Diabetes mellitus and its treatment with the help of Aloe vera.
Diabetes is a disorder of metabolism--the way your body uses digested food for growth and energy. Most of the food you eat is broken down into glucose, the form of sugar in the blood. Glucose is the main source of fuel for the body. After digestion, glucose passes into the bloodstream, where it is used by cells for growth and energy.
Insulin is produced by the pancreas, a large gland behind the stomach. This hormone regulates levels of sugar in the blood. It must be present in order for glucose to get into cells. When we eat, the pancreas automatically produces the right amount of insulin to move glucose from blood into our cells.
In people with diabetes, however, the pancreas either produces little or no insulin, or the cells do not respond appropriately to the insulin that is produced. Glucose builds up in the blood, overflows into the urine, and passes out of the body. Thus, the body loses its main source of fuel even though the blood contains large amounts of glucose.
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When glucose builds up in the blood instead of going into cells, it can cause two problems:
* Right away, your cells may be starved for energy.
* Over time, high blood glucose levels may hurt your eyes, kidneys, nerves or heart.
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Diabetes mellitus is less common in non-western countries where the diet contains fewer calories and daily caloric expenditure is higher. However, as people in these countries adopt Western lifestyles, weight gain and type 2 diabetes mellitus are becoming virtually epidemic.
About 215,000 people younger 20 years had diabetes (type 1 or type 2) in 2010. Centers for Disease Control and Prevention (CDC) report estimates that nearly 26 million will have diabetes in 2011. Additionally, an estimated 79 million have pre-diabetes. Diabetes affects 10% of population of all ages and 13% of adults aged 20 years and older, according to the National Diabetes Fact Sheet for 2011. About 33% of those with diabetes--7 million Indians--do not know they have the disease. Pre-diabetes affects 45% of adults aged 20 years and older. Pre-diabetes, as defined by the ADA, is that state in which blood glucose levels are higher than normal but not high enough to be diagnosed as diabetes. It is presumed that most persons with elevated glucose levels approaching the level needed for the diagnosis of diabetes will subsequently progress to diabetes. Rates of diabetes are increasing worldwide. At least 171 million people currently have diabetes, and this figure is likely to more than double to 366 million by 2030. The top 10 countries, in numbers of people with diabetes, are currently India, China, the United States, Indonesia, Japan, Pakistan, Russia, Brazil, Italy, and Bangladesh. The greatest percentage increase in rates of diabetes will occur in Africa over the next 20 years. However, at least 80% of people in Africa with diabetes are undiagnosed, and many in their 30s to 60s will die from diabetes there.
Diabetes Mellitus is the most common form of the disease, and accounts for more than 90% of diabetes patients. Current understanding of disease progression in diabetes mellitus is that insulin resistance in peripheral tissues leads to compensatory hyperinsulinemia, followed by (3-cell failure, which leads initially to prandial and later to overt fasting hyperglycemia (1). The number of people diagnosed with diabetes mellitus is increasing at an alarming rate in western societies; prompted by a dramatic increase in the incidence of obesity and sedentary lifestyles. According to recent estimates, approximately 220 million people worldwide will be affected by the disease by 2011 (2).
Diabetes mellitus comprises an array of dysfunctions resulting from the combination of resistance to insulin action and inadequate insulin secretion. Its disorders are characterized by hyperglycemia and associated with microvascular (ie, retinal, renal, possibly neuropathic), macrovascular (ie, coronary, peripheral vascular), and neuropathic (ie, autonomic, peripheral) complications. It is characterized by the combination of peripheral insulin resistance and inadequate insulin secretion by pancreatic beta cells. Insulin resistance, which has been attributed to elevated levels of free fatty acids in plasma, leads to decreased glucose transport into muscle cells, elevated hepatic glucose production, and increased breakdown of fat.
For diabetes mellitus to occur, both defects must exist. For example, all overweight individuals have insulin resistance, but diabetes develops only in those who cannot increase insulin secretion sufficiently to compensate for their insulin resistance. Their insulin concentrations may be high, yet inappropriately low for the level of glycemia.
