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Part II: Physiology of the Skin--The Impact of Glycation on Skin
By Peter T. Pugliese, MD
Posted: March 27, 2008
page 2 of 2
Supplements. There are a few supplements that help to prevent glycation from occurring. The ones with the best record are the following:
Aminoguanidine—150–300 mg a day, best taken with food. Higher dosages are usually required for diabetic patients, around 300–600 mg daily, or even higher, since aminoiguandine last only four hours it should be taken in divided doses. It is best to consult with your physician before taking aminoguanidine since it tends to deplete B-6.
Benfotiamine—100 mg twice a day
Carnosine is a dipeptide consisting of alanine and histidine that has been shown to counteract free radicals and help prevent peroxidation of cell membranes. Pyridoxamine is a form of pyridoxine or vitamin B-6, but it does not have the side effects of B-6 and is an excellent glycation inhibitor.20 Benfotiamine is a lipid-soluble thiamine or B-1 vitamin. It also is an excellent glycation inhibitor. Aminoguanidine has a long use as a glycation inhibitor, but of late, there are some reports of low toxicity, mainly coupling with vitamin B-6.21 It cannot couple with pyridoxamine, however. It is widely used in animal studies with glycation products and has been shown to be very effective. The dosage for humans is 150–300 mg/day in divided doses. There are many suppliers for these products.
Even though glycation has been known about for more than 20 years, the information is only now becoming available to the general public, and very few doctors in the United States have heard of it. Antiglycation agents are widely used in Europe to treat both diabetes and heart disease. So far, the products on the market for topical treatment of glycation are few and not very effective. Actually, the extent of glycation in the skin can be measured with an instrument that measures a fluorometric chemical called pentosidine. Pentosidine accumulates in a linear fashion over time. A consumer can actually determine if a topical product is effective with this method and can monitor the progress of treatment in a client. The current instrument is only a research model that costs about $35,000, but as the treatment becomes popular, a more inexpensive version will become available. This could open a whole new era of skin care and anti-aging treatment.
Once the glycation product is formed, it is hard to break because there are no natural enzymes in the body that can dissolve the bond. There are products developed that have been shown to be effective in breaking AGE-associated links. Alt-711 is one of these products that improved the vascular system of older Rhesus monkeys.22 Known now as C16, a second type studied in rats was found to restore diabetes-associated cardiovascular diseases. This product was also a thiazolium type similar to Alt-711.23 A third product uses a different approach; an enzyme specific for glycation called an amadoriase. There are actually two enzymes—fructosyl lysine oxidase and fructosyl lysine 3-phosphokinase—isolated from bacteria that are capable of breaking glycation link proteins.24 Although not commercially available or tested on humans, it presents a possible method that could be a great addition to future treatment modalities in anti-aging.
Glycation is the non-enzymatic joining of a sugar and a protein, or a lipid. It is a process that occurs naturally in foods, especially when cooked. The Maillard reaction is one of these processes that starts by forming a Shiff base and proceeds to forming multiple chemicals called advanced glycation end-products, or AGEs, that have adverse effects on a person’s biological processes. AGEs can link up with many proteins and denature them or alter them to be nonfunctional, cross-linked collagens, which is an AGE protein complex responsible for stiffness of the skin.
Skin collagen has a long half-life; these cross-linked forms do not go away and are not fully reversible at present. Elastin is another long-lived protein that is easily glycated and lasts a long time. Denatured elastin is associated with slackened skin. AGEs have cellular receptors known as RAGEs that initiate inflammatory reactions when activated by an AGE complex. These reactions tend to be chronic and are associated with arterial diseases, metabolic disorders and rheumatoid arthritis. Once they are started, the AGE-RAGE system will accelerate and perpetuate itself.
In the skin, glycation accounts for accelerated aging, yellowing and stiffness of the skin, and decreased circulation. Skin cannot look young and healthy with glycation products. Treatment is best started with prevention by diet control, reducing total calories, avoiding high sugar foods and not cooking at high temperatures. Supplements such as aminoguanidine, pyridoxamine, carnosine and benfotiamine are excellent glycation preventors. A new class of drugs called glycation breakers is being developed to correct the existing glycation protein complexes associated with many chronic diseases. They will truly be the youth drugs of the future.
e. Elastostic material consists of abnormal elastin fibers and protein, usually associated with sun damage. It does not function like normal elastin and is quite stiff.
f. Immunological stains are prepared against specific proteins. They are made in animals, purified and then combined with a dye to visualize the protein. They will only stain the protein for which they are specific.
g. Half-life means how long it takes to remove or replace half of a substance. For one gram of carbon 14, a radioactive substance that has a half-life of 5,000 years, to completely decay, it would take 5,000 years for 0.5 grams to be lost, another 5,000 years to lose 0.25 grams, 5,000 more years to lose another 0.125 grams and another 5,000 to lose .0625 grams. So, in 20,000 years, there will still be a lot left over. That is the basis for carbon dating.
h. S-100 is normally present in cells derived from the neural crest (Schwann cells, melanocytes and glial cells), chondrocytes, adipocytes, myoepithelial cells, macrophages, Langerhans cells, dendritic cells and keratinocytes. It may be present in some breast epithelial cells. It is involved in the regulation of protein phosphorylation, transcription factors, Ca++ homeostasis, the dynamics of cytoskeleton constituents, enzyme activities, cell growth and differentiation, and the inflammatory response.
i. Late-passage keratinocytes show signs of slowing down and nearing death. They are unable to divide.
j. Glycotoxins are mixtures of cigarette smoke chemicals that combine with glucose in the lungs.
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