Dietary indole glucosinolates and skatole: Do they have a role in idiopathic pulmonary fibrosis: Case series data and review

Abstract

Background: Idiopathic Pulmonary Fibrosis appeared as a new clinical entity alongside fibrotic radiographs of known occupational lung disease from the late 1970’s. The veterinary world also recognised an acute fatal lung injury and a slower progressive fibrosis in farm animal’s especially older males. They identified the pneumotoxicant to be linked to forage Brassica ingestion and reproduced both conditions in the field by varying exposure levels. In the UK, dietary Brassica intake has increased by the progressive replacement of sunflower oil by the Brassica derived oilseed rape in foods. Method: We have examined the effects of ingestion of this oil in 8 healthy medical staff and measured 10 serum mediators relevant to IPF. We have clinically followed a group of patients (9 IPF and 7 Fibrotic-NSIP) who also reduced their dietary rapeseed oil intake by 70%. Results: The medical staff showed elevations in serum tumour necrosis factor-α (p=0.036), caspase-3 (p=0.0046), matrix metalloprotease-7 (p=0.011), vascular endothelial growth factor (p=0.045), cardiac troponin (p=0.038) and plasma thiocyanate (p=0.028). Alpha-1 antitrypsin levels decreased (p=0.0024) while transforming growth factor β, cytochrome C and Pink1 showed non-significant reductions in levels. With daily oil intake of 20 ml, Caspase-3 and cardiac troponin showed a positive correlation (r=0.8214: p=0.0286), as did thiocyanate, caspase-3 and vascular endothelial growth factor (r=0.8986: p=0.0241)). A negative correlation was for transforming growth factor β and VEGF levels (r=0.8214: p=0.0286) and cytochrome C and thiocyanate (r=0.9820; p=0.0021). For the patients, coughing resolved within 4 weeks with reasonable stability of forced vital capacity, walking tests and HRCT scores unless impacted by COVID-19 infections or other significant medical events. The mean patient follow-up was 4.8-5.2 years. Conclusion: We discuss the findings within these 2 groups and review the veterinary data and information on the Brassica family and the effects of their released glucosinolates.