There is much evidence that the Mediterranean diet (MD) has a powerful effect on human physiology, including cognitive improvements. There is little knowledge as to the mechanisms by which this occurs. A recent study looked at the metabolite output in people on an MD and the associations between this profile and the cognitive performance in this group.

Study: Mediterranean diet related metabolite profiles and cognitive performance. Image Credit: Marian Weyo/Shutterstock

Introduction

The MD is unique in its pattern of high olive oil, vegetables, fruits, nuts and legumes, fish, and alcohol (such as red wine) in moderate amounts but little red or processed meat. However, the question to be answered here is its effect on cognition.

Cognitive degenerative disorders are of great concern to millions of people worldwide, limiting their independence and placing enormous burdens on their caregivers and society at large. The food we eat is important as a potential intervention to prevent such impairments. However, little is known about the MD in its effect on cognition.

Earlier research from the Epirus Health Study (EHS), a currently proceeding population-based prospective cohort study from Northwestern Greece, showed that the MD failed to affect cognitive outcomes.

Even so, the current study, published in Clinical Nutrition, aimed to include metabolomics as a tool for identifying potential nutritional biomarkers and the biological pathways that mediate the effect of food on cognition. Thus, for the first time, a global metabolomic profile is being used to investigate whether following the MD translates into lowering cognitive impairment risk.

The researchers included 1.250 healthy middle-aged people. All were Greeks, and the Mediterranean Diet Adherence Screener (MEDAS) was used to measure how far they followed the MD. This measure was thought to be superior to asking people how many different foods they ate.

Cognitive performance was assessed using the Trail Making Test, the Verbal Fluency test, and the Logical Memory test. The metabolite profile was generated with a high-throughput nuclear magnetic resonance (NMR) platform and analyzed for potential associations with the MEDAS scores and cognitive tests.

What did the study show?

Two-thirds of the participants were highly educated, and the mean body mass index (BMI) was above the upper limit of normal. The scores showed a moderate adherence to the MD.

The study's findings showed an association between the MEDAS score and a 42-component metabolite array. Most of these were lipoproteins of various subclasses.

For instance, large high-density lipoprotein (HDL) was mostly associated with the MEDAS score, while some were negatively associated. Some intermediate-density and one low-density lipoprotein (IDL and LDL, respectively) also showed positive associations with the score.

Very low-density lipoproteins, VLDL, also showed negative associations, whether small or very small in size, as well as large or very large particles. Extremely large VLDL showed positive associations as well.

Unsaturated fatty acids (FAs) (poly- and mono-unsaturated, PUFA and MUFA, respectively), along with short-chain FAs (SCFAs) and omega-3 FAs, were positively associated. Total triglycerides were lower, as were saturated fatty acids, omega-6 FA, and the ratio of omega-6 to omega-3 FA, and of PUFA to MUFA, with greater scores.

Amino acids like alanine and glycine were higher, but isoleucine and phenylalanine were lower on the MD. Energy metabolites, like citrate, glucose, and acetoacetate, were more abundant with increased adherence to the MD, while inflammation markers were reduced. The strongest correlations were for foods like fruits, red meat, sugar-sweetened beverages and sweets, and fish/seafood.

When confounding factors were adjusted for, no associations were observed between either MEDAS scores or the metabolite profile and the cognitive tests.

What are the implications?

The current study is the first to present the metabolomics of people on the MD using an NMR-based platform. The findings include 42 metabolites that seem characteristic of adherence to this diet, with positive and significant correlation despite large variations in individual profiles. This corroborates earlier reports, such as the PREDIMED study.

The MEDAS score correlates with reduced inflammatory metabolites, in proportion to fish and seafood intake in particular, while fiber-rich foods are linked to increased SCFAs.

Closer adherence to the MD could be linked to better esterification of cholesterol by HDL and reduced cholesterol ester transfer. Better HDL remodeling leads to increased packing of triglycerides into these particles, while the difference in the VLDL profile could reflect increased repackaging and removal of triglycerides from the plasma.

Better FA use for energy in place of glucose, with healthier amino acid concentrations, are also observable with the MD.

Despite these findings, adherence to the MD does not seem to improve cognitive function. The results of this study do not support an effect of the MD on cognitive performance, as assessed by the MEDAS score or the metabolite profile from this diet, among middle-aged people from the Mediterranean country of Greece. Further research would help validate these conclusions and extend the findings to other populations.

Journal reference:

• Papandreou, C. et al. (2023) "Mediterranean diet related metabolite profiles and cognitive performance", Clinical Nutrition, 42(2), pp. 173-181. doi: 10.1016/j.clnu.2022.12.012. https://www.clinicalnutritionjournal.com/article/S0261-5614(22)00440-X/fulltext