A Summary of the article “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”
Background and Objectives
The article by Pachter et al., is an original research article published in The American Journal of Clinical Nutrition in 2024. This study serves as a post hoc analysis of the 18-month Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS).
Age-related brain atrophy, characterized by a reduction in brain volume, is a natural aging process and an early biomarker for cognitive decline. However, conditions such as type 2 diabetes, hypertension, and inflammation are associated with accelerated brain atrophy. Individuals with type 2 diabetes often exhibit greater structural brain abnormalities, particularly in the hippocampus. The researchers had previously reported that both Mediterranean (MED) and green-MED diets significantly attenuated age-related brain atrophy by approximately 50% over 18 months compared to a control group.
The objective of this specific analysis was to explore the contribution of specific diet-induced parameters to brain-volume deviation from chronological age. The core hypothesis was that improved glycemic control contributes significantly to the neuroprotective effects of diet on brain age.
Methods
The DIRECT PLUS trial enrolled 294 participants, of whom 224 completed the trial with eligible whole-brain MRIs. Participants (88% male; mean age 51.1 y; mean BMI 31.2 kg/m²) with abdominal obesity or dyslipidemia were randomly assigned to one of three 18-month intervention groups: 1) healthy dietary guidelines (HDG, control), 2) a calorie-restricted traditional MED diet, or 3) a green-MED diet. Both MED diets included 28g of walnuts daily. The green-MED diet was higher in polyphenols, low in red meat, and further supplemented with green tea (3–4 cups/d) and a Mankai green shake (from the Wolffia globosa aquatic plant), providing an additional 800 mg/d of polyphenols.
The primary neurodegeneration marker used was the Hippocampal Occupancy (HOC) score, which is the ratio of hippocampal volume to the combined volume of the hippocampus and the inferior lateral-ventricle. This score acts as a proxy for brain age.
Key Findings
At baseline, individuals exhibiting a “younger brain age” (higher HOC deviation than expected for their chronological age) presented with significantly lower levels of body weight, waist circumference, diastolic and systolic blood pressure, insulin, and HbA1c.
Crucially, the post hoc analysis revealed that after 18 months, greater changes in HOC deviations (i.e., attenuation of brain-age decline) were independently associated with improved glycemic control markers. Specifically, improvements in HbA1c (β = –0.254), HOMA-IR (β = –0.200), fasting glucose (β = –0.155), and C-reactive protein (CRP) (β = –0.153) were significantly linked to HOC improvements. Furthermore, a decline in HbA1c was associated with greater deviation changes in the thalamus, caudate nucleus, and cerebellum.
Participants whose diabetes status improved (transition from prediabetes/diabetes to normal status) demonstrated greater mean HOC deviation changes than those with no change or an unfavorable change.
The study highlighted the role of the green-MED components: greater consumption of Mankai and green tea was directly associated with greater HOC deviation changes, even after adjusting for weight loss. The green-MED group also saw the greatest proportion of participants (58.33%) improve their glycemic status. Mediation analyses suggested that Mankai consumption impacted HOC deviation changes through HOMA-IR and insulin.
Conclusion
The study concluded that glycemic control contributes significantly to the neuroprotective effects of both the MED and green-MED diets on brain age. These neuroprotective benefits appear to be independent of overall weight loss. The incorporation of polyphenol-rich components, such as Mankai and green tea, may contribute to achieving a more youthful brain age.
References
Pachter, D., Kaplan, A., Tsaban, G., Zelicha, H., Meir, A. Y., Rinott, E., Levakov, G., Salti, M., Yovell, Y., Huhn, S., Beyer, F., Witte, V., Kovacs, P., von Bergen, M., Ceglarek, U., Blüher, M., Stumvoll, M., Hu, F. B., Stampfer, M. J., Shai, I. (2024). 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. The American Journal of Clinical Nutrition, 120(5), 1029–1036. https://doi.org/10.1016/j.ajcnut.2024.09.013
This post is based on Open Access research and is for informational purposes only.
