Formaldehyde, Aspartame, and Migraines: A Possible Connection

Sharon E. Jacob; Sarah Stechschulte


Dermatitis. 2008;19(3):E10-E11. 

In This Article


Aspartame is a widely used artificial sweetener that has been linked to a multitude of ailments, particularly pediatric and adolescent migraines[1] ( Table 1 and Table 2 ).[2,3,4] Studies suggest that aspartame is a significant migraine trigger, especially when consumption is prolonged.[1] Upon ingestion, aspartame is broken down into aspartic acid, aspartic acid methyl ester, and phenylalanine in the gut wall.[5] The methyl ester is subsequently converted into methanol, which is oxidized to formaldehyde and formic acid in various tissues.[6] Formaldehyde is known to form chemical adducts with nucleic acids and proteins. These adducts have been found to be difficult to remove by normal metabolic pathways; hence, accumulation may occur.[6]

To our knowledge, aspartame-associated migraines related to clinically relevant positive reactions to formaldehyde on patch testing have not previously been reported. In 2003, Hill and Belsito reported a case of a nonmigraine patient with chronic eyelid dermatitis that cleared when aspartame was discontinued. This case presented the possibility that formaldehyde from aspartame breakdown could trigger a systemic contact dermatitis in formaldehyde-sensitive patients.[7] Like Hill and Belsito's patient, our sixth patient (the only patient who did not have migraines) demonstrated a flare of his dermatitis with consumption of aspartame and clearance with avoidance of aspartame. Our five migraine cases suggest that aspartame-induced migraines may be a harbinger for formaldehyde sensitivity and an important historical point to be elucidated during the initial work-up of a patient with presumed allergic contact dermatitis.

Although we recognize the limitations of drawing conclusions from a small sample of patients, we believe this observed association warrants further investigation. A larger case study with a double-blind placebo-controlled challenge study with aspartame capsules and placebo capsules (including nondermatitic control patients with aspartame-induced migraines) is needed to firmly establish the association between aspartame breakdown products, migraines, systemic contact dermatitis, and positive patch-test reactions to formaldehyde and FRPs.

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