• Studies show that the levels of certain blood metabolites, which are the intermediate or end-products of the human metabolism, are associated with cognitive function.
  • Blood metabolite levels are influenced by health status, genetics, and environmental factors, and can differ among different ethnic or racial groups.
  • A recent study characterized blood metabolites that were associated with cognitive function among various ethnic/racial groups.
  • The study’s findings suggest that dietary habits could potentially influence the levels of these metabolites and subsequently cognitive performance, highlighting the importance of a healthy diet.

Individuals of minoritized ethnic or racial groups are often underrepresented in research, thus hindering the understanding of risk factors and the efficacy of treatments for diseases in these minoritized groups.

A recent study published in the journal Alzheimer’s & Dementia found that the levels of six plasma metabolites were associated with lower cognitive function across all racial/ethnic groups, and the levels of most of these blood metabolites were associated with adherence to a Mediterranean diet.

Speaking to Medical News Today, the study’s corresponding author Dr. Tamar Sofer, a professor at Brigham and Women’s Hospital at Harvard University, said:

“We identified a few metabolites (small molecules) in blood that their levels are correlated with cognitive function, and they are all related to diet. While there are clinical trials showing that diet can influence cognitive function, identifying specific metabolites can help identify [a] specific mechanism, specific components of [a] diet that are more important than others, and biomarkers to measure [the] success of dietary changes.”

However, Dr. Sofer added that “There is still work to do to make these steps happen, but this is a good start, especially because the results held up in a few different studies, so the findings are very reliable.”

An elderly man with a long beard and wearing glasses looks at this tablet computer smilingly as he eats a Mediterranean salad accompanied by a glass of red wineShare on Pinterest
Metabolites from healthier diets may help protect brain health, according to new research. Ivan Gener/Stocksy

Technological advances have made it possible to profile hundreds of metabolites at once and identify metabolites associated with a diseased state. For instance, studies have shown that levels of plasma metabolites are associated with cognitive function and dementia.

Characterizing metabolites associated with cognitive function can help researchers understand the mechanisms underlying the development of dementia. Moreover, blood metabolites can be easily measured and could serve as biomarkers for cognitive function.

A previous study involving older Puerto Rican individuals enrolled in the Boston Puerto Rican Health Study (BPRHS) showed that the levels of 13 blood metabolites were associated with global cognitive function, which is a composite measure of multiple cognitive abilities.

Metabolite levels are influenced by the interplay between genetics, health status, and environmental factors, including diet, other lifestyle factors, and socioeconomic factors, which may differ among and even within ethnic/racial groups.

Given the influence of such a multitude of factors on blood metabolite levels, the study’s authors examined whether the results from the BPRHS could be replicated in a different sample of individuals of Puerto Rican heritage in the United States. The researchers also investigated whether these findings could be generalized to the broader Hispanic/Latino population and other ethnic groups.

Several metabolites identified by the BPRHS have been shown to be influenced by dietary habits. Thus, modifying one’s dietary habits could potentially help preserve cognitive health.

Hence, the study’s authors also examined the causal role of the blood metabolites and dietary habits in influencing cognitive function.

To assess the generalizability of the results from the BPRHS to the broader Hispanic/Latino population in the U.S., the researchers used data from 2,222 adults enrolled in the Community Health Study/ Study of Latinos (HCHS/SOL). HCHS/SOL is a longitudinal cohort study examining the health of individuals from different Hispanic/Latino backgrounds, including those of Cuban, Dominican, Puerto Rican, Mexican, Central American, and South American descent.

Using blood samples from the HCHS/SOL cohort, the researchers were able to estimate the level of 11 out of the 13 metabolites assessed by the BPRHS.

They found that the direction of effects of blood metabolites on cognitive function in HCHS/SOL Puerto Rican and all HCHS/SOL participants was similar to that observed in the BPRHS.

Moreover, there was a significant correlation between the levels of certain metabolites with global cognitive function in HCHS/SOL Puerto Ricans and all HCHS/SOL participants.

Among these metabolites, higher levels of beta-cryptoxanthin and lower levels of gamma-CEHC glucuronide were associated with cognitive function in both HCHS/SOL Puerto Ricans and all HCHS/SOL participants.

To examine the association between blood metabolites and cognitive function in other racial/ethnic groups, the researchers used data from 1,365 European Americans and 478 African Americans enrolled in the Atherosclerosis Risk in Communities (ARIC) study. The researchers then conducted a meta-analysis to assess the association between blood metabolite levels and cognitive function using data from the BPRHS, HCHS/SOL, and ARIC studies.

The meta-analysis showed that six blood metabolites were associated with lower cognitive function across all ethnic/racial groups. Four out of the six metabolites associated with overall cognitive function were sugars, including glucose, ribitol, mannose, and mannitol/sorbitol.

Since the previous analysis only showed a correlation between metabolites and cognitive function, the researchers conducted additional analysis to determine whether any of the blood metabolites had a causal effect on cognitive function.

Out of the six metabolites, the analysis revealed a potential causal effect of only ribitol on cognitive function.

The researchers also assessed the association between dietary habits, including adherence to a Mediterranean diet and intake of food groups (i.e. intake of legumes, fruits, vegetables, meat, fish, etc.), and blood metabolite levels.

They found that adhering to a Mediterranean diet or its component food groups was correlated with several blood metabolites assessed in the study.

Notably, the strongest association was observed between beta-cryptoxanthin and fruit intake in HCHS/SOL Puerto Ricans and all HCHS/SOL participants.

Beta-cryptoxanthin is a carotenoid with antioxidant properties found in fruits and vegetables, and beta-cryptoxanthin levels are associated with a lower risk of insulin resistance and liver dysfunction.

The researchers then examined whether the intake of specific food groups had a causal effect on cognitive performance.

Although food groups played a causal role in cognitive performance, cognitive function had a much stronger causal effect on the intake of specific food groups. Cognitive function is associated with socioeconomic status, which may mediate the effects of cognitive status on dietary habits.

In sum, these results suggest that dietary habits could potentially influence cognitive performance by modulating blood metabolite levels.

The authors acknowledge that the study had a few limitations. They noted that the BRPHS, HCHS/SOL, and ARIC studies used different methods for assessing cognitive function, and the causal effects of metabolites on cognitive function must be interpreted with caution.

Dr. Perminder Sachdev, professor of neuropsychiatry at the University of New South Wales, who was not involved in this study, told MNT:

“There are several challenges in interpreting these results in relation to the role of specific nutritional groups and brain health. This is a cross-sectional study from which causal relationships cannot be drawn. Not only can nutrition affect brain health, but poor cognitive function can also influence nutrition, suggesting a bi-directional relationship.”

Furthermore, Dr. Sachdev also noted that “blood metabolites have multiple determinants, with diet being only one of them. Genetic factors, health co-morbidities, and lifestyle are all important. A direct attribution to diet is therefore difficult.”

“[T]his study is a step in the right direction in relation to examining the role of diet and the body’s metabolism for brain health. It provides suggestive evidence that adherence to a good diet such as the Mediterranean style diet may be beneficial for brain health over a wide age range.”
— Dr. Perminder Sachdev

Dr. Sachdev added that much more work was needed.

“We need to understand the plasma metabolome better to know what determines their blood levels before we can begin to interpret such studies. We need longitudinal studies with multiple measurements in large samples, followed by intervention studies, so that causal relationship can be established,” he said.