Sugar is one of the most vital commodities in living things.  It allows an athlete to run a 26-mile marathon or bicycle the grueling Tour de France.  It helps generate the energy for repair following an auto accident or surgery.  It fuels our brains’ extraordinary complexity 24 hours a day, every day of our lives, and allows us to retain vast amounts of information.  In one respect, sugar is the energy prize that allows us to move and function in the world with remarkable ease and efficiency.

Yet, sugar has a dark side of which few people are aware.  Indeed, sugar may be one of the most powerful aging substances known.  In the drama of premature aging there are at least two main characters:  sugar and protein.  They team up to form an unruly family of compounds called A.G.E.

What is A.G.E.?

A.G.E. is an acronym for Advanced Glycation Endproducts.  It is a term we will use throughout this section.  You can think of A.G.E. as a family of rogue molecules that develop when sugars in your body react with the different kinds of structural and functional proteins.  They are like the mutants in a science fiction movie who rove the planet creating havoc and chaos in everything they touch.

One might picture sugar molecules like the little plastic balls with velcro strips attached.  You could picture the velvet target as a matrix of protein similar to that found in the skin, bone, muscle, brain, or cartilage.  When you throw a velcro ball at the velvet target it sticks.  Throw two or three or 50 and you begin to clog up the velvet surface with the “sticky” little balls.  In the body, we can accumulate sugars that chemically bond, or “stick,” to our body proteins in a way that alters their structure and function.  With more sugar, more of our proteins become “glycated” or aged.

So when you think of A.G.E., think of sugars that stick to your body proteins creating wrinkles, stiffness, browning, and malfunction.  A.G.E. is central to the accelerated aging process.  If you can slow down the formation of A.G.E. you dramatically lower the stress on your system.

Browning and Stiffening from the Inside Out

As just noted, the process of glycation is a reaction between sugar molecules and protein.
Another way to view A.G.E. is to explore the browning of a turkey.  As a turkey bakes in the oven, natural sugars gradually interact with the proteins in the turkey's skin.  With time, the sugars and proteins become bonded, causing a brownish hue.  The longer the turkey is baked, the deeper the browning effect.  The same occurrence takes place when many other foods, such as bread, are baked in the oven.  The inner portion of the bread is soft and moist, while the crust is brown and hard.  If we were to test the crust of these newly browned foods, we would find they contained A.G.E.s, or modified proteins.  Just as the skin of a turkey becomes brown from basting in the oven, our human interiors also “brown” from years of cooking at our natural body temperature.  Just as the turkey’s skin becomes more rigid and stiff, so too do our own tissues become rigid and stiff.

As glycation takes place in our bodies through the bonding of sugars with proteins, the structure of our proteins becomes modified.  In some ways, they become unrecognizable.  As we consume more and more sugars, we hasten the biological aging of the body by increasing these A.G.E.s.  As A.G.E.s accumulate they create cross-links or bridges between proteins that support out body structures.  Skin, cartilage, muscle, ligaments, brain tissue, eye tissue, and others begin to stiffen and wrinkle.  In essence, the longer this process is left unchecked, the less mobility we have with age.  This may be one of the most extraordinary discoveries yet as we try to understand the aging process.

Why Is Protein Important?

These proteins have a full array of roles to play, and these roles are determined by the actual size and shape of the proteins themselves. Proteins are vital to every area of our being.  Once a protein is modified and inactivated by the chemical process of A.G.E.s it can create myriad disorders.  Following are just three examples of many:

*Albumin.  Albumin is the most abundant, versatile, soluble, and remarkable of all proteins in the blood.  It has been called the life factor by many top researchers, due to the fact that the more albumin you have, the healthier you are, and the longer you live.  The shocking reality, however, is that this life-marking protein can easily be damaged by A.G.E.s when there is too much sugar circulating in the blood.  In a surprising discovery, out of hundreds of blood samples, it was shown that one-third of the albumin molecules tested were damaged beyond  repair by A.G.E.s.

