We investigated in detail the ability of the potent cysteine-derived compounds found in aged garlic extract (AGExt) to provide potentially anti-atherogenic/endothelial protective effects and provide justification for their consideration as main-line additional supplements or prescriptions for patients at risk of cardio/cerebro-vascular disease (De Ferrari et al 2011). In vitro studies have demonstrated that AGExt and in particular its most active components, including the water-soluble cysteinyl moieties S-allylcysteine (SAC), S-allylmercaptocysteine (SAMC) and N-Acetylcysteine (NAC) are exceptionally powerful anti-oxidant phytochemicals (Morihara et al 2011), protective against oxidative stress and inhibiting subsequent cellular damage. They have also been shown to protect against protein glycation in diabetic patients ) (Santos et al, 2008). Therefore, we carried out a thorough investigation of the individual bio-active components of both AGExt and black AGExt alone and in combination in order to maximise their potential therapeutic effects. we performed in vitro studies to assess their endothelial protective effects using human vasa vasorum (HVVEC) and coronary artery-derived endothelial cells (HCAEC) and produce an optimised mixture providing maximal beneficial effects against oxidative stress, cell apoptosis (induction by hypoxia and re-oxygenation) and protein glycation (induction by exposure to high glucose levels and methylglyoxal). This allows us to optimise prevention of EC damage (key to the initiation and progression of atherosclerosis) and EC activation (associated with inflammation and plaque progression). Our results show that AGExt has a strong protection against the AGEs potential damage to these two kinds of cells at a reasonable low concentration (125µg/ml) in vitro.