Dietary habits can be assessed not only through a person’s own account of what they eat, but also by examining changes in their blood composition. This approach has enabled researchers to identify a link between a metabolic profile characteristic of the Mediterranean diet and a reduced risk of death—a finding that has been replicated across several independent study cohorts.
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The Mediterranean diet emphasizes a high intake of vegetables, fruits, legumes, nuts, fish, and olive oil, while limiting red and processed meats, animal fats, refined grains, and sweets. Research has consistently linked this dietary pattern to a lower risk of cardiovascular disease and type 2 diabetes. However, adherence to this diet is typically evaluated using questionnaires in which participants self-report the types and frequency of the foods they consume.
Because this method does not always accurately reflect actual dietary habits—nor does it reveal how the body responds to what is consumed—Estefanía Toledo of the University of Navarra (Spain) and her colleagues set out to investigate the relationship between mortality risk (from all causes) and biomarkers of the Mediterranean diet—a specific set of blood markers that provide an objective measure of the metabolic processes associated with this way of eating. Their findings were published in The American Journal of Clinical Nutrition.
The researchers began by analyzing data from 1,880 participants in the Spanish PREDIMED study. At the time of enrollment, the mean age of the volunteers was 67.1 years. These individuals did not have cardiovascular disease but were at high risk, either due to type 2 diabetes or several other risk factors, such as hypertension, smoking, or abnormal cholesterol levels. Participants were randomly assigned to groups: one was advised to follow a Mediterranean diet supplemented with extra-virgin olive oil or nuts, while the other was advised to follow a low-fat diet.
The observation period lasted an average of 13.2 years. It was found that individuals whose metabolic profile most closely aligned with the Mediterranean diet had a 23% lower risk of death from all causes compared to those whose profiles showed the least alignment. This difference remained significant even after adjusting for age, sex, body mass index (BMI), lifestyle habits, diabetes, hypertension, and other factors.
The findings were subsequently verified using three independent American cohorts—long-term health studies involving healthcare professionals. The analysis included data from 12,704 men and women who were followed for an average of 25 years. A similar association was observed: participants whose metabolic signature most closely matched that of a Mediterranean diet had a 23% lower risk of death compared to those with the lowest level of alignment. This pattern persisted even after accounting for BMI.
The metabolic signature comprised a wide range of markers: 45 types of lipids (fat-like compounds that serve structural and energy-related functions) and acylcarnitines (involved in fatty acid metabolism), 19 amino acids, two vitamins, and one xenobiotic. Crucially, it is the combination of these substances that matters; their overall profile showed a consistent correlation with a lower risk of death.
The study’s authors suggest that these results reflect several beneficial biological processes occurring simultaneously. The Mediterranean diet includes olive oil, nuts, and fish—sources of various fatty acids that can influence lipid metabolism and cardiometabolic health. This overall metabolic profile may be associated with lower levels of chronic inflammation, increased antioxidant capacity, and improved insulin sensitivity.
However, these mechanisms have not been tested directly; researchers have only demonstrated an association. Furthermore, the findings for specific causes of death were not as compelling as those for overall mortality risk. In American study cohorts, higher adherence to a Mediterranean diet was linked to a lower likelihood of death from cardiovascular disease, whereas no significant association was found for cancer upon further analysis.
Another important detail is that the metabolic signature was assessed not only at the beginning of the observation period but also one year later. While this timeframe was also associated with a reduced risk of death, long-term dietary habits and metabolic characteristics played a more significant role than short-term changes in diet.
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