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Researchers identify plasma metabolomic markers for the Mediterranean diet among pregnant women

Previous studies have described the importance of analyzing dietary patterns, rather than analyzing the nutritional content of individual food products, to better understand overall dietary quality, promote better health status, and ultimately mitigate disease risk.

A recent Clinical Nutrition study identifies blood metabolomic markers and metabolite panels linked to the Mediterranean diet in pregnant women. 

Study: Metabolomic biomarkers of the Mediterranean diet in pregnant individuals: a prospective study. Image Credit: Africa Studio /


The Mediterranean diet includes higher consumption of fruits, vegetables, fish, nuts, legumes, olive oil, and cereals, as well as a reduced intake of processed meat, red meat, and sweets. Both high-quality randomized controlled trials (RCTs) and meta-analyses have confirmed the favorable neurological and cardiometabolic effects of the Mediterranean diet across varied populations, including pregnant women.

To better understand the underlying mechanisms associated with diet and health outcomes, it is important to identify biomarkers of dietary intake to objectively measure dietary patterns. Previous studies of individual biomarkers of a single nutrient or food failed to assess the synergistic interactions among different food groups and nutrients. Nevertheless, recent studies using high-throughput untargeted metabolomic profiling techniques have been able to identify biomarkers for dietary patterns in a more systematic and comprehensive manner.

Through the quantification of downstream metabolic products or small molecules, scientists have elucidated interactions between nutrients/foods and genes for individuals. This approach has enabled the identification of novel biomarkers or biological pathways associated with the dietary pattern of an individual.

Although some studies have identified blood metabolomic biomarkers for the Mediterranean diet in a non-pregnant group, no evidence related to the identification of metabolomic markers for this healthy dietary pattern in the pregnant population was found.

During pregnancy, women undergo several psychological changes, such as alterations in basal metabolic rate, hormone levels, and energy storage. Thus, the metabolic responses to diet in pregnant women are likely different from non-pregnant women.

About the study

The current study included racially diverse pregnant individuals who participated in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort (FGS).

Study participants were recruited from twelve United States-based clinical sites between July 2009 and January 2013. The cohort consisted of 2,802 individuals between 18 and 40 years of age. All study participants were within eight and 13 weeks gestation. 

A total of 186 participants were also included in the current study from a nested gestational diabetes mellitus (GDM) case-control study within FGS who presented both dietary consumption and blood plasma metabolomic profiling data. Individuals’ dietary consumption patterns were assessed for the past three months, which included pre-conception and first trimester, based on a semi-quantitative Food Frequency Questionnaire (FFQ). 

During the second trimester, dietary intake was determined using an automated self-administered 24-hour dietary recall (ASA24). This data was used to measure pregnant women’s adherence to the Mediterranean diet, which was represented by an alternate Mediterranean score (aMED). A high score indicated better adherence to the Mediterranean diet. 

Scientists used high-throughput liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS/MS) and gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS) for untargeted metabolomic profiling.

Study findings

Several plasma metabolomic markers of the Mediterranean diet in the pre-conception and first trimester or recent diet were identified. A total of fourteen metabolites were significantly related to the Mediterranean diet in both study periods. Multi-metabolite panels with good-to-excellent predictability were identified for the Mediterranean diet in the pregnant population. 

Most Mediterranean diet-related metabolites included lipids, such as long-chain free fatty acids (e.g., linoleic acid, palmitoleic acid, and oleic acid), acylcarnitines (medium/long-chain), triglycerides (TG), phosphatidylcholines (PC), glyceryl palmitate, and cholesterol ester (CE). Novel markers, such as certain amino acids including aspartic acid, 3-hydroxybutyric acid, and glycolic acid, as well as sugar alcohols (e.g., lyxitol and xylitol) and organic acids (e.g., citric acid and isocitric acid), were also identified. These metabolites could be potential biomarkers of the Mediterranean diet. 

CE plasma levels were associated with the dietary intake of olive oils, monosaturated fatty acids (MUFAs), and seafood. Previous studies have shown that CEs with longer and more unsaturated acyl chains increase the risk of diabetes and cardiovascular diseases (CVD). Acylcarnitines, which have been linked to markers of meat and plasma disturbances, were associated with the development of diabetes and CVD in non-pregnant and pregnant women.

The exact role of TGs and PCs, both individually and in combination, in pregnant women is not clear. However, linoleic acid was found to be inversely associated with the Mediterranean diet in pregnant women.


The novel metabolites identified in the current study could provide new information on differences in physiological conditions between pregnant and non-pregnant populations. Importantly, the current study detected metabolites associated with the Mediterranean diet in pregnant individuals, which requires further research to elucidate their association with pregnancy and fetal outcomes.

Journal reference:

  • Chen, L., Dai, J., Fei, Z., et al. (2023) Metabolomic biomarkers of the Mediterranean diet in pregnant individuals: a prospective study. Clinical Nutrition. doi:10.1016/j.clnu.2023.01.011

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