Beta cell dysfunction is a major factor across the spectrum of pre-diabetes to diabetes. A study of obese adolescents confirms what is increasingly being stressed in adults as well: Beta cell function happens early in the pathological process and does not necessarily follow stage of insulin resistance (3). Singular focus on insulin resistance as the "be all and end all" is gradually shifting, and hopefully better treatment options that focus on the beta cell pathology will emerge to treat the disorder early. In the progression from normal glucose tolerance to abnormal glucose tolerance, postprandial blood glucose levels increase first; eventually, fasting hyperglycemia develops as suppression of hepatic gluconeogenesis fails.
The major risk factors for diabetes mellitus are the following:
* Age greater than 45 years (though, as noted above, type 2 diabetes mellitus is occurring with increasing frequency in young individuals)
* Weight greater than 120% of desirable body weight
* Family history of type 2 diabetes in a first-degree relative (eg, parent or sibling)
* Hispanic, Native American, African American, Asian American, or Pacific Islander descent
* History of previous impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)
* Hypertension (>140/90 mm Hg) or dyslipidemia (high-density lipoprotein [HDL] cholesterol level < 40 mg/dL or triglyceride level >150 mg/dL)
* History of gestational diabetes mellitus or of delivering a baby with a birth weight of >9 lb
* Polycystic ovarian syndrome (which results in insulin resistance)
People with diabetes mellitus benefit by reducing blood sugar levels through exercise and a healthy diet. However, it is not uncommon for people with diabetes mellitus to require medication to stimulate the pancreas to produce more insulin, decrease the amount of glucose made by the liver, slow the absorption of starches in the diet, or take a combination of medications to control blood sugar. But the management of diabetes without any side effects is still a challenge and has increased the demand for research on natural products with antidiabetic activity.
Aloe vera is a widely distributed Liliaceae plant in tropical regions and cosmetic and medicinal products are made from the mucilaginous tissue in the centre of the A. vera called A. vera gel. The peripheral bundle of sheath cells produce intensely bitter, yellow latex, commonly termed aloe juice, or sap or aloes. Unlike aloes, A. vera gel contains no anthraquinones, which are responsible for the strong laxative effects of aloe. The pharmacological actions of A. vera was studied in vitro or in vivo (in most cases the total leaf extract was used), include anti-inflammatory, anti- arthritic, antibacterial and hypoglycemic effects (4,5).
Aloe Vera has been the subject of more than 400 scientific studies, many of which focused on its cosmetic properties and therapeutic effectiveness. Although some of the studies have reached contrary conclusions, the cumulative evidence supports the use of Aloe Vera for numerous medical conditions. These include treatment of genital herpes, ulcerative colitis, psoriasis, digestive issues such as irritable bowel syndrome and heartburn, healing of first or second degree burns, accelerated healing of wounds, and lowered blood lipids in patients suffering from elevated serum lipid concentrations. Most importantly, perhaps, is Aloe Vera's ability to improve fasting blood glucose levels in diabetes mellitus patients (6,7,8,9).
Scientific Background Of Aloe Vera's Antidiabetic Efficacy
The March 2009 edition of the peer-reviewed journal Phytomedicine (10) featured a recent study that examined the effect of a processed form of Aloe Vera gel on the progression of the diseases--non-insulin-dependent diabetes mellitus.
The study used mice as the models, since their non-insulin dependent diabetes mellitus closely resembles the human manifestation of the disease. For 21 weeks, the mice were fed a high-fat diet, resulting in a 30% increase in body weight. The mice were then randomly separated into two groups. One group was given oral doses of Aloe Vera for 12 weeks, while continuing to consume the high-fat diet. The control group also continued to eat the high-fat diet, but was not given any Aloe Vera. Two weeks after administering Aloe Vera to the first group of mice, anti- hyperglycemic effects were apparent. Despite the continued consumption of a high-fat diet, fasting blood glucose levels in the test mice were reduced to normal. Following 12 weeks of treatment with Aloe Vera, liver and blood triglyceride levels showed a significant decrease, as did concentrations of plasma insulin.
