Advanced glycation end-products, their harmful effects on the body and their prevention
Advanced glycation end-products (AGEs) are proteins or lipids that become glycated or oxidized after exposure to sugar, which results in their molecular rearrangement. They are also known as glycotoxins. Glucose can bind with proteins in a process called glycation making cells stiffer, less pliable and susceptible to damage. The factors responsible for the formations of AGEs are glycoxidation, hyperglycemia and oxidative stress. If one or two such factors are present, both intra-cellular and extra-cellular proteins may be glycated and oxidized. Once AGEs are formed, they are irreversible. Enzymes such as glyoxalase-1 have the ability to detoxify AGE precursors and inhibit AGE production.
AGEs can affect nearly every type of cell and molecule in the body. They are formed both inside and outside the body. Outside the body, AGEs can be formed by heating, for example cooking. AGEs speed up the oxidative damage to the cells and, therefore, alter their normal behavior. Intermediate products in the formation of an AGE are known as Amadori, Schiff base and Maillard products named after the researchers who described them first.
Modern diets are largely heat processed as a result of which they contain high levels of AGEs. Animal derived foods are rich in fat and protein and are generally AGE rich; they are also prone to new AGE formation during cooking. In contract, foods such as vegetables, fruits, whole grains and milk contain relatively few AGEs, even after cooking. Formation of new AGEs can be reduced significantly by cooking with moist heat, using shorter cooking times, cooking at low temperatures and by using acidic ingredients like lemon juice and vinegar.
Harmful effects of AGEs –
AGEs are able to affect every cell and molecule of the body. They are an important factor in the aging process. They can also affect significantly age-related chronic diseases. Oxidative stress, hyperglycemia and hyperlipidemia can increase the AGEs formation beyond normal levels. The deleterious effects of AGEs in the body are attributed to their chemical, pro-oxidant and inflammatory actions.
Aging – A higher concentration of AGEs is found in healthy older adults in whom it is responsible for aging to a significant extent. They are found in still higher concentrations in old adults with chronic degenerative diseases. At best, AGEs speed up body’s and mind’s aging.
Cardiovascular diseases – AGE-lipids from the food tend to stick to our arteries and promote blockages in them. AGEs contribute to changes in cardiovascular system such as arterial stiffening, myocardial abnormalities, atherosclerosis and endothelium dysfunction. AGEs are believed to have a key role in the development and progression of cardiovascular diseases in patients suffering from diabetes mellitus. There is a co-relation between serum AGE levels and the development and severity of heart failure. Levels of serum AGEs can also predict the outcome of cardiac surgery in elderly patients.
Diabetes mellitus – The process of advanced glycation appears to be increased in diabetes patients. This is not only because of hyperglycemia and oxidative stress but also because of high quantities of free fatty acids in these patients. AGEs lead to pro-inflammatory and pro-sclerotic effects. Toxic AGE (TAGE) represents dominant form of advanced gycation end product. Higher levels of AGEs in people suffering from diabetes encourage all the complications of the disease viz. diabetic retinopathy, neuropathy, nephropathy, cardio-myopathy and diabetic foot. There appears to be a strong involvement of AGE in all of the micro and macro-vascular complications of diabetes mellitus, especially type-2 diabetes.
Skin – Food AGEs play an important role in aging of the skin. As these AGEs build up, they cause inflammation, which damages the protein fibres of collagen and elastin. Skin starts to lose its elasticity and is no longer firm and supple. It cannot spring back into its original position after a smile or a frown and wrinkles start to appear. Sugar also damages even the more stable collagen 1, 2 and 3. So, the diabetics are more susceptible to the skin aging. Significantly, more AGEs occur in sun exposed skin than in protected skin.
Stroke – Normally, AGEs accumulate in the human brain with increasing age, increasing the risk a cerebro-vascular stroke. It has been found that AGEs participate in the development of increased neuro-toxicity and cerebral infarct damage during ischemic stroke in diabetic patients.
