A plant-forward version of the Mediterranean diet, dubbed the Green Mediterranean or Green-MED diet, was associated with higher blood folate levels and improvements in several cardiometabolic markers in data reported from the DIRECT-PLUS randomized controlled trial. Medical News Today covered the findings, which were published in the journal Clinical Nutrition.
The published analysis found that participants assigned to the Green-MED pattern had greater increases in circulating folate than those following a standard healthy-diet plan or a traditional Mediterranean diet. Higher folate concentrations were linked to better insulin sensitivity, lower levels of the inflammatory marker interleukin-6, improved blood lipid measures, and reductions in both visceral and liver fat.
Why this matters
Folate, a B vitamin found in leafy greens, legumes, and some fortified foods, participates in one-carbon metabolism. That biochemical network helps build and repair DNA and provides methyl groups that influence gene activity without changing the DNA sequence. Impaired folate processing has been associated with higher homocysteine, inflammation, and elevated cardiometabolic risk.
The study is notable because it suggests that an overall dietary pattern rich in plant-based foods and polyphenols may improve folate status and related metabolic pathways, not just single-nutrient supplementation. The researchers also explored whether diet might partly offset the effects of a common genetic variation in the MTHFR gene, which can reduce the efficiency of folate metabolism for some people.
What the study found
Data come from the DIRECT-PLUS randomized trial, which compared a standard healthy diet, a traditional Mediterranean diet, and a Green-MED diet that emphasized polyphenol-rich plant foods and included a daily shake made with the aquatic plant mankai (Wolffia globosa), also called duckweed.
Key reported associations in the Green-MED group included higher blood folate and concurrent improvements in insulin sensitivity, lower interleukin-6 (an inflammatory marker), improved lipid profiles, and less visceral and liver fat accumulation.
The investigators also examined gene expression in blood samples. In people carrying two copies of a common MTHFR variant (the rs1801133 TT genotype), they observed upregulation of some alternative folate-processing genes, including MTHFD2 and DHFR, after greater intake of plant-derived nutrients. The authors interpret this as evidence that diet may activate alternative pathways to help process folate when MTHFR activity is reduced.
The analysis further suggested that among people with the higher-risk TT genotype, those who adhered closely to the mankai-enriched Green-MED pattern showed reductions in calculated cardiovascular risk scores, whereas low mankai intake was linked to increased scores over time. The trial was not designed to isolate the effect of mankai alone, however.
What to keep in mind
Important limitations affect how far these findings can be generalized. The study reports changes in biomarkers and gene activity, not clinical endpoints such as heart attacks, strokes, or diabetes onset. Gene-expression data came from blood samples, which do not necessarily reflect changes in other tissues such as liver or vascular endothelium.
The role of mankai in the observed benefits cannot be separated from the overall dietary pattern within this study. Details such as sample size, participant demographics, and follow-up length influence how confidently results apply to different populations; those specifics matter and should be checked in the full Clinical Nutrition publication. Finally, randomized trials can reduce some biases, but even well-conducted dietary interventions have challenges with adherence and measurement of intake.
As always, if you have a known genetic variant, a chronic condition, or are taking medication, discuss dietary changes with a qualified health professional before making major adjustments or starting supplements.
The bottom line
The Green Mediterranean diet in the DIRECT-PLUS trial was associated with increased blood folate and favorable shifts in several cardiometabolic biomarkers. The study adds to evidence that whole dietary patterns rich in plant foods and polyphenols can influence metabolic pathways and even gene activity related to folate processing.
Practical steps for readers interested in the Green-MED approach include emphasizing leafy greens, legumes, nuts (for example, walnuts), whole grains, green tea, and a diversity of vegetables and pulses. Mankai is highlighted in this trial as a folate-containing aquatic plant that can be blended into smoothies, but it is not widely available in all markets, and the trial did not prove that any single food is solely responsible for the benefits.
In short, focusing on consistent, plant-forward Mediterranean-style eating may improve folate status and several markers linked to cardiometabolic health, but larger and longer studies are needed to confirm effects on clinical outcomes and to clarify the roles of specific foods such as mankai. Talk with your clinician or a registered dietitian to adapt dietary choices to your individual health needs.
