to discover when this drug is most appropriate ever be done?
Given the difficulties the drug has run into so far and the recent development
of new drugs that perform some of the same functions, Mr. Bristol is doubtful.
Others, however, such as Dr. Jacob and Dr. de la Torre, see the FDA approval of
DMSO for interstitial cystitis and the more recent FDA go-ahead for DMSO trials
with closed head injury as new indications of hope. The cystitis approval means
that physicians may use it at their discretion for other uses, giving DMSO a new
legitimacy.
Dr. Jacob continues to believe that DMSO should not even be called a drug but is
more correctly a new therapeutic principle, with an effect on medicine that will
be profound in many areas. Whether that is true cannot be known without
extensive a publicly reported trials, which are dependent on the willingness of
researchers to undertake rigorous studies in this still-unfashionable tack and
of pharmaceutical companies and other investors to back them up. That this is a
live issue is proved by the difficulty the investigators with approval to test
DMSO for closed head injury clinically are having finding funds to conduct the
trials.
In 1980, testifying before the Select Committee on Agin of the U.S. House of
Representatives, Dr. Scherbel said, "The controversy that exists over the
clinical effectiveness of DMSO is not well-founded--clinical effectiveness may
be variable in different patients. If toxicity is consistently minimal, the drug
should not be restricted from practice. The clinical effectiveness of DMSO can
be decided with complete satisfaction if the drug is made available to the
practicing physician. The number of patient complaints about pain and the number
of phone calls to the doctor's office will decide quickly whether or not the
drug is effective."
It may be premature to call for the full rehabilitation of DMSO, but it is time
to call for a full investigation of its true range of capabilities.
References
Kolb, K.H., Jaenicke, G., Kramer, M., Schulze, P.E. Absorption, distribution,
and elimination of labeled dimethyl sulfoxide in man and animals. Ann NY Acad
Sci 141:85-95, 1967.
Herschler, R., Jacob, S.W. The case of dimethyl sulfoxide. In: Lasagna, L.
(Ed.), Controversies in Therapeutics. Philadelphia: W.B. Saunders, 1980.
Evans, M.S., Reid, K.H., Sharp, J.B. Dimethyl sulfoxide (DMSO) blocks conduction
in peripheral nerve C fibers: A possible mechanism of analgesia. Neurosci Lett
150:145-148, 1993.
Demos, C.H., Beckloff, G.L., Donin, M.N., Oliver, P.M. Dimethyl sulfoxide in
musculoskeletal disorders. Ann NY Acad Sci 141:517-523, 1967.
Lockie, L.M., Norcross, B. A clinical study on the effects of dimethyl sulfoxide
in 103 patients with acute and chronic musculoskeletal injures and inflammation.
Ann NY Acad Sci 141:599-602, 1967.
Percy, E.C., Carson, J.D. The use of DMSO in tennis elbow and rotator cuff
tendinitis: A double-blind study. Med Sci Sports Exercise 13:215-219, 1981.
Itoh, M., Guth, P. Role of oxygen-derived free radicals in hemorrhagic
shock-induced gastric lesions in the rat. Gastroenterology 88:1126-1167, 1985.
Salim, A.S., Role of oxygen-derived free radical scavengers in the management of
recurrent attacks of ulcerative colitis: A new approach. J. Lab Clin Med
119:740-747, 1992.
Shirley, S.W., Stewart, B.H., Mirelman, S. Dimethyl sulfoxide in treatment of
inflammatory genitourinary disorders. Urology 11:215-220, 1978.
Scherbel, A.L., McCormack, L.J., Layle, J.K. Further observations on the effect
of dimethyl sulfoxide in patients with generalized scleroderma (progressive
systemic sclerosis). Ann NY Acad Sci 141:613-629, 1967.
Engel, M.F., Dimethyl sulfoxide in the treatment of scleroderma. South Med J
65:71, 1972.
Sobel, D., Klein, A.C. Arthritis: What Works. New York: St. Martins Press, 1989.
Santos, L., Tipping, P.G. Attenuation of adjuvant arthritis in rats by treatment
with oxygen radical scavengers. Immunol Cell Biol 72:406-414, 1994.
Matsumoto, J. Clinical trials of dimethyl sulfoxide in rheumatoid arthritis
patients in Japan. Ann NY Acad Sci 141:560-568, 1967.
de la Torre, J.C., et al. Modifications of experimental spinal cord injuries
using dimethyl sulfoxide. Trans Am Neurol Assoc 97:230, 1971.
de la Torre, J.C., et al. Dimethyl sulfoxide in the treatment of experimental
brain compression. J Neurosurg 38:343, 1972.
de la Torre, J.C., et al. Dimethyl sulfoxide in the central nervous system
trauma. Ann NY Acad Sci 243:362, 1975.
Lawrence, H.H., Goodnight, S.H. Dimethyl sulfoxide and extravasion of
anthracycline agents. Ann Inter Med 98:1025, 1983.
Lubredo, L., Barrie, M.S., Woltering, E.A. DMSO protects against
adriamycin-induced skin necrosis. J. Surg Res 53:62-65, 1992.
Alberts, D.S., Dorr, R.T. Case report: Topical DMSO for mitomycin-C-induced skin
ulceration. Oncol Nurs Forum 18:693-695, 1991.
Cruse, C.W., Daniels, S. Minor burns: Treatment using a new drug deliver system
with silver sulfadiazine. South Med J 82:1135-1137, 1989.
Miller, L., Hansbrough, J., Slater, H., et al. Sildimac: A new deliver system
for silver sulfadiazine in the treatment of full-thickness burn injuries. J Burn
Care Rehab 11:35-41, 1990
Salim, A. Removing oxygen-derived free radicals delays hepatic metastases and
prolongs survival in colonic cancer. Oncology 49:58-62, 1992.
Feldman, W.E., Punch, J.D., Holden, P. In vivo and in vitro effects of dimethyl
sulfoxide on streptomycin-sensitive and resistant Escherichia coli. Ann Acad Sci
141:231, 1967.
Source: Alternative & Complementary Therapies, July/August 1996, pages 230-235.
DMSO Organization would like to thank the publisher for permission to place this
fine article on the World Wide Web. The Publisher retains all copyright. To
order reprints of this article, write to or call: Karen Ballen, Alternative &
Complementary Therapies, Mary Ann Liebert, Inc., 2 Madison Avenue, Larchmont, NY
10538, (914) 834-3100.
--------------------------------------------------------------------------------
Submit comments and questions to Dr. Jacob at [email protected]
© 2001 DMSO Organization All rights reserved
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