References and Professional Synopsis: Capece, U.; Moffa, S.; Improta, I.; Di Giuseppe, G.; Nista, E.C.; Cefalo, C.M.A.; Cinti, F.; Pontecorvi, A.; Gasbarrini, A.; Giaccari, A.; et al. Alpha-Lipoic Acid and Glucose Metabolism: A Comprehensive Update on Biochemical and Therapeutic Features. Nutrients 2023, 15, 18. https://doi.org/10.3390/nu15010018
Alpha-Lipoic Acid (ALA) has therapeutic features that include: positive effects on insulin sensitivity, regulation of glucose metabolism and lipid profiles; antioxidant properties and reduction of oxidative stress; treatment of diabetic neuropathy by improving symptoms such as neuropathic pain and nerve function; association with weight loss in some studies; effects on pancreatic beta-cells and potential therapeutic role beyond diabetes; management of conditions like polycystic ovary syndrome (PCOS) and obesity; improvement in nerve blood flow and reduction of oxidative stress; neuroprotection against ischemia-reperfusion injury; potential alternative treatment for diabetic polyneuropathy; impact on cardiovascular autonomic neuropathy and prevention of diabetic macular edema. Specifically, alpha-lipoic acid (ALA) plays a significant role in insulin signaling through multiple mechanisms including: stimulating glucose uptake by promoting GLUT4 translocation and activation, activating AMPK to enhance insulin sensitivity and glucose uptake, acting as a direct binding activator of the insulin receptor, improving insulin signaling, improving insulin sensitivity, glucose disposal, and lipid profiles in individuals with diabetes, counteracting inhibition of glucose-stimulated insulin release, protecting against oxidative stress, reducing insulin resistance, enhancing glucose uptake in skeletal muscle, modulating insulin sensitivity indices and ameliorating insulin resistance, increasing insulin sensitivity in metabolic diseases by decreasing FPG, HbA1c, and insulin concentrations, improving insulin sensitivity in Type 2 Diabetes and obese patients, enhancing glucose disposal rates and insulin-mediated glucose disposal, decreasing insulin resistance in obese patients with PCOS, improving metabolic profiles related to insulin signaling, impacting nerve function and autonomic responses related to insulin signaling, acting as an insulin mimetic agent, stimulating the insulin receptor cascade, activating PI3K, AKT phosphorylation, and p38 MAPK activity for glucose uptake, influencing mitochondrial biogenesis, endoplasmic reticulum activity, and antioxidant enzymes expression, protecting pancreatic beta-cells and influencing insulin secretion, activating the insulin receptor by extracellular binding and AMPK through cell membrane crossing, contributing to the Krebs cycle initiation and potentially modifying insulin structure in certain conditions.
References and Professional Synopsis: Rebecca B. Costello, Johanna T. Dwyer, Leila Saldanha, Regan L. Bailey, Joyce Merkel, and Edwina Wambogo. Do Cinnamon Supplements Have a Role in Glycemic Control in Type 2 Diabetes – A Narrative Review? J Acad Nutr Diet. 2016 November ; 116(11): 1794–1802. doi:10.1016/j.jand.2016.07.015.
A review of 11 randomized clinical trials on cinnamon supplements for adults with type 2 diabetes mellitus showed modest effects on fasting plasma glucose and hemoglobin A1c, albeit characteristics of cinnamon intervention products used in clinical trials varied in terms of manufacturers, doses, placebo formulations, and product formulations.
References and Professional Synopsis: Satyakumar Vidyashankar, Uddagiri Venkanna Babu, Pralhad Sadashiv Patki. Gymnemasylvestre derived compounds inhibit GSH depletion and increase cGMP and nitric oxide to attenuate advanced glycation end products induced hypertrophic growth in renal tubular epithelial cells. Toxicology Reports 2014(1); 834–842. http://dx.doi.org/10.1016/j.toxrep.2014.08.015
Gymnemasylvestre addresses complications of diabetes related to advanced glycation end products (AGE) induced cellular hypertrophy in renal tubular epithelial cells. It helps in restoring nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels, preventing glutathione (GSH) depletion, inhibiting the formation of glutathione disulfide (GSSG), and increasing antioxidant enzyme activities to reduce reactive oxygen species (ROS) generation in cells. Additionally, Gymnemasylvestre aids in reducing markers of cellular hypertrophy, suggesting its role in inhibiting cellular differentiation observed during diabetic nephropathy (DN) complications. This document explores the effects of Gymnema Sylvestre organic extract (GE) on advanced glycation end products (AGE) induced hypertrophic growth in renal tubular epithelial cells. GE demonstrates potential in restoring nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels, preventing glutathione (GSH) depletion, inhibiting glutathione disulfide (GSSG) formation, and enhancing antioxidant enzyme activities to mitigate reactive oxygen species (ROS) generation. The findings suggest that Gymnemasylvestre may play a role in reducing markers of cellular hypertrophy, potentially influencing cellular differentiation observed in diabetic nephropathy (DN) complications.
References and Professional Synopsis: Scott Fuller and Jacqueline M Stephens. Diosgenin, 4-Hydroxyisoleucine, and Fiber from Fenugreek: Mechanisms of Actions and Potential Effects on Metabolic Syndrome. Adv Nutr 2015;6:189–197. doi:10.3945/an.114.007807.
Fenugreek and its components (we here refer to as Diosgenin and 4-OH-Ile) have been studied for their effects on various physiological markers related to metabolic syndrome. Multiple studies have shown their effects on lipid metabolism, adipocyte function, cholesterol homeostasis, and cardioprotection. Diosgenin and 4-OH-Ile have antidiabetic properties and can improve glycemia, insulin concentrations, and lipid levels. 4-OH-Ile acts as an insulin sensitizer and improves insulin sensitivity.
Fenugreek, through its bioactive components, could be part of new strategies to treat metabolic diseases, and further research and clinical trials are ongoing for efficacy and standardization.