Mediterranean diet’s neuroprotective effects linked to glycemic control

Recent research has uncovered a link between diet, blood sugar control, and brain health in aging adults. The study, conducted as part of the DIRECT PLUS trial and published in The American Journal of Clinical Nutrition, found that dietary interventions, particularly a Mediterranean diet enriched with polyphenol-rich foods like green tea and Mankai duckweed, can slow age-related brain atrophy. These findings suggest that improved glycemic control not only reduces risks associated with conditions like type 2 diabetes but may also help preserve cognitive function by promoting a more youthful brain age.

As people age, brain atrophy—the loss of neurons and brain tissue—becomes inevitable, often signaling the onset of cognitive decline and conditions like Alzheimer’s disease. However, factors such as type 2 diabetes, high blood pressure, and poor diet can accelerate this process. The study’s researchers aimed to determine whether improved glycemic control, through targeted dietary interventions, could mitigate these effects and preserve brain health. They hypothesized that controlling blood sugar levels and incorporating polyphenol-rich foods might protect against age-related neurodegeneration.

“The brain is a vital organ that is not routinely examined in clinical practice. We have been particularly interested in exploring factors that influence brain age, which does not always align with chronological age. Our focus is on modifiable factors, such as nutrition and glycemic control, that individuals can actively change to promote brain health and slow aging,” said Dafna Pachter, a PhD student at Ben-Gurion University of the Negev and the first author of the paper.

The study, conducted as part of the DIRECT PLUS Brain MRI trial, aimed to assess whether dietary interventions could slow brain aging through improved glycemic control. It involved 294 participants, all aged 30 or older, with abdominal obesity or dyslipidemia. Participants were randomly assigned to one of three groups: a healthy dietary guideline group (the control group), a calorie-restricted Mediterranean diet group, or a calorie-restricted green-Mediterranean diet group enriched with polyphenol-rich foods. Each group followed their respective diet plans for 18 months.

The Mediterranean diet emphasized vegetables, poultry, fish, and walnuts while limiting red and processed meats. The green-Mediterranean diet went further by incorporating green tea (3–4 cups per day) and Mankai duckweed shakes (500 milliliters daily), both known for their high polyphenol content. All participants received free gym memberships and were encouraged to engage in regular physical activity. They also participated in group sessions where nutrition and exercise guidance were provided.

Over 18 months, the participants underwent brain MRI scans to assess structural changes in the hippocampus, a region critical for memory and learning. These scans were analyzed using NeuroQuant, an FDA-approved software, which calculated the hippocampal occupancy score, a marker of brain age based on hippocampal volume relative to the surrounding brain structures. Researchers also monitored metabolic markers such as fasting glucose, insulin, and hemoglobin A1c levels to measure glycemic control. The participants’ adherence to their dietary protocols and physical activity routines was supported through regular consultations and workplace-based guidance.

The findings highlighted significant benefits associated with the Mediterranean and green-Mediterranean diets, particularly for brain aging. Participants in these groups exhibited reduced hippocampal atrophy compared to the control group, with the green-Mediterranean diet yielding the most pronounced effects. Those adhering to the green-Mediterranean diet showed a 50% slower decline in their hippocampal occupancy score, reflecting a younger brain age.

Improvements in glycemic control were a key driver of these benefits. Participants who achieved better blood sugar regulation, as indicated by lower fasting glucose and hemoglobin A1c levels, experienced the greatest reduction in brain aging. This effect was independent of weight loss, suggesting that managing blood sugar levels directly influences brain health. Furthermore, participants who consumed higher amounts of green tea and Mankai shakes exhibited the most substantial improvements in both glycemic control and brain aging metrics.

Interestingly, while weight loss and improved metabolic health were observed across all groups, the green-Mediterranean diet’s unique combination of polyphenol-rich foods appeared to amplify the neuroprotective effects. The study suggested that these polyphenols might cross the blood-brain barrier, reducing inflammation and promoting cellular repair in the brain.

“The key takeaway is that even non-radical lifestyle changes, such as adopting a Mediterranean or green-Mediterranean diet and glycemic control can positively impact our health and even slow brain aging within just 18 months,” Pachter told PsyPost. “This shows how small, consistent adjustments to our daily habits can lead to improvements in long-term brain health. It is important to start these changes early in life, rather than waiting until later stages when the effects of aging may become less reversible.”

While the results are promising, the study has some limitations. Most participants were male, limiting the generalizability to females. Additionally, the researchers did not assess participants’ cognitive performance, which would have provided more direct evidence of the diets’ effects on memory and thinking abilities. Although the green-Mediterranean diet appeared particularly beneficial, its effects might not be solely due to polyphenols; reduced red meat consumption may also have contributed.

The study, “Glycemic control contributes to the neuroprotective effects of Mediterranean and green-Mediterranean diets on brain age: the DIRECT PLUS brain-magnetic resonance imaging randomized controlled trial,” was authored by Dafna Pachter, Alon Kaplan, Gal Tsaban, Hila Zelicha, Anat Yaskolka Meir, Ehud Rinott, Gidon Levakov, Moti Salti, Yoram Yovell, Sebastian Huhn, Frauke Beyer, Veronica Witte, Peter Kovacs, Martin von Bergen, Uta Ceglarek, Matthias Blüher, Michael Stumvoll, Frank B. Hu, Meir J. Stampfer, Alon Friedman, Ilan Shelef, Galia Avidan, and Iris Shai.