* Hemoglobin.  Another vital protein is hemoglobin, the oxygen transport protein found in our red blood cells.  One molecule of hemoglobin can carry 4 molecules of oxygen.  Whenever hemoglobin levels fall or when hemoglobin is damaged, it cannot efficiently carry oxygen to the brain, muscles, and other tissue.  As a consequence of this dysfunction, all tissues can suffer from a lack of vital energy and begin to prematurely age.  Energy cannot be produced without sufficient oxygen and over the last 20 to 30 years we have seen a large increase in energy deficit disorders (chronic fatigue, etc.).

As circulating sugars become too high over time, hemoglobin becomes damaged through A.G.E.s.  As a predictor of the oncoming damage, doctors now routinely test for glycated hemoglobin.  Basically A.G.E. damage to our most vital oxygen-carrying molecule is a scientific fact and is occurring with ever-increasing frequency.

*Collagen.  Collagen is the connective tissue protein that forms the structure of our skin, bone, cartilage, ligaments, and tendons.  Studies have repeatedly shown that excess sugars cause the collagen tissue to cross-link in ways that make them weak, rigid, and unstable.  This contributes to arthritis, heart disease, neurological disease, and other conditions common as we pass age 35.

A look at a short list of protein functions shows that we cannot function without them:

1.  Structure of our bones, ligaments, tendons, muscles, skin, and hair.
2. Enzymes that digest our food.
3. Neurotransmitters that run the elegant network within our brain.
4. Enzymes that help manufacture a vast array of vital proteins, hormones, etc.
5. Transporters that carry vital oxygen and nutrients from place to place.

Sugar:  The Sweet Double Agent

Every good spy movie has a double agent, the one who is outwardly attractive, but hides a sinister side of deception and danger.  In our body, sugar is the sweet double agent.  It looks good and tastes good.  We need it in order to generate the energy currency called ATP.  With too little sugar our cells may die, which, if severe enough, would be followed by our own death.  With too much sugar our cells slowly malfunction or, in the worst case, we may die.  This life and death capacity that lies within the domain of this very simple molecule has been widely appreciated for many, many years.  The process of glycation is not so dramatic as life and death, but it is a slow, silent disabler of multiple body systems.

The Agents by Name

The sugars most commonly known to contribute to A.G.E. are:

1. Glucose
2. Fructose
3. Galactose

The first two are found in most of the sweeteners used throughout the food industry.  Glucose is found in common table sugar in high amounts.  Fructose is found in high fructose corn syrup in large amounts.   Galactose is found in milk products such as milk and ice cream.

The average North American consumes between 120 to 150 pounds of sugar each year.  One of the fastest growing sweeteners in the food industry is a natural sugar found in fruit called fructose.  It is not uncommon to find most beverages on the market laced with 20 to 30 grams of fructose, as high fructose corn syrup.  That is equivalent to taking 20 to 30 vitamin capsules, only in this case, they would be filled with fructose.  In fact, North Americans consume 48 pounds of fructose each year.

A startling animal study published in the Journal of Nutrition in September, 1998 compared the effects of fructose-fed groups with other sugar-fed groups.  The study revealed that animals consuming fructose developed significant A.G.E.s of the skin, which would contribute to advanced wrinkling in humans. The same animals showed A.G.E. damage to bone as well. This is just one dramatic illustration of how a common sweetener can cause accelerated aging in the body.

Recently, galactose from milk sugar has been associated with stiffening of the heart’s blood vessels and stiffening of the lens of the eye.  Glucose, fructose, and galactose are all dietary sugars that appear to advance the aging process in surprising ways. 

Increased levels of A.G.E.s are believed to be associated with many degenerative processes.  In the end, one can confidently state that as A.G.E. levels increase, the premature aging of the human body increases right along with it.  If we are to attack aging where it counts most, in the cells of the body, then we must without a doubt control the rate at which we experience A.G.E.

Free Radicals and AGE

One of the disturbing things about AGE is that they contribute to extraordinary amounts of free radicals in the body.  They seem to participate in this in two ways.  First, by one estimate AGE proteins produce up to 50 times more free radicals than normal body proteins that have not been damaged by sugars (non-AGE proteins).  Second, when the body detects AGE proteins it attempts to remove them.  One way by which this is accomplished is by producing free radicals.  Remarkably, the body actually generates free radicals in an effort to essentially “bleach” the AGE proteins out of existence. 

