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Nutrients That Block Sugar-Protein Damage
We now know that sugars can damage joints over time. This occurs by sugars "sticking" to the proteins in ligament, tendon, cartilage, and bone, making them brittle and aging them prematurely.
But there is now promising evidence that selected nutrients can slow or block this process. In fact, certain nutrients are an absolute requirement to detoxify some of the most troublesome glycating agents formed in the body and found in the diet.
Remember that our exposure to joint-damaging sugars can occur because of:
1) Excessive dietary sugar intake or intake of high glycemic foods
2) High blood sugar from insulin resistance or diabetes
3) Combination of excessive sugar intake and high blood sugar (from insulin resistance/diabetes)
As we've discussed, the excessive "sticking" of sugar to proteins in joints is called glycation. Left unchecked, it can lead to formation of a wide range of what are called A.G.E. (advanced glycation endproducts), an end stage process that is difficult to reverse. If you imagine overcooked turkey skin or overcooked crust on bread you'll have the general idea. Certain nutrient molecules are quite good at protecting our cells from these sugar-protein interactions at the early and middle stages of this glycation process. But it is also important to know that nutrients cannot (as far as we can tell) reverse the A.G.E. process once these advanced products have formed. In other words, once the bread is baked, we cannot "uncrust" the crust. We cannot "unbake" the turkey.
However, we can limit this process by limiting our sugars and we can further limit the process by providing nutrients that slow the "browning" and "stiffening" in our joint proteins. This is one reason why it is important to do the following while you have relatively good joint health.
1) Have adequate amounts of these nutrients
2) Gain control of your blood sugar
3) Limit your intake of dietary sugars.
To extend our analogy, while we cannot "uncrust" the crust, we might be able to keep the crust from forming--in our joints. This is where nutrients come in. It does not that taking nutrients means we can eat sugar with impunity. But it does imply that nutrients can help protect us. It should also be made clear that excessive sugar can actually deplete some of the very same nutrients needed to protect us from the sugars, setting up a viscious cycle. This is one reason why someone may need selected nutrients, even though they may not be classically deficient in that nutrient. (See <Why Carnitine Levels Might be Low>)
A list of the main nutrients that appear to slow, block, or prevent the glycation process is found below. This is followed by a brief discussion of some of the more important nutrients. The Insulite System for Healthy Joints has incorporated some of these nutrients into the functional food formulas in the interest in making sure that additional quantities of these nutrients are avaiable as you work to restore your mobility.
The Nutrient Defenses Against A.G.E. fall into three basic categories:
1. Nutrients that help balance blood sugar and insulin.
2. Nutrients that protect against free radicals.
3. Nutrients that directly prevent the reaction where sugars link with joint proteins
Some of the most important protective nutrients are listed below. [create table]
Vitamin B1 Compounds (Benfotiamine, thiamine, and thiamine pyrophosphate)
Vitamin B6 Compounds (Pyridoxal-5-phosphate, pyridoxamine, B6)
Vitamin B2 Compounds (Riboflavin, Riboflavin-5-phosphate)
Glutathione (glutathione, acetyl-glutathione)
N-acetylcysteine
alpha-Lipoic acid
Taurine
Chromium
L-Carnitine (also N-acetyl-L-carnitine)
Carnosine
Plant extracts (curcumin, green tea, etc)
Vitamin B1 Compounds
Vitamin B1 is one of most studied nutrients with regard to preventing glycation reactions. There are three primary forms that have shown positive results. This includes thiamine, thiamine pyrophosphate, and benfotiamine. Since glycation involves numerous different mechanisms and numerous sugars, it is not yet clear which of these forms of vitamin B1 is superior.
Vitamine B6 Compounds
Vitamin B6 is another compound that is very strong in preventing glycation reactions. One way that this occurs via the natural inclination of vitamin B6 to saddle up and bind to the amino acid lysine, while that lysine is free or bound to proteins. Lysine is highly sensitive to damage by sugar, since sugar also has a love affair with lysine (so sugars really glom on to lysine residues). There are two main forms of vitamin B6 that are studies: pyridoxamine and pyriodoxal-5-phosphate. Both forms have shown strong capacity to prevent glycation.
