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Supplementation to manage diabetes

By Yousry Naguib, Ph.D.

Vitamin Retailer magazine, June 2006

All sugar, natural or refined, ends up as glucose in our blood stream. Glucose is the major carbohydrate used as fuel in our body to provide energy. In the fasting state, as in the morning before breakfast, the blood glucose level is between 80 mg and 90 mg/dL (dL= deciliter, equals one tenth of a liter) of blood in healthy people.

After a meal containing carbohydrates the blood glucose rises to a level of 120 mg to 140 mg after one and half to two hours, and then gradually falls to normal level in approximately four hours.

In diabetes, the blood sugar may reach 180 mg and higher after a meal containing carbohydrates. This high level of blood sugar is termed “hyperglycemia.” Blood sugar below 70 is termed “hypoglycemia,” which is characterized by feelings of weakness, shakiness, an unusual hunger, and a certain level of irritability.

As we grow older our glucose tolerance starts to decline, and as it continues to worsen, it increases our risk for diabetes. Diabetes is a metabolic disorder in which the body cannot control the level of sugar in the blood.

Diabetes is one of the most costly and burdensome chronic diseases of our time and is a condition that is increasing in epidemic proportions in the U.S. and throughout the world [1]. Diabetes affects 16 million Americans, and more than 125 million people worldwide. Diabetes is the fourth-leading cause of death by disease in the U.S. About two-thirds of the nearly 16 million people with type II diabetes in the U.S. are overweight, according to the American Diabetes Association. The pancreas in diabetic people produces little or no insulin, the hormone responsible for facilitating uptake of glucose by cells to produce energy.

There are two main types of diabetes: adult-onset diabetes, also called Type II or non-insulin-dependent diabetes mellitus (NIDDM); and childhood-onset diabetes, also called Type I, or insulin-dependent diabetes mellitus (IDDM).

In Type I, which accounts for 5 to 10 percent of diabetes, the pancreas cannot make the insulin needed to process glucose. Type I diabetes most often occur in children and young adults. Individuals suffering from Type I diabetes are totally insulin dependent. Without regular injections of insulin the sufferer lapses into a coma and dies.

Type II diabetes, the most prevalent type of diabetes, accounts for 90 to 95 percent of diabetes, is usually of gradual onset and progresses slowly, and occurs mainly in people over 40. Type II diabetes is a metabolic disorder resulting from the body’s inability to make enough, or properly use, insulin to meet the body’s needs. Type II diabetes is nearing epidemic proportions due to a greater prevalence of obesity.

Diabetics suffer from significantly higher rates of kidney disease, stroke, eye ailments, neuropathy, and poor circulation requiring amputation of limbs. Heart attacks account for 60% and strokes for 25% of deaths in all diabetics. Neuropathy is characterized by a distorted nerve function, particularly in the nerves responsible for sensation.

Diabetes may be controlled with insulin, medications, and in some cases through careful diet. Weight loss is considered the cornerstone of treatment in people with Type II diabetes because it allows the body to better use insulin and thus lowers blood sugar.

Researchers at Harvard found that more than 90 percent of the 3,300 women who developed diabetes over a 16-year study period were overweight, inactive, and smokers [2]. The study suggests that most of diabetes can be prevented through diet and exercise. Maintaining a healthy weight is the most important way to reduce risk of Type II diabetes.

Herbs, such as fenugreek, bitter melon, ginseng, gymnema sylvestre, with purported anti-diabetic activity have been used in folk medicine for many years. Many modern pharmaceuticals used in conventional medicine today have natural plant origins. Among them is metformin (Glucophage®) derived from the flowering plant, Galega officinalis (Goat’s Rue or French Lilac), which was a common traditional remedy for diabetes.

Fenugreek

Fenugreek (Trigonella foenumgraecum) is one of the oldest medicinal plants. It has been used to aid labor and delivery, stimulate lactation, aid digestion, and as a general tonic. Several studies suggest that this herb can lower blood sugar. In a recent double-blind placebo controlled study, twenty-five newly diagnosed patients with Type II diabetes (fasting glucose less than 200 mg/dl) were randomly assigned to receive one-gram daily hydro-alcoholic extract of fenugreek seeds or a placebo for two months. The fenugreek-group had significantly lower insulin resistance and improved glycemic control [3].

The hypoglycemic activity of fenugreek has been attributed to the active constituents galactomannan (soluble fibers), and the amino acid 4-hydroxy-isoleucine. In an animal study, the soluble fibers extract showed significant hypoglycemic activity when fed simultaneously with glucose to rats; it showed no effect on the fasting blood glucose levels of non-diabetic rats [4].

