Abstract

Botanical seed oils reduce the generation of leukotrienes in patients with asthma.Our objective was to determine the efficacy of a botanical seed oil combination against airflow obstruction in asthma, and to determine the pharmacogenomic effect of the leukotriene C4 synthase (LTC4S) polymorphism A-444C.We conducted a randomized, double-blind, placebo-controlled, cross-over clinical trial in mild to moderate asthmatics to determine the change in FEV1 after 6 weeks of therapy with borage and echium seed oils versus corn oil placebo. We also examined the effect of the variant LTC4S -444C allele on the change in lung function.We did not identify a difference in FEV1 in the study cohort as a whole (n = 28), nor in the group of A homozygotes. In the C allele carriers (n = 9), FEV1 improved by 3% after treatment with borage and echium seed oils and declined by 4% after placebo corn oil (p = 0.02). All 9 C allele carriers demonstrated an improvement in their FEV1 on active treatment compared to placebo as compared to only 7 out of 19 A allele homozygotes (p = 0.007). We observed transient differences in ex vivo leukotriene generation from circulating basophils and granulocytes. We did not observe significant differences in urinary LTE4 levels.We conclude that compared to corn oil, a combination of borage and echium seed oils improves airflow obstruction in mild to moderate asthmatics who carry the variant allele in the LTC4S gene (A-444C). Botanical oil supplementation may have therapeutic potential in asthma if used in a personalized manner.Trial registration: This trial was registered at http://www.clinicaltrials.gov as NCT00806442.

Highlights

  • Botanical seed oils reduce the generation of leukotrienes in patients with asthma

  • We hypothesized that dietary supplementation with the botanical seed oil combination would improve airflow obstruction in asthmatics when compared to placebo, preferentially in those who carried the variant C allele at the leukotriene C4 synthase (LTC4S) A-444C locus

  • This study demonstrates that a combination of omega-3 and omega-6 dietary medium chain Polyunsaturated fatty acid (PUFA), provided over six weeks in a fixed ratio in the form of borage and echium seed oils, results in a significant difference in Forced expiratory volume in one second (FEV1) compared with corn oil placebo in subjects bearing at least one copy of a polymorphic LTC4S allele in a small proof-of-concept crossover study

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Summary

Introduction

Botanical seed oils reduce the generation of leukotrienes in patients with asthma. Our objective was to determine the efficacy of a botanical seed oil combination against airflow obstruction in asthma, and to determine the pharmacogenomic effect of the leukotriene C4 synthase (LTC4S) polymorphism A-444C. We conclude that compared to corn oil, a combination of borage and echium seed oils improves airflow obstruction in mild to moderate asthmatics who carry the variant allele in the LTC4S gene (A-444C). Studies have demonstrated that dietary supplementation with marine or botanical seed oils containing omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can decrease airway inflammation by reducing the generation of leukotrienes and pro-inflammatory cytokines, and attenuating neutrophil function (Barros et al 2011; Chilton-Lopez et al 1996; Lee et al 1985). We hypothesized that dietary supplementation with the botanical seed oil combination would improve airflow obstruction in asthmatics when compared to placebo, preferentially in those who carried the variant C allele at the LTC4S A-444C locus

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