Glutathione: The Premier Protector
Glutathione is one of the body’s brilliant sentinels. In the world of protecting ourselves against A.G.E. glutathione is a molecule we cannot do without. Glutathione is called a tripeptide, a sort of mini-protein that is made up of three amino acids. The amino acids are cysteine, glycine, and glutamic acid. If we are low in any of these amino acids we cannot make enough glutathione to protect our bodies from a range of threatening substances. Of the three, the amino acid we are most likely to be deficient in is cysteine, a sulfur-bearing amino acid. This is one of the key points to know about protecting against A.G.E. If we don’t have enough protective sulfur compounds we will not be well protected against A.G.E. (See also The Importance of Sulfur)
To make glutathione in the body we also need magnesium and potassium, two nutrients commonly low in modern humans. Scientists have discovered that an enzyme the body uses to eliminate sugar-damaged molecules before they become A.G.E. proteins must use glutathione as a cofactor. Thus, without glutathione we simply cannot get rid of two entire families of A.G.E. proteins. Glutathione is not easily absorbed, though a newer formed called acetyl-glutathione is now being used.
One way to increase glutathione levels naturally is to provide raw materials that support the body’s natural manufacture of this vital substance. One of the best glutathione builders is whey protein, a by-product of cheese manufacturing. Whey protein isolates are an abundant source of the amino acid cystine. Cystine is converted in the body to cysteine, which is one of the key building blocks of glutathione. Newer whey proteins that use a microfiltration isolation process contain up to 2.5 times the cysteine levels present in other whey protein isolates, providing an excellent source of natural glutathione builders. People often take other glutathione building blocks like N-acetylcysteine and alpha-lipoic acid. (People with diabetes should consult a doctor before taking glutathione.)
N-acetylcysteine (NAC)
N-acetylcysteine is a sulfur compound that is a close relative of cysteine mentioned above. We can use NAC to help manufacture our own glutathione. In experimental studies of A.G.E., NAC has been shown to be a very useful preventive substance. Doses commonly range from 50 to 600 mg per day.
alpha-Lipoic Acid (ALA)
alpha-Lipoic acid is another sulfur compound vital to the human body. ALA has a couple of key functions in protecting against A.G.E. First, it has been shown to help regulate blood sugar. This is because lipoic acid is required for three key processes in the processing of sugar from the diet. It could be said that lipoic acid is vital for turning sugar into energy. Any time a person can better metabolize sugar, she lowers the chance that excess sugars will be around to stick to proteins. Second, ALA appears to prevent the formation of different complicated molecules associated with A.G.E. Finally, ALA appears to be one of the best ways to increase the body’s own production of glutathione. Beside being a powerful antioxidant, glutathione is the primary way that we get rid of the seriously toxic glycating molecule called glyoxal. (Remember, glyoxal is 200 times more powerful a glycating agent than regular sugar--glucose.)
In this regard, ALA becomes a kind of glutathione insurance policy. Doses range from 50 to 600 mg per day. In studies of diabetic neuropathy, a condition where A.G.E. proteins damage nerves throughout the body, 600 mg per day have been found useful. For prevention, lower doses seem reasonable.
Taurine
Taurine is yet another amino acid that contains sulfur. These sulfur molecules are vital to protecting against glycation damage from sugars.
Acta Physiol Scand. 2004 Jul;181(3):297-303.
Stimulation of glucose utilization and inhibition of protein glycation and AGE products by taurine.
Department of Biochemistry, Faculty of Science, Annamalai University, Tamil Nadu, India.
AIM: Pathological effects of the process of non-enzymatic glycation of proteins are reflected in chronic complications of diabetes mellitus. We investigated the antiglycating effect of taurine in high fructose fed rats in vivo and the inhibiting potency of taurine in the process of in vitro glycation. Additionally, we investigated whether taurine enhances glucose utilization in the rat diaphragm. METHODS: Rats fed a high fructose diet (60% total calories) were provided 2% taurine solution for 30 days. The effects of taurine on plasma glucose, fructosamine, protein glycation and glycosylated haemoglobin in high fructose rats were determined. For in vitro glycation a mixture of 25 mm glucose and 25 mm fructose was used as glycating agent, bovine serum albumin as the model protein and taurine as the inhibitor. Incubations were carried out in a constant temperature bath at 37 degrees C for 3-30 days. Amadori products and advanced glycation end products (AGEs) formed were measured. In vitro utilization of glucose was carried out in the rat diaphragm in the presence and absence of insulin in which taurine was used as an additive. RESULTS: The contents of glucose, glycated protein, glycosylated haemoglobin and fructosamine were significantly lowered by taurine treatment to high fructose rats. Taurine prevented in vitro glycation and the accumulation of AGEs. Furthermore, taurine enhanced glucose utilization in the rat diaphragm. This effect was additive to that of insulin and did not interfere with the action of insulin. CONCLUSIONS: These results underline the potential use of taurine as a therapeutic supplement for the prevention of diabetic pathology.