In a test tube experiment, 4-hydroxy-isoleucine was shown to increase glucose-induced insulin release in human and rat pancreatic islet cells [5]. Recent research findings from type II diabetes rat model also support the role of 4-hydroxyisoleucine in balancing blood sugar, reducing body fat, and aiding muscle growth and recovery [6].

Bitter melon

Bitter melon (Momordica charantia Linn.), commonly known as Karela, has been reported to have anti-diabetic, and anti-tumor activities. In a recent clinical study, Bitter melon was shown to significantly reduce both fasting and post-prandial (blood-sugar levels after carbohydrate consumption) serum glucose levels in non-insulin dependent diabetes mellitus patients [7].

In an animal study, the aqueous extract of the fresh unripe and dried whole fruits at a dose of 20 mg/kg body weight was found to reduce fasting blood glucose by 48% in diabetic rats. No signs of nephro-toxicity and hepato-toxicity were observed [8].

However, in another recent publication, bitter melon was reported to have adverse effects, including hypoglycemic coma and convulsions in children, and headaches [9].

Panax Ginseng

Ginseng is traditionally considered a tonic and has been shown to help lowering blood glucose levels. In a recent randomized placebo controlled study, researchers in Toronto, Canada, examined the effects of American ginseng (Panax quinquefolius) on the blood sugar levels of 19 subjects. Ten non-diabetics took 3 g of American ginseng or placebo, either forty minutes before or at the same time they ingested a high-sugar solution. Nine subjects with Type II diabetes also received the same treatments. Taking the ginseng before the sugar dose led to a significant reduction in glucose absorption among both the diabetics and the non-diabetics. When the sugar solution was taken simultaneously with the American ginseng, the diabetics still experienced a reduction, whereas the non-diabetics did not [10].

Garcinia

The South Asian fruit Garcinia cambogia is about the size of an orange and looks similar to a small pumpkin. It contains the popular weight loss ingredient hydroxycitric acid. Hydroxycitric acid derived from Garcinia cambogia works at the cellular level to keep carbohydrates from turning into fat, and to suppress appetite and to provide energy [11].

Animal studies have demonstrated that inhibition of ATP citrate lyase enzyme by hydroxycitric acid leads to a decrease in the synthesis of both cholesterol and fatty acids [12]. The enzyme catalyzes the cleavage of citrate into acetyl coenzyme A, which is responsible for cholesterol and fatty acid synthesis de novo. A typical dosage of hydroxycitric acid is 250 to 1,000mg three times daily.

Gymnema sylvestre

Gymnema is a tropical plant of the milkweed family native to India. The leaf is the primary part used in medicinal purposes. Gymnema sylvestre has been used traditionally for stomach problems, constipation, and control Type II diabetes. Ayurvedic doctors in India noticed that chewing Gymnema sylvestre leaves suppressed the taste of sugar.

The active ingredient of Gymnema sylvestre is gymnemic acid, which was found to have the ability to fill the receptor sites on the taste buds, thereby preventing the sweet taste of sugar molecules. Gymnemic acid also has the ability to occupy the receptor sites in the absorptive layers of the intestine, thereby blocking the absorption of sugar molecules from the intestine [13].

In one study extracts from the leaves of Gymnema sylvestre (400 mg/day) were administered for 18 to 20 months to 22 patients with Type II diabetes taking conventional medication. All patients showed a significant reduction in blood glucose levels. Five of the 22 patients were able to maintain their blood glucose levels without conventional drugs and the dose was reduced in the other patients. The study also found higher levels of insulin in the blood indicating that the insulin beta cells of the pancrease may be regenerated in Type II diabetes on Gymnema sylvestre supplementation [14].

In another study, extracts of Gymnema were able to increase the number insulin producing cells in diabetic rat pancreas. The study suggested that Gymnema may improve health of pancreas thereby providing a second mechanism for its action in diabetes [15]. There are no reports of severe adverse reactions with gymnema when it is ingested in the usual daily dose of 400mg.

Glucotrim®

Glucotrim® is a standardized extract from Lagerstroemia speciosa L. leaves. Lagerstroemia speciosa is commonly known as Crepe Myrtle, and is widely distributed in the tropical countries, such as the Philippines, India, and China. In the Philippines, a tea from the leaces has been used as a beverage as well as for the treatment of diabetes mellitus. The leaves contain significant amounts of corosolic acid, which has previously been shown to possess anti-diabetic properties and significant amounts of tannins, of which Lagerstoemin, flosin B, and reginin A were identified.

