New Research Suggests Low Blood Sugar & Polyphenols Are Linked to Slower Brain Aging

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A natural part of aging is brain atrophy, which is characterized by a reduction in brain volume. Brain atrophy has been identified as an early biomarker for cognitive decline and brain aging(1).  

Although age-related brain atrophy is an unavoidable process, type 2 diabetes, inflammation, hypertension, high cholesterol, and accumulation of β amyloid and tau markers have all been found to be associated with accelerated brain atrophy and cognitive impairment(2).  

Individuals with type 2 diabetes are differentiated by greater structural brain abnormalities, such as atrophy predominantly in the hippocampus(3).  

Shrinkage of the hippocampus is a morphologic feature of a mild cognitive impairment and Alzheimer’s disease.  A recent study investigated the effects of a caloric-restricted Mediterranean diet, and of a further enriched high-polyphenol green- Mediterranean diet, on age-related brain atrophy(4).   

Results from this research indicate that Mediterranean and green-Mediterranean diets significantly attenuated age-related brain atrophy by ∼50% within 18 months.  Based on these findings, a follow-on study examined the specific diet-induced parameters that may contribute to brain-volume deviation compared with chronologic age(5). Researchers also aimed to elucidate the mechanism by which the slowing brain atrophy unfolds, and what they discovered was very exciting.
 

Major Findings

This research indicates that improved glycemic control following

weight loss interventions may have an independent beneficial effect on Magnetic Resonance Imaging (MRI)-assessed brain age.  Younger brain age was driven by greater consumption of high polyphenols: green tea and Mankai (a high-protein aquatic plant). These findings suggest a potential mechanistic pathway for driving the favorable impact of high-polyphenol diets. Moreover, the consumption of polyphenol-rich foods, such as green tea and Mankai, may enrich the blood–brain barrier, reduce blood pressure, and attenuate age-related brain atrophy(6).


The hippocampus plays a major role in learning and memory, and evidence indicates that atrophy of the hippocampus due to aging may serve as an early biomarker for cognitive decline. 

Disrupted metabolic parameters such as

body mass index, cholesterol, and glycemic parameters are correlated with accelerated brain atrophy and cognitive decline(7).

The fact that greater changes to neurodegeneration markers and brain-age proxy were observed in participants with improved glycemic control and inflammation markers beyond weight loss supports our hypothesis that reduction in glycemic biomarkers has an independent effect on the neuroprotective benefits of diet and may play a major role in

attenuating neurodegeneration.

The potential underlying mechanism of such a favorable association between Mediterranean diets and age-related neurodegeneration could be partially attributed to the high content of polyphenols that are present in plant-based food sources.  The Mankai plant includes more than 200 polyphenols and phenolic metabolites(8) and has high phenolic and antioxidant content, with a high concentration of the flavonoid-class polyphenols luteolin and apigenin derivatives.

Green tea contains catechins, specifically epigallocatechin, epicatechin gallate, and epigallocatechin gallate polyphenols.

Consuming green tea, as either a beverage or an extract, has numerous reported health benefits, including improvements in cardiometabolic health, weight management, and cognitive function. Polyphenols are known to be able to cross the blood-brain barrier, reduce neuroinflammation, and induce cell proliferation and adult-onset neurogenesis in the hippocampus(9).

Summary

This study shows that

maintaining low blood sugar levels, and keeping it regulated in the normal range shows potential for preserving a younger brain, especially when combined with a healthy nutrition program and consistent physical activity. This study is one of the first large-scale trials to directly link dietary changes, particularly those associated with the Green-Mediterranean diet (polyphenol-rich), to improve glycemic control and slower brain aging.  

While further research is needed to fully understand the mechanisms at play, these results suggest a potential avenue for reducing the risk of age-related cognitive decline through relatively simple dietary adjustments.

If you’d like to learn more about the potential neuroprotective benefits of polyphenols found in foods like berries, you can learn more

here.

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References:


    1.    Ekman U, Ferreira D, Westman E: The A/T/N biomarker scheme and patterns of brain atrophy assessed in mild cognitive impairment. Sci Rep 8:8431, 2018
    2.    Callisaya ML, Beare R, Moran C, et al: Type 2 diabetes mellitus, brain atrophy and cognitive decline in older people: a longitudinal study. Diabetologia 62:448-458, 2019
    3.    Garfield V, Farmaki AE, Eastwood SV, et al: HbA1c and brain health across the entire glycaemic spectrum. Diabetes Obes Metab 23:1140-1149, 2021
    4.    Kaplan A, Zelicha H, Yaskolka Meir A, et al: The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS). Am J Clin Nutr 115:1270-1281, 2022
    5.    Pachter D, Kaplan A, Tsaban G, et al: 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


    6.    Figueira I, Tavares L, Jardim C, et al: Blood-brain barrier transport and neuroprotective potential of blackberry-digested polyphenols: an in vitro study. Eur J Nutr 58:113-130, 2019
    7.    Taki Y, Kinomura S, Sato K, et al: Relationship between body mass index and gray matter volume in 1,428 healthy individuals. Obesity (Silver Spring) 16:119-24, 2008
    8.    Yaskolka Meir A, Tuohy K, von Bergen M, et al: The Metabolomic-Gut-Clinical Axis of Mankai Plant-Derived Dietary Polyphenols. Nutrients 13, 2021
    9.    Dias GP, Cavegn N, Nix A, et al: The role of dietary polyphenols on adult hippocampal neurogenesis: molecular mechanisms and behavioural effects on depression and anxiety. Oxid Med Cell Longev 2012:541971, 2012

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