Study finds 10 metabolites associated with risk of stroke

Metabolites offer a window into the body’s functioning and its risk of disease. The emerging field of metabolomics, the study of the metabolites, has begun to reveal how these molecules found in the body’s cells may be associated with certain illnesses, highlighting new potential biomarkers to help develop diagnostic and therapeutic approaches.


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Results from a new study are published in this month’s online issue of Neurology®, the medical journal of the American Academy of Neurology, which identifies 10 metabolites that are associated with a person’s risk of stroke. The findings will assist scientists in improving prevention methods for those at risk of stroke.

The link between metabolites and health

A growing body of evidence is revealing how metabolites play a significant role in human disease. Studying the relationship between metabolites and specific diseases is allowing scientists to gain a deeper understanding of the pathogenesis of a disease, as well as open up avenues to the development of new diagnostic, therapeutic, and preventative strategies.

The body produces metabolites as a result of metabolic reactions that convert food sources into energy sources. This process is vital to the regular functioning of the cell. Metabolites include molecules such as amino acids, carbohydrates, fatty acids, and lipids. Factors such as the environment, disease, and genetics can impact levels of metabolites, which can act as an indicator of cell health and overall health.

Given that cardiovascular disease is the world’s leading cause of death, claiming the lives of 17.9 million annually, and that stroke and heart attacks account for 85% of these deaths, scientists recognize the need for new effective ways of identifying those who are at high risk of suffering a stroke. To address this need, a team at Erasmus University Medical Center in Rotterdam, the Netherlands, analyzed the pooled data of seven studies.

In total, 38,797 people were included who did not have a stroke at the beginning of the study. Blood samples and health histories were collected and medical exams were conducted. Nuclear magnetic resonance technology was used to analyze the blood samples and measure the levels of 147 metabolites. Throughout the study, 1,791 people had a stroke. Through analyzing the data, researchers were able to identify 10 metabolites that were associated with a person’s risk of stroke.

Histidine, an amino acid found in various protein sources considered vital for maintaining life, was found to have the strongest association with the risk of stroke. Researchers found that higher levels of histidine were linked with a reduced risk of ischemic stroke, caused by blood vessel blockage, suggesting histidine’s role in cardiovascular health.

The results are not surprising given the function of the amino acid as a neurotransmitter that has been linked with reduced blood pressure and inflammation. Findings demonstrate that a person’s risk of stroke is reduced by 10% with every one standard deviation increase in histidine levels.

HDL and HDL2, high-density lipoprotein cholesterols that come from foods like fish and nuts and are considered to be sources of good cholesterol, were found to reduce a person’s risk of ischemic stroke. Conversely, low-density lipoprotein cholesterols, known as bad cholesterols, and triglycerides, were related to an elevated risk of stroke.

Pyruvate was another key metabolite identified by the research. Pyruvate is generated followed by the breakdown of glucose within a cell. Elevated levels of the metabolite were found to be associated with a higher risk of stroke, with an increase of one standard deviation translating to a 13% increased chance of ischemic stroke. Previous studies have linked higher levels of pyruvate to an increased risk of cardiovascular disease, however, other studies had linked it to reduced inflammation.

More research is needed to define the role of pyruvate in stroke, as well as to better understand the influence of the 9 other metabolites identified in the research.

The study’s results provide new avenues of research to be explored which may lead to enhanced diagnostic, preventative, and therapeutic approaches to stroke.

Journal reference:
  • Association of circulating metabolites in plasma or serum and risk of stroke: Meta-analysis from seven prospective cohorts
    Dina Vojinovic, Marita Kalaoja, Stella Trompet, Krista Fischer, Martin J. Shipley, Shuo Li, Aki S. Havulinna, Markus Perola, Veikko Salomaa, Qiong Yang, Naveed Sattar, Pekka Jousilahti, Najaf Amin, Claudia L. Satizabal, Nele Taba, Behnam Sabayan, Ramachandran S. Vasan, M. Arfan Ikram, David J. Stott, Mika Ala-Korpela, J. Wouter Jukema, Sudha Seshadri, Johannes Kettunen, Mika Kivimaki, Tonu Esko, Cornelia M. van Duijn
    Neurology Dec 2020, 10.1212/WNL.0000000000011236; DOI: 10.1212/WNL.0000000000011236
Sarah Moore

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Sarah Moore

After studying Psychology and then Neuroscience, Sarah quickly found her enjoyment for researching and writing research papers; turning to a passion to connect ideas with people through writing.


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