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Smith, E., Ottosson, F., Hellstrand, S., et al. Ergothionein is associated with reduced mortality and a reduced risk of cardiovascular diseases.Heart. 2020;106(9):691–697.
Learning objectives
The study goals were twice: the identification of plasmametabolites associated with the health -conscious nutritional pattern (HCFP) and the evaluation as to whether these metabolites predict cardiometabolic diseases and mortality
Draft
Baseline investigation of a Swedish population-based prospective cohort study, the Malmö Diet and Cancer (MDC) study
Participant
The original MDC study consisted of 28,098 participants, all of whom underwent baseline assessments between 1991 and 1996. From this cohort, a cardiovascular cohort (MDC-CC) was randomly selected to study carotid artery disease (n = 6,103). From this MDC-CC cohort, a random sample of 3,833 was selected to provide a baseline measurement of plasma metabolites.
The exclusion criteria included participants with a prevailing coronary heart disease (KHK, N = 80), strokes in the anamnesis (n = 26) and/or type 2 diabetes (n = 348) at the beginning of the course as well as participants with incomplete data on kovariables (n = 43) or food intake (n = 120). This qualified 3,236 participants for the study, of which 2,513 had sufficient information on compliance with the HCFP so that the test doctors could assess the relationship with the measured plasma tabolites.
The 2,513 participants analyzed in this study were an average of 57.4 (± 6.0) years old, 60 % female and had an average body mass index (BMI) of 25.3 kg/m2.
Study parameters assessed
The MDC study measured 112 plasma metabolites in participants at baseline. HCFP was determined using validated methods: a combination of a 7-day dietary history record and a detailed dietary history questionnaire administered through interviews. HCFP-associated metabolites were determined using liquid chromatography-mass spectrometry (LC-MS) techniques.
Cardiovascular diseases, diabetes mellitus and deaths of any cause were pursued over the follow-up period of 21.4 years using the Swedish national registers: Swedish Hospital Dischharge Register, The Swedish Cause of Death Register and The Swedish Coronary Angiography and Angioplasty Registry (Scaar).
Primary result measurements
Cardiometabolic morbidity and mortality were the primary endpoints. Using Cox proportional hazard models, researchers examined the relationship of 5 plasma metabolites closely linked to healthy dietary intake to cardiometabolic disease and mortality to determine whether they are independent biomarkers of risk.
Important knowledge
There were 5 metabolites that were closely associated with HCFP at baseline (P<0.004): ergothioneine, proline betaine, methylproline, acetylornithine and pantothenic acid.
Ergothioneine was most strongly associated with HCFP, and its concentrations were associated with a lower risk of coronary disease as measured by standard deviation increment (HR = 0.85,P= 0.01), cardiovascular mortality (HR = 0.79,P=0.002) and all-cause mortality (HR=0.86).
Circulating ergothioneine was an independent marker of cardiovascular disease and mortality.
Practice implications
Metabolomics is generally defined as the comprehensive measurement of all metabolites and small molecules in a biological sample. This study established the correlation of certain metabolites and a healthy diet, with ergothioneine being the only metabolite that was an independent marker of disease and mortality. A citrus-rich metabolite, proline betaine, was also highly correlative.1
In this study, Ergothionein had the strongest association with a lower risk of CHK, cardiovascular mortality and overall mortality.
Citrus fruits have been associated with positive health for many years, and higher citrus fruit consumption has been linked to a reduced risk of coronary heart disease (CHD).2Citrus fruits are a great source of dietary flavonoids, which may reduce the risk of cardiovascular disease. In a single-blind, randomized, crossover study of 22 healthy volunteers, it was found that sweet orange (Citrus sinensis)-juice lowered the blood pressure of the test subjects.3Citrus fruits are a good source for essential nutrients such as vitamin C, potassium and folic acid, which are all heart -healthy nutrients. Vitamin C is an antioxidant that reduces oxidative stress in endothelial cells, which reduces the risk of arteriosclerosis. Stachhydrin, another metabolite pursued in this study, is a part of citrus fruits that help to promote vascular voltage by inhibiting the NADPH-Oxidase (nicotinamide-dinucleotide phosphate).4Also grapefruit (Citrus paradisi) has demonstrably hypolipidemic effects.5There is also an association with daily intake of citrus fruits (oranges, grapefruit, orange juice, grapefruit juice) and a 22% lower risk of endometriosis.6
In this study, Ergothionein had the strongest association with a lower risk of CHK, cardiovascular mortality and overall mortality. Ergothionein is an amino acid that contains sulfuric acid, which in non -yeast mushrooms (mainly basidiomycetes) and some bacteria (actinomycetales and cyanobacteria including spirulina,Arthrospira Maxima7), but neither in plants nor in mammals.8It is highest in mushrooms, but is also found in some organ meats, black and red beans, and oat bran. However, in a prospective study, ergothioneine was associated with fish, shellfish, and alcohol consumption.9This may reflect incidental consumption, as ergothioneine is sometimes added to fish to reduce discoloration.10
When ingested by humans, ergothioneine accumulates at relatively high concentrations in erythrocytes, liver, seminal fluid, bone marrow, eye lens, cornea, brain, spleen, intestines, heart and kidneys via a highly specific transporter, OCTN1.11.12Ergothioneine, often compared to glutathione, has been shown in preclinical data to be effective in scavenging hydrogen peroxide, superoxide ions, singlet oxygen, lipid peroxides, hydroxyl radicals, and reactive nitrogen species (RNS), while protecting nitric oxide from destruction.13In the article "Ergothioneine Antioxidant Function: From Chemistry to Cardiovascular Therapeutic Potential", Servillo and his team in Italy showed that ergo the proinflammatory zytokin production (interleukin-1 beta [il-1β] and tumor necrosis factor alpha [tnf-α]) regulates the vascular Zelladhäsion molecule 1 (VCAM-1), the intercellular adhesion molecule 1 (icam-1) and the e-selectin adhesion molecules down, inhibits the monozyte binding to the endothel and has a positive modulation of Sirtuin 1 (Sirt1) and Sirtuin 6 () signal paths.13There are also preclinical data showing that ergothioneine and a mushroom extract containing ergothioneine inhibit myeloperoxidase (MPO),14A predictor for the progression of the plaque and the likelihood of unwanted events.fifteen
Mushrooms contain more ergothioneine than plants, but still in relatively low concentrations. Researchers have been working to create an inexpensive source of ergothioneine through bacterial fermentation.16According to initial reports, the yield was still very low and the costs were high. Newer techniques incorporate multiple bacterial enzymes for improved synthesis.17In addition, ergothioneine has been granted Generally Recognized as Safe (GRAS) status by the FDA.18and Novel food status by the European Union.19It will be interesting to see what the future of ergothionein has in store, a potentially naturally naturally obtained intervention on cardiovascular support.