Graph.1. fasting blood glucose concentration vs. time
During the past 20 years, reports have shown that Aloe preparations have beneficial therapeutic effects on diabetes. The hypoglycemic effect of Aloe species was first demonstrated in 1985 by Agarwal. During this previous study, a prescribed diet containing the leaves of Aloe vera was administered to 3167 diabetic patients twice daily for 5 years, and was found to markedly decrease blood sugar and serum total cholesterol and triglyceride levels (6). Since then the antidiabetic effects of Aloe preparations have been demonstrated in diabetic patients (11,12,13,14), and in alloxan or streptozotocin-induced diabetic animal models (15,16).
The anti-diabetic effects of dietary administration of Aloe arborescens Miller components on multiple low-dose streptozotocin-induced diabetes in mice were investigated. The mice were fed ad libitum with basal diets supplemented with components of Aloe vera. There was no significant effect on the blood glucose level with Aloe vera leaf pulp powder. On the contrary, the whole aloe leaf significantly decreased the blood glucose level (17,18,19).
It has been reported that Aloe vera gel and its derived phytosterols have a long-term blood glucose level control effect and would be useful for the treatment of type 2 diabetes mellitus (20,21,22,23).
The anti-diabetic activity of Aloe excelsa on male albino rats was also studied. The study showed that the Aloe excelsa powder produced a dose-dependent reduction in blood glucose levels (24).
The clinical trial on the anti-diabetic activity of Aloe vera juice suggested the potential use of Aloe vera as an anti-diabetic agent. In a clinical trial on 5000 patients with angina pectoris, it was found that adding aloe gel to the diet produced marked reduction in total cholesterol, triglycerides, fasting and post-prandial blood sugar levels in diabetic patients (11).
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Graph.2. Fasting blood glucose, triglycerides, cholesterol levels in STZ rats
Aloe vera gel extract at a dose of 300 mg/kg body weight per day was administered to STZ-induced diabetic rats for a period of 21 days. It resulted in a significant reduction in fasting blood glucose, hepatic transaminases (AST and ALT), plasma and tissue (liver) cholesterol, triglycerides, free fatty acids and phospholipids and a significant improvement in plasma insulin. In addition, the decreased plasma levels of high- density lipoprotein-cholesterol and increased plasma levels of low-density lipoprotein- and very low-density lipoprotein-cholesterol in diabetic rats were restored to near normal levels following treatment with the extract (graph.2.). Furthermore, they analyzed the fatty acid composition of the liver and kidney and found that the altered fatty acid composition in the liver and kidney of diabetic rats was restored following treatment with the extract. They recommended use of Aloe vera as an antidiabetic agent (25,26,27).
A growing body of in vitro and in vivo research shows Aloe vera has significant antidiabetic activity. In a human clinical trial conducted at the Mahidol University of Bangkok, Thailand, 72 patients with high fasting blood sugar and typical diabetic curve of glucose tolerance who had never been treated with hypoglycemic drugs were selected to participate in the study. The placebo controlled, single blind trial was conducted to evaluate the effects of oral aloe supplementation on blood sugar, cholesterol and triglycerides. The treatment group received 15 milliliters of aloe gel twice a day, in the morning and before bedtime, for 42 days. Blood samples were taken weekly for measurement of fasting blood glucose levels and every two weeks for triglyceride and cholesterol analyses. Before treatment, the patients in the control and treated groups showed no significant differences in blood markers. After treatment, blood sugar in the treatment group had been reduced 43 percent, blood triglycerides were reduced by 44 percent and there was no change in cholesterol. No adverse side effects were reported due to aloe supplementation, and there was no difference in weight or appetite in the treatment group. The authors note that this trial confirmed a report published in 1985. In that study, 5,000 patients with atheromatous heart disease were studied over a five-year period. Out of 5,000 patients, 3,167 were diabetics, 2,572 had a history of smoking and 2,151 had evidence of hypertension. All patients were instructed not to consume alcohol during the study and smoking was not allowed. All patients were instructed to take 100 g of Aloe vera gel and 20 grams of Husk of Isabgol (for fiber), mixed with wheat flour and prepared in bread, that was consumed at lunch and dinner daily for the five-year period of the study. During the initial phase of the study participants remained on the same schedule of medications they were on prior to the study (11).
