Citrin: a novel food allergen in citrus seeds and citrus-derived pectin that shows cross-reactivity with cashew and pistachio.

BACKGROUND: Patients exquisitely sensitive to cashew/pistachio are at risk for allergic reactions to citrus seeds and pectin. OBJECTIVE: In this study, we sought to evaluate whether pectin is contaminated with citrus seeds, to identify a culprit antigen in citrus seeds, and to assess for cross-reactivity among allergens in citrus seeds, citrus pectin, and cashew or pistachio. METHODS: Proteins from orange seed coats, orange seed endosperms, lemon seeds, grapefruit seeds, citrus pectin, apple pectin, and grapefruit pectin were extracted. Protein concentrations in all extracts were determined and visualized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis technique. Immunoglobulin E-binding capacity was determined with Western blot analyses and tandem mass spectrometry for the identification of the culprit allergen in citrus seeds and pectin. RESULTS: In subjects with citrus seed, pectin, and cashew allergies, there was strong immunoglobulin E-reactivity to bands between 17 to 28 kDa and 28 to 38 kDa. The tandem mass spectrometry analysis of these bands indicated the presence of citrin as the culprit allergen. Citrin and Ana o 2 are both 11S globulins belonging to the cupin superfamily, and significant homology was found between these proteins. CONCLUSION: Citrus pectin may be contaminated with citrus seeds. Citrin, a newly identified allergen in citrus seeds, seems to be the culprit antigen in citrus seeds and contaminated citrus pectin. Citrin is highly homologous with Ana o 2 in cashew and Pis v 2 in pistachio, suggesting potential for cross-reactivity and providing an explanation for co-allergenicity of cashew or pistachio, citrus seeds, and citrus pectin.

Double-Blind, Placebo-Controlled Study of E-B-FAHF-2 in Combination With Omalizumab-Facilitated Multiallergen Oral Immunotherapy.

BACKGROUND: Oral immunotherapy (OIT) is limited by adverse events, and most patients require continued treatment to maintain their increased threshold. Adjunctive treatments have been explored to increase the safety and efficacy of OIT. OBJECTIVE: This study aimed to determine the safety and efficacy of enhanced, butanol purified Food Allergy Herbal Formula-2 (E-B-FAHF-2) for inducing remission in subjects undergoing omalizumab-facilitated multiallergen OIT (multi-OIT). METHODS: In this double-blind, placebo-controlled clinical trial, subjects were randomized 1:1 to receive either E-B-FAHF-2 or placebo, starting 2 months before OIT and continuing throughout OIT. All subjects received a 4-month course of omalizumab, starting 2 months before OIT through the 2-month OIT build-up phase. After 24 months of multi-OIT (maintenance dose of 1000 mg of each allergen), desensitization and remission were assessed. The primary objective was to determine if subjects in the E-B-FAHF-2 group (EOIT) were more likely than the placebo group (OIT) to develop remission to all 3 allergens treated with multi-OIT, as defined by the absence of dose-limiting symptoms to a cumulative dose of 4444 mg of protein after discontinuing treatment for 3 months. RESULTS: Thirty-three subjects were randomized. A total of 63.6% were desensitized to 4444 mg of protein for each allergen at 26 months, and 24.2% met the primary outcome of remission at 29 months, with no difference between the treatment groups. There was good adherence (>85%) with study medications, with no difference between the treatment groups. There was no difference in reported overall adverse events between the treatment groups. CONCLUSION: Omalizumab-facilitated multifood OIT was safe and effective, and remission was achieved in about a quarter of subjects. However, outcomes were not improved by the addition of E-B-FAHF-2.

Investigation of peanut oral immunotherapy with CpG/peanut nanoparticles in a murine model of peanut allergy.

