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LE Magazine December 2006
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The Deadly Connection Between Diabetes and Alzheimer's

By Edward R. Rosick, DO, MPH, DABHM

Effects of Diet in Maintaining Healthy Blood Sugar

Now that diabetes appears to be associated with Alzheimer's, it is imperative to take action to protect against this burgeoning epidemic. The first two steps are ones that almost everyone can implement: eat a healthy diet and exercise regularly.

The typical modern American diet, with its preponderance of meats, trans-fatty acids, and sugar, significantly increases the prevalence of insulin resistance and type II diabetes.15 Additionally, the American diet is typically low in healthful monounsaturated and omega-3 polyunsaturated fats, which are critical to optimal health and can also help improve insulin resistance.

Trans fats, found in hydrogenated vegetable oils and hard-stick margarine, worsen insulin sensitivity. By contrast, monounsaturated fats, such as those in olive oil, almonds, and avocados, improve insulin sensitivity.16 Similarly, studies suggest that minimizing saturated fats, found in high amounts in animal products such as red meat and whole milk, may help to lessen one's risk for type II diabetes.16

Omega-3 fatty acids from fish oil, such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), may be helpful in maintaining healthy glucose levels and optimal insulin action. Studies suggest that intake of omega-3 fats from fish oil is associated with accelerated glucose uptake and maintenance of normal glucose metabolism. Additionally, fish oil enhances insulin secretion from the cells of the pancreas.17

A healthy diet may thus help guard against diabetes and, by association, Alzheimer's disease.

Regular Exercise Improves Insulin Resistance

In addition to eating a diet that is low in saturated fat and sugar, high in monounsaturated fats, and rich in vegetables, fruits, and fiber, getting regular exercise is another vitally important way to both prevent and correct insulin resistance.

Exercise can improve insulin sensitivity in skeletal muscle and fat tissue, and has been shown to consistently reduce insulin and fasting blood sugar levels.18 Moreover, recent studies demonstrate that a healthy diet and regular exercise can improve cognition in people who are at high risk for insulin resistance and diabetes.19 In one such study, researchers showed that a group of adults with insulin resistance who followed a basic American Heart Association diet and exercised three times a week on a treadmill for one hour had increased memory retention compared to adults in a control group. The authors concluded that exercise and good nutrition may facilitate improvements in memory for older adults who are at high risk for type II diabetes. These findings may also have implications for guarding against the development of impaired memory and Alzheimer's.

Magnesium, Chromium Fight Insulin Resistance and Diabetes

Magnesium and chromium are two important minerals that have significant effects on insulin resistance and type II diabetes.

Multiple studies attest to the importance of magnesium supplementation, as exemplified by a controlled, randomized, double-blind trial published in 2003 in the journal Diabetes Care.20 In this study, 63 people with type II diabetes were randomly assigned to receive either 2.5 grams of magnesium or a placebo daily for 16 weeks. At the end of the study period, scientists found that those who took the magnesium supplements had statistically significant improvements in insulin sensitivity, indicating better metabolic control of their diabetes.

Chromium has also been shown to be safe and effective in the management of patients with insulin resistance and type II diabetes. In a study of 180 men and women with type II diabetes, those who took 200-1000 mcg of chromium daily showed numerous improvements in blood sugar metabolism. These beneficial changes included significant decreases in levels of fasting glucose, fasting insulin, and two-hour insulin.21

By improving insulin sensitivity, magnesium and chromium may help prevent conditions associated with insulin resistance, including inflammation, diabetes, and Alzheimer's.

Lipoic Acid Provides Powerful Antioxidant Protection

Lipoic acid, a powerful antioxidant, is also known for its ability to improve insulin sensitivity. In one study, 74 patients with type II diabetes were randomly assigned to receive either a placebo or 600, 1200, or 1800 mg a day of alpha-lipoic acid.22 After four weeks, those receiving alpha-lipoic acid supplements had statistically improved insulin sensitively. All three doses of alpha-lipoic acid were effective in improving insulin sensitivity.

