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 drugs [NSAID]), nasal polyps and bronchial asthma [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].

Conclusion

The recommendation to reduce dietary salicylates to treat ASA intolerance has no pathophysiological background. In contrast, such a reduction poses the risk of dysnutrition. Nutritional therapy should aim for a diet high in vegetables. This ensures the supply of antioxidants, trace elements, as well as secondary plant and mineral substances. An increased intake of eicosapentaenoic acid and docosahexaenoic acid in fish (oil) at the same time as reducing the intake of arachidonic acid can have a favorable effect on fat intake.