BACKGROUND: Treatments to reverse peanut allergy remain elusive. Current clinical approaches using peanut oral/sublingual immunotherapy are promising, but concerns about safety and long-term benefit remain a barrier to wide use. Improved methods of delivering peanut-specific immunotherapy are needed. OBJECTIVE: We sought to investigate the efficacy and safety of peanut oral immunotherapy using CpG-coated poly(lactic-co-glycolic acid) nanoparticles containing peanut extract (CpG/PN-NPs) in a murine model of peanut allergy. METHODS: C3H/HeJ mice were rendered peanut allergic by means of oral sensitization with peanut and cholera toxin. Mice were then subjected to 4 weekly gavages with CpG/PN-NPs, vehicle (PBS), nanoparticles alone, peanut alone, CpG nanoparticles, or peanut nanoparticles. Untreated mice served as naive controls. After completing therapy, mice underwent 5 monthly oral peanut challenges. Anaphylaxis was evaluated by means of visual assessment of symptom scores and measurement of body temperature and plasma histamine levels. Peanut-specific serum IgE, IgG1, and IgG2a levels were measured by using ELISA, as were cytokine recall responses in splenocyte cultures. RESULTS: Mice with peanut allergy treated with CpG/PN-NPs but not vehicle or other treatment components were significantly protected from anaphylaxis to all 5 oral peanut challenges, as indicated by lower symptom scores, less change in body temperature, and a lower increase of plasma histamine levels. Importantly, CpG/PN-NP treatment did not cause anaphylactic reactions. Treatment was associated with a sustained and significant decrease in peanut-specific IgE/IgG1 levels and an increase in peanut-specific IgG2a levels. Compared with vehicle control animals, peanut recall responses in splenocyte cultures from nanoparticle-treated mice showed significantly decreased levels of TH2 cytokines (IL-4, IL-5, and IL-13) but increased IFN-γ levels in cell supernatants. CONCLUSIONS: Preclinical findings indicate that peanut oral immunotherapy with CpG/PN-NPs might be a valuable strategy for peanut-specific immunotherapy in human subjects.

Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy.

BACKGROUND: Food Allergy Herbal Formula-2 (FAHF-2) is a 9-herb formula based on traditional Chinese medicine that blocks peanut-induced anaphylaxis in a murine model. In phase I studies FAHF-2 was found to be safe and well tolerated. OBJECTIVE: We sought to evaluate the safety and effectiveness of FAHF-2 as a treatment for food allergy. METHODS: In this double-blind, randomized, placebo-controlled study 68 subjects aged 12 to 45 years with allergies to peanut, tree nut, sesame, fish, and/or shellfish, which were confirmed by baseline double-blind, placebo-controlled oral food challenges (DBPCFCs), received FAHF-2 (n = 46) or placebo (n = 22). After 6 months of therapy, subjects underwent DBPCFCs. For those who demonstrated increases in the eliciting dose, a repeat DBPCFC was performed 3 months after stopping therapy. RESULTS: Treatment was well tolerated, with no serious adverse events. By using intent-to-treat analysis, the placebo group had a higher eliciting dose and cumulative dose (P = .05) at the end-of-treatment DBPCFC. There was no difference in the requirement for epinephrine to treat reactions (P = .55). There were no significant differences in allergen-specific IgE and IgG4 levels, cytokine production by PBMCs, or basophil activation between the active and placebo groups. In vitro immunologic studies performed on subjects' baseline PBMCs incubated with FAHF-2 and food allergen produced significantly less IL-5, greater IL-10 levels, and increased numbers of regulatory T cells than untreated cells. Notably, 44% of subjects had poor drug adherence for at least one third of the study period. CONCLUSION: FAHF-2 is a safe herbal medication for subjects with food allergy and shows favorable in vitro immunomodulatory effects; however, efficacy for improving tolerance to food allergens is not demonstrated at the dose and duration used.

Effect of Antiasthma Simplified Herbal Medicine Intervention on neutrophil predominant airway inflammation in a ragweed sensitized murine asthma model.

