Resveratrol and Quercetin for Diabetes

by on April 29, 2011

Diabetes costs our nation more than the conflicts in Iraq, Afghanistan, and the global war on terrorism combined-an estimated $174 billion per year. With over 60 percent of Americans overweight or obese, one million new cases are added a year. If current trends continue, 1 in 3 people born in 2000 and 1 in 2 members of minorities will develop diabetes in their lifetime. The personal cost from its associated blindness, kidney failure, heart attacks, strokes, poor wound healing, infections, blood sugar complications, and amputated limbs is inestimable.

Diabetes is a disease of sugar and fat metabolism caused by problems with insulin secretion by the pancreas, or with the insulin sensitivity of the cells. Insulin, a hormone, facilitates the uptake of sugar required by every cell to produce energy. There are two primary types of diabetes. Type 1, which is the more serious, develops when the body’s immune system destroys the insulin-secreting cells in the pancreas. This type accounts for 5 to 10 percent of all cases and usually strikes children and young adults, although it can occur at any age. Type 2 diabetes, often called “adult-onset diabetes,” accounts for 90 to 95 percent of all diagnosed cases. This type usually begins when cells do not use insulin properly and develop resistance to it. To compensate, the pancreas attempts to produce more insulin and gradually loses the ability to do so, or burns out.

Pre-diabetes patients taking resveratrol supplements demonstrated lower post-meal glucose levels and improved insulin sensitivity – an encouraging outcome with potential implications for those with type 2 diabetes or at high risk for the condition.

Today approximateiy twenty-one million Americans, or 7 percent of the population, suffer from diabetes. One in four has the disease or is at risk of getting it. Six million are unaware they have it. Overeating, starchy diets, and lack of exercise are the primary causes. Foods that contain a significant amount of carbohydrates-grains, fruits, vegetables, and beans-are rated on a scale according to how high they raise blood sugar levels, called the “glycemic index,” or GI. A recent analysis of the dietary habits of nearly two million healthy men and women showed that people who ate the diets highest in foods that spike blood sugar levels (high-Gl foods) were more likely to develop not only diabetes but also heart disease, gallstones, and some types of cancer. According to Alan Barclay of the University of Sydney in Australia, lead author of the study; “If you have constantly high blood sugar and insulin levels due to a high-Gl diet, you may literally wear out your pancreas over time. Eventually it may lead to diabetes.”

Medical anthropologists refer to diabetes and obesity as “diseases of civilization.”

It was when aboriginal populations began to adopt a high-sugar, high-fat, “Western” diet for the first time that obesity and diabetes suddenly appeared. The Pima Indians of Arizona and the indigenous people of Hawaii provide dramatic demonstrations of this phenomenon. In both instances, the abandonment of their traditional plant-rich, high-fiber diet was followed by skyrocketing rates of diabetes, obesity, and cancer.

Glycemic Index and Glycemic Load

The glycemic index was developed to help researchers understand the spikes and troughs of blood sugar. This index ranks food according to its ability to release sugar into the bloodstream. A food with a high glycemic index (GI), like potatoes, white bread, or cornflakes, raises blood sugar and insulin levels more quickly than one with a low GI, like green peas or carrots. Another index is the glycemic load (GL): the number of grams of carbohydrate in the food multiplied by its GI. The GL provides a better indicator of the amount of insulin needed to digest a given food. The amount needed is based on the quantity of carbohydrates and how fast they are converted to glucose. For example, carrots have a GI of 47, and pasta, 44. But because pasta is so high in carbohydrates, it has a GL of 21 versus 4 for carrots. High-GL diets are strongly associated with diabetes.

Americans are eating and drinking themselves to death. Studies indicate that a reduction in the intake of refined sugar and a thirty minute walk a day would cut the incidence of diabetes in the United States by around half. But just the opposite is occurring, as Americans consume more sugar products and become more sedentary. As a result, diabetes has been compared to a sleeping giant that is ready to awaken and overwhelm our current health care system. In the last twenty-five years, the number of adults between the ages of eighteen and seventy-nine with newly diagnosed diabetes almost tripled, from approximately 493,000 to 1.4 million. By the year 2025, it is predicted that around 9 percent of the U.S. population will have diabetes, or approximately twenty-five million to thirty million people.

What does all this have to do with xeno factors? To answer that, let’s take a look at the current drugs used to treat diabetes and then see how xeno factors may playa part.

