Ergothioneine: A Promising Biomarker Linking Health-Conscious Food Patterns to Reduced Cardiometabolic Disease Risk and Mortality

This article discusses a population-based prospective study that aimed to identify plasma metabolites associated with a health-conscious food pattern (HCFP) and a lower risk of cardiometabolic morbidity and mortality during a long-term follow-up. The study found that increased levels of the amino acid ergothioneine were strongly and independently associated with both HCFP and a lower risk of future coronary artery disease (CAD), cardiovascular, and all-cause mortality. These findings suggest novel pathways linking diet to cardiometabolic health.

Several metabolites associated with the HCFP have previously been correlated with self-reported intake of specific food groups or items. Ergothioneine exists in many dietary sources and has especially high levels in mushrooms, tempeh, and garlic. It has previously been associated with a higher intake of vegetables, seafood, and a lower intake of solid fats and added sugar, as well as being associated with healthy food patterns. This is in line with the study's results concerning the association between ergothioneine, intake of vegetables, seafood, and the HCFP.

Proline betaine, also known as stachydrine, and methylproline are both known biomarkers for citrus fruit intake, which could explain their association with fruit intake in this study. Acetylornithine has been associated with a higher intake of vegetables, which was also confirmed in this study. Pantothenate, also known as vitamin B5, is widely distributed in all food groups. In contrast, urobilin, which displayed a negative association with the HCFP in this study, has not previously been associated with any dietary intake. The correlation between metabolite levels and food groups was modest, but the correlation coefficients between ergothioneine and food groups were similar to previously reported values. Despite the extensive dietary sampling method used in the Malmö Diet and Cancer (MDC) study, measurement inaccuracies are likely to attenuate the observed correlations.

Ergothioneine had the strongest association with the HCFP and the most evident protective associations with cardiometabolic morbidity and mortality, independent of traditional risk factors. The results suggest ergothioneine as a biomarker of both healthy dietary intake and low risk of future cardiometabolic disease. Ergothioneine has been shown to protect rodents from ischemic reperfusion injury and has also been suggested as an antioxidant with potential beneficial effects on the human body. Ergothioneine differs from other suggested antioxidants by having a specific transporter that has been suggested to be upregulated in areas of inflammation, providing ergothioneine with a potential for a more controlled antioxidant function. Having higher levels of ergothioneine could protect from oxidative stress in a reactionary manner, which is thought to be an important factor in the pathogenesis of cardiovascular disease (CVD) and could explain the findings of the study.

A recent study conducted in healthy humans showed that oral administration of ergothioneine increased the levels of circulating ergothioneine and decreased levels of some biomarkers of oxidative damage. Intervention trials with randomized treatment regimen designs are required to investigate if this potential antioxidant effect can decrease the risk of cardiometabolic disease.

The positive correlation between ergothioneine and alcohol intake has previously been demonstrated, an association that can either be explained by ergothioneine being present in alcoholic beverages or by alcohol changing the absorption efficiency of ergothioneine present in other dietary sources.

In conclusion, this study found that higher levels of ergothioneine were linked to a lower risk of cardiometabolic disease and mortality, suggesting that a specific healthy diet could potentially influence these outcomes by impacting specific metabolic pathways and mechanisms. The strong and independent association of ergothioneine with both HCFP and a lower risk of future CAD, cardiovascular, and all-cause mortality highlights the importance of understanding the molecular events resulting from dietary intakes and their relationship to disease and health outcomes. This knowledge would facilitate future intervention studies by identifying diet-modifiable metabolic pathways and disease mechanisms, enabling the design of more effective dietary interventions to improve cardiometabolic health.

References:

1. Smith E, Ottosson F, Hellstrand S, et alErgothioneine is associated with reduced mortality and decreased risk of cardiovascular diseaseHeart 2020;106:691-697.