What we eat cannot change the genes we are born with, but it may affect how some nutrition-related pathways work. A new clinical trial suggests that may be especially relevant for folate, plant-forward eating patterns and a common gene variant involved in folate metabolism.
The study, published in Clinical Nutrition, found that people assigned to a green Mediterranean diet had a larger rise in circulating folate levels than those assigned to a traditional Mediterranean diet or standard healthy dietary guidelines. The green Mediterranean diet included green tea, walnuts, a daily shake made with Mankai, an aquatic plant also known as duckweed, and reduced red and processed meat.
The findings come from the DIRECT-PLUS trial, an 18-month randomized clinical trial that examined diet, cardiometabolic health and body fat distribution. This analysis focused on serum folate, a B vitamin involved in one-carbon metabolism, a process that helps regulate DNA maintenance, methylation and gene expression. Researchers also examined whether response to the diet differed based on a common MTHFR gene variant, rs1801133, that can reduce activity of an enzyme involved in folate metabolism.
That may sound like a story about food changing genes, but the more accurate framing is narrower. The study suggests that a plant-rich dietary pattern may raise folate levels and may help support biological pathways linked with metabolic health. It does not show that Mankai, walnuts or any other single food prevents cardiovascular disease, type 2 diabetes or aging.
Participants following the green Mediterranean diet had a significant rise in serum folate. Higher folate levels were associated with improvements in insulin sensitivity, inflammatory markers such as IL-6, the triglyceride-to-HDL cholesterol ratio, visceral fat and liver fat.
The researchers paid special attention to people carrying the TT genotype of the MTHFR variant studied. This genetic profile is associated with lower folate levels across life. In the study, TT carriers with low Mankai intake had an increase in cardiovascular risk score, while TT carriers with high adherence to the Mankai-enriched green Mediterranean diet had a 7.74-point reduction in Framingham Risk Score.
The team also reported changes in gene expression patterns among TT carriers. Blood mRNA analyses showed increased expression of alternative folate-pathway genes, including MTHFD2 and DHFR. Researchers interpreted this as a possible adaptive response that may help compensate for reduced inherited enzyme activity.
Prof. Iris Shai, principal investigator of the study, said the findings support a broader view of folate than simply preventing deficiency.
“Our findings show that a diet rich in green plant-based foods may influence folate-related metabolic pathways associated with cardiometabolic health,” Shai said. “The relationship we observed between folate levels, visceral fat reduction, and genetic responsiveness strengthens the scientific basis for personalized nutrition and advances the field of Nutri-Omics.”
That personalized nutrition angle is promising, but it also deserves caution. Genetic differences can affect how people process nutrients, but most people do not need to interpret a single gene variant as destiny or make major diet changes based on direct-to-consumer genetic testing alone. The study suggests diet may matter even in people with a genetic pattern linked to lower folate status. It does not mean genetics can be “fixed” by one food or supplement.
Dr. Hila Zelicha Peer, first author of the study, said the findings point to a broader role for folate as a marker of diet quality and biological response.
“Until now, folate has primarily been viewed through the lens of nutritional deficiency,” Zelicha Peer said.
In the study, Mankai received particular attention because it is rich in protein, fiber, minerals, essential amino acids and naturally occurring folate. Participants with higher Mankai intake appeared to have stronger folate responses and more pronounced clinical and gene-expression changes.
For U.S. readers, though, Mankai is not a common grocery-store ingredient. The more practical point is not that everyone needs a daily duckweed shake. The broader diet pattern matters: more plant foods, polyphenol-rich foods, nuts, green tea and less red and processed meat.
The study also fits with earlier DIRECT-PLUS findings linking the green Mediterranean diet with improvements in several cardiometabolic measures, including liver fat and visceral fat. But this paper should not be read as proof that the diet prevents disease. Some of the outcomes were biomarkers and risk scores, not heart attacks, diabetes diagnoses or long-term clinical events.
Still, the study adds useful nuance to the conversation about food and health. It suggests that dietary patterns may influence the biochemical pathways that connect nutrients, genes and metabolic health. That is different from saying food rewrites DNA. A better way to understand the findings is that diet may affect how certain biological systems operate, especially in people with genetic differences that shape nutrient metabolism.
This work was supported by grants from the Deutsche Forschungsgemeinschaft under Germany’s Excellence Strategy, the Israel Ministry of Health, the Israel Ministry of Science and Technology and the California Walnuts Commission. Walnuts were part of the green Mediterranean diet intervention.