Iron-containing lozenges reduce birch, grass pollen allergy symptoms

A lozenge that delivers iron directly to immune cells reduced the symptoms of birch and grass pollen allergies as effectively as immunotherapy, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.

“We discovered nearly 10 years ago that the majority of allergens can affect the iron status of allergic subjects and that iron deficiency alone not only is sufficient to facilitate allergic sensitization, but it is also associated with inflammation and an exaggerated immune response,” Franziska Roth-Walter, PhD, head of the working group at Messerli Research Institute in Vienna, told Healio.

Also, Roth-Walter said that the researchers knew that not everyone is prone for allergies, but so-called atopic individuals have an inherent tendency to produce IgE antibodies and be hypersensitive to allergens.

Franziska Roth-Walter

“We thus aimed to address whether treating functional iron deficiency, or iron deficiency that affects the immune cells, could ameliorate atopy,” Roth-Walter said.

The researchers chose beta-lactoglobulin, a whey protein, to carry micronutrients directly to immune cells to prevent atopic responses due to an iron deficiency.

“For beta-lactoglobulin, dietary uptake is reported to go via the lymphatic system and thus precisely to the immune cells,” Roth-Walter said.

The study’s design, results

The randomized, double-blind study involved 47 premenopausal women (mean age, 31 years) with birch or grass pollen allergies.

In the test arm (n = 25), 68% were allergic to birch and 88% were allergic to grass pollen. In the placebo arm (n = 22), 77% were allergic to birch and 81% were allergic to grass pollen.

The researchers collected blood and stool samples from each participant and conducted nasal provocations at the beginning and end of the study. Also, researchers instructed participants to consume two lozenges each day for 6 months and record their daily symptoms and medication use in a pollen diary.

The holoBLG lozenge (Biomedical International R+D GmbH) included whey concentrate, less than 1 mg of iron, catechins, retinoic acid, zinc and sorbitol as carrier material, with mountain herbs for flavor. The placebo lozenges had no active ingredients.

Total nasal symptom scores (TNSS) did not differ between the groups at the beginning of the study, but the participants taking the holoBLG lozenge experienced significantly lower scores after 6 months compared with the placebo group. TNSS scores in the placebo group fell from a mean of 4.37 to 3.82, for an average individual improvement of 12.9%, whereas scores for the holoBLG group fell from a mean of 4.78 to 2.58, or an average individual improvement of 42.4% (P = .0005).

Also, the researchers found that both groups had significantly less nasal discharge after 6 months, but the holoBLG group had a significantly larger reduction in nasal outflow (reduction in nasal symptom burden, 42% vs. 13%; P = .04).

Analyses of symptom burden showed the holoBLG group experienced statistically significant average improvements relative to placebo of 45% in their combined symptom medication score (CSMS), 39% in their daily symptom score (dSS) and 41% in their symptom medication score (SMS; all, P < .0001) during the birch pollen peak season.

During the entire grass pollen season, the holoBLG group experienced 40% improvements in the CSMS and 26% in dSS and SMS compared with the placebo group (all, P < .0001).

“Though all our preclinical data were very encouraging, we were still surprised by the degree of symptoms improvement as the improvements were completely allergen-independent,” Roth-Walter said.

At baseline, both groups had comparable allergen-specific and total IgE levels. Allergen-specific IgE increased in both groups with no statistically significant differences between them during the study period, but total IgE only increased in the placebo group.

The placebo group also had significantly higher C-reactive protein values and a trend toward less absolute lymphocyte counts compared with the holoBLG group by the end of the study period, according to the researchers.

Further, the holoBLG group had significantly improved hematocrit levels and reduced width of red cell distribution. Supplementation also seemed to strengthen cellular components of myeloid lineage, according to the researchers.

“Though the lozenge only contained a very low amount of iron, we indeed could measure improved iron parameters in the white blood cells, and even some red blood cell parameters improved slightly,” Roth-Walter said.

The researchers did not find any significant differences in the relative numbers of monocytic CD14⁺ cells before or supplementation in either group, but the holoBLG group did show increases in intracellular labile iron content in circulating CD14⁺ monocytes after the study.

Overall, the researchers found that the holoBLG lozenge effectively delivered its micronutritional cargo to monocytes but not to lymphocytes. The researchers also found the lozenges tolerable with no adverse events reported. Only two participants did not like the taste, the researchers continued, and adherence generally was high.

The study’s implications

“The most important finding is that, indeed, micronutritional deficiencies matter and should be treated as they can drive the symptom burden,” Roth-Walter said.

“Tiredness of an atopic patient might not only be due to their illness, but because iron deficiency is present. In current practice, micronutritional dietary recommendations should be included,” she continued.

Although allergen immunotherapy is considered the only causative treatment option for ameliorating atopic diseases, Roth-Walter said, providing micronutrients to immune cells seems to have similar efficacy and may be another causative cure for allergies.

“The lozenge calms the immune system in a more generalized manner. As such, it may be particularly useful when the specific allergen is not known or when specific allergen immunotherapy is not feasible,” Roth-Walter said. “Since it is basically food, it could also be taken in adjunct with specific allergen immunotherapy.”

The researchers plan to continue their studies.

“Currently, one clinical study with people allergic to cats is being completed, and another with pollen-allergic individuals is planned,” Roth-Walter said. “As also animals suffer from atopic diseases, we also plan to conduct a study with dog patients suffering from atopic dermatitis.”

Reference:

• Targeted micronutrition ameliorates allergy symptoms. https://www.meduniwien.ac.at/web/en/about-us/news/2022/news-in-june-2022/gezielte-mikroernaehrung-lindert-symptome-bei-allergien/. Posted June 7, 2022. Accessed June 13, 2022.

For more information:

Franziska Roth-Walter, PhD, can be reached at franziska.roth-walter@meduniwien.ac.at.