Ameliorating Atopy by Compensating Micronutritional Deficiencies in Immune Cells: A Double-Blind Placebo-Controlled Pilot Study

Bartosik, Tina; Jensen, Sebastian A.; Afify, Sheriene Moussa; Bianchini, Rodolfo; Hufnagl, Karin; Hofstetter, Gerlinde; Berger, Markus; Bastl, Maximilian; Berger, Uwe; Rivelles, Elisa; Schmetterer, Klaus G.; Eckl‐Dorna, Julia; Brkic, Faris F.; Vyskocil, Erich; Guethoff, Sonja; Graessel, Anke; Krämer, Matthias; Jensen‐Jarolim, Erika; Roth‐Walter, Franziska

doi:10.1016/j.jaip.2022.02.028

Cited by 15 publications

(17 citation statements)

References 90 publications

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“…Holo- BLG promoted Treg cells through AhR activation and downregulation of antigen presentation in monocytes and DC via transport of iron (101). In a follow-up clinical pilot trial, the same authors assessed the efficacy of a FSMP (food for special medical purposes) lozenge containing BLG with iron, polyphenols, retinoic acid, and zinc in allergic women and could show that this holo-BLG lozenge improved nasal symptom score after nasal provocation as well as symptom medication score during birch or grass pollen season by more than 40% compared to the placebo group (102).…”

Section: Current Therapeutic Applications In Allergic Diseases: I Ind...mentioning

confidence: 99%

Current Strategies to Modulate Regulatory T Cell Activity in Allergic Inflammation

2022

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Over the past decades, atopic diseases, including allergic rhinitis, asthma, atopic dermatitis, and food allergy, increased strongly worldwide, reaching up to 50% in industrialized countries. These diseases are characterized by a dominating type 2 immune response and reduced numbers of allergen-specific regulatory T (Treg) cells. Conventional allergen-specific immunotherapy is able to tip the balance towards immunoregulation. However, in mouse models of allergy adaptive transfer of Treg cells did not always lead to convincing beneficial results, partially because of limited stability of their regulatory phenotype activity. Besides genetic predisposition, it has become evident that environmental factors like a westernized lifestyle linked to modern sanitized living, the early use of antibiotics, and the consumption of unhealthy foods leads to epithelial barrier defects and dysbiotic microbiota, thereby preventing immune tolerance and favoring the development of allergic diseases. Epigenetic modification of Treg cells has been described as one important mechanism in this context. In this review, we summarize how environmental factors affect the number and function of Treg cells in allergic inflammation and how this knowledge can be exploited in future allergy prevention strategies as well as novel therapeutic approaches.

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Section: Current Therapeutic Applications In Allergic Diseases: I Ind...mentioning

confidence: 99%

Current Strategies to Modulate Regulatory T Cell Activity in Allergic Inflammation

2022

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“…Consumption of this holoBLG lozenge for 3 months led to an amelioration of allergic symptoms in patients with allergic rhinitis to house dust mites, reducing total nasal symptoms by 60%, and they reported greater perceived wellbeing measurable even up to 8 months after cessation of holoBLG supplementation ( 248 , 249 ) (NCT04477382, NCT04872868, and NCT05455749). Similarly, also in a double-blind, placebo-controlled pilot trial, 6-month supplementation with this holo-BLG lozenge significantly ameliorated symptoms by about 40% over placebo in grass and birch pollen allergic women ( 45 ) (NCT03816800). In line with the beneficial impact of dietary intake of heat-sensitive whey proteins, in a human pilot study, it was found that drinking raw milk is tolerated better in allergic children than highly processed shop milk ( 250 ) (Bo/06/2009).…”

Section: Dietary Intervention For Disease Prevention and Amelioration...mentioning

confidence: 94%

“…By degrading ferroportin, which enables exporting iron into circulation, hepcidin decreases iron absorption from the gastrointestinal tract and decreases the accessibility of iron stored in macrophages. The blocking of iron absorption and mobilization is a critical clinical finding, which is associated with a worsened prognosis and outcome in chronic diseases such as congestive heart failure ( 30 , 31 ), chronic kidney diseases ( 32 – 34 ) (NCT03029208, NCT02940860, and NCT01864161), autoimmune diseases ( 35 – 39 ), inflammatory bowel disease ( 40 , 41 ), cancer ( 42 – 44 ), atopic diseases ( 45 , 46 ) (NCT03815981 and NCT03816800), and even in obesity ( 47 – 50 ) (NCT00030238). Importantly, in iron-deficient children who are not anemic, inflammation is a common finding ( 51 ).…”