Chromium: The Key Trace Element in the Battle Against A.G.E.
Chromium has been shown to inhibit the formation of A.G.E. by virtue of its effect on insulin and blood sugar. A study of over 40,000 people revealed that chromium levels decrease nearly 50 percent in our bodies as we age. Surprisingly, the very mineral capable of preventing A.G.E. and slowing the aging process is actually depleted as we age.
Numerous studies have also confirmed that eating sugar causes more chromium to be dumped from the body to be lost in the urine. Remarkably, the sugars that contribute to A.G.E. formation also cause us to lose the one mineral that acts as a powerful A.G.E. protector—chromium. The daily dosage of chromium that has been shown to reduce one form of A.G.E. protein (glycosylated hemoglobin) ranges from 600 to 1,000 mcg. These levels have been used in people with diabetes and may not be necessary for everyone. A reasonable dose may be 100 to 400 mcg for people without diabetes.
Carnitine
Carnitine appears to have very strong ability to slow or limit the process of glycation. There are two main forms that are typically used: L-carnitine and N-acetyl-L-carnitine. These two forms of carnitine work by different means, so having both may be important. L-carnitine helps with energy efficiency, by improving our ability to burn fatty acids as fuel. Carnitine is also needed when people have blood sugar disorders, since sugar "sticks" to the lysine we need to make our own carnitine.
This is important to restate. Sugar sticks to the main building block of carnitine called lysine. Therefore, sugar can lower our production of the body's main fat transport molecule: carnitine.
Another form of carnitine, called acetyl-L-carnitine contains an extra tiny group--the acetyl group. These acetyl groups also appear to protect our proteins from glycation by sugars. Aspirin contains an acetyl group as well and aspirin has shown some blocking capabilities as well. For these and many other reasons, doctors believe extra carnitine should be used to prevent glycation by sugars and to improve the efficiency of fat burning.
Effect of L-carnitine on skeletal muscle lipids and oxidative stress in rats fed high-fructose diet.
Carnosine
Carnosine, though it sounds a bit like carnitine, is a distinctly different amino acid. It has been widely studied as a simple molecule that protects against glycation.
Herbs and Spices
Plants contain a wide variety of molecules that appear to slow the glycation process. Some of these come from our favorite spices and teas, such as curcumin (from turmeric) and EGCG (from green tea). Others include
In one study, curcumin was able to reduce the process of glycation in the tail and skin of rats with diabetes. It was evident from this study that curcumin was better at preventing glycation than at reversing glycation that had alread occurred. [i]
Another study tested 17 herbs and spices for their capacity to stop glycation in test tube experiments. The five most active in slowing or blocking this process were ginger, cumin, cinnamon, black pepper, and green tea. [Saraswat, M, Reddy, PY, Muthenna, P, Reddy, GB.Prevention of non-enzymic glycation of proteins by dietary agents: prospects for alleviating diabetic complications. Br J Nutr 2008 Nov 6:1-8.]
Yet another study looked at 24 different herbs and spices. In general, spices inhibited glycation more than herbs. The most potent inhibitors included extracts of cloves, ground Jamaican allspice, and cinnamon. Potent herbs tested included sage, marjoram, tarragon, and rosemary.
[Dearlove, RP, Greenspan, P, Hartle, DK, et al. Inhibition of protein glycation by extracts of culinary herbs and spices. J Med Food 2008;11(2):275-81.]
[i]Sajithlal, GB, Chithra, P, Chandrakasan, G. Effect of curcumin on the advanced glycation and cross-linking of collagen in diabetic rats. Biochem Pharmacol 1998;56(12):1607-14.
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