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Life Extension Magazine

LE Magazine July 2006
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Metabolic Syndrome

The Twenty-First Century Epidemic By Steven V. Joyal, MD

DHA/EPA. The long-chain omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have a multitude of health benefits, including increased fat burning and improved glucose metabolism.21 In addition, EPA and DHA decrease the expression of genes involved in fat storage,22 down-regulate genes involved in inflammation,23 and lower levels of C-reactive protein, a marker of inflammation.24

Be careful, however, if you consume large amounts of fish, as you may be unwittingly ingesting large amounts of mercury, a kidney toxin that is found in high amounts in fish such as swordfish, shark, and even tuna.25,26 Supplementing with a high-quality omega-3 fatty acid product that has been tested and found to be free of contaminants and pollutants is a smart alternative to eating mercury-contaminated fish.

Bioflavonoids. Inflammation is an important factor in the development of insulin resistance and metabolic syndrome.27,28 Bioflavonoids like quercetin, resveratrol, and olive polyphenols have natural anti-inflammatory properties and may offer protection against metabolic syndrome.

Quercetin, a potent bioflavonoid found in vegetables, inhibits pro-inflammatory cytokines (proteins involved in immunity and inflammation).29 Resveratrol, found in the skin of red fruits like grapes, has been shown to inhibit the expression of genes involved in inflammation better than the potent prescription corticosteroid dexamethasone.30

GREEN TEA’S REMARKABLE METABOLIC BENEFITS

Green tea is a super-nutrient. Life Extension members have long known about the anti-cancer benefits of green tea rich in epigallocatechin gallate (EGCG). Green tea also has valuable metabolic advantages.

Green tea promotes healthy blood sugar (glucose) metabolism in humans and obese, diabetic mice without increasing insulin levels.32 Life Extension has long warned about the dangers of excess insulin levels. Green tea rich in EGCG enhances insulin action instead of promoting insulin release.33 Furthermore, green tea and EGCG reduce fat cell creation and growth, as well as blood levels of triglycerides and cholesterol.34

As an added bonus, green tea protects against protein oxidation and glycation (the process by which tissues become damaged by high levels of circulating blood glucose).35

In addition to having potent anti-inflammatory effects,31 olive polyphenols have beneficial benefits on the cardiovascular system. Studies show that olive polyphenols dramatically increase the resistance of cholesterol to oxidation.36 This is very important, as oxidized cholesterol serves as a trigger for atherosclerosis (hardening of the arteries).37 Olive polyphenols also benefit the vascular endothelium, the lining of blood vessel walls. Hydroxytyrosol, a principal polyphenol in olives, reduces the “stickiness” of cells in the vascular endothelium.38 Cell “stickiness” may increase the tendency to form blood clots in the arteries.

Carotenoids and retinoids. Carotenoids (found in foods like carrots, squash, and tomatoes) and retinoids, which are beneficial to eye health, also play an important role in preventing metabolic disease.

Interestingly, experiments in early growth and development show that low vitamin A intake decreases insulin-producing cells,39 pointing to the importance of adequate vitamin A intake for development of the insulin-producing cells of the pancreas.

The National Health and Nutrition Examination Survey found that even after adjusting for confounding factors like age, sex, ethnicity, education, smoking status, and physical activity, people with metabolic syndrome had significantly lower concentrations of carotenoids and retinyl esters (a type of vitamin A).40

Evidence suggests that there may be a threshold for vitamin A consumption in terms of metabolic benefit. In one study, daily vitamin A intake of more than 10,000 IU significantly lowered blood sugar and insulin levels in healthy human volunteers, while daily intake of less than 8000 IU was associated with higher blood sugar levels.41

Water-soluble cinnamon extracts. Exciting data show that a special extract from cinnamon holds tremendous promise for normalizing blood sugar levels naturally.

A 2003 study of patients with type II diabetes examined the effects of cinnamon on blood sugar. Participants received one, three, or six grams per day of cinnamon or placebo. After 40 days, the three groups receiving cinnamon demonstrated significant reductions in blood sugar of up to 29%, in triglycerides of up to 30%, and in cholesterol of up to 26%.42

So, all you need to do to prevent metabolic disease is consume large amounts of cinnamon, right? Wrong!