Studies show that alpha-lipoic acid also helps protect help the brain against damage caused by free-radical-induced oxidative stress, which could have important implications for its potential role in protecting against Alzheimer's disease.23,24

By restoring insulin sensitivity and protecting the brain against oxidative stress, alpha-lipoic acid shows promise as a weapon against both diabetes and Alzheimer's.

Cinnamon Promotes Healthy Blood Sugar Metabolism

Cinnamon, a common spice used the world over, has shown value in managing insulin resistance and type II diabetes in both laboratory and human studies. Cinnamon contains many beneficial chemical constituents such as flavonoids that act as potent antioxidants.

Cinnamon

A recent randomized, placebo-controlled study published in Diabetes Care examined the effects of supplementing with 1, 3, or 6 grams of cinnamon daily in 60 middle-aged men and women with type II diabetes.25 At the end of the 40-day study, the subjects who took cinnamon at all three dosages significantly decreased their fasting serum glucose, triglycerides, total cholesterol, and low-density lipoprotein (LDL).

Cinnamon's ability to promote healthy blood sugar metabolism suggests a therapeutic role for this spice in preventing and managing insulin resistance and diabetes. Its efficacy in supporting optimal blood sugar levels further suggests a potential role in averting the dangers of Alzheimer's disease.

Carnosine Counters Damaging Effects of Glycation

Growing evidence demonstrating the damaging effects of advanced glycation end products—and the strong association between AGEs, free radicals, and crippling diseases such as diabetes and Alzheimer's—underscore the need to protect against these destructive chemicals. One way to do this is by supplementing with carnosine.

Carnosine, a natural compound made up of the amino acids beta-alanine and L-histidine, is present in high concentrations in brain and skeletal muscle tissue. Scientists have shown that carnosine can inhibit free-radical-induced cellular damage,26 delay the impairment of eyesight associated with aging,27 and even extend the life span of mammals.28 Carnosine confers these beneficial effects through its ability to prevent the formation of advanced glycation end products.

Curcumin Promotes Healthy Blood Sugar, Protects Nervous System

Derived from the curry spice turmeric, curcumin is a potent antioxidant whose ability to relieve inflammation and help fight cancer has been the subject of much scientific study.32 New evidence suggests curcumin may also be an important ally in averting diabetes and Alzheimer's disease.

Scientists have noted that curcumin has numerous beneficial effects on blood sugar metabolism. Using animals with experimentally induced diabetes, they found that curcumin normalized blood sugar levels and restored enzymes involved in blood sugar metabolism to normal levels of activity.33 Other researchers have found that curcumin helps relieve oxidative stress related to elevated glucose levels, thus preventing some of the biochemical dysfunction associated with diabetes.34

In addition to supporting healthy blood sugar levels, curcumin may help to protect the nervous system and avert Alzheimer's disease. Scientists report that curcumin's antioxidant and anti-inflammatory effects offer important, targeted support for the health of the brain and nervous system. Additionally, laboratory and animal studies indicate that curcumin helps prevent the dangerous effects of one of the hallmark pathological changes of Alzheimer's disease: beta amyloid deposits in the brain.35

By supporting healthy blood sugar metabolism and fighting the effects of inflammation and beta amyloid in the brain, curcumin offers promise in the fight against both diabetes and Alzheimer's disease.

Experimental studies have shown that carnosine specifically protects the brain against damage induced by free radicals and AGEs, a finding that may have important implications for the prevention and treatment of Alzheimer's disease.29-31 One study showed that carnosine protects the brain against the toxic effects of malondialdehyde, an AGE-like compound that is formed when lipids react with free radicals.30 Using cultured rat brain cells, researchers demonstrated that carnosine protects brain cells from malondialdehyde-induced toxicity and prevents this compound from dangerously altering proteins in the body.

A recent article examined carnosine's protective effects against beta amyloid.31 Using rat brain cells in the laboratory, researchers showed that introducing beta amyloid to the cultures produced measurable toxic effects. The researchers then demonstrated that damage to the brain cells could be substantially mitigated by adding carnosine to the mixture, leading them to conclude that carnosine protects brain cells by quenching oxidative stress and preventing damaging glycation reactions—both of which are implicated in the neuronal cell damage characteristic of Alzheimer's disease. Carnosine therefore appears be a useful therapeutic in protecting neurons against the toxic effects of beta amyloid.

