Diabetes - Nrf2 and Oxidative Stress (XGevity™)



Type 2 diabetes is the most common form, becoming more prevalent in the population with age. Hyperglycemia is the initial indicator of a pre-diabetic condition, which affects the body by creating insulin resistance, and damaging the cells through a process termed glycation. The process of glycation is the non-reversible attachment of the excessive sugar to protein (cells, tissue) which causes dysfunction of the tissue and accelerates aging in the body. As this process continues, it enters into an increasing spiral of inflammation, creating more insulin resistance and ultimately causes the death of the insulin producing beta cells of the pancreas.

Glycation leads next to Advanced Glycation End Products (AGES) .AGES are extremely destructive oxidative and become a significant source of continuous oxidative stress and leads to DNA damage and destruction to the affected cells. Methylglyoxal is the most powerful precursor of AGES, and is believed to play a significant role in the progression of Alzheimer's Disease. Decreasing levels of methylglyoxal is an effective target for addressing the inflammation and oxidative stress associated with diabetes.(1)



• SUPRESSION OF DIABETES (via NRF2).  Diabetes is a chronic disease which affects the entire body, and is characterized by high levels of oxidative stress and inflammation. It also provokes a imbalance between protective antioxidants and destructive pro-oxidants. Nrf2 is the cellular defense transcription factor which sets into motion a cascade of antioxidant protective response. However, the Nrf2 system becomes comprised in diabetes. Researchers propose that diabetes progression can be suppressed by a reversal of oxidative state with the addition of Nrf2 activators.(1) Sulforaphane (a product of Glucoraphanin metabolism) is a potent Nrf2 activator. Other Nrf2 activators include andrographolide, curcumin, carnosic acid (rosemary), EGCG (green tea), apigenin and luteolin.        

• MAINTAINENCE OF BLOOD VESSEL INTEGRITY (Retina and brain). Healthy micro-circulation to the retina and the brain require a minimum number of pericytes - the contractile components of the vessels, which maintain the health of the blood flow. When pericytes are loss, then blood vessels are compromised, leading to leakage form the vessels and hemorrhaging. Diabetes results in a loss of pericytes, consequently causing:  

  1. Diabetic Retinopathy. Retinopathy is the destruction of eye sight caused by leaking of blood into the eye, effectively blocking vision. 
  2. Alzheimers Disease (AD) and other Cognition Issues. Essential for brain health is adequate blood flow which transports oxygen and nutrients. When blood flow is compromised, such as the damage to pericytes, the neurons will eventually succumb, and brain problems are incurred.   
  3. Failure of the Blood Brain Barrier (BBB). The BBB plays an important neuro protective role in keeping substances that my harm the brain from passing into brain blood flow. Pericytes are an integral component of the BBB, and loss of pericytes damages this barrier.

• SULFORAPHANE PROTECTS PERICYTES FROM DAMAGE. Sulforaphane suppresses the AGES damage to pericytes, in part by blocking the receptor for AGES, thereby acting as a therapeutic agent in the prevention and treatment of diabetic retinopathy. Preservation of pericytes is also critical for maintaining the microcirculation to the brain which is important for healthy brain function. (2)   

• SULFORAPHANE DETOXIFIES METHYLGLYOXAL TOXICITY. Methylglyoxal is highly reactive precursor in the formation of AGES.  High levels of methylglyoxal have been found in the cerebrospinal fluid of patients with Alzheimer's Disease (AD). Sulforaphane has been shown to increase the detoxification of methylglyoxal, by increasing the activity of an enzyme which breaks down methylglyoxal.(3) Studies indicate that methylglyoxal and AGES are significant contributors in the development of AD.(4)



 • ANT-GLYCATION HERBS. Herbs that prevent the damage of sugar attaching  to protein include: apigenin (5), luteolin (6), hesperidin (7), curcumin (8)



XGEVITY   (Sulforaphane plus other Nrf2 activators)



1. Bhakkiyalakshmi E, et al. The emerging role of redox-sensitiveNrf2-Keap1 pathway in diabetes. Pharmacol Res. 2015 Jan.

2. Maeda S, et al. Sulforaphane inhibits advanced glycation end product - induced pericyte damage by reducing expression of receptor for advanced glycation end products. Nutr Res. 2014 Sept.

3. Angeloni C, et al. Neuroprotective effect of sulforaphane against methylglyoxal cytotoxicity. Chem Res Toxicol.2015 May 1.

4. Angeloni C, et al. Role of methylglyoxal in Alzheimer's disease. Biomed Res Int. 2014.

5. Choi JS, et al. Effects of C-glycosylation on anti-diabetic, anti-Alzheimer's disease and anti-inflammatory potential of apigenin. Food ChemToxicol. 2014 Feb.

6. Choi, JS, et al. The effects of C-glycosylation of luteolin on its antioxidant, anti-Alzheimer's disease, anti-diabetic, and anti-inflammatory activities. Arch Pharm Res. 2014 Oct

7. Li D, et al. Protective effects of hesperidin derivatives and their stereoisomers against advanced glycation end-products formation. Pharm Biol. 2012 Dec.

8. Tang Y, et el. Curcumin eliminates the effect of advanced glycation end-products (AGEs) on the divergent regulation of gene expression of receptors of AGEs by interrupting leptin signaling. Lab Invest. 2014 May.

9. An L, et al. Protective effect of Schisandrae chinensis oil on pancreatic β-cells in diabetic rats. Endocrine. 2015 Apr.