Dr Janice Joneja explores this little-known and not very well understood sensitivity to aspirin and related chemicals.
Acetylsalicylic acid (ASA), or Aspirin, is the only form of salicylate that has been definitively shown to cause an adverse reaction. Salicylates, rather than acetylsalicylic acid (1), occur naturally in many foods but although they are suspected of causing adverse reactions in people who are sensitive to acetylsalicylic acid, there have not, as yet, been any research studies that actually show that they do.
It is the amount of salicylic acid that is probably the crucial factor in salicylate sensitivity. Consumption of salicylate in food is estimated to be 10 to 200 mg daily (4), whereas the usual dose in a regular aspirin is 325 mg; in extra-strength or arthritis pain relief aspirins, the dose is 600 to 650 mg of acetylsalicylic acid; and in a children’s aspirin, it is 80 mg.
Absorption may also be relevant in the amount of salicylate available. In a medication, ASA is in the ‘free form’ – that is, it is not linked to another compound, and is immediately available to the body. When the salicylate is in a food, it is complexed with many other compounds, so it will not become active until released in its free form, which will take a certain length of time and will reduce the body’s immediate response to the chemical.
Aspirin sensitivity has also frequently been thought to be a cause of urticaria (hives) and angioedema (tissue swelling); respiratory symptoms, including rhinitis and possibly nasal polyps; and digestive tract disturbances. (4)
Salicylate sensitivity (6) has also been implicated in childhood hyperactivity but there is no research to substantiate this. Recent studies indicate a role for benzoates and food dyes in triggering hyperactivity in children; salicylates were not implicated as triggers in these studies. (7)
In an allergic reaction, preformed inflammatory mediators are released from mast cells, which act on tissues to produce symptoms. In addition, some of these preformed mediators are enzymes that promote additional steps in the process. An essential enzyme in this respect is phospholipase A2. This enzyme breaks down phospholipids in cell membranes and releases arachidonic acid (AA) in the process. AA is a key 20-carbon chain omega-6 fatty acid that is the precursor (provides the building blocks) for more inflammatory mediators to augment the protective inflammatory response.
Two key enzyme pathways then act on AA to produce two groups of powerful inflammatory mediators: (a) the cyclooxygenase pathway that leads to the production of the prostanoids (prostaglandins; prostacyclins and thromboxane) and (b) the lipoxygenase pathway that leads to the production of leukotrienes. Each of these groups plays an extremely important role in body processes such as smooth muscle contraction and relaxation and in the widening and narrowing of blood vessels.
Some of these mediators also lead to symptoms such as pain (the prostaglandins) and the bronchospasm of asthma (the leukotrienes). A high level of leukotrienes is found in the inflamed tissues of allergic conditions in the skin such as eczema (9) and urticaria. Antileukotriene drugs are increasingly being used to treat these conditions. (10)
In the treatment of pain, reducing the level of the prostaglandins involved in the process is required. Aspirin achieves this by inhibiting the cyclooxygenase enzyme pathway which leads from AA to prostaglandins. Other analgesics—for example, ibuprofen, acetaminophen, and paracetamol—have a similar effect.
However, by inhibiting one enzyme pathway, a buildup of substrate (AA) leads to enhancement of the other. So inhibition of the cyclooxygenase pathway results in an increased production of leukotrienes via the lipoxygenase pathway. Leukotrienes cause the bronchoconstriction of asthma, thus explaining the observation that many asthmatics are aspirin intolerant. Research also indicates that an additional effect of the process is the release of histamine from mast cells and other granulocytes (e.g., basophils, eosinophils, macrophages, platelets) in a non-immunologically mediated reaction. (4, 11)
A diagnosed sensitivity to aspirin is sometimes assumed to indicate a salicylate sensitivity but, because the levels of salicylic acid in aspirin and foods are so different, it is unwise to assume that an aspirin-sensitive person requires a salicylate-restricted diet.
Some practitioners believe that, although avoiding foods high in salicylates is unlikely to diminish the symptoms of most people sensitive to acetylsalicylic acid, a salicylate-restricted diet may help those who are very acetylsalicylic acid sensitive and have not found any other treatments helpful. Since salicylate intolerance, as in all food intolerances (as opposed to food allergies), is dose-related, it is probably sufficient that a person with suspected salicylate sensitivity avoid foods with the highest levels of salicylate.
Several researchers have developed tables to indicate the level of salicylate in foods. (12–14) However, the reported levels are not entirely consistent between data banks, because the level of salicylate in a food will vary according to plant variety, conditions in the growing environment, and methods of analysis in the laboratory.
Furthermore, the level of salicylate detected in the body (by analysis of a research subject’s serum) varies, probably depending on individual absorption patterns and metabolism of salicylate within the body. (4, 15, 16) There is still a great deal to learn before we can diagnose and manage either aspirin or salicylate intolerance effectively.
A salicylate-restricted diet should not be followed for longer than 4 weeks initially. After this time, sequential incremental dose challenge of salicylate-rich foods should be undertaken to confirm salicylate intolerance.
First published November 2013Back to top