BACKGROUND: Neutrophil-predominant asthma is less responsive to steroids and associated with poorer disease control. The effects of Antiasthma Simplified Herbal Medicine Intervention (ASHMI), a traditional Chinese medicine formula reported to be efficacious in asthmatic patients and murine asthma models, on neutrophil predominant asthma are unknown. OBJECTIVE: To determine the effects of standard ASHMI and refined formula ASHMI (ASHMI(II)) in a neutrophil-predominant murine model of ragweed (RW) asthma and explore underlying mechanisms. METHODS: BALB/c mice were systemically sensitized, intranasally challenged with RW extract, and orally treated with ASHMI, ASHMI(II), or vehicle (water). In a separate experiment, some RW sensitized mice were treated with dexamethasone before challenge. After RW challenge, airway hyperreactivity (AHR), total and differential bronchoalveolar lavage fluid leukocyte counts, lung histologic features, and bronchoalveolar lavage fluid cytokine and chemokine levels were assessed. RW stimulation of the murine macrophage cell line RAW264.7 was used to determine effects of ASHMI active compound ganoderic acid C1 (GAC1) on tumor necrosis factor α (TNF-α) production and regulation of phosphorylated IκB and histone deacetylase 2 (HDAC2) levels. RESULTS: ASHMI and ASHMI(II) markedly reduced AHR, mucous production, neutrophilic inflammation, and TNF-α, interleukin 8, and interleukin 17 levels and decreased eosinophilic inflammation and TH2 responses in vivo (P < .01-.001 for all). GAC1 inhibited TNF-α production in RW-stimulated RAW264.7 cells in association with suppression of phosphorylated IκB and increased HDAC2 expression. Dexamethasone failed to reduce AHR and neutrophilic inflammation. CONCLUSION: ASHMI treatment was efficacious in a murine model of neutrophil-predominant asthma via modulation of innate chemokines, TH2 responses, nuclear factor-κB, and HDAC2. ASHMI, and/or its constituent GAC1, may be a valuable option for treating neutrophil-predominant asthma.

The anti-asthma herbal medicine ASHMI acutely inhibits airway smooth muscle contraction via prostaglandin E2 activation of EP2/EP4 receptors.

Our previous studies have shown that the anti-asthma traditional Chinese medicine herbal formula ASHMI (anti-asthma simplified herbal medicine intervention) inhibits acetylcholine-induced contractions of tracheal rings from ovalbumin-sensitized and naive mice in a ß-adrenoceptor-independent manner. We sought to determine whether acute in vivo ASHMI administration inhibits airway hyperreactivity (AHR) in a murine model of allergic asthma and acetylcholine-induced tracheal ring constriction ex vivo and to elucidate the cellular mechanisms underlying these effects. Ovalbumin-sensitized mice received a single oral ASHMI dose 2 h before intravenous acetylcholine challenge. AHR was determined by invasive airway measurements. Myography was used to determine the effects of ASHMI on acetylcholine-induced constriction of tracheal rings from asthmatic mice with or without epithelial denudation. The effect of cyclooxygenase inhibition and EP2/EP4 receptor blockade on ASHMI attenuation of acetylcholine contractions was evaluated. Tracheal cAMP and PGE2 levels were measured by ELISA. A single acute oral dose of ASHMI dramatically reduced AHR in response to acetylcholine provocation in ovalbumin-sensitized mice (P < 0.001). In ex vivo experiments, ASHMI significantly and dose-dependently reduced tracheal ring constriction to acetylcholine (P < 0.05-0.001), which was epithelium independent and associated with elevated cAMP levels. This effect was abrogated by cyclooxygenase inhibition or EP2/EP4 receptor blockade. ASHMI also inhibited contraction to high K(+) (P < 0.001). ASHMI increased tracheal ring PGE2 release in response to acetylcholine or high K(+) (P < 0.05 for both). ASHMI produced direct and acute inhibition of AHR in vivo and blocked acetylcholine-induced tracheal ring constriction via the EP2/EP4 receptor pathway, identifying the mechanism by which ASHMI is an orally active bronchoprotective agent.

