Histidine alpha-ketoglutarate (HAKG) is primarily used in clinical settings for its protective effects on the vascular system, especially during procedures involving ischemia and reperfusion, such as cardiac and vascular surgeries. The scientific justification for its use centers on its role as a component of preservation solutions (notably, the University of Wisconsin solution and variants like HTK solution) used to flush and preserve organs and vascular grafts. HAKG helps maintain the integrity of endothelial and smooth muscle cells in arteries by buffering pH, chelating calcium, and reducing oxidative stress, thereby minimizing ischemic injury and reperfusion damage.

Multiple clinical and experimental studies have demonstrated that HAKG-containing solutions reduce vascular spasm, improve arterial function, and enhance graft patency compared to traditional saline or other preservation fluids. The histidine component acts as a buffer, stabilizing intracellular pH, while alpha-ketoglutarate provides metabolic support and protects against free radical injury. These mechanisms are particularly relevant in the context of arterial grafts and vascular surgery, where protection of the arterial wall is critical. While HAKG is not typically used as a dietary supplement for arterial health, its use in surgical and transplant medicine for arterial and vascular protection is supported by robust scientific evidence.