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Dietary Supplements for Diabetes
US Pharm. 2005; 11:86-91 (November 2005)
by Jake Mossman, BSPh, RPh, President and Pharmacist-in-Charge
Taos Pharmacy and Total Health and Wellness Center, Taos, NM

Dietary supplements can help patients with diabetes control their blood glucose levels.

Currently, there is no method to prevent or cure diabetes. The disease may only be moderately controlled with conventional treatment. As a result, a growing number of individuals are looking to dietary supplements to help manage their disease. This article will look at the use of dietary supplements as complementary and alternative therapy for diabetes.

Etiology
Diabetes is a chronic metabolic disorder characterized by abnormalities in carbohydrate, fat, and protein metabolism. The primary characteristic of diabetes is hyperglycemia, a condition that results from defects in insulin secretion or insulin action.³ There are four clinical classifications of diabetes—type 1, type 2, gestational, and other specific types. Type 1 diabetes is an immune-mediated condition. Its onset is usually abrupt and occurs before age 30.³ Destruction of the beta-cells of the pancreas by the immune system results in a patient's dependence on insulin for survival. Gestational diabetes occurs as a result of hormonal changes during pregnancy and affects 2% to 4% of women, usually in the second or third trimester.³ Insulin antagonist hormone levels increase during this time, resulting in insulin resistance. In a normal pregnancy, increased insulin secretion offsets this insulin resistance. Other specific types of diabetes affect the smallest number of patients with the disease. These types result from hormonal syndromes, certain diseases of the pancreas, exposure to drugs, rare conditions of insulin receptors, and other genetic defects.³

Type 2 diabetes represents about 90% of all known cases of diabetes in the U.S.³ Onset of the disease usually occurs after 30 years of age and is associated with defects in both insulin action (insulin resistance) and insulin secretion.³ While patients with type 2 diabetes have the ability to produce insulin, the insulin levels are insufficient to overcome insulin resistance. Incidence of type 2 diabetes increases with age and degree of obesity.³ In addition, prevalence of the disease is markedly increased in Native American, Hispanic and African-American populations.³ This article will focus on the management of type 2 diabetes, which affects a large percentage of the total patient population.

Nutrition Therapy for Diabetes
Major treatment goals for type 2 diabetes include achievement of normal metabolic control and prevention of both microvascular and macrovascular complications. Specific goals of therapy include eliminating symptoms, optimizing metabolic parameters, achieving and maintaining a reasonable body weight, reducing cardiovascular risk factors, preventing microvascular complications, and achieving optimal health and well-being.³ Conventional treatment of type 2 diabetes has typically focused on dietary modifications, regular exercise, and the use of insulin and pharmacologic agents.³ For some patients, proper nutrition and exercise are enough to control metabolic abnormalities such as hyperglycemia, hyperlipidemia, and hypertension. In overweight patients, caloric intake is adjusted to produce long-term weight loss. For all patients with type 2 diabetes, carbohydrate intake should be distributed throughout the day to maintain steady levels of blood glucose.³

Nutrition recommendations for type 2 diabetes should also address hyperlipidemia, atherosclerosis, and hypertension, if present. Regular physical activity can improve insulin sensitivity, promote weight loss and maintenance of ideal weight, improve cardiovascular health, reduce the need for medications and insulin, and enhance productivity, quality of life, and sense of well-being.³ When a patient cannot achieve normal or near-normal blood glucose levels with nutrition and exercise, medication therapy is considered. Oral hypoglycemic agents include those that increase insulin secretion (e.g., sulfonylureas), improve insulin sensitivity (e.g., metformin), and reduce carbohydrate absorption (e.g., acarbose).³ Insulin is added when glucose control cannot be achieved with these oral agents.

Two new agents have recently been introduced as adjunct therapies to improve glucose control. Symlin (pramlintide), a synthetic analog of the human pancreatic hormone amylin, is used with insulin to slow the entry of glucose into the circulation.⁴ Pramlintide slows gastric emptying which, in turn, slows intestinal glucose absorption. The drug also produces a sense of satiety that reduces food intake. The second agent, Byetta (exenatide), is used as an adjunct to oral hypoglycemic agent therapy.⁵ It is used in patients taking a sulfonylurea, metformin, or both. Exenatide improves the body's natural response to changes in blood glucose as they occur. As blood glucose levels increase, exenatide increases insulin secretion in the pancreas. As blood glucose decreases, insulin secretion is reduced.

The goals of nutrition therapy for diabetes include attaining and maintaining optimal metabolic control, preventing and treating chronic complications of diabetes, improving overall health through diet and physical activity, and addressing individual nutritional needs based on cultural preferences and lifestyle.⁶ Optimal metabolic control is characterized by blood glucose levels that are as close to normal as is safely possible, a lipid and lipoprotein profile that reduces the risk of macrovascular disease, and blood pressure levels that reduce the risk of vascular disease.⁶ Specific nutrition recommendations from the American Diabetes Association for patients with type 1 and type 2 diabetes are shown in TABLE 1.

