Effect of a soy isoflavone supplement on lung function and clinical outcomes in patients with poorly controlled asthma: a randomized clinical trial

Abstract

Importance: Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control.

Objective: To determine whether a soy isoflavone supplement improves asthma control in adolescent and adult patients with poorly controlled disease.

Design, setting, and participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted between May 2010 and August 2012 at 19 adult and pediatric pulmonary and allergy centers in the American Lung Association Asthma Clinical Research Centers network. Three hundred eighty-six adults and children aged 12 years or older with symptomatic asthma while taking a controller medicine and low dietary soy intake were randomized, and 345 (89%) completed spirometry at week 24.

Interventions: Participants were randomly assigned to receive soy isoflavone supplement containing 100 mg of total isoflavones (n=193) or matching placebo (n=193) in 2 divided doses administered daily for 24 weeks.

Main outcomes and measures: The primary outcome measure was change in forced expiratory volume in the first second (FEV1) at 24 weeks. Secondary outcome measures were symptoms, episodes of poor asthma control, Asthma Control Test score (range, 5-25; higher scores indicate better control), and systemic and airway biomarkers of inflammation.

Results: Mean changes in prebronchodilator FEV1 over 24 weeks were 0.03 L (95% CI, -0.01 to 0.08 L) in the placebo group and 0.01 L (95% CI, -0.07 to 0.07 L) in the soy isoflavone group, which were not significantly different (P = .36). Mean changes in symptom scores on the Asthma Control Test (placebo, 1.98 [95% CI, 1.42-2.54] vs soy isoflavones, 2.20 [95% CI, 1.53-2.87]; positive values indicate a reduction in symptoms), number of episodes of poor asthma control (placebo, 3.3 [95% CI, 2.7-4.1] vs soy isoflavones, 3.0 [95% CI, 2.4-3.7]), and changes in exhaled nitric oxide (placebo, -3.48 ppb [95% CI, -5.99 to -0.97 ppb] vs soy isoflavones, 1.39 ppb [95% CI, -1.73 to 4.51 ppb]) did not significantly improve more with the soy isoflavone supplement than with placebo. Mean plasma genistein level increased from 4.87 ng/mL to 37.67 ng/mL (P < .001) in participants receiving the supplement.

Conclusions and relevance: Among adults and children aged 12 years or older with poorly controlled asthma while taking a controller medication, use of a soy isoflavone supplement, compared with placebo, did not result in improved lung function or clinical outcomes. These findings suggest that this supplement should not be used for patients with poorly controlled asthma.

Trial registration: clinicaltrials.gov Identifier: NCT01052116.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Smith reports receipt of personal fees for Data and Safety Monitoring Board membership from Merck and co-chairing an educational program from Scientific Therapeutics Information. Dr Kalhan reports receipt of personal fees from Forest Laboratories, Boerhinger Ingelheim, Merck, and Quantia Communications and grants to his institution from Boerhinger Ingelheim, GlaxoSmithKline, PneumRx, and Spiration. Dr Wise reports receipt of personal fees for consultancy from Boerhinger Ingelheim, GlaxoSmithKline, Forest Laboratories, Novartis, Sunovion, AstraZeneca, Janssen, Genentech, Bristol-Myers Squibb, Pulmonx, Merck, Spiration, and Teva and grants/grants pending to his institution from GlaxoSmithKline/American Lung Association, AstraZeneca, BIPI, Forest Laboratories, Pearl, and Sunovion. No other disclosures were reported.

Figures

Figure 1. Flow of Participants in the Study of Soy Isoflavones in Asthma Randomized Clinical Trial

FEV1 indicates forced expiratory volume in the first second. aFor 1 individual in this group, it was also reported that poor asthma control was not demonstrated.

Figure 2. Change in Prebronchodilator FEV1 During 24 Weeks of Treatment

Model-based mean change in prebronchodilator forced expiratory volume in the first second (FEV1) at each study visit compared with baseline values. Error bars indicate with 95% confidence intervals. Evaluable FEV1 results were not available at the randomization visit for 1 participant in the placebo group and 2 participants in the soy isoflavone group.