Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease

Abstract

ObjectivesWe recently identified a health conscious food pattern (HCFP) associated with reduced risk of cardiometabolic disease. However, the molecular events linking the healthy food pattern to reduced risk of cardiometabolic disease are unknown. Our aim was to identify plasma metabolites associated with the HCFP and test if such metabolites predict cardiometabolic disease and mortality.MethodsUsing liquid-chromatography mass-spectrometry, 112 plasma metabolites were measured in 3236 participants without cardiovascular disease (CVD) and diabetes mellitus from the population-based Malmö Diet and Cancer study. Metabolites associated with the HCFP were identified using multivariable adjusted linear regressions followed by Bonferroni correction. The healthy dietary biomarkers were subsequently related to risk of cardiometabolic disease and mortality during long-term follow-up with multivariable adjusted Cox proportional hazards models.ResultsDuring a median follow-up time of 21.4 years, 603 participants developed CVD, 362 developed diabetes mellitus and 843 participants died. Five healthy dietary biomarkers were associated with the HCFP at baseline (p<0.0004) and four predicted at least one of the studied end points (p<0.05). Ergothioneine was the metabolite most strongly connected to the HCFP and was associated with a lower risk of coronary disease (HR per 1 SD increment of ergothioneine, HR=0.85, p=0.01), cardiovascular mortality (HR=0.79, p=0.002) and overall mortality (HR=0.86, p=4e-5).ConclusionsWe identified that higher ergothioneine was an independent marker of lower risk of cardiometabolic disease and mortality, which potentially can be induced by a specific healthy dietary intake.

Plasma Metabolites Associate with All-Cause Mortality in Individuals with Type 2 Diabetes

“…Moreover, hippurate was associated with lower risk of all-cause mortality, even when adjusting for traditional risk factors. N-methylproline was recently shown to associate with healthy eating, to be decreased after following the Dietary Approaches to Stop Hypertension (DASH) diet [23] and to associate with decreased risk of CAD and all-cause mortality in individuals free from CMD [24]. In concert with these previous findings, our study indicates that healthy eating, particularly intake of citrus fruit, is beneficial in individuals with diabetes.…”

The biology of ergothioneine, an antioxidant nutraceutical

“…This is not an issue with ERG, however, partly because it can chelate them, and ERG levels are decreased, or ERG has been proposed as a useful antioxidant, in diseases such as acute respiratory distress syndrome (505) , CVD (506,507) , chronic obstructive pulmonary disease (223) , preeclampsia (8) (see also Turner et al (128) ), overhydrated hereditary stomatocytosis (508) , and is significantly lowered in others such as certain leukaemias (121,122) . The evidence for this comes from a variety of sources, including metabolite measurements in human subjects (121,122,509) , and intervention studies in both animals (505) and cell lines (3,124,506) . In particular, there is a notable relationship between ERG consumption and longevity ( Fig.…”

“…In particular, there is a notable relationship between ERG consumption and longevity ( Fig. 6 in Beelman et al (10) ), while in a 3236-participant Swedish study, ERG was the metabolite most strongly connected to a 'health conscious food pattern' and was associated with a lower risk of coronary disease (hazard ratio (HR) per 1 SD increment of ERG, HR = 0•85; P = 0•01), cardiovascular mortality (HR = 0•79; P = 0•002) and overall mortality (HR = 0•86; P = 4 × 10 -5 ) (509) .…”

Effect of L-Ergothioneine on the metabolic plasma profile of the RUPP rat model of pre-eclampsia

“…In recent years, metabolomics techniques have become crucial tools in drug discovery [51]. A number of recent metabolomic alterations detected in pathologies, such as Alzheimer's diseases [52], frailty [53], atherosclerosis [54], cardiovascular disease [21], or autism and schizophrenia [55], have led to new hypotheses on their aetiologies and new drug targets. The study of pathologies using metabolomics approaches allows for the detection of elevated or lower levels of specific metabolites, which are regulated by enzymes for either biosynthesis or used as a substrate in a biochemical reaction, and these enzymes can be targeted and new drug treatments can be tested [51].…”

“…The radical scavenging properties of ET are established, and this has led scientists to test it as a therapeutic agent in a range of pathologies, such as non-alcoholic fatty liver disease [19]. In addition, there is evidence that ET can accumulate in the mitochondrial fraction of hepatic cells in rats [20,21].…”