Glycyrrhiza uralensis flavonoids present in anti-asthma formula, ASHMI™, inhibit memory Th2 responses in vitro and in vivo.

Allergic asthma is associated with Th2-mediated inflammation. Several flavonoids were isolated from Glycyrrhiza uralensis, one of the herbs in the anti-asthma herbal medicine intervention. The aim of this investigation was to determine whether Glycyrrhiza uralensis flavonoids have inhibitory effects on memory Th2 responses in vitro and antigen-induced Th2 inflammation in vivo. The effects of three Glycyrrhiza uralensis flavonoids on effector memory Th2 cells, D10.G4.1 (D10 cells), were determined by measuring Th2 cytokine production. Isoliquiritigenin, 7, 4'-dihydroxyflavone (7, 4'-DHF) and liquiritigenin significantly suppressed IL-4 and IL-5 production in a dose-dependent manner, 7, 4'-DHF being most potent. It was also evaluated for effects on D10 cell proliferation, GATA-3 expression and IL-4 mRNA expression, which were suppressed, with no loss of cell viability. Chronic treatment with 7, 4'-DHF in a murine model of allergic asthma not only significantly reduced eosinophilic pulmonary inflammation, serum IgE levels, IL-4 and IL-13 levels, but also increased IFN-γ production in lung cell cultures in response to antigen stimulation.

Efficacy and immunological actions of FAHF-2 in a murine model of multiple food allergies.

BACKGROUND: Food Allergy Herbal Formula-2 (FAHF-2) prevents anaphylaxis in a murine model of peanut allergy. Multiple food allergies (MFA) are common and associated with a higher risk of anaphylaxis. No well-characterized murine model of sensitization to multiple food allergens exists, and no satisfactory therapy for MFA is currently available. OBJECTIVE: To determine the effect of FAHF-2 in a murine model of MFA. METHODS: C3H/HeJ mice were orally sensitized to peanut, codfish, and egg concurrently. Oral FAHF-2 treatment commenced 1 day after completing sensitization and continued daily for 7 weeks. Mice were subsequently orally challenged with each allergen. RESULTS: Antibodies in sera from mice simultaneously sensitized with peanut, codfish, and egg recognized major allergens of all 3 foods, demonstrating sensitization to multiple unrelated food allergens (MFA mice). Sham-treated MFA mice exhibited anaphylactic symptoms accompanied by elevation of plasma histamine and hypothermia. In contrast, FAHF-2-treated MFA mice showed no anaphylactic symptoms, normal body temperature, and histamine levels after challenge with each allergen. Protection was accompanied by reduction in allergen-specific immunoglobulin E levels. Allergen-stimulated Th2 cytokine interleukin-4 and interleukin-13 production levels decreased, whereas the Th1 cytokine interferon-γ levels were elevated in cultured splenocytes and mesenteric lymph node cells in FAHF-2-treated mice. CONCLUSION: We established the first murine model of MFA. FAHF-2 prevents peanut, egg, and fish-induced anaphylactic reactions in this model, suggesting that FAHF-2 may have potential for treating human MFA.

Treatments for food allergy: how close are we?

Food allergy continues to be a challenging health problem, with prevalence continuing to increase and anaphylaxis still an unpredictable possibility. While improvements in diagnosis are more accurately identifying affected individuals, treatment options remain limited. The cornerstone of treatment relies on strict avoidance of the offending allergens and education regarding management of allergic reactions. Despite vigilance in avoidance, accidental ingestions and reactions continue to occur. With recent advances in the understanding of humoral and cellular immune responses in food allergy and mechanisms of tolerance, several therapeutic strategies for food allergies are currently being investigated with the hopes of providing a cure or long-term remission from food allergy.

Clinical safety of Food Allergy Herbal Formula-2 (FAHF-2) and inhibitory effect on basophils from patients with food allergy: Extended phase I study.

