Akoge (Alpha-KetoglutaratE)

Akoge is more or less a cornerstone in the Lemon Protocol™. It is a dietary supplement that we essentially recommend to everyone, and it's advantageous to take it for a long time.

Alpha-ketoglutarate is formed in all cells of the body and participates under normal circumstances in energy production in the mitochondria. It has been shown that the amount of alfa-ketoglutarate decreases with age, and research on mice has shown that if this substance is replenished, the mice live longer and stay healthier and fresher into old age.

The positive effects of alfa-ketoglutarate usually do not come from increasing energy production but rather from acting as a switch during inflammation. When a cell is activated, glycolysis is upregulated (which we inhibit with Symbios), and mitochondrial function is simultaneously altered, leading to the production of more of certain substances relative to alfa-ketoglutarate. This altered ratio plays an important role in epigenetic regulation, and one could say that alfa-ketoglutarate determines which 'path' the cell will take, whether inflammation occurs or not. By increasing the amount of alfa-ketoglutarate in the cell, one counteracts the epigenetic regulation that the cell seeks during inflammation. For example, studies have shown that the amount of alfa-ketoglutarate determines whether macrophages become pro-inflammatory (M1) or anti-inflammatory (M2), but this also applies to other immune cells.

This is a dietary supplement and should not replace a varied diet. The product is not recommended for pregnant and breastfeeding women to err on the side of caution. Store in a dry place and out of reach of children.

Further reading:
1. Asadi Shahmirzadi A, Edgar D, Liao CY, et al. Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice. Cell Metab. 2020;32(3):447-456.e6. doi:10.1016/j.cmet.2020.08.004

2. Naeini SH, Mavaddatiyan L, Kalkhoran ZR, Taherkhani S, Talkhabi M. Alpha-ketoglutarate as a potent regulator for lifespan and healthspan: Evidences and perspectives.
Exp Gerontol. 2023;175:112154. doi:10.1016/j.exger.2023.112154

3. Milanović M, Bekić M, Đokić J, Vučević D, Čolić M, Tomić S. Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response. Int J Biol Sci. 2024;20(3):1064-1087. Published 2024 Jan 20. doi:10.7150/ijbs.91109

4. Shrimali NM, Agarwal S, Kaur S, et al. α-Ketoglutarate Inhibits Thrombosis and Inflammation by Prolyl Hydroxylase-2 Mediated Inactivation of Phospho-Akt. EBioMedicine. 2021;73:103672. doi:10.1016/j.ebiom.2021.103672

5. Bravo Iniguez A, Tian Q, Du M, Zhu MJ. Alpha-Ketoglutarate Promotes Goblet Cell Differentiation and Alters Urea Cycle Metabolites in DSS-Induced Colitis Mice. Nutrients. 2022;14(6):1148. Published 2022 Mar 9. doi:10.3390/nu14061148

6. Si X, Song Z, Liu N, Jia H, Liu H, Wu Z. α-Ketoglutarate Restores Intestinal Barrier Function through Promoting Intestinal Stem Cells-Mediated Epithelial Regeneration in Colitis. J Agric Food Chem. 2022;70(43):13882-13892. doi:10.1021/acs.jafc.2c04641

7. Agarwal S, Kaur S, Asuru TR, et al. Dietary alpha-ketoglutarate inhibits SARS CoV-2 infection and rescues inflamed lungs to restore O2 saturation by inhibiting pAkt. Clin Transl Med. 2022;12(9):e1041. doi:10.1002/ctm2.1041

8. Tran TQ, Hanse EA, Habowski AN, et al. α-Ketoglutarate attenuates Wnt signaling and drives differentiation in colorectal cancer. Nat Cancer. 2020;1(3):345-358. doi:10.1038/s43018-020-0035-5

9. Tan H, Liu J, Huang J, et al. Ketoglutaric acid can reprogram the immunophenotype of triple-negative breast cancer after radiotherapy and improve the therapeutic effect of anti-PD-L1. J Transl Med. 2023;21(1):462. Published 2023 Jul 12. doi:10.1186/s12967-023-04312-2

10.  Liu PS, Wang H, Li X, et al. α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol. 2017;18(9):985-994. doi:10.1038/ni.3796