Section: Micronutrientsmentioning

confidence: 99%

Lack of iron, zinc, and vitamins as a contributor to the etiology of atopic diseases

et al. 2023

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Micronutritional deficiencies are common in atopic children suffering from atopic dermatitis, food allergy, rhinitis, and asthma. A lack of iron, in particular, may impact immune activation with prolonged deficiencies of iron, zinc, vitamin A, and vitamin D associated with a Th2 signature, maturation of macrophages and dendritic cells (DCs), and the generation of IgE antibodies. In contrast, the sufficiency of these micronutrients establishes immune resilience, promotion of regulatory cells, and tolerance induction. As micronutritional deficiencies mimic an infection, the body’s innate response is to limit access to these nutrients and also impede their dietary uptake. Here, we summarize our current understanding of the physiological function of iron, zinc, and vitamins A and D in relation to immune cells and the clinical consequences of deficiencies in these important nutrients, especially in the perinatal period. Improved dietary uptake of iron is achieved by vitamin C, vitamin A, and whey compounds, whereas zinc bioavailability improves through citrates and proteins. The addition of oil is essential for the dietary uptake of beta-carotene and vitamin D. As for vitamin D, the major source comes via sun exposure and only a small amount is consumed via diet, which should be factored into clinical nutritional studies. We summarize the prevalence of micronutritional deficiencies of iron, zinc, and vitamins in the pediatric population as well as nutritional intervention studies on atopic diseases with whole food, food components, and micronutrients. Dietary uptake via the lymphatic route seems promising and is associated with a lower atopy risk and symptom amelioration. This review provides useful information for clinical studies and concludes/emphasizes that a healthy, varied diet containing dairy products, fish, nuts, fruits, and vegetables as well as supplementing foods or supplementation with micronutrients as needed is essential to combat the atopic march.

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“…The combined symptom-medication score, considered the gold standard of allergen immunotherapy, ( 366 ) was in the group, taking the holoBLG lozenges 45% lower in the birch pollen peak season and 40% lower in the grass pollen season compared to the placebo-supplemented study arm. Additionally, blood values improved, and peripheral blood monocytic cells had, compared to the monocytes of the placebo arm, a significant higher labile iron pool ( 12 , 347 , 367 , 368 ).…”

Section: Clinical Studies: Balancing Micronutrient Requirements As a ...mentioning

confidence: 97%

Iron-Deficiency in Atopic Diseases: Innate Immune Priming by Allergens and Siderophores

Roth‐Walter

2022

Front. Allergy

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Although iron is one of the most abundant elements on earth, about a third of the world's population are affected by iron deficiency. Main drivers of iron deficiency are beside the chronic lack of dietary iron, a hampered uptake machinery as a result of immune activation. Macrophages are the principal cells distributing iron in the human body with their iron restriction skewing these cells to a more pro-inflammatory state. Consequently, iron deficiency has a pronounced impact on immune cells, favoring Th2-cell survival, immunoglobulin class switching and primes mast cells for degranulation. Iron deficiency during pregnancy increases the risk of atopic diseases in children, while both children and adults with allergy are more likely to have anemia. In contrast, an improved iron status seems to protect against allergy development. Here, the most important interconnections between iron metabolism and allergies, the effect of iron deprivation on distinct immune cell types, as well as the pathophysiology in atopic diseases are summarized. Although the main focus will be humans, we also compare them with innate defense and iron sequestration strategies of microbes, given, particularly, attention to catechol-siderophores. Similarly, the defense and nutritional strategies in plants with their inducible systemic acquired resistance by salicylic acid, which further leads to synthesis of flavonoids as well as pathogenesis-related proteins, will be elaborated as both are very important for understanding the etiology of allergic diseases. Many allergens, such as lipocalins and the pathogenesis-related proteins, are able to bind iron and either deprive or supply iron to immune cells. Thus, a locally induced iron deficiency will result in immune activation and allergic sensitization. However, the same proteins such as the whey protein beta-lactoglobulin can also transport this precious micronutrient to the host immune cells (holoBLG) and hinder their activation, promoting tolerance and protecting against allergy. Since 2019, several clinical trials have also been conducted in allergic subjects using holoBLG as a food for special medical purposes, leading to a reduction in the allergic symptom burden. Supplementation with nutrient-carrying lipocalin proteins can circumvent the mucosal block and nourish selectively immune cells, therefore representing a new dietary and causative approach to compensate for functional iron deficiency in allergy sufferers.

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Ameliorating Atopy by Compensating Micronutritional Deficiencies in Immune Cells: A Double-Blind Placebo-Controlled Pilot Study

Cited by 15 publications

References 90 publications

Current Strategies to Modulate Regulatory T Cell Activity in Allergic Inflammation

Current Strategies to Modulate Regulatory T Cell Activity in Allergic Inflammation

Lack of iron, zinc, and vitamins as a contributor to the etiology of atopic diseases

Iron-Deficiency in Atopic Diseases: Innate Immune Priming by Allergens and Siderophores

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