Eighteen‑carbon trans fatty acids and inflammation in the context of atherosclerosis

Abstract

Endothelial dysfunction is a pro-inflammatory state characterized by chronic activation of the endothelium, which leads to atherosclerosis and cardiovascular disease (CVD). Intake of trans fatty acids (TFAs) is associated with an increased risk of CVD. This risk is usually associated with industrial TFAs (iTFAs) rather than ruminant TFAs (rTFAs); however it is not clear how specific TFA isomers differ in their biological activity and mechanisms of action with regard to inflammation. Here we review the literature on 18‑carbon TFAs, including the research associating their intake or levels with CVD and studies relating 18‑carbon TFA exposure to modulation of inflammatory processes. The evidence associating iTFAs with CVD risk factors is fairly consistent and studies in humans usually show a relation between iTFAs and higher levels of inflammatory markers. In contrast, studies in humans, animals and in vitro suggest that rTFAs have null or mildly beneficial effects in cardiovascular health, metabolic parameters and inflammatory markers, although the evidence is not always consistent. More studies are needed to better identify the beneficial and detrimental effects of the different TFAs, including those with 18 carbons.

Introduction

Inflammation is an essential component of innate immunity, helping to defend the host against infections. The initial acute phase of the inflammatory response is followed by resolution and recovery, with activation of negative feedback mechanisms that oppose the inflammatory signals, remove damaged cells and tissue debris, and promote the repair of damaged tissues. In many chronic illnesses, the self-limiting nature of inflammation is lost, contributing to the pathology of the disease due to on-going (i.e. chronic) inflammation [1,2]. This has been described for many highly prevalent conditions such as obesity, coronary heart disease (CHD), non-alcoholic fatty acid liver disease (NAFLD) and type 2 diabetes [3,4].

Fatty acids (FAs) are key components of cell membrane phospholipids, through which they are able to modify cell responses to inflammatory signals. Among FAs, trans fatty acids (TFAs) are unsaturated FAs containing one or more double bonds in the trans rather than the cis geometric configuration. Since humans cannot produce TFAs de novo, plasma and tissue levels of TFAs reflect dietary intake. Dietary TFAs can have two origins, being produced either through metabolism in a living organism or through industrial or processing manipulations of fats and oils. The main source of TFAs in western diets is partially hydrogenated vegetable oils, which have been extensively associated with adverse health outcomes, particularly, increasing risk factors for cardiovascular disease (CVD) and systemic inflammation. A high intake of partially hydrogenated vegetable oil TFAs has been shown to induce an altered blood lipid profile, with increased levels of triacylglycerols (TAGs) and low density lipoprotein (LDL)-cholesterol and decreased levels of high density lipoprotein (HDL)-cholesterol, together with a pro-inflammatory state and endothelial dysfunction [5,6]. A second type of dietary TFAs are the ones produced naturally via biohydrogenation of unsaturated fats by ruminant bacteria. There remains debate regarding the health effects of ruminant fat intake; however, growing evidence suggests that the major ruminant TFAs (rTFAs) are neutral or even beneficial for health. Most prospective studies show that diets enriched in rTFAs have no significant effects on plasma C-reactive protein (CRP) levels or blood lipids, while decreasing plasma levels of cytokines like interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α [[7], [8], [9]].

CHD and stroke have remained the leading causes of death globally in the last 15 years [10]; therefore, decreasing the risk for these CVDs by reducing the intake of harmful TFAs continues to be a major public health objective worldwide. Even before the World Health Organisation announcement in 2018 recommending the elimination of industrially produced TFAs from the food supply [11], many countries had adopted TFA regulations, including the European Union [[12], [13], [14]]. Nevertheless, >110 countries have not yet established regulations against TFAs, meaning that 5 billion people are still at risk from iTFA exposure (World Health Organisation, 2019). However, it is not clear how specific TFA isomers differ in their biological activity and mechanisms of action with regard to inflammation. Considering the need for greater knowledge about the possible differential effects of TFAs on inflammation, the aim of this article is to review the current evidence in this matter. A previous review described the broad-ranging effects of conjugated linoleic acids (CLAs) and their mechanisms of action [15]. There have been a number of studies of CLAs published since that review. In addition, the current review also considers common trans monounsaturated fatty acids and focusses upon inflammation in the context of atherosclerosis.