Whole cinnamon contains volatile oils, which are well-known irritants that may trigger allergic reactions. Even more worrisome is that toxicology studies in mice show that consuming raw cinnamon rich in these oils can cause tumors, including squamous cell papillomas.43 Therefore, the best strategy is to avoid the danger of cinnamon’s volatile oils while still obtaining the remarkable benefits of cinnamon.

Fortunately, these oils are not responsible for cinnamon’s impressive effects in stabilizing blood sugar. Instead, cinnamon’s water- soluble polyphenol polymers are the key components responsible for its beneficial metabolic effects.44

The polyphenol type-A polymers from cinnamon up-regulate genes involved in blood sugar control.45 Other cinnamon polyphenol polymers such as methylhydroxychalcone have additional beneficial effects on blood sugar control.46 Recent studies consistently show the anti-diabetic effects of cinnamon extracts in validated animal models of metabolic disease.47,48

Cinnamon extract not only supports healthy blood sugar levels, but also has excellent antioxidant properties. The natural water-soluble cinnamon extract inhibits oxidation even better than the powerful synthetic antioxidant butylated hydroxytoluene, or BHT.49

Coffee polyphenols. Who would have ever thought that a water-soluble extract of coffee acts to boost the key target hormone that multi-billion-dollar pharmaceutical companies are targeting as the next breakthrough treatment for metabolic disease?

A very large study (14,629 men and women) published in the Journal of the American Medical Association in 2004 showed that the greater your coffee consumption, the lower your risk of metabolic disease, including type II diabetes mellitus.50 Another very large study that followed 41,934 men showed a similarly powerful association between increased coffee intake and decreased risk of type II diabetes, even after adjusting for age, body mass index, and other risk factors.53

BANABA LEAF OFFERS BLOOD SUGAR SUPPORT

A traditional folk remedy from Southeast Asia, banaba leaf extract may offer powerful support for people seeking to maintain healthy blood sugar levels. Banaba (Lagerstroemia speciosa L.) contains an active ingredient called corosolic acid. Laboratory, animal, and human studies show that corosolic acid effectively helps to support optimal glucose metabolism.51

Adults with diabetes or impaired glucose metabolism who received corosolic acid prior to an oral glucose tolerance test demonstrated significantly lower post-challenge glucose levels than people who did not take corosolic acid.51

A randomized clinical trial showed that banaba leaf extract rich in corosolic acid benefited adults with type II diabetes. When the diabetic individuals took a standardized corosolic acid supplement each day for two weeks, their blood glucose levels decreased by 20-30%.52

These findings suggest that banaba leaf extract standardized for corosolic acid content may benefit the millions of Americans who seek support for optimal blood sugar levels.

Before you decide to drink a pot of coffee a day or open your own Starbucks, be advised that drinking large amounts of coffee is not the best strategy for preventing metabolic disease.

Coffee can cause insomnia and may induce high blood pressure in some people, largely due to its caffeine content. Moreover, results of the 2004 ATTICA study showed that coffee consumption dramatically increases markers of inflammation like C-reactive protein, interleukin-6, and tumor necrosis factor-alpha.54

A smart strategy is to identify and isolate the components of coffee that are responsible for its beneficial effects on metabolism, including blood sugar control. Scientists have found that water extracts of roasted coffee residues, including the primary coffee polyphenols caffeic acid and chlorogenic acid, are key components responsible for coffee’s beneficial metabolic effects.

Preclinical studies show that chlorogenic acid improves blood sugar control and decreases cholesterol and triglycerides.55

In human studies, chlorogenic acid, a major polyphenol in water extracts of coffee, has improved the release of hormones critical to blood sugar control. For example, in healthy human volunteers, consuming coffee polyphenols like chlorogenic acid dramatically increased glucagon-like peptide 1 (GLP-1) secretion.56 This finding is remarkable because several GLP-1-related pharmaceutical agents are targeting this hormone as a treatment for metabolic disease, including the recently FDA-approved GLP-1 analog BYETTA™ (exenatide). Chlorogenic acid acts to increase GLP-1.57

