Formaldehyde, Aspartame, and Migraines: A Possible Connection

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Formaldehyde, Aspartame, and Migraines: A Possible Connection

Sharon E. ; Stechschulte Dermatitis. 2008;19(3):E10-E11. ©2008 American Contact Dermatitis Society

Posted 09/17/2008

Abstract and Case Series

Abstract

Aspartame is a widely used artificial sweetener that has been linked to pediatric and adolescent migraines. Upon ingestion, aspartame is broken, converted, and oxidized into formaldehyde in various tissues. We present the first case series of aspartame-associated migraines related to clinically relevant positive reactions to formaldehyde on patch testing.

Case Series

Six patients (ages 16 to 75 years) were referred for evaluation of recalcitrant dermatitis. By history, five of the patients were noted to have developed migraines following aspartame consumption; the sixth reported dermatitis flares associated with diet cola consumption of ≥ 2 liters/day. All six patients had current environmental exposures to formaldehyde or formaldehyde-releasing preservatives in their personal hygiene products and/or regular consumption of "sugar-free food" artificially sweetened with aspartame. Based on their histories and clinical presentations, these patients were patch-tested with the North American Contact Dermatitis Group 65-allergen Standard Screening Series and selected chemicals from the University of Miami vehicle, fragrance, bakery, and textile trays.

All six patients had positive reactions to formaldehyde, and four had additional positive reactions to formaldehyde-releasing preservatives (FRPs). Expert counseling on allergen avoidance (including avoidance of formaldehyde, FRPs, and aspartame) and alternative product recommendations were provided to the patients.

At their follow-up appointments (between 8 and 12 weeks), all the patients showed clearance of their dermatitis. Four patients (two inadvertently) resumed their consumption of aspartame and subsequently returned for an additional follow-up visit. Three of the first five patients had recurrences of both their migraines and their dermatitis; the sixth patient (who had no migraines) had a positive rechallenge dermatitis. These four patients were again counseled on avoidance regimen.

Discussion

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 ).[2-4] 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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Table 1. Aspartame in Foods and Drinks

Food or Drink

Average Amount of Aspartame per Unit

Carbonated soft drink

180 mg/12 oz can (354 mL)

Yogurt

124 mg/8 oz (237 mL)

Powdered soft drink

120 mg/12 oz (354 mL)

Gelatin

95 mg/4 oz (118 mL)

Fruit drink (10% juice)

70 mg/6 oz (177 mL)

Ice cream

50 mg/4 oz (118 mL)

Hot chocolate

50 mg/6 oz (177 mL)

Chewing gum

6–8 mg per stick

Chewable children's vitamins (Flintstones Vitamins, Bayer, town, NJ)

4 mg per vitamin

Breath mints

1.5 mg per mint

Table 2. Artificial Sweetener Brand Names

Artificial Sweetener

Brand Names

Aspartame

Equal, NutraSweet

Sucralose

Splenda

Saccharin

Sweet 'N Low, Sweet Twin, Necta Sweet, Hermesetas

Acesulfame potassium

AceK, Sweet One, Sunett

Cyclamate

Sugar Twin, Sucaryl, Weight Watchers TM

Neotame

No Name Brand

References

Millichap JG, Yee MM. The diet factor in pediatric and adolescent migraine Pediatr Neurol 2003;28:9-15. The NutraSweet Company: statments. Available at: http://www.nutrasweet.com/articles/article.asp?Id=47 (accessed July 19, 2007). Flintstones vitamins - the heading brand moms trust and kids love! Available at: http://www.bayercare.com/htm/flintfaq.htm (accessed February 6, 2007). US Food and Drug Administration: artificial sweeteners: no calories...sweet! Available at: http://www.fda.gov/fdac/features/2006/406_sweeteners.html (accessed July 19, 2007). Murray TG, Burton TC, Rajani C, et al. Methanol poisoning. A rodent model with structural and functional evidence for retinal involvement Arch Ophthalmol 1991;109:1012-6. Trocho C, Pardo R, Rafecas I, et al. Formaldehyde derived from dietary aspartame binds to tissue components in vivo Life Sci 1998;63:337-49. Hill AM, Belsito DV. Systemic contact dermatitis of the eyelids caused by formaldehyde derived from aspartame? Contact Dermatitis 2003;49:258-9.

Sharon E. and Stechschulte, Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, FL

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