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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00602160.

Figure 1

Manufacturing process. Ling-Zhi were cut into small pieces, soaked in water overnight, and then boiled twice for 2 hours each time. The decoctions were combined, dried, and ground into fine powder. Hong-Shen was extracted twice with 80% aqueous ethanol. The ethanol extract was filtered, combined, and evaporated until no residual ethanol was present. The residue was combined with the rest of the 7 herbs and boiled twice in water for 1.5 hours each time. The decoction was collected, combined, and concentrated to 1.05 to 1.10 g/mL and purified by ethanol precipitation and then combined with the Hong-Shen ethanol extract. The extract was dried under reduced pressure (60°C). Both the 8-herb substance and Ling-Zhi powder were granulated and mixed together to form the food allergy herbal formula 2 (FAHF-2) extract.

Figure 2

High-performance liquid chromatography (HPLC) chromatogram. HPLC fingerprints of the food allergy herbal formula 2 (FAHF-2) (A) and 3 key individual herbs, Wu-Mei, Huang-Bai, and Ling-Zhi (B–D, respectively). HPLC conditions: column, Agilent Zorbax SB-C18 column (150 × 4.6-mm internal diameter; 5-mm particle size); flow rate, 1 mL/min; wavelength, 254 nm; column temperature, 27°C; mobile phase A, 0.10% H₃PO₄; and mobile phase B, acetonitrile. Data were processed using Waters Empower software.

Figure 3

Cytokine levels of patient peripheral blood mononuclear cells (PBMCs) before and after food allergy herbal formula 2 (FAHF-2) treatment in ex vivo. Patient PBMCs from the phase 1 study separated on a Ficoll gradient were cultured in AIM-V media with media alone, allergen, or phytohemagglutinin A for 72 hours at baseline and after a week of treatment with FAHF-2 or placebo. The supernatants were analyzed by enzyme-linked immunosorbent assay. Statistical analysis was performed with the Wilcoxon signed rank test. Bars indicate medians of each group (FAHF-2, n = 7–9; placebo, n = 4–5).

Figure 4

The in vitro effect of food allergy herbal formula 2 (FAHF-2) treatment on cytokine levels of patient peripheral blood mononuclear cells (PBMCs). Patient PBMCs separated on a Ficoll gradient were cultured in AIM-V media with media alone, allergen, allergen plus FAHF-2, or phytohemagglutinin A for 72 hours. The supernatants were analyzed by enzyme-linked immunosorbent assay. Closed circles indicate an FAHF-2 concentration of 250 μg/mL; open circles, FAHF-2 concentration of 100 μg/mL. Statistical analysis was performed with the Wilcoxon signed rank test. Bars indicate medians of each group (n = 11).