In type 1 diabetes, injections of insulin keep the body’s level of blood sugar under control. In type 2 diabetes, where cells still produce insulin, but not enough, oral medications are the first line of treatment. These drugs lower blood sugar by increasing insulin output from the “tired” pancreas and by improving insulin sensitivity Most scientists believe that lower blood sugar will decrease the complications of diabetes, including heart attacks, blindness, and kidney failure.
Since the therapeutic effects of all current drugs used to treat type 2 diabetes depend either directly or indirectly on insulin, the development of a new class of insulin-independent drugs that lower blood sugar would be tremendously valuable.

In 1985 scientists discovered that two components in red wine and grape juice, quercetin and epicatechin, enhanced insulin release in rats by 44 percent to 70 percent in certain cells. After their report, the therapeutic use of those natural compounds for diabetes lay dormant in the medical literature until quite recently.

In another study quercetin was administered to a group of diabetic rats and discovered that it regenerated pancreatic cells and increased insulin release. The study confirmed that quercetin reduced blood sugar and decreased appetite in diabetic and healthy animals.

The development of type 2 diabetes is related to increased amounts of fat circulating in the bloodstream.  Scientists also discovered that resveratrol appears to counter the effects of elevated free fatty acids, allowing normal insulin uptake in muscle cells and also that this polyphenol could increase glucose absorption in a manner different from insulin and was not dependent on the action of enzymes typically needed to allow glucose to enter the cell.

In January 2006 Hui-Chen Su and his associates in Taiwan evaluated the effect of resveratrol in diabetic rats.

They confirmed the findings of previous investigators, and showed that resveratrol stimulated the uptake of glucose by liver, fat, and muscle cells. Again, resveratrol appeared to act through a mechanism different from that of insulin.

These observations on resveratrol and the mechanisms of glucose, insulin, and fat metabolism are so revolutionary that a pharmaceutical company called Sirtris was formed with the specific goal of developing resveratrol-like compounds to give people the same boosts in blood sugar control that resveratrol gave mice. After quickly raising $165 million, Sirtris analyzed nearly five hundred thousand compounds and has targeted diabetes as the first disease to treat. The company is presently evaluating its resveratrol product in diabetic patients. Preliminary results indicate that the resveratrol-like compound is safe, increases insulin sensitivity, enhances blood sugar control, and has huge potential to safely help millions of people.

Quercetin, also found in red wine and red grape juice, has likewise shown promise in animals with diabetes. It appears to be effective in reducing the high spike in insulin that occurs when sugary food is ingested; sensing the sugar, the pancreas releases this jolt of insulin to help drive it into cells. These insulin peaks are responsible for the hunger cravings that occur soon after someone eats a meal loaded with processed sugar.

In addition to reducing these insulin peaks and slowing the absorption of sugars, quercetin is also a potent inhibitor of sugars in the intestine, contributing to a steadier energy state. Investigators also confirmed that not only quercetin but several other plant polyphenols found in grape skins (like myricetin and catechin gallate) also slowed sugar absorption in the intestines. All of these naturally derived xeno factors-resveratrol, quercetin, myricetin, carechins, and more-hold great potential for diabetic management in the near term.

Scientists also evaluated the ability of resveratrol to reduce diabetic neuropathic pain. Looking at various inflammatory markers associated with this pain, they discovered that daily oral intake of resveratrol at 5, 10, and 20 milligrams per kilogram of body weight significantly reduced pain sensitivity in treated animals with induced nerve damage.

What, then, is the relationship between xeno factors and diabetes?

Through their action of decreasing insulin resistance, enhancing glucose’s ability to enter the cells, and stabilizing weight, polyphenols provide a complementary way to attack the disease. Additionally, studies have confirmed that polyphenols are potent anti-inflammatories, that they reduce free radicals, and that they inhibit the formation of damaging advanced glycation end products, or AGEs.

It is the prevention of diabetic complications that may be the greater role for plant-produced polyphenols. As discussed earlier in theories of aging, these glycation end products (AGEs) are formed by a cellular interaction of blood proteins that become bound to circulating glucose molecules. And the AGEs can occur more frequently in poorly controlled diabetics. These AGEs can stick to blood vessel walls and induce the development of diabetic vascular complications.

We are just beginning to understand how these naturally occurring compounds ingested over thousands of years activate ancient genetic pathways to enhance health and prolong longevity: But one of the most exciting possibilities is their potential for drug-free management of the diabetes pandemic.

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