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Wintergreen plants are the source for oil of Wintergreen, which contains methyl salicylate (C₈H₈O₃), an extremely versatile substance with beneficial, commercial, and toxicologic properties that humans have been using for more than 100 years.

Methyl salicylate (MS) is a natural organic ester that can be extracted from select plants including Gaultheria procumbens L. (American wintergreen, teaberry). This is a low-growing evergreen native to North America recognized by its shiny, oval, dark green leaves. It has a strong, minty smell when crushed. The plant has white berries that turn bright red as they mature and reportedly have a tart taste.

Other natural sources of MS are Gaultheria fragrantissima (fragrant wintergreen found in Asia) and Betula lenta L. (Sweet birch, Black birch) .¹The molecule is thought to be used by plants to signal to others that herbivorous insects are present ². More commonly, MS is chemically synthesized for larger-volume home or commercial use.

Properties

Methyl salicylate is a natural organic ester that can be extracted from select plants, such as the Gaultheria procumbens L.

Its most notable attribute is a remarkable smell. Wintergreen has a distinct aroma that has been described as “refreshingly minty” with notes of sweet and spicy and also has  been described as “a fresh, cool breeze.” Because of this, it is used to enrich food flavors and to add attractive scents for confections, candies, chewing gum, cosmetics (e.g., toothpaste and mouthwash), and perfumes.

Wintergreen’s MS content is structurally related to aspirin. Traditionally, the leaves and bark have been used to make teas or infusions to treat rheumatism, fever, and gastrointestinal illnesses because of their carminative properties (relieves flatulence); and topically for burns, wounds, and bruises.³ Commercially, and in the modern apothecary, it is used for its anti-inflammatory, antiseptic, and scent properties to treat joint, ligament, and soft tissue pain.

Absorption and Mechanism of Action

Ten to 20 percent of MS is absorbed through the skin after application. The degree of absorption depends where on the body it is applied, the skin’s thickness, and its vascular engorgement.²

MS helps with musculoskeletal discomforts with its analgesic, anti-inflammatory, and rubefacient/counter-irritant properties. When topically applied, MS:

1. produces a local vasodilatory action which increases dermal blood flow, a local rise in temperature, and a sense of warmth;
2. creates a local irritation that stimulates dermal sensory fibers that are contiguous with deeper sensory fibers which serves to diminish (confuse) stimulation coming from muscle or joint aches and pains; and
3. after dermal absorption undergoes rapid hydrolysis to salicylic acid, which has a degree of local cyclooxygenase enzyme inhibition that decreases inflammation-generated pain by prostaglandin and thromboxane A2.²

Toxicologic Significance

Ingestion of pure oil of Wintergreen, such as in aromatherapy products, has caused poisoning and death in children due to its high concentration of MS — up to 98 percent in some products.⁴ Almost all swallowed Wintergreen oil is quickly absorbed through the GI tract.

Ingestion of one teaspoon (one toddler mouthful, 5 mL) contains approximately 7 g of salicylate, which is equivalent to approximately 22 325-mg aspirin tablets⁵.

Although food and many consumer products have MS concentrations of <1 percent, some liniments and joint pain creams may be 5 to 20 percent.² Products with >5 percent must be labeled in containers stating, “Keep away from children.”

Approximately 10-20 percent of MS is absorbed through the skin within 10 hours of topical application. The kinetics and degree of absorption are affected not only by the thickness of the skin, but by the presence of other ingredients.⁶ Interestingly, when mixed with menthol or camphor, the conversion of MS to salicylic acid through esterase activity is significantly inhibited.⁷

There are many reports of MS products causing salicylism, injury, and even death.^8-14

Treatment

Treatment is similar to managing aspirin overdoses: Decontaminate the skin of any topically applied creams with wiping and washing, GI decontamination in appropriate circumstances, and salicylate level monitoring. Pay attention to acid base, fluid, glucose, and electrolytes abnormalities. Promote enhanced elimination with urinary alkalinization or hemodialysis, as needed. A case report has described exchange transfusion as a treatment in one episode of overdose.¹⁰

Dr. Hack is chief of the division of medical toxicology and vice chair for research at East Carolina University in Greenville, North Carolina.

References

1. The National Formulary, 18th ed.; United States Pharmacopeial Convention: Rockville, MD, USA, 1994; pp. 2266–2267
2. Anderson A, McConville A, Fanthorpe L, Davis J. Salicylate Poisoning Potential of Topical Pain Relief Agents: From Age Old Remedies to Engineered Smart Patches. Medicines (Basel). 2017; Jun 30;4(3):48. doi: 10.3390/medicines4030048. PMID: 28930263; PMCID: PMC5622383.
3. Angier, Bradford. “Field Guide to Medicinal Plants.” Stackpole BooksMechanicsburg, Pa.,1978; pp. 56-60.
4. Chyka PA, Erdman AR, Christianson G, et al. Salicylate poisoning: An evidence-based consensus guideline for out-of-hospital management, Clin Toxicol 2007; 45:2, 95-131.
5. Wolowich WR, Hadley CM, Kelley MT, et al. Plasma salicylate from methyl salicylate cream compared to oil of wintergreen. J Toxicol Clin Toxicol 2003;41:355-358.
6. Morra P,Bartle WR, Walker SE, et al. Serum concentrations of salicylic acid following topically applied salicylate derivatives. Ann Pharmacother 1996;(30): 935-940.
7. Yano T, Kanetake T, Saita M, Noda K. Effect of l-menthol and dl-camphor on the penetration and hydrolysis of methyl salicylate in hairless mouse skin. Pharmacobiodyn 1991;14: 663-669.
8. Cann HM, Verhulst HL. The salicylate problem with special reference to methyl salicylate. J Pediatr 1958; 53:271-276.
9. Diamond EF, DeYoung VR. Acute poisoning with oil of wintergreen treated by exchange transfusion. AMA J Dis Child 1958; (95)3:309-310.
10. Done AK, Otterness LJ. Exchange transfusion in the treatment of oil of wintergreen (methyl salicylate) poisoning. Pediatrics 1956; 18(1):80-85.
11. Howrie DL, Moriarty R, Breit R. Candy flavoring as a source of salicylate poisoning. Pediatrics 1985; 75(5):869-871.
12. Lester H, Davis K. Oil of wintergreen. Vet Hum Toxicol 1984; 26:308.
13. Malik AS, Zabidi MH, Noor AR. Acute salicylism due to accidental ingestion of a traditional medicine. Singapore Med J 1994; 35:215-216.
14. Stevenson CS. Oil of wintergreen (methyl salicylate) poisoning. Report of three cases, one with autopsy, and a review of the literature. Am J Med Sci 1937; 193:772-788.

*Images of Gaultheria procumbens are from Smithsonian public domain (free of copyright restrictions).