By inhibiting oxidative stress and AGE formation, carnosine may be a powerful weapon against both diabetes and Alzheimer's disease.

Limiting formation of AGEs Protects Against Diabetes, Alzheimer's, and Age-Related Disease

One critically important factor linking aging, diabetes, and Alzheimer's disease is the formation, accumulation, and receptor binding of advanced glycation end products (AGEs).36 Formed through the interaction of sugars with proteins, lipids, or nucleic acids, AGEs alter the structure and function of proteins, rendering them less capable of carrying out their many crucial functions throughout the body.

The formation of advanced glycation end products throughout the body contributes to the aging of biological macromolecules and tissues. Two extracellular proteins, collagen and elastin, are particularly affected. AGE-related changes to these proteins are believed to contribute to stiffness of blood vessels and the urinary bladder, as well as impaired functioning of the kidneys, heart, retina, and other organs and tissues. Furthermore, damaging glycation reactions trigger inflammatory signaling, which scientists believe could provoke tissue damage and cancers.37

In diabetes, the rapid formation and accumulation of AGEs contribute to complications of the disease, including injury to small blood vessels (microangiopathy) that impairs kidney and eye health. Advanced glycation end products have similarly devastating effects on the nervous system, where they may contribute to degenerative processes. A particularly dangerous form of AGE that has toxic effects against neurons has been found to accumulate in the region of the brain associated with memory and emotion, an area that sustains damage in Alzheimer's disease.36 Furthermore, AGEs promote the accumulation and cross-linking of harmful beta amyloid plaques in the brain, which may contribute to the pathological changes and progressive dementia of Alzheimer's disease.38 Scientists report that AGEs may also play a role in amyotrophic lateral sclerosis, also known as Lou Gehrig's disease.36

Given the crucial role that advanced glycation end products play in aging, diabetes, and Alzheimer's disease, strategies to prevent their formation are more important than ever. Scientists have identified numerous dietary and nutritional approaches that may help protect against AGEs.

Since high blood sugar contributes to the formation of advanced glycation end products, strategies to maintain optimal blood sugar levels are crucial. In addition to those formed within the body, AGEs can also be introduced by external sources. For example, tobacco smoke contains precursors to advanced glycation end products, which increase AGE levels in the body. Foods that have been subjected to processing and heat also act as sources of advanced glycation end products.39 Additionally, foods high in protein and fat are rich dietary sources of AGEs.40 A dietary strategy for minimizing exposure to AGEs should emphasize fresh foods that have been cooked with brief applications of heat.39

One of the best-known nutrients for protecting against the damaging effects of AGEs is carnosine.26-31 Other strategies for fighting advanced glycation end products include antioxidants, B vitamins, and alagebrium, a novel remedy currently under investigation. Specifically, the antioxidants vitamin C and vitamin E have been reported to inhibit the formation of AGEs.41 Scientists report that the B vitamins pyridoxamine (a form of vitamin B6) and benfotiamine (a fat-soluble form of vitamin B1) show promise in reducing the accumulation of AGEs.42 Alagebrium is currently undergoing clinical trials, with evidence suggesting that it is capable of breaking AGE crosslinks.42

Given the devastating effects of advanced glycation end products in promoting aging and disease processes, protecting yourself against them should be considered a core element of every anti-aging strategy.

Conclusion

Growing scientific evidence suggests that diabetes and Alzheimer's disease—two epidemic yet seemingly different disorders that threaten the health of tens of millions of Americans—may not be so dissimilar after all. These two apparently divergent conditions share a striking number of biochemical similarities, and scientists increasingly believe that the two diseases may be closed related.

Given the growing prevalence of insulin resistance and diabetes in the United States and other Western nations, this news has far-reaching implications. Fortunately, substantial research demonstrates that a program incorporating dietary modifications, regular exercise, and scientifically substantiated nutritional supplements can help aging adults to greatly lessen their risk for the twin afflictions of diabetes and Alzheimer's disease.

Edward R. Rosick, DO, MPH, DABHM, is a board-certified physician in preventive and holistic medicine, and assistant professor of medicine at Michigan State University.

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