The anti-diabetic activity of an extract from the leaves of Lagerstroemia speciosa standardized to 1% Corosolic acid has been demonstrated in a clinical trial, sponsored by Soft Gel Technologies, involving Type II diabetics, who received a daily oral dose of the standardized extract in either a soft gel capsule or powder formulation. The soft gel formulation-group showed a 30 percent decrease in blood glucose levels compared to a 20 percent drop seen with dry-powder filled hard gelatin capsule formulation, suggesting that the soft gel formulation has a better bioavailability than a dry powder formulation [16].

Cinnamon

Cinnamon grows in abundance in various parts of the world; it is used as a spice, and has recently been demonstrated to control type II diabetes.

Daily consumption of one to six grams cinnamon has been demonstrated in a recent clinical trial to reduce serum glucose, triglycerides, LDL cholesterol, and total cholesterol in people with type II diabetes. Sixty people with type II diabetes, 30 men and 30 women aged average 52 years, were randomly divided into six groups. Groups 1, 2, and 3 received 1, 3, or 6 grams cinnamon daily, respectively; and groups 4, 5, and 6 received placebo, for 40 days. All three cinnamon groups showed a reduction in the mean fasting serum glucose (18-29%), triglycerides (23-30%), LDL (7-27%), and total cholesterol (12-26%); no significant changes were noted in the placebo groups [17].

Recently, researchers at the Human Nutrition Research Center of the US Department of Agriculture have isolated and characterized insulin-enhancing complexes, water-soluble polyphenolic polymers, from cinnamon that may function as antioxidants, and may alleviate or control glucose intolerance and diabetes [18].

Stevia

The plant Stevia rebaudiana Bertoni has been used as a tea for many years in the treatment of diabetes among Indians in Paraguay and Brazil. The active ingredient of the Stevia leaf stevioside accounts for about 40 percent of the total artificial sweetener market in Japan. Stevia has no calories. It stimulates the release of insulin via a direct action on the pancreatic beta cells and normalizes the response to glucose, especially in Type II diabetes [19].

In a most recent clinical trial, stevioside was found to reduce postprandial blood glucose levels in twelve type 2 diabetic patients, indicating that stevioside may be advantageous in the treatment of type 2 diabetes [20].

Alpha-lipoic acid

Alpha-lipoic acid (ALA) plays key roles in our health, as an antioxidant, as well as a cofactor for a number of vital enzymes responsible for metabolism of glucose, and fatty acids to cellular energy. ALA also helps regulate blood sugar, and prevents diabetic retinopathy, and reduces symptoms of neuropathy. Studies in Europe showed that taking 600 mg twice a day improved the symptoms of diabetic neuropathy, numbness and tingling in the hands and feet [21].

In a multi-center, double-blind placebo-controlled study, 328 patients with Type II diabetes and symptomatic peripheral neuropathy were randomly assigned to treatment with intravenous infusion of ALA or placebo for three weeks. Symptoms (pain, burning, and numbness) in the feet decreased significantly in the ALA-group taken 600mg daily, as compared to the placebo. The study concluded that intravenous treatment with ALA (600 mg daily) over three-weeks is safe and effective in reducing symptoms of diabetic peripheral neuropathy in Type II diabetes [21]. Diabetics are recommended to take 200 mg ALA three times daily.

Vitamins / Minerals

Vitamin B12 (cyanocobalamine), and vitamin B6 (pyridoxine) work together to help metabolizing glucose in the cells [22]. One milligram of B12 and 10 mg of B6 are recommended. Diabetics also have increased free radical oxidation so adding Vitamins E and C gives antioxidant protection. Vitamin E also reduces glycosylation (the process of adding sugar units to proteins).

Mineral supplements are also recommended to support glucose metabolism, but they are poorly absorbed by the body, their absorption can be increased by chelating (binding) the mineral to an organic substance, in particular amino acids [23]. Vanadium has been shown to have an insulin-mimicking effect in rats. Artificially induced diabetes in rats can be reversed with vanadium. Black pepper and dill seed are the richest sources of vanadium. Vanadium can be harmful if it is overdosed so it is not recommended in patients unless they are being strictly monitored. The beneficial dose is 250 mcg three times a day [24].

Magnesium modulates glucose transport and is also a cofactor involved in glucose oxidation. Ketoacidosis (the accumulation of ketone molecules, such as acetone, in body tissues and fluids) promotes an increased urinary loss of magnesium [22].

Chromium is an essential nutrient required for the proper sugar and fat metabolism. Chromium deficiency is relatively common in patients with Type II diabetes. Chromium is poorly absorbed, only 2 to 10 percent of dietary intake being absorbed. Organic chromium, such as chromium picolinate and niacin-bound chromium are absorbed more efficiently than inorganic chromium such as chromium chloride.

