Hormonal
Activation of the Nrf2/Keap1/ARE pathway improves insulin sensitivity, reduces hyperglycemia, and protects pancreatic beta-cells in type II diabetes models, whereas classic direct antioxidants have failed to show benefit.
Focus on lifestyle and dietary choices that naturally support your body's antioxidant defenses (like the Nrf2 pathway) rather than relying on high-dose direct antioxidant supplements. The paper highlights that compounds like sulforaphane (found in cruciferous vegetables) and resveratrol (found in grapes/berries) may help activate this pathway, potentially improving insulin sensitivity and protecting cells, whereas direct antioxidant supplements have not shown clinical benefit for diabetic complications.
Studies by Uruno et al. in murine models of Nrf2 overexpression via both genetic Keap1 knockdown and pharmacological induction suggest that Nrf2 activation can improve insulin sensitivity in diabetes and abrogate diabetes and obesity in mice... classic antioxidants, low molecular-weight compounds that can scavenge reactive oxygen intermediates, have not been proven beneficial in the treatment of diabetic complications. In contrast to these classic or direct antioxidants, the battery of cytoprotective agents that are upregulated by the Nrf2/Keap1/ARE pathway have been termed 'ultimate antioxidants'...
Why this rating
Evidence is primarily from animal models (mice) and in vitro studies; human clinical trials (BEACON) showed mixed/negative results for specific drugs, though the pathway's general relevance is supported.
Source
The Nrf2/Keap1/ARE Pathway and Oxidative Stress as a Therapeutic Target in Type II Diabetes Mellitus
Joshua A. David et al. · Journal of Diabetes Research · 2017
DOI 10.1155/2017/4826724
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