BACKGROUND: Food allergy is a common and increasing health concern in westernized countries. No effective treatment is available, and accidental ingestion can be life-threatening. Food Allergy Herbal Formula-2 (FAHF-2) blocks peanut-induced anaphylaxis in a murine model of peanut-induced anaphylaxis. It was found to be safe and well tolerated in an acute phase I study of patients with food allergy. OBJECTIVE: We sought to assess the safety of FAHF-2 in an extended phase I clinical trial and determine the potential effects on peripheral blood basophils from patients with food allergy. METHODS: Patients in an open-label study received 3.3 g (6 tablets) of FAHF-2 three times a day for 6 months. Vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiographic data were acquired at baseline and at 2-month intervals. During the course of the study, basophil activation and basophil and eosinophil numbers were evaluated by using CCR3/CD63 staining and flow cytometry. RESULTS: Of 18 patients enrolled, 14 completed the study. No significant drug-associated differences in laboratory parameters, pulmonary function study results, or electrocardiographic findings before and after treatment were found. There was a significant reduction (P < .010) in basophil CD63 expression in response to ex vivo stimulation at month 6. There was also a trend toward a reduction in eosinophil and basophil numbers after treatment. CONCLUSION: FAHF-2 was safe and well tolerated and had an inhibitory effects on basophil numbers in an extended phase I clinical study. A controlled phase II study is warranted.

Future therapies for food allergies.

Food allergy is an increasingly prevalent problem in westernized countries, and there is an unmet medical need for an effective form of therapy. A number of therapeutic strategies are under investigation targeting foods that most frequently provoke severe IgE-mediated anaphylactic reactions (peanut, tree nuts, and shellfish) or are most common in children, such as cow's milk and hen's egg. Approaches being pursued are both food allergen specific and nonspecific. Allergen-specific approaches include oral, sublingual, and epicutaneous immunotherapy (desensitization) with native food allergens and mutated recombinant proteins, which have decreased IgE-binding activity, coadministered within heat-killed Escherichia coli to generate maximum immune response. Diets containing extensively heated (baked) milk and egg represent an alternative approach to food oral immunotherapy and are already changing the paradigm of strict dietary avoidance for patients with food allergy. Nonspecific approaches include monoclonal anti-IgE antibodies, which might increase the threshold dose for food allergen in patients with food allergy, and a Chinese herbal formulation, which prevented peanut-induced anaphylaxis in a murine model and is currently being investigated in clinical trials. The variety of strategies for treating food allergy increases the likelihood of success and gives hope that accomplishing an effective therapy for food allergy is within reach.

Safety, tolerability, and immunologic effects of a food allergy herbal formula in food allergic individuals: a randomized, double-blinded, placebo-controlled, dose escalation, phase 1 study.

BACKGROUND: Food allergy is a common and serious health problem. A new herbal product, called food allergy herbal formula 2 (FAHF-2), has been demonstrated to have a high safety profile and potent long-term efficacy in a murine model of peanut-induced anaphylaxis. OBJECTIVE: To evaluate the safety and tolerability of FAHF-2 in patients with food allergy. METHODS: In this randomized, double-blinded, placebo-controlled, dose escalation, phase 1 trial, patients received 1 of 3 doses of FAHF-2 or placebo: 2.2 g (4 tablets), 3.3 g (6 tablets), or 6.6 g (12 tablets) 3 times a day for 7 days. Four active and 2 placebo patients were treated at each dose level. Vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiogram data were monitored. Immunomodulatory studies were also performed. RESULTS: Nineteen food allergic participants were included in the study. Two patients (1 in the FAHF-2 group and 1 in the placebo group) reported mild gastrointestinal symptoms. One patient withdrew from the study because of an allergic reaction that was unlikely related to the study medication. No significant differences were found in vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiogram data obtained before and after treatment visits. Significantly decreased interleukin (IL) 5 levels were found in the active treatment group after 7 days. In vitro studies of peripheral blood mononuclear cells cultured with FAHF-2 also demonstrated a significant decrease in IL-5 and an increase in culture supernatant interferon gamma and IL-10 levels. CONCLUSIONS: FAHF-2 appeared to be safe and well tolerated in patients with food allergy.

