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Blood Test Can Determine Adherence to a Mediterranean Diet and Cardiovascular Disease Risk

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What is a Mediterranean diet?

Likelihood is that you've heard of the Mediterranean diet; if you suffer from particular health conditions, such as high blood pressure or heart disease, you may have even been prescribed it by a physician.

Countries bordering the Mediterranean Sea, such as Greece, France, Italy and Spain each have their own variations of Mediterranean diets, and so it does vary. Generally, it is a diet that encompasses lots of vegetables, fruits, legumes, nuts, beans, cereals, fish, unsaturated fats such as olive oil and grains. Little amounts of dairy products and meat are consumed.

Research continues to show the health benefits associated with adopting a Mediterranean diet, including a reduced risk of developing cardiovascular disease, stroke and Type 2 diabetes, to name just a few examples.1

From a clinical perspective, monitoring an individual's adherence to a Mediterranean diet has traditionally relied on self-reported data, obtained through means such as questionnaires; however, the reliability and validity of collecting data in this way is dubious.

A team of scientists led by Harvard T.H. Chan School of Public Health with collaborators from the Broad Institute of MIT and Harvard and Spain have worked to develop a metabolic signature as a biological measure to evaluate adherence and metabolic response. Metabolites are small chemicals that are produced via different metabolic processes in cells. They circulate in the blood stream, and thus, can be measured using a blood sample.

“The metabolic signature and metabolites included in the signature could [also] help researchers better understand how the Mediterranean diet can benefit people with complex metabolic diseases,” said Jun Li, research scientist of nutrition and epidemiology at Harvard Chan School and the first author of the paper. The team's work is published in the European Heart Journal.2

A robust metabolic signature

To develop the metabolic signature, the researchers utilized a machine-learning model to assess hundreds of metabolites in blood samples from 1,859 participants in the Spanish PREDIMED study. The subjects' adherence to the Mediterranean diet was first assessed using a Mediterranean Diet Adherence Screener, and their blood plasma was profiled using liquid chromatography-mass spectrometry to screen the metabolome.

Applying the machine-learning model, the researchers were able to identify a metabolic signature that comprised of 67 metabolites. Collectively, these analytes indicated whether a subject had followed the Mediterranean diet and demonstrated a metabolic response to the diet. Genome-wide association analysis demonstrated that the metabolic signature was significantly associated with genetic loci implicated in fatty acid and amino acid metabolism.

The research has diagnostic elements too. In multivariable Cox regressions, the metabolic signature demonstrated a significant inverse association with cardiovascular disease incidence once researchers adjusted for known risk factors. In simplistic terms, a higher level of the metabolic signature was associated with a lower-long term risk of cardiovascular disease.

To validate the signature, the team applied their methods to blood samples from 6,868 participants in the U.S.-based Nurses' Health Study, Healthy Study II and Health Professional's Follow-up Survey. They found that the signature was able to determine adherence and metabolic response to the Mediterranean diet and determine cardiovascular disease risk in this population. The results were highly reproducible across the entire study population, regardless of variation in dietary habits, lifestyle choices and environmental exposures.

“This study is the first to develop a metabolic signature for the Mediterranean diet based on comprehensive metabolomic profiles. It demonstrates that the level of dietary adherence and individual’s response to diet can be objectively measured,” said Liming Liang, associate professor of epidemiology and biostatistics at Harvard Chan School and co-senior author of the paper. “The reproducibility of the findings in the U.S. and Spanish populations indicate the robustness of the approach.”

Li said: “Given that the metabolic signature is reflective of individuals’ metabolic response to diet and CVD risk, the signature has potential in the future to help facilitate personalized nutrition interventions.”


1.      Estruch et al. (2018). Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med. DOI: 10.1056/NEJMoa1800389.

2.      Li et al. (2020). The Mediterranean diet, plasma metabolome, and cardiovascular disease risk. European Heart Journal. DOI: 10.1093/eurheartj/ehaa209.