Q:

11/10/2015  
Would citric acid trigger an allergic reaction in someone with a citrus allergy?

A:


The short answer is “no” as citric acid does not provoke an immune response, a requirement for allergy. There may be adverse effects of citric acid but not specific antibody to a small chemical like citric acid (see the archived Ask The Expert question below). There have been immunologic reactions to other components of citrus fruit (see the archived Ask The Expert question below). Citrus allergy has been reported to orange, mandarin and grapefruit but these reactions are not related to citric acid (1-5). Immune responses to lipid transfer proteins, profilin and pectin have been associated with citrus allergy. Lipid transfer proteins are a conserved, protein family found in many plants and responsible for cross reactivity among different foods. Lipid transfer proteins are also homologous with seed storage proteins and trypsin-alpha amylase inhibitors resulting in potential reactions with multiple foods. Profilins are found in pollen as well as foods and sensitivity may explain pollen food syndromes in which a patient is allergic to airborne pollens and experiences food reactions, usually confined to the oral cavity.

1. Ahrazem O, Ibanez MD, Lopez-Torrejon G, Sanchez-Monge R, Sastre J, et al. (2005) Lipid transfer proteins and allergy to oranges. Int Arch Allergy Immunol 137: 201-210.
2. Ahrazem O, Ibanez MD, Lopez-Torrejon G, Sanchez-Monge R, Sastre J, et al. (2006) Orange germin-like glycoprotein Cit s 1: an equivocal allergen. Int Arch Allergy Immunol 139: 96-103.
3. Lopez-Torrejon G, Ibanez MD, Ahrazem O, Sanchez-Monge R, Sastre J, et al. (2005) Isolation, cloning and allergenic reactivity of natural profilin Cit s 2, a major orange allergen. Allergy 60: 1424-1429.
4. Ebo DG, Ahrazem O, Lopez-Torrejon G, Bridts CH, Salcedo G, et al. (2007) Anaphylaxis from mandarin (Citrus reticulata): identification of potential responsible allergens. Int Arch Allergy Immunol 144: 39-43.
5. Iwamoto M, Toma S, Nara H, Sato H, Minota S (2005) A case of food-dependent exercise-induced anaphylaxis after grapefruit ingestion. Allergol Int 54: 495.

Allergy to citric acid?
Q: 10/29/2012
I am not able to find reliable sources for information regarding a citric acid food allergy. We have patients who report they had it and I understand there may be chemotherapy treatments that need to have foods with citric acid avoided during treatment. How severe can a citric acid food allergy be and do all sources including berries need to be considered?

A: Unfortunately, I am not sure that I can be of very much help to you. There is very little information in the medical literature on citric acid intolerance. In fact, there is no evidence whatsoever that citric acid can cause an allergy in the true sense of the word. That is, via an immunologic response in the same manner that, for example, peanuts do.

There are rare reports in medical literature of an intolerance to citric acid (1, 2), but these occur in the older literature, and there has been nothing that I could find recently to confirm this information. In the few scattered cases where citric acid seemed to produce a reaction it found that the reaction was not, as mentioned, truly allergic, but rather perhaps an irritant response.

In addition, it would be very unusual for a simple chemical like this to produce a true allergic response. Also, since citric acid is ubiquitous, found in many foods, if a person were truly allergic to citric acid, they would react to a very large diverse group of foods, not only citrus fruits but berries and a number of vegetables. Also addition, since the substance is used quite commonly as an additive and ripening agent, it would be very difficult to avoid. Since allergic reactions occur to minute amounts of the agent responsible, a true allergy to citric acid would make the person would be susceptible to having repeated, perhaps life-threatening allergic reactions because of its ubiquitous presence.

Nonetheless, it is certainly possible that intolerance to citric acid in larger amounts can occur. If so, the only treatment would be avoidance.

As to the effect of citric acid on chemotherapies, I could find nothing in the medical literature about this topic. I am not personally aware of citric acid interfering with chemotherapy in any way.

Thus, unfortunately, I can give you very little help regarding your question, and the only treatment for a true allergy to citric acid would be avoidance of all foods containing it. As you are well aware, this would be extremely difficult, necessitating, if it was a true allergy, the avoidance of all sources including berries.

In summary, although it is certainly feasible that a person could have an intolerance to higher concentrations of citric acid, I have not been able to find any case of a true allergy to this substance. This is important because when patients have true allergies, they respond to minute amounts of the substance responsible, and therefore could not tolerate any source of citric acid. On the other hand, patients who are intolerant can often tolerate smaller doses, having only a reaction to a larger amount.

