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.
- 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.
| Description |
Item
# |
Price |
| DMSO
(Dimethyl Sulfoxide) solvent 8 fl. oz. |
DMSO |
$15.00
 |
| DMSO
(Dimethyl Sulfoxide) solvent (1 gal.) |
DMSOG |
$75.00
|
