eng Science and Education Publishing American Journal of Food and Nutrition 2374-1163 2024-07-03 12 3 87 93 10.12691/ajfn-12-3-2 AJFN20241232 article Madhurima Chatterjee 1 Anna Goc 1 Aleksandra Niedzwiecki author@drrath.com 1 Matthias Rath 1 Dr. Rath Research Institute, 5941 Optical Court, San Jose, CA 95138, USA Background: Diabetes is a global health crisis. Chronic hyperglycemia leads to the formation of glycated proteins known as Advanced Glycated End Products (AGEs) which damage multiple organs resulting in diabetes-related retinopathy, atherosclerosis, neuropathy and other pathologies. Therefore, prevention and reversal of protein glycation is an important aspect in diabetes management, especially involving natural, non-toxic approaches. Methods and Results: We tested the efficacy of natural compounds, including Krebs cycle mediators and amino acids in different aspects of diabetes. Firstly, we demonstrated that these compounds work individually and synergistically to prevent glycation of bovine serum albumin caused by glucose and fructose. Secondly, our study showed that the test compounds reverse glycation of L-lysine by converting N¦Å-(1-Carboxymethyl)-L-lysine to L-lysine in vitro, implying that natural removal of AGEs is possible. We also demonstrated that combinations of natural compounds can address important aspects of diabetes metabolism, such as impaired mitochondrial bioenergetics and cellular damage by oxidative stress. Conclusion: Our data show that the combination of natural compounds stimulates mitochondrial activity and mitobiogenesis in skeletal muscle cells, which are impaired in diabetes and linked to the development of diabetic cardiomyopathy. In addition, these natural compounds protect microglial cells from oxidative stress ¨Ca common hallmark of hyperglycemia implicated in neuropathy, vascular systems damage and other pathologies. Our data demonstrate that a combination of selected natural compounds has superior biological efficacy compared to its individual components in important metabolic aspects of diabetes and should be further evaluated as a non-toxic alternative in diabetes treatment and/or management. https://pubs.sciepub.com/ajfn/12/3/2/ajfn-12-3-2.pdf diabetes Advanced Glycation End products (AGEs) micronutrients