Advanced glycation end products And Antioxidants Is it possible that by eating too many metabolically active dense carbohydrates, you are much more likely to accelerate aging and disease?
Each time we eat a meal containing carbohydrates, blood glucose levels increase. According to the insulin sensitivity theory, as we age blood glucose levels tend to increase and insulin becomes less and less effective at bringing them down.
Sustained high levels of sugars in the blood ultimately cause proteins to stick together thereby damaging the function of the proteins. For example, excess blood sugar is more likely to react with proteins such as collagen in the skin which can lead to brown splotches or "age spots" as well as loss of elasticity and premature wrinkling.
These sugar-damaged, very dangerous cross-linked proteins are called advanced glycation end products, or AGE!
According to one of the world’s leading antioxidant researchers, Lester Packer, Ph.D., "the acronym AGE is quite appropriate, since a high number of these damaged proteins can…wreak havoc on virtually all other body tissues…and lead to premature aging."1
If excess blood sugar damages proteins in the lens of the eye, cataracts and eventual blindness can result.
If collagen in the arteries suffers damage from the protein/sugar complex called AGE, fatty plaques are more likely to form.
Similarly, if the collagen in our connective tissues becomes cross-linked as a result of AGE, arthritis could occur.
The process of glycation (sugar damaged proteins) has even been linked as a "likely culprit" in the destruction of nerve cells in the brain that can eventually lead to Alzheimer’s and other neuro-degenerative diseases.2
Furthermore, glycation accelerates the formation of damaging free radical molecules which can accelerate aging and increase risk of disease.
The Mechanism of Glycation
The process of glycation occurs in everyone. Normally, special enzymes are able to "unstick" the potentially dangerous matrix of glycated proteins. But when blood sugar concentrations increase while enzyme concentrations stay the same, the enzymes are unable to cope, causing the equilibrium to shift in favor of AGE formation.
As a result, proteins stick together in a process of glycation that damages the functioning of proteins in tissues throughout the body. This is the kind of environment often seen in hyperglycemic (high blood sugar) individuals, which may explain the increased levels of damaging glycation end products seen in diabetics.
The Role of Alpha Lipoic Acid
According to Dr. Packer, the damage that can be inflicted by excess glucose, insulin resistance and diabetes needs to be controlled as early as possible. Although he does not propose lipoic acid as a cure, Dr. Packer suggests that it can have a remarkably beneficial effect in terms of helping to control symptoms and preventing some of the serious problems that can arise as a result of hyperglycemia and diabetes.5
For example, it is well known that high blood sugar can contribute to coronary heart disease. Diabetes patients are known to be particularly vulnerable to heart problems. Previous clinical studies have established that AGE increase atherosclerosis by glyco-oxidation of low density lipoproteins (bad cholesterol) and the promotion of vascular cell adhesion molecules (VCAM) on artery walls. Researchers investigating the effect of alpha lipoic acid on VCAM reported reductions in AGE induced adhesion molecules of 22% – 13.8%.3,4
In addition to boosting antioxidant levels, lipoic acid can reduce protein damaging AGE in both humans and animals. Since advanced glycation end products are thought to be a factor in the aging process itself, there is good evidence that lipoic acid may help to slow down aging in general.4
The Role of Acetyl L-Carnitine
Those who are susceptible to high levels of blood sugar and accumulation of damaging advanced glycation end products in the lens of the eye can develop cataracts or other serious vision disorders. In a Medical College of Georgia study calves’ lens tissues were incubated in two glucose solutions for 15 days; one with L-carnitine and the other with acetyl L-carnitine. The solution containing L-carnitine showed no effect on glycation (formation of protein-sugar matrix) in the calf lens tissue. However, the acetyl L-carnitine (ALC) decreased glycation by 42%. ALC also demonstrated a positive effect on antibodies to AGE. These findings suggest that acetyl L-carnitine may hold potential for preventing or slowing AGE processes and specifically blindness caused by cataracts.6
The Role of Chromium
More than 90% of Americans are deficient in the trace mineral chromium. Chromium is often called the "Godfather" of sugar metabolism because both chromium and insulin are essential to help the body utilize sugar and metabolize fat.7 High carb, high sugar diets are known to deplete the body of chromium, triggering increased sugar cravings. The more sugar eaten, the more chromium levels are depleted.8 Even the slightest deficiency of chromium interferes with the body’s metabolism of glucose.
USDA studies showing that chromium can help improve glucose tolerance, suggest it may be extremely beneficial for those with hyperglycemia (high blood sugar), insulin resistance and diabetes.9 It stands to reason that chromium can play an important role in reducing the risk for health damaging AGE by supporting healthy glucose metabolism and blood sugar levels.
The Role of Taurine
The sulfur containing amino acid taurine can offer potent antioxidant protection against the ravages of AGE. Furthermore, emerging research suggests that taurine may be especially valuable for its ability to support healthy increased insulin sensitivity while helping to maintain longer term reduced blood sugar levels.10 In a European Journal of Pharmacology report, researchers suggest that taurine levels in the pancreas (where insulin is made and secreted), may play a crucial role in blood sugar control.11 Perhaps that’s why those with blood sugar disorders, frequently have below normal levels of taurine, which can compound their susceptibility to AGE, retinopathy (nerve damage) and cardiovascular disease.
Lester A. Packer, Ph.D. Professor Department of Molecular and Cell Biology and Director of the Lawrence Berkeley Laboratory Membrane Bioenergetics Group. Dr. Packer received his Ph.D. from Yale University in microbiology and biochemistry. His scientific research has mainly focused on vitamin E and related compounds at the membrane and cellular levels. Dr. Packer is the executive editor of Archives of Biochemistry and Biophysics, and serves on the editorial advisory boards of Free Radical Biology and Medicine, The Journal of Applied Nutrition, and The Journal of Optimal Nutrition. He is a member of eight professional societies and is President of the International Society for Free Radical Research, and Vice President of UNESCO’s Global Network of Molecular and Cell Biology.
1 Packer, Lester, Ph.D., The Antioxidant Miracle p. 47-7.
3 Clin Sci 1999 Jan 96, p.75-82.
4 Colaco, Camilo, The Glycation Hypothesis of Atherosclerosis (Medical Intelligence Unit) May 1997.
5 Packer, Lester, p. 45-46.
6 Swamy-mruthinti S., et al., "Acetyl-L-carnitine decreases glycation of lens proteins: in vitro studies." Exp Eye 1999 Jul;69(1):109-15.
7 Atkins, R., M.D., Vita Nutrient Solution p. 145.
8 Anderson, R., Biological Trace Element Research, 1992;32:19-24.
9 Packer, p.190.
10 Franconi, F., et al., Am J Clin Nutr, 1995;61:1115-19.
11 Tokunaga, H. et al., Eur J Phamacol 1983 Feb 18;87(2-3):237-43.