As AGE proteins accumulate in the body, free radicals are produced with greater frequency.  This begins to tax our antioxidant defenses and may even deplete certain antioxidants.  What’s more, one of the key AGE-protecting enzymes is actually dependent upon a specific antioxidant called glutathione.  In short, AGE proteins set up a vicious cycle of free radicals coupled with depleted antioxidants.  As you might guess, proper antioxidant defenses are crucial for preventing AGE and premature aging of the body.

Diseases of A.G.E.

As A.G.E. proteins accumulate in the body they may contribute to wide range of disorders that are seen commonly in adults.  For example, one study showed that stiffness increased in the heart chambers due to sugar-protein interactions resulting from elevated blood sugars.

Doctors studying non-diabetic people found that stiffening and glycation products (AGEs) in the skin increased by 33 percent from age 30 to 80.  In  diabetics, glycated proteins increased by almost 100 percent over the same time span.  Thus, A.G.E. may be associated with aging of the skin.

Another study showed that A.G.E. compounds found in the skin was associated with increased A.G.E. in the blood vessels.  In fact, A.G.E. in blood vessels may be one of the key ingredients in coronary artery disease, a leading from of heart disease.  AGE may also affect the brain.  Recent studies have linked accumulation of AGE proteins to at least some of the damage that occurs in diseases like Alzheimer’s.

AGE proteins may also impair our ability to generate energy because they can damage the mitochondria within our cells.  Mitochondria are the tiny energy-generating units that exist within every cell.  They are sensitive to free radical damage.  In fact, when the DNA of mitochondria is damaged, the damaged DNA can be passed on and on as mitochondria produce new mitochondria.  In this way, the damage to our energy system caused by AGE can actually spread. (Gerbityz, KD, Gempel, K, Brdiczka, D. Mitochondrial and Diabetes.  Genetic, Biochemical, and Clinical Implications of the Cellular Energy Circuit. Diabetes 1996;45:113-26.)

A.G.E. products have been implicated in arthritis, especially rheumatoid arthritis. Scientists have recently discovered that cigarette smoke contains vast amounts of proteins that have already been glycated in the processing of tobacco.  Smokers, in essence, bathe themselves in untold trillions of A.G.E. molecules with every puff of cigarette smoke.  Smokers engage in a deliberate daily ritual to coat their facial skin with layer upon layer of A.G.E. proteins that stick to and link with the delicate collagen proteins that make up the skin.  This wrinkling and leathering process that is so common in the face of smokers is a classic example of how A.G.E. can cause wrinkling of any protein matrix within the body.

AGE-Damaged Proteins, Health, and Disease

Stiffening of Connective Tissue (muscles, ligaments, tendons, etc.)
Stiffening of heart muscle
Stiffening and wrinkling of skin
Stiffening of joints (cartilage)
Allergic responses
Gum disease
Eye disease
Brain disorders

Food and A.G.E.

Food has a significant affect on the formation of A.G.E. within the human body.  As mentioned previously, the amount of sugar in the diet influences the amount of sugar that enters the blood stream.  Increased sugar means an increased risk to forming A.G.E. 

Now it appears that cooking methods influence the levels of A.G.E. to which we are exposed through our foods.  Scientists have known for many years that cooking proteins with sugars in the absence of water creates advanced glycation endproducts (A.G.E.).  The troubling new evidence is that eating foods with these advanced glycation products raises blood and tissue levels of A.G.E. and may increase nerve damage in susceptible individuals. 

One group of individuals is diabetics, who suffer a very high incidence of nerve, artery, and kidney damage because high blood sugar levels in their bodies markedly accelerate the chemical reactions that form A.G.E.s.  A presentation at a recent meeting of the American Diabetes Association in San Francisco reviewed evidence that eating foods with A.G.E. proteins aggravated their neurological and blood vessel symptoms.

