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Original research
Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease
  1. Einar Smith,
  2. Filip Ottosson,
  3. Sophie Hellstrand,
  4. Ulrika Ericson,
  5. Marju Orho-Melander,
  6. Céline Fernandez,
  7. Olle Melander
  1. Department of Clinical Sciences, Lund University, Malmö, Sweden
  1. Correspondence to Mr Einar Smith, Department of Clinical Sciences, Lund University, Malmö 21428, Sweden; einar.smith{at}


Objectives We 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.

Methods Using 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.

Results During 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).

Conclusions We 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.

  • Translational cardiovascular science
  • Epidemiology
  • Coronary artery disease

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  • CF and OM are joint senior authors.

  • Contributors ES contributed to study design, acquisition and interpretation of data, statistical analyses and drafted the manuscript. UE, SH and FO contributed to collection and interpretation of data and statistical analysis. MO-M assisted in data interpretation. CF and OM contributed to study concept and design, interpretation of data and statistical analyses. All authors made intellectual contributions to drafting and/or revising the manuscript and approved the final version. ES, CF, FO and OM had full access to the data. The manuscript is original research, has not been published and is not submitted to be considered for publication elsewhere, in whole or in part, in any language. There are no potentially overlapping papers in preparation, submission or published. The authors declare that there is no duality of interest associated with this manuscript.

  • Funding This study was funded by Crafoordska Stiftelsen, Vetenskapsrådet, Novo Nordisk, Åke Wiberg Stiftelse, Göran Gustafssons Stiftelse för Naturvetenskaplig och Medicinsk Forskning, Knut och Alice Wallenbergs Stiftelse, Kungliga Fysiografiska Sällskapet i Lund, the Ernhold Lundström Research Foundation, Region Skåne, Skåne University Hospital, European Foundation for the Study of Diabetes (grant no: EFSD 2015/338), Hjärt-Lungfonden, H2020 European Research Council, Diabetesfonden, Direktör Albert Påhlssons Stiftelse. OM was supported by Knut and Alice Wallenberg Foundation, Göran Gustafsson Foundation, the Swedish Heart and Lung Foundation, the Swedish Research Council, the Novo Nordisk Foundation, Region Skåne, Skåne University Hospital. CF was supported by the Albert Påhlsson Research Foundation, the Crafoord Research Foundation, the Ernhold Lundström Research Foundation, the Royal Physiographic Society of Lund and the Åke Wiberg Foundation. MO-M was supported by the European Research Council (Consolidator grant nr 649021, Orho-Melander), the Swedish Research Council, the Swedish Heart and Lung Foundation, the Novo Nordic Foundation, the Swedish Diabetes Foundation, the European Foundation for Study of Diabetes (EFSD 2015/338) and the Region Skåne, Skåne University Hospital. FO was supported by the Ernhold Lundström Research Foundation.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study was approved by the Ethics Committee of Lund University, Lund, Sweden (LU 51–90).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.