Alfa-ketoglutaarzuur
Het nieuwe anti-agingsupplement?

Kan suppletie met alfa-ketoglutaarzuur (AKG) de levensduur van de mens verlengen? Recentelijk uitgevoerde studies met wormen en muizen ondersteunen deze hypothese. Ook zijn er enkele onderzoeken bij mensen gepubliceerd die wijzen op potentiële gezondheidsvoordelen van AKG. In dit artikel een overzicht van de invloed van AKG op het verouderingsproces, de gevolgen van de natuurlijke afname ervan op de gezondheid en de wetenschap achter suppletie voor een lang en gezond leven.

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Auteur

Andrea van Vuuren

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Referenties

  1. Kennedy BK, Berger SL, Brunet A, et al. Geroscience: linking aging to chronic disease. Cell. 2014;159(4):709–13.
  2. Barardo D, Thornton D, Thoppil H, et al. The DrugAge database of aging‐related drugs. Aging Cell. 2017;16(3):594–7.
  3. He L, Xu Z, Yao K, et al. The physiological basis and nutritional function of alpha-ketoglutarate. Curr Protein Pept Sci. 2015;16(7):576–81.
  4. Karsegard VL, Raguso CA, Genton L, et al. L-ornithine α-ketoglutarate in HIV infection: effects on muscle, gastrointestinal, and immune functions. Nutrition. 2004;20(6):515–20.
  5. Ledwidge R, Blanchard JS. The dual biosynthetic capability of N-acetylornithine aminotransferase in arginine and lysine biosynthesis. Biochemistry. 1999;38(10):3019–24.
  6. Liu S, He L, Yao K. The antioxidative function of alpha-ketoglutarate and its applications. Biomed Res Int. 2018;2018.
  7. Matuleviciute R, Cunha PP, Johnson RS, et al. Oxygen regulation of TET enzymes. FEBS J. 2021;288(24):7143–61.
  8. Wang Y, Deng P, Liu Y, et al. Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations. Nat Commun. 2020;11(1):5596.
  9. Bayliak MM, Gospodaryov DV, Lushchak VI. Mimicking caloric restriction for anti-aging effects: The pro-oxidant role of alpha-ketoglutarate. Curr Opin Toxicol. 2022;30:100339.
  10. Hartman AL, Gasior M, Vining EPG, et al. The neuropharmacology of the ketogenic diet. Pediatr Neurol. 2007;36(5):281–92.
  11. Harrison AP, Pierzynowski SG. Biological effects of 2-oxoglutarate with particular emphasis on the regulation of protein, mineral and lipid absorption/metabolism, muscle performance, kidney function, bone formation and cancerogenesis, all viewed from a healthy ageing perspective state. J Physiol Pharmacol. 2008;59(Suppl 1):91–106.
  12. Bayliak MM, Lushchak VI. Pleiotropic effects of alpha-ketoglutarate as a potential anti-ageing agent. Ageing Res Rev. 2021;66:101237.
  13. Wu N, Yang M, Gaur U, et al. Alpha-ketoglutarate: physiological functions and applications. Biomol Ther (Seoul). 2016;24(1):1.
  14. Filip R, Pierzynowski SG. The absorption, tissue distribution and excretion of enteraly administered α‐ketoglutarate in rats. J Anim Physiol Anim Nutr (Berl). 2008;92(2):182–9.
  15. Cynober L, Coudray-Lucas C, De Bandt JP, et al. Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects. J Am Coll Nutr. 1990;9(1):2–12.
  16. Shahmirzadi AA, Edgar D, Liao C-Y, et al. Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice. Cell Metab. 2020;32(3):447–56.
  17. Radzki RP, Bieńko M, Filip R, et al. The protective and therapeutic effect of exclusive and combined treatment with alpha-ketoglutarate sodium salt and ipriflavone on bone loss in orchidectomized rats. J Nutr Health Aging. 2016;20:628–36.
  18. Ullah F, Liang A, Rangel A, et al. High bioavailability curcumin: an anti-inflammatory and neurosupportive bioactive nutrient for neurodegenerative diseases characterized by chronic neuroinflammation. Arch Toxicol. 2017;91(4):1623–34.
  19. Niemiec T, Sikorska J, Harrison A, et al. Alpha-ketoglutarate stabilizes redox homeostasis and improves arterial elasticity in aged mice. J Physiol Pharmacol. 2011;62(1):37.
  20. Donati L, Ziegler F, Pongelli G, et al. Nutritional and clinical efficacy of ornithine alphaketog-ketoglutaratein severe burn patients. Clin Nutr. 1999;18(5):307–11.
  21. Cynober L. Ornithine alpha-ketoglutarate in nutritional support. Nutrition. 1991;7(5):313–22.
  22. Cynober LA. The use of α-ketoglutarate salts in clinical nutrition and metabolic care. Curr Opin Clin Nutr Metab Care. 1999;2(1):33–7.
  23. Demidenko O, Barardo D, Budovskii V, et al. Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test. Aging (albany NY). 2021;13(22):24485.
  24. Dąbek M, Kruszewska D, Filip R, et al. α‐Ketoglutarate (AKG) absorption from pig intestine and plasma pharmacokinetics. J Anim Physiol Anim Nutr (Berl). 2005;89(11‐12):419–26.