Finally, I am not aware of and could not find a reference to any adverse effect of citric acid on any form of chemotherapy. However, I am not an expert in this regard, and I noticed that you are writing from Cleveland Clinic. It may be that an oncologist at your institution has more information in this regard.

References:
1. Allergy. Volume 49, Issue 1, pages 31–37, January 1994.
2. Pediatr Allergy Immunol. 1993 Aug;4(3):123-9.

Sincerely,
Phil Lieberman, M.D.

Asthma due to the inhalation of the peels of lemons and oranges
Q: 1/20/2013
54 year old black female with asthma and allergic rhinitis.
Patient uses Advair bid and Singulair, has Albuterol for rescue. Rarely uses Albuterol. Last po steroid burst 14 months ago. She is occasionally using Flonase and po antihistamine. Patient states if she is in an environment where oranges or lemons have been peeled or cut the smell will trigger asthma, nasal congestion and sneeze. Albuterol inhaled and Benadryl help decrease the symptoms. She can eat peeled and then washed fresh orange with no reaction, she can drink lemonade, tea with fresh lemon with no reaction. Is there something in the peel of the orange and lemon that is triggering symptoms? Should I suggest an Epi pen? I have suggested she avoid areas where oranges and/or lemons are being peeled or cut.

A: Asthma due to the inhalation of the peels of citrus fruits has been described a number of times in the literature. I have copied some of the references for you below, and a link to one of the references which you can download free of charge is also copied below.

The most commonly described agent responsible for asthma in this circumstance is pectin. However, asthma has been thought to be due to enzymes in peels as well.

Pectin has also caused anaphylaxis (as you can see by the Annals of Allergy reference cited below). So, theoretically, your patient could be at risk for anaphylaxis, but in my opinion this would be extremely unlikely. I cannot give you a definitive answer as to whether or not you should prescribe an automatic epinephrine injector; you would need to make a judgment based upon your assessment of the severity of this patient’s previous reactions and her ability to avoid future exposures.

Occupational asthma caused by pectin inhalation during the manufacture of jam.

1. A J Cohen; M S Forse; S M Tarlo. Chest. January 1993;103(1):309-311. doi:10.1378/chest.103.1.309
2. Ronald M. Ferdman, Annals of Allergy, Asthma & Immunology Volume 97, Issue 6, December 2006, Pages 759–760
3. Asthma caused by occupational exposure to pectin. Jaakkola MS, Tammivaara R, Tuppurainen M, Lahdenne L, Tupasela O, Keskinen H. J Allergy Clin Immunol. 1997 Oct;100(4):575-6. No abstract available.
4. Pectin-induced occupational asthma. Baldwin JL, Shah AC. Chest. 1993 Dec;104(6):1936-7.
5. Sen et al: Occupational asthma in fruit salad processing. Clinical & Experimental Allergy. Volume 28, Issue 3, pages 363–367, March 1998
Background: Three subjects employed in the preparation of fruit for fruit salads reported work-related respiratory symptoms. Their work entailed removing the peel from citrus fruits, primarily oranges, following soaking of the fruits in a bath of enzymes including fungal derived pectinase and glucanase.
Objectives: To investigate the respiratory symptoms reported by these workers and determine their causes.
Methods: The three workers were investigated by a respiratory physician, including spirometry and serial peak flow measurements. Blood was taken for the measurement of IgE and IgG antibody responses against the enzyme solution.
Results: Predominant symptoms in these workers were shortness of breath, chest tightness and wheezing which were all alleviated at weekends and holidays only to occur when returning to work. Serial peak flow measurements showed a clear work-related pattern. All three had strong IgE responses to the enzyme solution used at the workplace and showed distinct patterns of binding in immunoblots. All three improved immensely following withdrawal from the workplace environment.
Conclusion: Enzymes appear to be widely used in the preparation of fruit and although they are used in liquid form, exposure can occur to induce immunological sensitization and asthma.

Sincerely,
Phil Lieberman, M.D.

I hope this information is of help to you and your practice.

All my best.
Dennis K. Ledford, MD, FAAAAI


Editor’s note (September 24, 2019):
While not indicative of an IgE mediated allergy to citric acid, recent case reports of a delayed inflammatory reaction to possible manufactured citric acid (not naturally occurring) have been reported. The mechanism behind these putative reactions is unclear.

Sweis IE, Cressey BC. (2018) Potential role of the common food additive manufactured citric acid in eliciting significant inflammatory reactions contributing to serious disease states: A series of four case reports. Toxicol Rep 5: 808-812.

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