Food allergy.

Adverse immune responses to foods affect approximately 5% of young children and 3% to 4% of adults in westernized countries and appear to have increased in prevalence. Food-induced allergic reactions are responsible for a variety of symptoms and disorders involving the skin and gastrointestinal and respiratory tracts and can be attributed to IgE-mediated and non-IgE-mediated (cellular) mechanisms. Genetic disposition and environmental factors might abrogate oral tolerance, leading to food allergy. Disease outcomes are influenced by the characteristics of the immune response and of the triggering allergen. Diagnosis is complicated by the observation that detection of food-specific IgE (sensitization) does not necessarily indicate clinical allergy. Therefore diagnosis requires a careful medical history, laboratory studies, and, in many cases, an oral food challenge to confirm a diagnosis. Novel diagnostic methods, including ones that focus on immune responses to specific food proteins or epitopes of specific proteins, are under study. Currently, management of food allergies consists of educating the patient to avoid ingesting the responsible allergen and to initiate therapy (eg, with injected epinephrine for anaphylaxis) in case of an unintended ingestion. Improved therapeutic strategies under study include oral and sublingual immunotherapy, Chinese herbal medicine, anti-IgE antibodies, and modified vaccines.

Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-gamma-producing CD8+ T cells.

BACKGROUND: Food allergy is a serious and sometimes fatal condition for which there is no cure. We previously reported that Food Allergy Herbal Formula (FAHF)-2) protected peanut-allergic mice against anaphylactic reactions as long as 4 weeks posttherapy. This formula is now in clinical trials in the United States. OBJECTIVE: We sought to determine whether FAHF-2-mediated protection could be extended long-term and explored the mechanisms underlying its persistent immunomodulatory effects. METHODS: Peanut-allergic mice received FAHF-2 daily orally by gavage for 7 weeks, and then received 7 oral peanut challenges at intervals of 4 to 10 weeks over a period of 36 weeks. For mechanistic studies, some mice received CD4(+) or CD8(+) T-cell-depleting antibodies or IFN-gamma-neutralizing antibodies. Anaphylactic symptoms, body temperatures, and plasma histamine levels were recorded after each challenge, and peanut-specific immunoglobulin levels and cytokine profiles of splenocytes, mesenteric lymph node cells, and purified CD4(+) and CD8(+) T cells were determined. RESULTS: Food Allergy Herbal Formula-2 treatment protected mice from anaphylaxis for more than 36 weeks after discontinuing treatment. Peanut-specific IgE levels were reduced as much as 50%, whereas IgG(2a) levels were increased as much as 60%, and these effects persisted over time. T(H)2 cytokine production by CD4(+) T cells from FAHF-2-treated mice was reduced as much as 75%, whereas CD8(+) T-cell IFN-gamma production was markedly increased by as much as 85% at the final challenge. Neutralization of INF-gamma and depletion of CD8(+) T cells markedly attenuated FAHF-2 efficacy. CONCLUSIONS: Food Allergy Herbal Formula-2 provides long-term protection from anaphylaxis by inducing a beneficial shift in allergen-specific immune responses mediated largely by elevated CD8(+) T-cell IFN-gamma production.

Food allergy: recent advances in pathophysiology and treatment.