  25. Chin RM, Fu X, Pai MY, et al. The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature. 2014;510(7505):397–401.
  26. Żurek A, Mizerska-Kowalska M, Sławińska-Brych A, et al. Alpha ketoglutarate exerts a pro-osteogenic effect in osteoblast cell lines through activation of JNK and mTOR/S6K1/S6 signaling pathways. Toxicol Appl Pharmacol. 2019;374:53–64.
  27. Colman RJ, Anderson RM, Johnson SC, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009 Jul 10;325(5937):201-4.
  28. Baracco EE, Castoldi F, Durand S, et al. α-Ketoglutarate inhibits autophagy. Aging (Albany NY). 2019;11(11):3418.
  29. Lin A-L, Zhang W, Gao X, et al. Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain. Neurobiol Aging. 2015;36(7):2296–303.
  30. Wernerman J, Hammarqvist F, Vinnars E. α-Ketoglutarate and postoperative muscle catabolism. Lancet. 1990;335(8691):701–3.
  31. Leander U, Fürst P, Vesterberg K, et al. Nitrogen sparing effect of ornicetil® in the immediate postoperative state clinical biochemistry and nitrogen balance. Clin Nutr. 1985;4(1):43–51.
  32. Filip RS, Pierzynowski SG, Lindegard B, et al. Alpha-ketoglutarate decreases serum levels of C-terminal cross-linking telopeptide of type I collagen (CTX) in postmenopausal women with osteopenia: six-month study. Int J Vitam Nutr Res. 2007 Mar;77(2):89-97.
  33. Mangia S, Giove F, DiNuzzo M. Metabolic pathways and activity-dependent modulation of glutamate concentration in the human brain. Neurochem Res. 2012;37:2554–61.
  34. Nilsson GE, Lutz PL. Role of GABA in hypoxia tolerance, metabolic depression and hibernation—possible links to neurotransmitter evolution. Comp Biochem Physiol Part C Comp Pharmacol. 1993;105(3):329–36.
  35. Hares P, James IM, Pearson RM. Effect of ornithine alpha ketoglutarate (OAKG) on the response of brain metabolism to hypoxia in the dog. Stroke. 1978;9(3):222–4.
  36. Jeppsson A, Ekroth R, Friberg P, et al. Renal effects of α-ketoglutarate early after coronary operations. Ann Thorac Surg. 1998;65(3):684–90.
  37. Kjellman U, Björk K, Ekroth R, et al. α-Ketoglutarate for myocardial protection in heart surgery. Lancet. 1995;345(8949):552–3.
  38. Wu G, Morris Jr SM. Arginine metabolism: nitric oxide and beyond. Biochem J. 1998;336(1):1–17.
  39. Chen S, Bin P, Ren W, et al. Alpha-ketoglutarate (AKG) lowers body weight and affects intestinal innate immunity through influencing intestinal microbiota. Oncotarget. 2017;8(24):38184.
  40. He L, Zhou X, Huang N, et al. Administration of alpha-ketoglutarate improves epithelial restitution under stress injury in early-weaning piglets. Oncotarget. 2017;8(54):91965.
  41. Hou Y, Wang L, Ding B, et al. Dietary α-ketoglutarate supplementation ameliorates intestinal injury in lipopolysaccharide-challenged piglets. Amino Acids. 2010;39:555–64.
  42. Nagaoka K, Mulla J, Cao K, et al. The metabolite, alpha-ketoglutarate inhibits non-alcoholic fatty liver disease progression by targeting lipid metabolism. Liver Res. 2020;4(2):94–100.
  43. James IM, Dore G, Hall S, et al. Effect of ornithine alpha ketoglutarate on disturbances of brain metabolism caused by high blood ammonia. Gut. 1972;13(7):551.
  44. Yao K, Yin Y, Li X, et al. Alpha-ketoglutarate inhibits glutamine degradation and enhances protein synthesis in intestinal porcine epithelial cells. Amino Acids. 2012;42:2491–500.
  45. Riedel E, Hampl H, Steudle V, et al. Calcium alpha-ketoglutarate administration to malnourished hemodialysis patients improves plasma arginine concentrations. Miner Electrolyte Metab. 1996;22(1–3):119–22.
  46. Tennant DA, Frezza C, MacKenzie ED, et al. Reactivating HIF prolyl hydroxylases under hypoxia results in metabolic catastrophe and cell death. Oncogene. 2009;28(45):4009–21.
  47. Matsumoto K, Imagawa S, Obara N, et al. 2‐oxoglutarate downregulates expression of vascular endothelial growth factor and erythropoietin through decreasing hypoxia‐inducible factor‐1α and inhibits angiogenesis. J Cell Physiol. 2006;209(2):333–40.
  48. Pollard PJ, Briere JJ, Alam NA, et al. Accumulation of Krebs cycle intermediates and over-expression of HIF1α in tumours which result from germline FH and SDH mutations. Hum Mol Genet. 2005;14(15):2231–9.
  49. Tian Q, Zhao J, Yang Q, et al. Dietary alpha‐ketoglutarate promotes beige adipogenesis and prevents obesity in middle‐aged mice. Aging Cell. 2020;19(1):e13059.
  50. Gyanwali B, Lim ZX, Soh J, et al. Alpha-Ketoglutarate dietary supplementation to improve health in humans. Trends Endocrinol Metab. 2022;33(2):136–46.

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