Higher Brain Glucose | Prediabetes Diabetes - Connection to Dementia - Alzheimer's Disease

Scientific evidence indicates that higher levels of blood glucose in the brain, due to the inability of the brain to process the glucose (impaired fasting glucose metabolism) is strongly linked to cognitive decline including brain shrinkage and dementia including Alzheimer's Disease (AD). Neurons in the brain must have a continuous supply of glucose, which is utilized as their primary energy source. Transport of glucose into the neuron is through the  glucose transport proteins GLUT1 and GLUT3 which are not dependent on insulin. Since the brain is so dependent on GLUT1 and GLUT3 to sustain energy for the function of the neurons, any loss of GLUT functioning results in the death of neurons. Furthermore. the higher levels of uncontrolled glucose causes destructive pathological changes to the brain associated with Alzheimer's Disease. The impaired ability of the brain to properly metabolize glucose is often referred to as "type 3 diabetes". (1-6)


HYPERGLYCEMIA (Including High-Normal Glucose Levels). Dysregulation of glucose homeostasis leads to higher levels of glucose in brain tissue including brain shrinkage, and the formation of brain pathologies such as beta amyloid plaques and fibrils. Higher blood sugar levels (including high normal, prediabetes and type 2 diabetes) begin with insulin resistance, whereby blood glucose cannot be adequately absorbed by the cells, and glucose levels in the blood stream increase.

Higher plasma glucose levels is correlated to increases in brain glucose. Furthermore, this continues to be exacerbated when GLUT1 and GLUT3 transporters are decreased in function and/or number, and glucose is unable to reach the neurons. GLUT transporters are affected by glycation in diabetics, and may render the transport mechanism non-functional.  Higher glucose levels correlate to the most severe loss of brain function in Alzheimer's Disease. (11)

Classifications of fasting blood glucose levels:

  • Normal Fasting Blood Sugar. 50-100 mg/dL
  • Prediabetes: 101-125 mg/dL.



Impaired glucose metabolism in brain tissue, including reduced levels of GLUT1 and GLUT3, are significantly linked to amyloid plaque accumulation and brain tau fibril entanglements.

Pathological changes in the brain linked to high blood glucose:

  • Atrophy of hippocampus and other brain structures (2,3)
  • Increases protein glycation, oxidative stress, and inflammation of brain (7)
  • Increases amyloid beta aggregation. (7)
  • Increases accumulation of tau-containing neurofibrillary tangles (tau).
  • Impaired glucose metabolism decreases levels of protein O-GlcNAcylation - a protein regulated by glucose metabolism. Therefore, high glucose results in INCREASED level of tau hyperphosphorylation.  Tau tangles are known as the neurofibrillary degeneration component of Alzheimer's disease.(8-10)


    GLUCOSE TRANSPORTERS - Impact on Brain Glucose Metabolism

    • GLUT1 is the primary method for the transport of glucose to glial cells including  astrocytes as well as brain endothelial (blood vessel) cells. Atsrocytes are a type of glial cell, which plays importance roles in synaptic nerve transmission and preserving the energetics at the blood brain barrier.
    • GLUT1 at the endothelium of the blood-brain barrier allows glucose to be transported into the brain.
    • GLUT3 is a protein that transports glucose to the neurons, and the neuron generates energy for the cell by a process of glycolysis.



    Natural Support for Glucose Homeostasis

    • Hericium erinaceus -  Novel mycelium polysaccharides in H. erinaceus protects the structure and function pancreas, in diabetic animal models. Glucose homeostasis is an important function of the beta cells of the pancreas. Diabetic complications are due to increased levels of inflammation, oxidative stress and reduction in antioxidant capacity. H. Erinaceus enhances antioxidant capacity and reduces oxidative stress.(12)  
    • Wolfberry ( Lycium Barbarum) - Decreases absorption of glucose in the intestine, thereby reducing glucose levels in the blood stream.(13)
    • Andrographolide - studies inidicate that andrographolide may significantly reduce blood glucose levels, may reverse decreases in critical protective antioxidants in the brain due to diabetes. (14)
    • Jujube - Fructose intake promotes hyperglycemia, glycation is a known promoter of insulin resistance, Jujube polysacchardies ameliorate fructose induced insulin resistance.(15)
    • Baicalin -  Alleviates obesity induced insulin resistance, through activation of Akt/GLUT4 pathways. GLUT4 reduces plasma glucose levels by increasing removal of glucose by skeletal muscle. (16)
    • Piperine - Insulin resistance models results demonstrate that piperine reverses glucose impairment in insulin resistance cell lines. Research indicates that piperine increases activity of AMPK signaling, which accounts for glucose improvement,(16) AMPK is involved as an energy sensor, and is also activated by exercise, which also increases insulin sensitivity in exercisers. (17,18)
    • Fucoidan - Plays dual role including regulating glucose homeostasis and protecting pancreatic beta cells.(19,20)
    • Yellows (Flavonoids Plus) -  Ginger (21), Apigenin and Luteolin (22), Curcumin (23) also baicalin.


