Sucralose and Migraine


We have read the anecdotal reports by Drs. Patel et al, in their “case report” under the journal's Clinical Notes,1 and by Dr. Hirsch, in his recent Letter to the Editor,2 as well as the report by Drs. Bigal and Krymchantowski,3 all regarding the potential for sucralose as a migraine trigger.

While it is important to report and analyze such cases for potential safety signals, drawing conclusions about causality from such limited data can be inappropriate. In this instance, there are only 3 published case reports arising from the hundreds of millions of exposures to products containing sucralose during more than 15 years these products have been available. In addition, in each of these single patient observations, there are potential confounders of taste or ingestion of other food products, which should give pause to any researcher or clinician trying to draw conclusions from such data.

There are abundant data demonstrating the safety of sucralose.4-12 In assessing the overall safety profile of sucralose, one cannot ignore the extensive data showing that sucralose is well tolerated and safe for use in amounts hundreds of times greater than maximum estimated intakes.4-8 Clinical studies similarly show that sucralose is as well tolerated as placebo.9,10,12

In relation to Dr. Hirsch's commentary on mechanisms of action for migraine triggers, sucralose has been shown to be both nonallergenic5,13 and without effect on blood glucose.9,10 The absence of such effects is not at all surprising in light of the chemical nature of sucralose. Sucralose is a substituted disaccharide4 and not a substrate for human intestinal disaccharidases,4,14 which carry out the essential first step in degradation of disaccharides.15 Thus, sucralose has no caloric value, and clinical studies in both normoglycemic individuals and persons with diabetes demonstrate that sucralose has no impact on glycemic control.9-10

With respect to allergenicity, typical allergens are proteins. Sucralose is not a protein. It is a substituted carbohydrate, which is substantively different. Sucralose is also a small molecule (MW < 400) that does not bind to blood or other proteins in the body and is not involved in the formation of haptens.4,14 Therefore, it is a molecule that would not be expected to be associated with an allergenic response. Additionally, sucralose is a remarkably stable molecule, essentially inert in the human body. It is also largely unabsorbed, is quickly eliminated, and does not bioaccumulate.4,12,14

The relationship of foods and food ingredients to migraine is not well understood. There is also debate regarding whether certain food substances long considered to be potential migraine triggers, such as tyramine (vasoactive amine in aged cheese and red wine) and chocolate are actually true triggers.16-18 In light of the many other potentially contributing factors, caution is warranted before making any connection between migraine and any food substance.

Consumers and physicians should also consider the broader benefits of a particular food substance in the diet. In addition to its excellent safety profile, sucralose offers another important option for many consumers in reducing caloric intake from common foods and beverages. Such tools for the management of caloric intake, combined with increased physical activity, can be valuable in managing health19-23 and helping to mitigate the health risks associated with the national epidemic of obesity.