In one study, chromium picolinate was found to improve glucose tolerance in Chinese people with Type II (non-insulin-dependent) diabetes. 180 Chinese subjects with non-insulin-dependent diabetes mellitus (NIDDM) were divided into three groups of 60 subjects each and supplemented with placebo, 100 or 500 mcg of chromium picolinate two times per day for four months.

Improvements in the glucose/insulin system were highly significant in the 500 mcg chromium-group, and less or no significant improvements in the both the placebo and 100 mcg chromium group. Plasma total cholesterol also decreased after 4 months in the subjects receiving 500 mcg chromium picolinate. These results indicate that the beneficial effects of chromium in individuals with diabetes are observed at levels higher than the upper limit of the Estimated Safe and Adequate Daily Dietary Intake [25].

In summary, natural products have long been used in alternative medicine for diabetes. Products in common use include fenugreek, bitter melon, panax ginseng, garcinia, gymnema sylvestre, Glucotrim®, stevia, cinnamon, and Caiapo.

References

[1] King H et al. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care 1998; 21:1414

[2] Hu FB et al. Diet, lifestyle, and the risk of type 2 daibetes mellitus in women. New Eng J Med 2001; 345:790

[3] Gupta A et al. Effect of Trigonella foenum-graecum (fenugreek) seeds on glycemic control and insulin resistence in type 2 diabetes mellitus: a double blind placebo controlled study. J Assoc Physicians India 2001; 49:1057

[4] Ali L et al. Characterization of the hypoglycemic effects of Trigonella foenum graecum seed. Planta Med 1995; 61:358

[5] Sauvaire Y et al. 4 Hydroxy-isoleucine: a novel amino acid potentiator of insulin secretion. Diabetes 1998; 47:206

[6] Broca C et al. 4-Hydroxyisoleucine: experimental evidence of its insulino-tropic and anti-diabetic properties. Am J Physiol 1999; 277 (4 Pt 1): E617

[7] Ahmad N et al. Effect of Momordica charantia extracts on fasting and post-prandial serum glucose levels in NIDDM patients. Bangladesh Med Res Coun Bull 1999; 25:11

[8] Virdi J et al. Antihyperglycemic effects of three extracts from Momordica charantia. J ethnopharmacol 2003; 88:107

[9] Basch E et al. Bitter melon (Momordica charantia): a review of efficacy and safety. Am J Health Syst Pharm 2003; 60:356

[10] Vuksan V et al. American ginseng (Panax quinquefolius L) reduces post-prandial glycemia in non-diabetic subjects and subjects with type 2 diabetes mellitus. Archives of Internal Medicine 2000; 160:1009

[11] Sergio W. A natural food, malabar tamarind, may be effective in the treatment of obesity. Medical Hypothesis 1988; 27:40

[12] Sullivan AC et al. Lipids 1977; 12:1; Triscari J and Sullivan AC. Comparative effects of hydroxycitrate on acetyl CoA carboxylase and fatty acid and cholesterol synthesis in vivo. Lipids 1977; 12:357

[13] Shimizu K et al. Suppression of glucose absorption by some fractions extracted from Gymnema sylvestre leaves. J Vet Med Sci 1997; 59:245

[14] Baskaran K et al. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol 1990; 30:295

[15] Shanmugasundaram ER. et al. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol 1990; 30:281

[16] Naguib Y et al. Antidiabetic activity of a standardized extract (Glucosol) from Lagerstroemia speciosa leaves in Type II diabetics: A dose-dependence study. J Ethnopharmacology 2003; 87:115

[17] Khan A et al. Cinnamon improves glucose and lipids of people with type 2 daibetes. Diabetes Care 2003; 26:3215

[18] Anderson RA et al. Isolation and characterization of polyphenol type-A polymers from cinnamon with insulin-like biological activity. J Agric Food Chem 2004; 52:65

[19] Jeppesen PB et al. Stevioside acts directly on pancreatic beta cells to secrete insulin. Metabolism 2000; 49:208

[20] Gregersen S et al. Anti-hyperglycemic effects of stevioside in type 2 diabetic subjects. Metabolism 2004; 53:73

[21] Ruhnau KJ, Ziegler D et al. Effect of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabetic Medicine 1999; 16:1040

[22] Mooradian,A.D.,et al. Selected vitamins and minerals in diabetes. Diabetes Care 1994; 17: 464-476

[23] Ashnead,H.D. The Roles of Amino Acid Chelates in Animal Nutrition. Noyes Press New Jersey: 1993

[24] LaValle JB. The nutritional solution to hyperinsulinemia and diabetes. Natural Pharmacy 2(3): 20-21,1998

[25] Anderson RA et al. Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type II diabetes. Diabetes 1997; 46:1786

 

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