According to the researchers, patients experienced positive improvements as early as the second week after the treatment with aloe was initiated. The disappearance of chest pains associated with heart disease, as well as improvement in their electrocardiogram results, even after treadmill tests, were seen in patients after three months, and none of them suffered fresh heart attacks during the study. After three months, the lipid profile of patients also improved. Serum cholesterol and triglyceride levels of 93 percent of the patients returned to normal and out of the 3,167 diabetic patients, 94 percent of the patients' blood sugar levels returned to normal. Of the 2,990 diabetic patients responding to the treatment, all the oral hyperglycemic medications had to be withdrawn by the end of two months' treatment with aloe. All patients taking beta blockers, calcium channel blockers and diuretics for hypertension and angina control had their medications reduced to half the dose they were taking prior to the study. Hypertensive patients did not show any significant change in blood pressure levels. At the conclusion of the study all 2,990 diabetic patients responding to the treatment remained on diet control alone. The study concluded aloe had a definite role in the prevention and management of atherosclerotic heart disease and in controlling the blood sugar level in diabetic patients.
Supporting evidence for the antidiabetic activity of Aloe vera has also been reported from animal studies. One study reported lifelong dietary aloe supplementation results in suppressed free radical-induced oxidative damage and age-related increases in hepatic cholesterol. In this age-related study on the hepatic cholesterol and oxidative status of rats it was found that hepatic cholesterol of aging animals in the control group was significantly increased in contrast to the aloe treated group, which showed a 30 percent lower cholesterol level. Superoxide dismutase (SOD) and catalase activity were both increased in the aloe treatment group and signs of oxidative tissue damage, such as lipid peroxidation, were decreased (27).
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Graph.3. anti-oxidant activity of Aloe vera
Another study found similar results in the treatment of neonatal streptozotocin- induced Type II diabetic rats. The author reported treatment with aloe decreased damage to the liver, increased glutathione and decreased lipid peroxidation, and concluded aloe gel has a protective effect comparable to glibenclamide against hepatotoxicity produced by diabetes when used in the treatment of Type II diabetes. The control of blood sugar is critical in the management of diabetes. Research has shown elevated blood sugar increases oxidative stress and the risk of cardiovascular disease, and patients with diabetes have decreased antioxidant defenses with lower levels of antioxidants such as vitamins C and E, or reduced activities of antioxidant enzymes such as catalase, superoxide dismutase and glutathione peroxidase. In the studies reported here, oral treatment with Aloe vera gel has been shown to aid in the normalization of blood sugar, stimulate the body's own antioxidant defenses and increase the bioavailability of antioxidant supplements. These studies indicate that aloe gel has a beneficial effect on the liver, as a hypoglycemic agent, and in cardiovascular disease by reducing oxidative stress (graph.3.) (28)
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Patients with diabetes have a lifelong challenge to achieve and maintain blood glucose levels as close to the reference range as possible. With appropriate glycemic control, the risk of micro vascular and neuropathic complications is decreased markedly. In addition, if hypertension and hyperlipidemia are treated aggressively, the risk of macro vascular complications decreases as well. Treatment with oral hypoglycemic agents is associated with side effects related to pharmacokinetic properties, secondary failure rates, hypoglycemia, gastrointestinal disturbances, skin reactions, hematological disorders, and rise in hepatic enzyme level. Management of diabetes without dyslipidemia and side effects is still a challenge to the medical community. For thousands of years plants and their derivatives are being used for treatment of diabetes mellitus. Although, herbal medicines have long been used effectively in treating diseases throughout the world and frequently considered to be less toxic and free from side effects as compared to synthetic ones. Fortunately for those unable to adhere to a reduced caloric diet, scientific reports have shown that preparations of Aloe Vera have beneficial effects on diabetes mellitus.
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(1) Prof. U.K. Chauhan, (2) Dr. Sanjeev Dubey and * (3) Shilpa Mishra
(1) Head of the Department, Centre for Biotechnology studies, Awadhesh Pratap Singh University, Rewa--486001 (M.P.)
(2) Head of Botany Department, Model Science College, Rewa--486001 (M.P.) India
(3) Junior Research Fellow, Centre for Biotechnology studies, Awadhesh Pratap Singh University, Rewa--486001 (M.P.) India
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