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JAN 29, 2015
ANALYZING SPORTS CREAMS




By Stan Reents

Stan Reents, PharmD, is a former healthcare professional. He holds Personal
Trainer and Lifestyle Counselor certifications from the American Council on
Exercise and has been certified as a tennis coach by the United States Tennis
Association. He is the author of Sport and Exercise Pharmacology, published by
Human Kinetics. A collection of Reents’s articles is available at
www.AthleteInMe.com and he can be reached at: Editor@athleteinme.com.

On April 3, 2007, Arielle Newman, a 17-year-old track and cross-country standout
for Notre Dame Academy on Staten Island, NY, died in her sleep.

Following a two-month investigation by the New York City medical examiner, a
spokeswoman for that office stated that Newman died of salicylate toxicity. It
was determined that, for relief from the typical aches and pains that result
from a grueling training regimen, she applied large amounts of sports creams to
her legs. She died from an accidental overdose of methyl salicylate, the
wintergreen-scented ingredient found in topical products like BenGay, Icy Hot,
and Tiger Balm because her body absorbed a toxic amount.

How could this happen? After all, Newman was a healthy high school athlete.

“Newman put the muscle cream on her legs and used adhesive pads containing the
anti-inflammatory, plus an unspecified third product,” said Ellen Borakove, a
spokeswoman for the medical examiner. “There were multiple products, used to
great excess, and that’s how she ended up with high levels,” Borakove said. “The
products were used and the chemical absorbed over time, rather than from a
single instance of overuse.”

Although no clear documentation exists on deaths resulting from the application
of sports creams, experts say they have never heard of one other than this.
Newman’s death was the first of its kind in the city, authorities said. Doctors
and athletic trainers alike are perplexed by Newman’s death. “This is an
extremely rare and unusual case,” says Eric Coris, MD, assistant professor in
the University of South Florida’s Department of Medicine in the division of
sports medicine. “I’ve never heard of another situation like this before.”

Robert Sallis, MD, president of the American College of Sports Medicine, says he
has never seen an overdose of methyl salicylate by topical application in his 20
years of practice. He believes Newman could have boosted the chemical’s
absorption by increasing the skin’s blood flow with intense exercise, or by
wrapping her skin after heavily applying the ointment.

But even with those methods, Sallis questions how Newman could have overdosed by
simply applying it topically. “I can’t imagine she was using large enough doses
[of the sports cream] to go across her skin to be fatal,” Sallis says. “And even
if she did, she would have experienced very specific symptoms that she would
have noticed long before it was potentially lethal.”

Coris believes there could be more to the story of Newman’s death that has not
been discovered, including possible dehydration. Until we know more, he says,
her death should be a warning to coaches, athletes, and parents.

WHAT IS “METHYL SALICYLATE”?

The ingredient in the sports creams responsible for Newman’s death is methyl
salicylate. The common name for methyl salicylate is oil of wintergreen.

Methyl salicylate is a chemical cousin of aspirin. Thus, both drugs belong to a
category of anti-inflammatory analgesics known as “salicylates.” However, it is
very dangerous to administer methyl salicylate orally, because it is more toxic
than aspirin. Yet, as the case of Arielle Newman proves, if enough methyl
salicylate is absorbed through the skin, toxicity is possible.

Topical application of methyl salicylate can be hazardous if: * it is smeared
over more than 40 percent of the body * the user has a skin condition, cut, or
abrasion * an occlusive dressing or heating pad is applied over the area to
which methyl salicylate was applied * it is applied when the body temperature is
elevated and the skin is flushed * the user is also using another
medication–such as the blood thinner warfarin (Joss, J.D., et al., 2000)–that
interacts with the product

Methyl salicylate has the ability to penetrate the skin even without the aid of
an ointment base or vehicle (Danon A., et al., 1986). Heat and exercise can each
increase the amount that is absorbed into the bloodstream.

The cutaneous absorption of methyl salicylate ointment was studied in six
healthy males (average age: 25 years) under four different scenarios: * at rest
at 72 degrees F (22 degrees C) * at rest at 104 degrees F (40 degrees C) * while
riding an exercise bike at 72 degrees F * while riding an exercise bike at 104
degrees F

It was found that a hot environment and exercise can each (independently)
increase the absorption of methyl salicylate through the skin. However, during
the phase when the subjects exercised in a hot environment, the absorption
increased threefold compared to when at rest in a 72-degree room (Danon, A., et
al., 1986). Exercise, in this study, consisted of cycling at 30 percent of
VO2max, which is considered “light” exercise.

