Inflammatory Diseases and Vitamin E—What Do We Know and Where Do We Go?

Abstract

Inflammation‐driven diseases and related comorbidities, such as the metabolic syndrome, obesity, fatty liver disease, and cardiovascular diseases cause significant global burden. There is a growing body of evidence that nutrients alter inflammatory responses and can therefore make a decisive contribution to the treatment of these diseases. Recently, the inflammasome, a cytosolic multiprotein complex, has been identified as a key player in inflammation and the development of various inflammation‐mediated disorders, with nucleotide‐binding domain and leucine‐rich repeat pyrin domain (NLRP) 3 being the inflammasome of interest. Here an overview about the cellular signaling pathways underlying nuclear factor “kappa‐light‐chain‐enhancer” of activated B‐cells (NF‐κB)‐ and NLRP3‐mediated inflammatory processes, and the pathogenesis of the inflammatory diseases atherosclerosis and non‐alcoholic fatty liver disease (NAFLD) is provided; next, the current state of knowledge for drug‐based and dietary‐based interventions for treating cardiovascular diseases and NAFLD is discussed. To date, one of the most important antioxidants in the human diet is vitamin E. Various in vitro and in vivo studies suggest that the different forms of vitamin E and also their derivatives have anti‐inflammatory activity. Recent publications suggest that vitamin E—and possibly metabolites of vitamin E—are a promising therapeutic approach for treating inflammatory diseases such as NAFLD.

Cardiovascular and Metabolic Protection by Vitamin E: A Matter of Treatment Strategy?

“…Similar findings have been reported for atherosclerosis and CVD [142,143]. During its development, several stages and severities of NAFLD can be defined [144], positively correlated with both the prevalence and the incidence of CVD [145]. Patients with non-alcoholic steatohepatitis (NASH), an advanced stage of fatty liver disease, appear to be at greater risk of CVD [145].…”

“…A recent study by our group investigating the effect of δ-T3-13 -COOH on the progression of atherosclerosis showed protective effects on intra-plaque inflammation, as measured by nitrotyrosine [219]. Furthermore, direct and indirect effects of LCM on the inflammasome NLRP3, which has been reported to play a key role in the development of atherosclerosis, have been discussed [144]. However, no effect on the formation of atherosclerotic plaques in high-fat diet fed Apoe −/− mice was observed [219].…”

“…Taking this into account, the effects of vitamin E seem to be complicated by the circulating hepatically formed LCM of vitamin E [223]. Therefore, we are confident that LCM need to be considered in evaluation of the role of vitamin E in CVD, and as potential leading structures for drug development for the treatment of CVD as well as NAFLD/NASH [144].…”

“…Interleukin-1β is mainly activated by the inflammasome nucleotide-binding domain and leucine-rich repeat pyrin domain (NLRP) 3, which has been shown to play a major role in atherosclerosis and CVD [224]. A recent review showed a blocking effect of vitamin E on the priming and activation process of the NLRP3 inflammasome and the related formation of IL-1β [144].…”

“…Beneficial effects of methotrexate were observed in patients suffering from rheumatoid arthritis, psoriasis, or polyarthritis, which are associated with a certain level of inflammation, whereas in the CIRT patients diagnosed with DMT2 and MetS were enrolled. Since the degree of inflammation is a key player in CVD, the study outcomes may have been altered due to this difference [144,225]. A beneficial effect of methotrexate on the cardiovascular event rate seems to be present in arthritis patients, whereas in others with a less inflammatory status beneficial effects may not be expected.…”