Coffee extracts offer other benefits as well. Water-soluble coffee polyphenols like chlorogenic acid scavenge free radicals and provide powerful protection against lipid peroxidation and oxidative damage by proteins.58

SEVERAL SUPPLEMENTS FOR SUPPORTING OPTIMAL BLOOD SUGAR (GLUCOSE) LEVELS
  • DHEA: 10-50 mg daily to start (men); 10-30 mg daily to start (women). Assess the effects of supplementation via repeat blood tests.
  • EPA: 1400 mg daily; DHA: 1,000 mg daily. Take with meals. Double these doses to combat high triglyceride levels.
  • Mixed bioflavonoids: 1400 mg twice daily.
  • Vitamin A: 4000 IU daily; mixed carotenoids (for example, lutein: 15-20 mg daily; lycopene: 3-30 mg daily; zeaxanthin: 3-10 mg daily)
  • Water-soluble cinnamon extract: 125 mg three times daily, 30 minutes before meals.
  • Chromium: 400-800 mcg daily.

Conclusion

With so much focus on cholesterol, little attention has been paid to the critical role of insulin resistance in the development of cardiovascular disease. Insulin resistance is the root cause of metabolic syndrome, a serious risk factor for heart disease and stroke that has received little attention until recently.

Identifying your risk for metabolic syndrome involves only a series of very simple tests. If you are found to be at risk, decreasing your body fat—particularly around your waist—is critically important. Avoid fad diets, eat a whole-food diet like those consumed by Mediterranean cultures, and get some physical exercise—your body will thank you for it!

Nutritional supplements can help improve blood sugar control and metabolic health naturally, without danger or stress to your body. Particularly compelling are polyphenol-rich, water-soluble extracts of cinnamon and coffee, along with green tea extract, chromium, and banaba leaf-derived corosolic acid. Documented evidence demonstrates the ability of these agents to help normalize blood sugar levels.

Avoiding the perils of metabolic syndrome is simple. First, get tested to see whether you are at risk. If laboratory testing and a physical examination reveal that you are at risk, immediately take the necessary steps—including exercise, a healthy diet, and targeted nutritional strategies—to prevent the dire cardiovascular consequences of insulin resistance and metabolic syndrome.

PHARMACEUTICAL OPTIONS FOR METABOLIC SYNDROME

Drug companies are keenly interested in developing new drug treatments for people with metabolic syndrome. Unfortunately, due to the overwhelming drive by multibillion-dollar pharmaceutical companies to continually make profits, one of the very best drugs to help increase insulin sensitivity and improve blood sugar control (without promoting weight gain) is rarely mentioned. This drug, metformin, is currently off patent and very cost-effective.

Metformin, which belongs to a class of drugs called biguanides, works in several different ways to improve insulin’s ability to work at the cellular level in tissues such as muscle and the liver. Metformin is not associated with weight gain—a major advantage over all other drugs used to treat diabetes. Of additional interest is that gene-chip research funded by Life Extension showed that metformin influences gene expression in ways similar to those of caloric restriction. This suggests that metformin may have potential anti-aging benefits in addition to its documented effects on blood sugar control.

Other currently available drugs that may be useful in treating metabolic syndrome include the thiazolidinediones, a class of drugs approved for the treatment of diabetes.

Thiazolidinediones include GlaxoSmithKline’s rosiglitazone (Avandia®) and Takeda/Eli Lilly’s pioglitazone (Actos®). Thiazolidinediones work by targeting PPARs (peroxisome proliferator-activated receptors), which are attractive drug targets for treating metabolic disease.

PPARs help regulate the expression of genes involved in the storage and use of dietary fats. Two subtypes, PPAR alpha and PPAR gamma, have insulin-sensitizing effects.

Among the new drugs in development for metabolic syndrome are AstraZeneca’s tesaglitazar, and Bristol-Myers Squibb’s muraglitazar.

Individuals with kidney disease should not use metformin. Rosiglitazone (Avandia®) and pioglitazone (Actos®) should not be used by people with a history of congestive heart failure or liver disease. Please consult your doctor before using any pharmaceutical drug to treat metabolic syndrome.

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