It appears that several of these risk factors contributed to excessive skin
absorption of methyl salicylate in the case of Arielle Newman: * the “dose” was
excessive (she was using multiple products simultaneously) * it’s possible she
applied the creams/skin products after exercising, or after showering, when the
skin was flushed, allowing for increased absorption * she used the products
daily, which leads to a cumulative effect

Remember, salicylate toxicity from topical application of methyl salicylate can
be just as serious as an overdose of aspirin tablets. The warning signs of
salicylate toxicity include a ringing in the ears, upset stomach, agitation,
rapid breathing, irregular heartbeat, dizziness, nausea, and convulsions. If
left untreated, this can result in heart failure, respiratory arrest, and death.

OTHER REPORTS OF TOXICITY FROM METHYL SALICYLATE CREAM

Not every healthcare professional is familiar with how readily methyl salicylate
can be absorbed into the bloodstream after topical application. However,
overdoses of oil of wintergreen are well known by poison control centers,
pharmacists, and most physicians for being highly toxic.

So, I visited the medical library in search of other reports of toxicity after
topical application of methyl salicylate. Summarized below are four cases I
found. (NOTE: I am not including cases involving topical application of
“salicylic acid.” Even though salicylic acid and methyl salicylate are related,
salicylic acid is much more corrosive to human skin and is not used in sports
creams.)

The following cases describe salicylate toxicity occurring after the topical
administration of methyl salicylate:

• Salicylate level of 68 mg/dl in a teenager: A teenager developed salicylate
toxicity after using Ben Gay while masturbating (Thompson, T.M., et al., 2006).

• Salicylate level of 52 mg/dl in a 62-year-old man: A 62-year-old man developed
tinnitus, blurred vision, and shortness of breath after using a methyl
salicylate ointment on his thigh twice daily for several weeks. Blood work
revealed a disruption of acid/base balance. He denied any use of aspirin or
other salicylate-containing medications (Morra, P., et al., 1996).

• Salicylate level of 48 mg/dl in a 40-year-old man: In Australia, a 40-year-old
man developed salicylate toxicity after an unknown yellow cream was applied by a
Chinese herbalist. In this case, the cream was applied over the entire body
followed by a body wrap of plastic cling film. The patient stated that symptoms
began within one hour and did not improve despite removing the plastic and
showering three times over the course of the afternoon (Bell, A.J., et al.,
2002).

• Salicylate level of 41 mg/dl in a three-month-old infant: A three-month-old
developed salicylate toxicity after his mother applied White Monkey Holding
Peach Balm topically. The label stated that it contained three percent methyl
salicylate, but after analysis, it was determined the concentration was actually
five percent (Smollin, C., et al., 2006).

All four of these subjects received medical treatment and survived.

NOT ALL SPORTS CREAMS ARE THE SAME

It’s important to realize that sports creams are different from one another.
Some contain methyl salicylate, while others do not.

However, it’s easy to get confused because some manufacturers produce different
formulations using the same product name. For example, Ben Gay “Ultra Strength”
contains a whopping 30 percent methyl salicylate, whereas Ben Gay “Greaseless”
contains a more moderate 15 percent, while Ben Gay “Vanishing Scent” contains
none at all. Flexall and Icy Hot products are also marketed with a variety of
concentrations of methyl salicylate. The Web site for Tiger Balm lists at least
10 different formulations under the same brand name but does not provide the
ingredients.

Even more confusing is Aspercreme. The name seems to imply that the active
ingredient is aspirin, however aspirin is never applied directly to the skin.

The active ingredients in sports creams can be grouped into two general
categories: * Salicylates: methyl salicylate, trolamine salicylate *
Counterirritants: camphor, menthol

In addition, capsaicin has also been incorporated into some sports creams, such
as Tiger Balm. This chemical is derived from peppers and is not a salicylate.

