Dietary implications in acetylsalicylic acid intolerance

Acetylsalicylic acid (ASA) may cause difficult-to-treat symptoms of the airways, skin, or gastrointestinal tract in hypersensitive patients. Due to the chemical relationship between salicylic acid and ASA, a role of a low-salicylate diet has been discussed. This review evaluates whether low salicylate diets are meaningful from an allergological or nutritional–physiological perspective. The body’s arachidonic acid metabolism plays a crucial role in the pathogenesis of ASA intolerance. Despite their chemical affinity, ASA and salicylic acid affect the arachidonic pathway differently. The intake of salicylic acid with food is low compared to therapeutic doses of ASA. There is increasing evidence that protective effects of a high fruit and vegetables diet is related in part to the intake of salicylates. In salicylate-low diets, fruit and vegetables are reduced, harboring the risk of an insufficient diet and malnutrition. Dietary therapy in ASA-intolerant patients is not recommended.


Summary
Background Acetylsalicylic acid (ASA) may cause difficult-to-treat symptoms of the airways, skin, or gastrointestinal tract in hypersensitive patients. Due to the chemical relationship between salicylic acid and ASA, a role of a low-salicylate diet has been discussed. Methods This review evaluates whether low salicylate diets are meaningful from an allergological or nutritional-physiological perspective. Results The body's arachidonic acid metabolism plays a crucial role in the pathogenesis of ASA intolerance. Despite their chemical affinity, ASA and salicylic acid affect the arachidonic pathway differently. The intake of salicylic acid with food is low compared to therapeutic doses of ASA. There is increasing evidence that protective effects of a high fruit and vegetables diet is related in part to the intake of salicylates. In salicylatelow diets, fruit and vegetables are reduced, harboring the risk of an insufficient diet and malnutrition. Conclusion Dietary therapy in ASA-intolerant patients is not recommended.

AERD
Aspirin-exacerbated respiratory disease ASA Acetylsalicylic acid COX Cyclooxygenase DAMP Damage-associated molecular pattern molecule HMGB1 Human high mobility group box 1 NSAID Non-steroidal anti-inflammatory drugs Intolerance to acetylsalicylic acid (ASA) is based on a non-IgE-mediated hypersensitivity reaction. In hypersensitive patients, ASA can trigger symptoms of the skin/mucosa as well as the respiratory and gastrointestinal tract. In its most severe form, ASA intolerance can manifest in the airways as Samter's triad. The latter refers to a combined onset of ASA intolerance (intolerance to non-steroidal anti-inflammatory  [1,2]. The term aspirin-exacerbated respiratory disease (AERD) is more recently used for the respiratory form of disease. ASA intolerance is caused by alterations in the arachidonic acid metabolism, followed by an imbalance of eicosanoids formed from arachidonic acid [3].
Oxidative degradation of arachidonic acids takes place through two enzyme systems: the lipoxygenase and the cyclooxygenase (COX) pathway. ASA mainly effects the COX-1 degradation pathway and causes impaired immunological homeostasis with an increased production of pro-inflammatory eiconsoids, primarily leukotrienes and prostaglandin E2, and can promote an accumulation of immunological effector cells (mast cells and eosinophils among others) [4][5][6].
ASA is a chemical compound that does not occur naturally. Nevertheless, some foods contain its parent substance, salicylic acid, a phenolic acid belonging to the secondary plant substances and possessing anti-inflammatory properties [7]. The relationship between the two substances has given rise to a discussion on whether the natural salicylic acid content in food should be taken into account for difficult-to-treat ASA intolerance. However, there is no scientific evidence as yet that dietary salicylic acid is relevant in the pathogenesis of ASA intolerance [8].
The main sources of salicylates in foods include alcoholic beverages, herbs, spices, fruit, fruit juice, tomato-based sauces and vegetables. Therefore, a reduction of the dietary intake of salicylates is necessarily associated with a high carbohydrate and protein diet. The increased consumption of cereals and cereal products, milk and milk products, meat, eggs, and fish that often results from this dietary change harbors a clear risk of an insufficient diet.
As such, a reduction in dietary salicylates would have a significant impact on the basic diet, an impact that cannot be justified from the perspective of nutritional science. The salicylate intake in a regular diet is around 3-5 mg/day, which is comparable with the intake of other secondary plant substances [9,10]. Despite the good bioavailability of dietary salicylates, serum levels are far below the triggering threshold dose shown in studies for ASA [11,12]. Moreover, even at pharmacological concentrations, salicylic acid has no direct effect on either COX-1 or COX-2, in contrast to ASA [13]. However, by binding to a newly identified protein (human high mobility group box 1 [HMGB1]) belonging to the group of alarmins (damage-associated molecular pattern molecule [DAMP]), salicylic acid and its derivatives can indirectly affect COX-2 and also inhibit the production of pro-inflammatory cytokines [14].
The intake of salicylates as part of a diet high in fruit and vegetables is rather associated with major health benefits. Efforts are underway to include salicylic acid as an essential vitamin: "vitamin S" [13][14][15][16][17][18][19][20].