Low-grade inflammation, diet composition and health: current research evidence and its translation

Abstract

The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled 'Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies'. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation-health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation-health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims.

Keywords: Biomarkers; Chronic diseases; Health claims; Low-grade inflammation.

Fig. 1

Two-hit model of non-alcoholic fatty liver disease. (A colour version of this figure can be found online at http://www.journals.cambridge.org/bjn).

Fig. 2

Schematic of topics to be addressed when building a dossier for a European Food Safety Authority (EFSA) health claim on control of chronic low-grade inflammation. The blue boxes indicate the main topics to be addressed; the white boxes state the actual content topics. Building a strong EFSA health claim dossier requires (1) a definition of the composition of the nutritional component including manufacturing procedures in scope and out of scope for the claim, (2) a clear definition of the target population, being the general population or a specific subpopulations at risk, including the defining parameters, (3) a definition of biomarkers measured to assess the health effects of the nutritional component, including a description of the proof of clinical relevance, or the clinical validity of the combination of inflammation biomarkers and related clinically relevant biomarkers for health benefit endpoints associated with the health claim, and (4) a full description of clinical study design for all studies included in the dossier, including statistical power analysis and safety evaluation. The red arrow indicates the primary hurdle for functional health claims in the area of chronic low-grade inflammation, which is the lack of (combinations of) inflammation biomarkers with established and therefore accepted clinical relevance. This is primarily the consequence of inflammatory responses being non-specific normal physiological responses to tissue damage, and discrimination between normal and abnormal levels or combinations has not been well established in relation to chronic low-grade inflammation. The description of the classification of clinical relevance of biomarkers (categories A–D) was adapted from Albers et al. ^{( 137 )}. RCT, randomised controlled trial. (A colour version of this figure can be found online at http://www.journals.cambridge.org/bjn).