Food allergies, defined as an adverse immune response to food proteins, affect as many as 6% of young children and 3%-4% of adults in westernized countries, and their prevalence appears to be rising. In addition to well-recognized acute allergic reactions and anaphylaxis triggered by IgE antibody-mediated immune responses to food proteins, there is an increasing recognition of cell-mediated disorders such as eosinophilic gastroenteropathies and food protein-induced enterocolitis syndrome. We are gaining an increasing understanding of the pathophysiology of food allergic disorders and are beginning to comprehend how these result from a failure to establish or maintain normal oral tolerance. Many food allergens have been characterized at a molecular level, and this knowledge, combined with an increasing appreciation of the nature of humoral and cellular immune responses resulting in allergy or tolerance, is leading to novel therapeutic approaches. Currently, management of food allergies consists of educating the patient to avoid ingesting the responsible allergen and initiating therapy if ingestion occurs. However, numerous strategies for definitive treatment are being studied, including sublingual/oral immunotherapy, injection of anti-IgE antibodies, cytokine/anticytokine therapies, Chinese herbal therapies, and novel immunotherapies utilizing engineered proteins and strategic immunomodulators.

Towards a cure for food allergy.

Over the past two decades, food allergies have become both more prevalent and long lasting. This burgeoning problem has not been met with any therapeutic options to date, and patients must attempt to avoid known allergenic foods and treat any allergic reactions with 'as-needed' medications. There are a number of promising emerging therapeutic modalities for food allergy, including allergen-specific and allergen non-specific immunotherapeutic approaches. Although the allergen-specific approaches have some distinct differences, they all attempt to induce tolerance by exposing the patient to an allergen via the mucosal route (oral tolerance induction). Allergen non-specific approaches include biologics to suppress free total IgE levels (e.g. anti-IgE antibody) or to induce more general immune suppression (Chinese herbal medication).

Hypoallergenicity and effects on growth and tolerance of a new amino acid-based formula with docosahexaenoic acid and arachidonic acid.

OBJECTIVE: In study 1, to compare the effect on growth in healthy infants of a new amino acid-based formula (AAF) and a control extensively hydrolyzed formula (EHF), with both docosahexaenoic acid (DHA) and arachidonic acid (ARA) at levels similar to those in human milk worldwide. In study 2, to evaluate the hypoallergenicity of this new AAF in infants and children with confirmed cow's milk allergy (CMA). STUDY DESIGN: In study 1, a total of 165 healthy, full-term, formula-fed infants randomly received the new AAF or control formula. Anthropometric measurements, tolerance, and adverse events were recorded throughout the study. Plasma amino acid profiles were evaluated in a subset of the infants. In study 2, the hypoallergenicity of the new AAF was evaluated in 32 infants and children using a double-blind, placebo-controlled food challenge; an open challenge; and a 7-day feeding. RESULTS: In study 1, overall growth, tolerance, and safety outcomes were similar in both groups. In study 2, 29 of the 32 subjects completed both challenges; no allergic reaction was seen in any of the 32 subjects. CONCLUSIONS: The new AAF with DHA and ARA at levels similar to those in human milk worldwide is hypoallergenic. It also is safe and supports growth in healthy, term infants.

Pharmacological and immunological effects of individual herbs in the Food Allergy Herbal Formula-2 (FAHF-2) on peanut allergy.

It was previously shown that a Chinese herbal formula, Food Allergy Herbal Formula 2 (FAHF-2) composed of nine herbs, blocked peanut-induced anaphylaxis in a murine model. The current study was designed to investigate the pharmacological actions of individual herbs comprising FAHF-2 on peanut-induced anaphylactic reactions in a murine model of peanut allergy and to determine if all nine herbs are necessary to prevent an anaphylactic reaction, or if a simplified formula containing fewer herbs would be equally effective. Some individual herbs reduced peanut-induced anaphylactic symptoms but no single herb offered full protection from anaphylactic symptoms equivalent to FAHF-2. The herbs had highly variable effects on histamine release, as well as peanut-specific serum IgE and IgG2a levels. The herbs also had variable effects on IL-4, IL-5 and IFN-gamma levels. A simplified formula comprising the most efficacious tested individual herbs showed only partial efficacy and was not able to reproduce comparably the effects of FAHF-2, suggesting that component herbs of FAHF-2 may work synergistically to produce the curative therapeutic effects produced by the whole formula, which appears to be the best option for future clinical trials.