Red blood cells (erythrocytes) – AGES accumulate in RBCs of the blood and alter their deformability. This causes anemia in diabetics with a high level of serum AGEs.
Liver diseases – AGEs play a role in certain liver diseases such as non-alcoholic steotohepatitis and cirrhosis.
Eyes diseases – AGEs accumulate in the lens and retina and cause cataracts and age-related macular degeneration. This is more so in diabetics.
Cancers – Tumors are generally characterized by an increased uptake of glucose and high rate of glycolysis. Presence of AGEs has been detected in human cancer tissues. AGEs have been found to be involved in liver injury and subsequent carcinogenesis.
Kidney diseases – The kidneys play an important role in clearance and metabolism of AGEs. They are also involved in the primary diseases of kidney. They have been implicated in the patho-physiology of diabetic nephropathy.
Skeletal muscle tissue – AGEs are involved in the aging of skeletal muscles resulting from changes in the skeletal muscle mass and function.
Alzheimer’s disease (AD) – Alzheimer’s disease is characterized by the deposits of beta amyloid peptide in the brain and cerebro-vascular tissue. Typically, 5 to 10 fold greater numbers of amyloid plaques is found in the brains of Alzheirmer’s disease patients than age matched healthy persons. AGEs enhance significantly more plaque formations of amyloid peptide in the brain. Accumulation of AGEs is accelerated in AD. In AD, AGEs can be detected in pathological deposits such as amyloid plaques and neurofibrillary tangles, which characterize AD.
Prevention of AGEs –
Smoking – Since tobacco leaves are dried in the presence of sugar, it results in formation of AGEs. Smoking is known to increase the levels of AGEs in the blood which is absorbed in the lungs during inhalations. Therefore, it is another important reason to quit smoking.
Foods – AGEs are formed from consumption of sugars with a propensity towards glycation such as fructose and galactose. It has been found that high temperature and low moisture strongly encourage AGEs formation in the food. But, on the other hand, brief heating time, low heating temperatures, high moisture and or pre-exposure to an acidic environment are effective strategies to limlt new AGE formation in foods. The traditional forms of cooking and food processing have a potential negative effect on our health due to increase in AGEs formation in foods. By increasing the consumption of fish, legumes, low-fat milk products, vegetables, fruits, and whole grains and by reducing intake of solid fats, fatty meats, full-fat dairy products, and highly processed foods, AGEs levels can be significantly reduced in the body.
Limit sugar intake – In particular, fructose is an extremely pro-inflammatory agent that creates AGEs. Fructose intake speeds up aging process. It promotes a kind of dangerous growth of fat cells around vital organs, which is particularly seen in patients of diabetes and heart diseases. Normally, in adults the total fructose consumption should be kept below 25 Gms per day.
Exercise – Regular moderate exercise has been found to reduce advanced glycation and ameliorate early diabetic nephropathy in obese rats. If validated in clinical studies in humans, regular moderate exercise could be an easy and effective approach to reduce advanced glycation.
Reduce stress – Negative effects of stress also include more formation of AGEs in the body; so stress reduction goes a long way in reducing formation of AGEs.
AGEs are glycotoxins that can adversely affect every cell and molecule in the body. They exist both inside and outside the body. Our foods contain AGEs in varying quantities – foods of animal origin contain more AGEs whereas foods of vegetable origin contain less. Our process of cooking can affect the formation of AGEs. Traditional forms of cooking and processing can increase formation of AGEs in the food. Apart from aging, AGEs are associated with many chronic degerative diseases. AGEs significantly contribute to cause diabetes, cardiovascular diseases, stroke, cancers, aging of the skin, eye diseases, kindney and liver diseases, and Alzheimer’s disease.
The formation of AGEs can be prevented by cooking food at low heating temperatures and high moisture for a short period of time. It can also be accomplished by cooking the food in an acidic environment. The formation of AGEs can also be reduced by limiting sugar intake, stopping smoking and doing regular moderate exercise.