Glycation of proteins has been shown to play a prominent role in the development of many diseases related to diabetes, including atherosclerosis, cataract formation, and retinopathy. Oxidation induced by glycation can wreak havoc on the eye. Protein glycation occurs when sugar molecules inappropriately bind to protein molecules, forming cross-links that distort proteins and consequently render them useless. High blood sugar also increases glycation activity, which may also explain the various kinds of tissue damage that characterize advanced diabetes. Controlling blood sugar is a major means of preventing or at least slowing the onset and progression of diabetic retinopathy. Glycation appears to increase oxidative processes, which may explain why both glycation and oxidation simultaneously increase with age.
Strategies for preventing diabetic complications should therefore aim to prevent the effects of both glycation and oxidative stress.
Aminoguanidine has been used successfully to protect against glycation (Guillausseau 1994). Compounds produced through metabolism of sugars bind preferentially to aminoguanidine rather than lysine proteins. Thus, aminoguanidine is able to inhibit advanced glycation end-product (AGE) formation and help prevent the harmful development of collagen cross-links and changes in proliferation of mesangial cells.
Aminoguanidine used in the dose of 300 mg daily can specifically inhibit glycation, as can the nutrients keto-glutarate and pyruvate. Studies have shown aminoguanidine to be useful in slowing complications of diabetes, such as retinopathy. Aminoguanidine can also inhibit the formation of atherosclerotic plaques.
Carnosine is a naturally occurring antiglycation agent found in red meat. In the lens of the eye, protein cross-linking is part of cataract formation. Carnosine eye drops have been shown to delay vision impairment in humans; they are effective in 100% of cases of primary senile cataract and 80% of cases of mature senile cataract (Wang 2000). The most widely used antiglycating therapy is 1000 mg daily of oral supplemental carnosine.
Benfotiamine, a relative of vitamin B1 (thiamin), protects cells by preventing glycation and accelerated aging triggered by elevated sugar levels. The body has several natural mechanisms to cope with chemical toxins produced by excess glucose, and these defense systems all require vitamin B1 as a cofactor (Beltramo 2008). When the system is awash with excess glucose, thiamine supplies become depleted. Because thiamine is water-soluble and the body cannot retain thiamine at levels high enough to prevent cumulative damage, additional supplemental thiamine does not significantly protect against glucose-induced tissue damage (Stracke 2001; Volvert 2008). Benfotiamine, however, is fat-soluble and can significantly increase thiamine levels within tissues as well as sustain them throughout the day (Beltramo 2008; Volvert 2008; Balakumar 2010).
Pyridoxal-5’-phosphate (P5P), the biologically active form of vitamin B6, is a powerful inhibitor of both protein and fat glycation (Khatami 1988; Higuchi 2006). Glycation reductions by P5P are credited with reducing sugar-induced blood vessel damage from diabetes (Nakamura 2005, 2007).