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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Inflammatory markers, kynurenines, and B-vitamins in relation to chronic disease and mortality in a population based prospective study

Awarded: NOK 5.7 mill.

Inflammation plays a key role in the onset of many chronic diseases. Although extensive research has been carried out in the past decades to unravel the role of B-vitamins in cardiovascular disease (CVD) and cancer, exact mechanisms behind observed inverse associations of B-vitamins with CVD and cancer are largely unknown. However, recent studies revealed lower vitamin B6 concentrations during inflammation. Since vitamin B6 is inversely associated with CVD and cancer, and because both vitamins B2 and B6 are cofactors in the kynurenine pathway - an important metabolic route related to inflammation - it may be hypothesised that inflammation is a predominant underlying cause of these inverse associations. The research carried out in this project is the first study focussing on potential determinants of kynurenines and related inflammatory markers, as well as on the relation of kynurenines and inflammatory markers with the incidence of chronic disease and mortality in a large population based study, the Hordaland Health study. This knowledge is of relevance in clinical medicine and public health because kynurenine metabolites may represent potential biomakers for future use in risk assessemnt of cardiovascular disease, cancer, and mortality

It is hypothesized that inflammation plays a key role in the onset of many chronic diseases. Although inverse associations of vitamins B6 and B2 with CVD and cancers are shown, mechanisms are unclear. However, recent studies revealed lower vitamin B6 leve ls with increased C-reactive protein - a common inflammatory marker. Inflammation increases the conversion of tryptophan to kynurenine, which is further metabolised by vitamins B6 and B2 as cofactors. As vitamin B6 is associated with CVD and cancer, and a s vitamin B6 and B2 are cofactors in the kynurenine pathway, B6 and B2 may form a link between the kynurenine pathway and CVD and cancer. A few small studies showed higher kynurenine concentrations in cancer- and CVD patients compared to controls. Additio nally, a mice study showed that kynurenine contributed to vascular relaxation and the regulation of blood pressure in inflammation. The Hordaland Health (HUSK, n=7.047) study has recently been linked to the Cancer Registry, the Cardiovascular Disease Reg istry Health Region West, and the Cause of Death Registry. The main aim is to prospectively investigate associations of vitamins B6 and B2, kynurenine metabolites and inflammatory markers with cancer (n=763) and CVD (n=1800) incidence, mortality (n=862), and components of the metabolic syndrome. Moreover, we will investigate whether inflammation is a predominant underlying cause of inverse associations of B6 with CVD and cancer, or that high vitamin B6 and low kynurenine collectively contribute to a prote ctive effect. Results will shed light on major gaps in the research field of inflammation, kynurenines, and B-vitamins in chronic inflammatory diseases. The proposed research will be in the front line of this research area. Depending on study results and considering how important the kynurenine pathway might be, it is not unlikely that kynurenine metabolites represent future biomarkers for use in risk assessment in relation to clinical outcomes.

Funding scheme:

FRIMEDBIO-Fri prosj.st. med.,helse,biol

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