Specific products and their active ingredients are listed below:

SOME METHYL SALICYLATE * Ben Gay “Greaseless” (methyl salicylate 15%, menthol
10%) * Ben Gay “Ultra Strength” (methyl salicylate 30%, menthol 10%, camphor 4%)
* Flexall “Ultra Plus” (methyl salicylate 10%, menthol 16%, camphor 3.1%) * Icy
Hot “Balm” (methyl salicylate 29%, Menthol 7.6%) * Icy Hot “Cream” (methyl
salicylate 30%, menthol 10%) * Icy Hot “Stick” (methyl salicylate 30%, menthol
10%) * Thera-Gesic “Maximum Strength” (methyl salicylate 15%, menthol 1%)

NO METHYL SALICYLATE: * Aspercreme (trolamine salicylate 10%) * Ben Gay
“Vanishing Scent” (menthol 2.5%) * Biofreeze (menthol 3.5%, camphor 0.2%) *
Flexall 454 (menthol 7%) * Flexall Maximum Strength (menthol 16%) * Icy Hot
Patch (menthol 5%) * Icy Hot Sleeve (menthol 16%) * Myoflex (trolamine
salicylate 10%) * SportsCreme (trolamine salicylate 10%)

READ THE LABEL

Experts say the death of Newman points to a need for clearer warnings about
toxicity risks, especially because sports creams have become a staple in locker
rooms around the country. “There has to be a heightened awareness that these
products are something that needs to be used under medical supervision,” says
Dr. Gerard Varlotta, Director of Sports Rehabilitation at the Rusk Institute of
Rehabilitation Medicine at New York University Medical Center.

The labels on both Ben Gay and Icy Hot say to stop using them if “condition
worsens or symptoms persist for more than seven days.” But a big problem is that
people don’t read warning labels on over-the-counter drugs, says Rebecca
Burkholder, Vice President for Health Policy at the National Consumers League.

Kimberley Rawlings, a spokeswoman for the FDA, says the agency is aware of
Newman’s death and is looking into it. She would not say whether the labeling
requirements for methyl salicylate products might be changed.

SUMMARY AND RECOMMENDATIONS

“The take-home message is for people to realize that just because it’s over the
counter, just because it’s a supplement, does not mean it’s totally safe and
they don’t have to be careful with its use,” says Coris. “We see this all the
time with athletes using oral supplements. They get into trouble because they
think if they can buy it at the local vitamin store they can take as much as
they want.”

“People are thinking it’s harmless if it’s on the shelf at their local
drugstore,” agrees Burkholder. “And they’re going to take as much as they need
to make the pain go away.”

Anyone using sports creams that contain methyl salicylate should keep the
following in mind: Don’t overuse it. This means: * don’t use it on more than 40
percent of your body’s surface * don’t apply it heavily * don’t use it more
frequently than suggested on the label * don’t use it for more than five days in
a row

Remember that several things can increase the absorption of methyl salicylate
through the skin: * exercise * using a heating pad or occlusive covering on the
same area where the sports cream was applied * using it for five or more days in
a row

REFERENCES

Algozzine GJ, Stein GH, Doering PL, et al. Trolamine salicylate cream in
osteoarthritis of the knee. JAMA 1982;247:1311-1313.

Bell AJ, Duggin G. Acute methyl salicylate toxicity complicating herbal skin
treatment for psoriasis. Emerg Med (Fremantle) 2002;14:188-190.

Brubacher JR, Hoffman RS. Salicylism from topical salicylates: review of the
literature. J Toxicol Clin Toxicol 1996;34:431-436.

Chan TY. Potential dangers from topical preparations containing methyl
salicylate. Hum Exp Toxicol 1996;15:747-750.

Cross SE, Anderson C, Roberts MS. Topical penetration of commercial salicylate
esters and salts using human isolated skin and clinical microdialysis studies.
Br J Clin Pharmacol 1998;46:29-35.

Danon A, Ben-Shimon S, Ben-Zvi Z. Effect of exercise and heat exposure on
percutaneous absorption of methyl salicylate. Eur J Clin Pharmacol
1986;31:49-52.

Joss JD, LeBlond RF. Potentiation of warfarin anticoagulation associated with
topical methyl salicylate. Ann Pharmacother 2000;34:729-733.

Morra P, Bartle WR, Walker SE, et al. Serum concentrations of salicylic acid
following topically applied salicylate derivatives. Ann Pharmacother
1996;30:935-940.

Roberts MS, Favretto WA, Meyer A, et al. Topical bioavailability of methyl
salicylate. Aust N Z J Med 1982;12:303-305.

Smollin C, Wiegand T, Meier K, et al. Infant salicylism after cutaneous
application of 5% methylsalicylate. Clinical Toxicology, 2006;44:625-783, #296.

Thompson TM, Lehrmann JF, Almeida E, et al. Salicylate toxicity caused by
genital exposure of a methylsalicylate-containing rubefacient. Clinical
Toxicology, 2006;44:625-783, #191.







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