    NEUROTREX (Jujube, Wolfberry, Piperine, more)


    HYPER LONGEVITY (Fucoidan, Piperine, more)


    YELLOW LONGEVITY (Yellow Glucose Homeostasis)

    MEMORY ACTION (Andrographolide, more)



    (1) An Y, et al, Evidence for brain glucose dysregulation in Alzheimer's disease.  Alzheimers Dement. 2017 Oct 19

    (2) Cherbuin N, et al. Higher normal fasting plasma glucose is associated with hippocampal atrophy: The PATH Study. Neurology. 2012 Sep

    (3) Mortby ME, et al, High "normal" blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the PATH through life study. PLoS One. 2013 Sep

    (4) Porter-Turner MM, et al. Relationship between erythrocyte GLUT1 function and membrane glycation in type 2 diabetes.  Br J Biomed Sci. 2011

    (5) Barros LF, et al. Near-critical GLUT1 and Neurodegeneration. J Neurosci Res. 2017 Nov

    (6) Vogelsang P, et al. Reduced glucose transporter-1 in brain derived circulating endothelial cells in mild Alzheimer's disease patients. Brain Res. 2017 Nov 1

    (7) Guo C, et al. Chronic hyperglycemia induced via the heterozygous knockout of Pdx1 worsens neuropathological lesion in an Alzheimer mouse model. Sci Rep. 2016 Jul 

    (8) Ying Liu, et al. Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer disease. J Neurochem 2009 Oct.

    (9) Liu F, et al. Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer's disease. Brain. 2009.

    (10) Gong CX, et al. O-GlcNAcylation: A regulator of tau pathology and neurodegeneration. Alzheimers Dement. 2016 Oct;

    (11) Mittal K, et al. Shared links between type 2 diabetes mellitus and Alzheimer's disease: A review. Diabetes Metab Syndr. 2016 Apr-Jun

    (12) Zhang, C, et a. Antihyperglycaemic and organic protective effects on pancreas, liver and kidney by polysaccharides from Hericium erinaceus SG-02 in streptozotocin-induced diabetic mice. Scientific Reports 7, Article number: 10847 (2017)  

    (13) Cai H, et al. Lycium barbarum L. Polysaccharide (LBP) Reduces Glucose Uptake via Down-Regulation of SGLT-1 in Caco2 Cell. Molecules. 2017 Feb.

    (14) Naik RR, et al. Andrographolide reorganise hyperglycaemia and distorted antioxidant profile in streptozotocin-induced diabetic rats. Cardiovasc Hematol Agents Med Chem. 2017 Oct 

     (15) Zhao Y, et al. Preventive effects of jujube polysaccharides on fructose-induced insulin resistance and dyslipidemia in mice. Food Funct. 2014 Aug

    (16) Fang P, et al. Baicalin against obesity and insulin resistance through activation of AKT/AS160/GLUT4 pathway.  Mol Cell Endocrinol. 2017 Jun

    (17) Wan CP, et al. [Piperine regulates glucose metabolism disorder in HepG2 cells of insulin resistance models via targeting upstream target of AMPK signaling pathway]. Zhongguo Zhong Yao Za Zhi, 2017 Feb

    (18) O'Neill HM. AMPK and Exercise: Glucose Uptake and Insulin Sensitivity.  Diabetes Metab J. 2013 Feb

    (19) Kim KJ, et al, Fucoidan regulate blood glucose homeostasis in C57BL/KSJ m+/+db and C57BL/KSJ db/db mice. Fitoweapia. 2012 Sep

    (20) Yu W, wt al. Fucoidan ameliorates pancreatic β-cell death and impaired insulin synthesis in streptozotocin-treated β cells and mice via a Sirt-1-dependent manner. Mol Butr Food Res. 2017 Oct;

    (21) de Las Heras N, et al. Molecular factors involved in the hypolipidemic- and insulin-sensitizing effects of a ginger (Zingiber officinale Roscoe) extract in rats fed a high-fat diet.  Appl Physiol Nutr Metab. 2017 Feb

    (22) Bumke-Vogt C, et al. The flavones apigenin and luteolin induce FOXO1 translocation but inhibit gluconeogenic and lipogenic gene expression in human cells. PLoS One. 2014 Aug 

    (23) Zhao NJ, et al. Curcumin suppresses Notch‑1 signaling: Improvements in fatty liver and insulin resistance in rats. Mol Med Rep. 2018 Jan;


    Gail Paige
    Gail Paige