Cooking with water prevents sugars from binding to proteins to form these poisonous chemicals.  Cooking without water causes sugars to combine with proteins to form these A.G.E.s.  So, baking, roasting and broiling cause the poisonous advanced glycation products to form, while boiling and steaming prevent them. 

According to these new findings, brown foods, such as brown cookies, brown bread crust, brown basted meats, brown beans, and even brown coffee beans may increase nerve damage, particularly in diabetics who are unusually susceptible to nerve damage.  On the other hand, since steamed and boiled vegetables, whole grains, beans and fruits are made with water, they do not contain significant amounts of A.G.E.s.  One more reason that you should eat your fruits, vegetables whole grains and beans, fresh, boiled or steamed.

This does not mean that you give up cooking your food.  It merely alerts us to the fact that cooking methods can increase A.G.E. proteins in the body and that they may, when coupled with other factors, contribute to poor health over time.  Eating more whole foods and ensuring that your protective nutrient defenses are in place is one approach minimizing the A.G.E. effect.  Nutrient defenses are turning out to be a vital insurance policy.

Nutrient Defenses Against A.G.E.

As we get older our ability to control our blood sugar slowly declines.  The combination of inactivity, dietary habits, nutritional deficiency, stress, and other factors contribute to a gradual malfunction of the system that regulates blood sugar.  This makes A.G.E. formation, to some degree, inevitable.  Fortunately, a variety of nutrient molecules protect against the formation of A.G.E. in our bodies.  The nutrients fall into three basic categories:

1. Those that help balance blood sugar and insulin.
2. Those that protect against free radicals.
3. Those that directly influence the reaction where sugars link with proteins (forming A.G.E.)

Some of the most important protective nutrients are listed below.

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.

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 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 very expensive and there is some debate as to how efficiently oral glutathione is absorbed.  It is presumed to be better absorbed in those who are deficient.  Doses range from 50 to 300 mg per day.  Diabetics should consult a doctor before taking glutathione.  While diabetics are commonly low in glutathione, glutathione can affect insulin levels.

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 precursors of glutathione.  Newer whey proteins that use a microfiltration isolation process (AlphaPure) contain up to 2.5 times the cysteine levels present in other whey protein isolates, providing an excellent source of natural glutathione builders.

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.  Any time one can better regulate blood sugar one 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.  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.

Vitamin E:  Fat Soluble Defense

Vitamin E is one of the body’s key fat-soluble nutrients.  It sits nestled in the body’s cell membranes to trap free radicals that may threaten the cell’s health.  Vitamin E also happens to be one nutrient that also influences the formation of A.G.E.

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 recent study of over 40,000 patients 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 diabetics and may not be necessary for everyone. A reasonable dose may be 100 to 400 mcg for non-diabetics.

Plant Protectors

Plants contain a vast pharmacy of phytonutrients that are among the most promising protectors against A.G.E.  As shown in chapter ____, phytonutrients are potent scavengers of free radicals.  This makes them among the most powerful A.G.E. protecting substances, since, as noted earlier, A.G.E. proteins are associated with a dramatic increase in free radical stress.  Plants also contain substances that directly block the formation of A.G.E. proteins even when there is too much sugar in the blood.  A short sample of phytonutrients that prevent A.G.E. includes:

Plant Constituent          Plant Source
-------------------------------------
Curcumin                     Turmeric
Thymol (susp)              Thymus vulgaris
Quercitin                     Onions (many others)
Resveratrol                  Red wine, grapes (skin)
EGCG                          Green Tea

Green tea constituents have multiple health benefits.  One of them, now, appears to be that they can block the glycation process by which sugars damage proteins.

THE BENEFITS OF TEA AND PLANT POLYPHENOLS

Sang S, Shao X, Bai N, et al. Tea polyphenol (-)-epigallocatechin-3-gallate: a new trapping agent of reactive dicarbonyl species. Chem Res Toxicol 2007;20(12):1862-70.

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ADVERSE EFFECTS OF FRUCTOSE

Research on Ingested Glycation Products

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