Antacids and dietary supplements with an influence on the gastric pH increase the risk for food sensitization

Abstract

Background: Elevation of the gastric pH increases the risk for sensitization against food allergens by hindering protein breakdown. This can be caused by acid-suppressing medication like sucralphate, H2-receptor blockers and proton pump inhibitors, as shown in recent murine experimental and human observational studies.

Objective: The aim of the present study was to assess the sensitization capacity of the dietary supplement base powder and of over-the-counter antacids.

Methods: Changes of the pH as well as of protein digestion due to base powder or antacids were measured in vitro. To examine the in vivo influence, BALB/c mice were fed codfish extract with one of the acid-suppressing substances. Read-out of antibody levels in the sera, of cytokine levels of stimulated splenocytes and of intradermal skin tests was performed.

Results: The pH of hydrochloric acid was substantially increased in vitro by base powder as well as antacids in a time- and dose-dependent manner. This elevation hindered the digestion of codfish proteins in vitro. A significant increase in codfish-specific IgE antibodies was found in the groups fed codfish combined with Rennie Antacidum or with base powder; the latter also showed significantly elevated IgG1 and IgG2a levels. The induction of an anaphylactic immune response was proven by positive results in intradermal skin tests.

Conclusions: Antacids and dietary supplements influencing the gastric pH increase the risk for sensitization against allergenic food proteins. As these substances are commonly used in the general population without consulting a physician, our data may have a major practical and clinical impact.

Fig. 1

(a) Dose-dependent and (b) time-dependent change of the pH after addition of base powder and antacids. Hydrochloric acid (pH 1.2, 10 mL) was mixed with (a) different amounts of base powder, Rennie® Antacidum or Rennie® Digestif or (b) an amount of 22 mg/mL of each substance and the pH measured at different time intervals.

Fig. 2

Digestion of codfish proteins is hindered under elevated pH. The incubation of codfish extract in simulated gastric fluid (SGF) with base powder, Rennie® Antacidum or Rennie® Digestif for (1) 30 s, (2) 10 min, (3) 30 min, (4) 60 min or (5) 120 min reveals protein preservation for up to 2 h, in contrast to rapid digestion under normal acidic conditions. Codfish was not digested when incubated with distilled water (0) for 120 min. (M) standard protein marker. Controls: (1) base powder in SGF; (2) Rennie® Antacidum in SGF; (3) Rennie® Digestif in SGF; and (4) SGF.

Fig. 3

Codfish-specific antibodies increase during feedings under concomitant acid suppression. Significantly elevated IgE, IgG1 and IgG2a levels in the last immune serum (after 6×2 feedings) reveal an enhanced immune response in groups fed codfish together with either base powder (codfish/BP) or with Rennie® Antacidum (codfish/RA). The OD values of pre-immune sera were subtracted from the values of immune sera. The boxes represent the range of the inner quartiles of the samples divided by the median. Sera with signals showing more than a 1.5-fold deviation from the end of the box were defined as outlines and marked as circles. Sera with titres lying more than threefold away were defined as extremes and marked with asterisks. Brackets indicate the groups that are statistically significantly different compared with the codfish-only group (*P≤0.05, **P≤0.01).

Fig. 4

Cytokine levels confirm the bias towards a T-helper type 2 reponse. Th2 cytokine levels of IL-4, IL-5 and IL-13 are elevated (although not significantly) in splenocyte supernatants after stimulation with codfish extract in mouse groups subjected to acid suppression with Rennie® substances during codfish feedings. The boxes represent the range of the inner quartiles of the samples divided by the median. Sera with signals showing more than a 1.5-fold deviation from the end of the box were defined as outlines and marked as circles. Sera with titres lying more than threefold away were defined as extremes and marked with asterisks.

Fig. 5

Positive reactions in intradermal skin tests underline the biological relevance of the humoral and cellular allergic response towards a food allergen when combined with anti-acid substances. The most intensive reactions to codfish were found in the groups treated with codfish together with either base powder, Rennie® Antacidum or Rennie® Digestif. Positive controls were performed with compound 48/80, and negative controls (data not shown) with phosphate-buffered saline and the control allergen hazelnut extract. Skin reactivity indexes were calculated as the diameter of skin reactivity×densitometrical signal intensity×number of reactive mice/number of tested mice.