Nutritional and Herbal Supplements for Diabetes
A study compared the prevalence of complementary and alternative medicine (CAM) and pattern of use in individuals with diabetes.⁷ Costs and patterns of use of CAM were compared in patients with diabetes and in individuals without the disease. The study found that patients with diabetes were 1.6 times more likely to use CAM than individuals without diabetes.⁷ The five most commonly used CAM therapies in individuals with diabetes (in order of importance) were nutritional advice and lifestyle diets, spiritual healing, herbal remedies, massage therapy, and meditation training.⁷ In addition, a nationally representative survey found that about one third of patients with diabetes use CAM for their condition.⁸

Another study by the National Center for Complementary and Alternative Medicine focused on six dietary supplements for diabetes—alpha-lipoic acid (ALA), chromium, coenzyme Q10, garlic, magnesium, and omega-3 fatty acids.⁹ The report found that the six dietary supplements appear to be generally safe at low to moderate doses. ALA is an antioxidant, a substance that prevents cell damage caused by free radicals in a process known as oxidative stress. High levels of blood glucose are one cause of oxidative stress, and it is theorized that ALA may be beneficial because of its antioxidant activity. In a few small studies, possible benefit from ALA was seen in glucose uptake in muscle, sensitivity of the body to insulin, diabetic neuropathy, and/or weight loss.^10,11 However, more research is needed to document whether there is any benefit of ALA for the treatment of diabetes.

Plant derivatives with purported hypoglycemic properties have been used in folk medicine and traditional healing systems around the world (e.g., Native American, Jewish, Chinese, East Indian, Mexican).¹² Many modern pharmaceuticals used in conventional medicine today also have natural plant origins. For example, metformin was derived from the flowering plant Galega officinalis (Goat's rue or French lilac), which was a common traditional remedy for diabetes. The use of vitamin and mineral supplements for primary or secondary disease prevention is of increasing interest.¹³ Dietary supplements are described in TABLE 2.

A study conducted a systematic review of published literature on the safety and efficacy of herbal and vitamin/mineral supplements for glucose control in patients with diabetes.¹² The study analyzed a total of 108 trials that examined the use of 36 herbs and nine vitamin/mineral supplements in 4,565 patients with diabetes or impaired glucose tolerance. High-quality randomized controlled trials (RCTs) examined Coccinia indica (ivy gourd), ginseng species, Bauhinia forficata (cow's foot), and Myrcia uniflora (TABLE 3). Other herbs such as Allium cepum (onion), Ocimum sanctum (holy basil), Ficus carica (fig leaf), Silibum marianum (milk thistle), Opuntia streptacantha (nopal or prickly pear cactus), and Trigonella foenum (fenugreek) have been studied in lower-quality RCTs. Gymnema sylvestre (gurmar)and Momordica charantia (bitter melon) have been studied only in nonrandomized controlled trials.

Vitamin and Mineral Supplements
Chromium: Chromium is a metal and an essential trace mineral found in meats, animal fats, fish, brown sugar, coffee, tea, some spices, brewer's yeast, and whole-wheat and rye breads.⁹ It is marketed in supplement form (capsules and tablets) as chromium picolinate, chromium chloride, and chromium nicotinate. There is currently not enough evidence demonstrating that chromium supplementation is beneficial for diabetes.⁹

Coenzyme Q10: Often referred to as CoQ10, coenzyme Q10 is a vitamin-like substance that helps cells make energy and acts as an antioxidant.⁹ Meats and seafood contain small amounts of CoQ10. Supplements are marketed as tablets and capsules. CoQ10 has not been shown to affect blood glucose control.⁹ The substance may prevent heart disease in people with diabetes, but there are no well-designed studies focusing on CoQ10 supplementation and heart disease outcomes in diabetic patients.⁹

Garlic (Allium sativum): Garlic is an herb used to flavor food. In some cultures, garlic is used for medicinal purposes. A claim exists that the rates of certain diseases are lower in countries where a great deal of garlic is consumed.⁹ There is no evidence that taking garlic reduces the risk of diabetes.⁹

Magnesium: Foods high in magnesium include green leafy vegetables, nuts, seeds, and some whole grains. Magnesium has many important functions in the body, such as glucose and protein synthesis. Low levels of magnesium are commonly seen in people with diabetes. Some studies have suggested that low magnesium levels may contribute to diabetes complications and make glucose control more difficult in patients with type 2 diabetes by interrupting insulin secretion in the pancreas and increasing insulin resistance.¹⁴ There is evidence that magnesium supplementation may be helpful for insulin resistance.¹⁴ Additional controlled studies are needed to confirm the benefit of magnesium supplementation for the treatment of diabetes.

Omega-3 fatty acids: Omega-3 fatty acids are found in food sources such as fish, fish oil, some vegetable oils (primarily canola and soybean), walnuts, wheat germ, and certain dietary supplements. Omega-3 acids are important in a number of bodily functions, including the movement of calcium in and out of cells, the relaxation and contraction of muscles, blood clotting, digestion, fertility, cell division, and growth.⁹ Studies have shown that omega-3 supplementation reduces the incidence of cardiovascular disease and events (such as heart attack and stroke) and slows the progression of atherosclerosis (hardening of the arteries).¹⁵ However, these studies did not focus on populations at high risk, such as individuals with type 2 diabetes.

Coccinia indica (ivy gourd): Coccinia indica is a creeping plant that grows in the wild in many parts of the Indian subcontinent. It is used in Ayurvedic medicine to treat "sugar urine." Ayurvedic medicine is a traditional East Indian healing system. Coccinia indica appears to have insulin-mimetic properties, although its effects are not well understood. In one controlled clinical trial of 70 participants, the use of dried herb pellets for 12 weeks was as effective as treatment with chlorpropamide (an oral hypoglycemic drug) for lowering blood glucose levels.¹² Evidence suggests that the use of Coccinia indica in diabetes warrants further study.

Ginseng: Ginseng species are often touted for their "cure-all" adaptogenic properties, immune-stimulant effects, and their ability to increase stamina, concentration, longevity, and overall well-being. Several different plant species are often referred to as ginseng. These include Chinese or Korean ginseng (Panax ginseng), Siberian ginseng (Eleutherococcus senticosus), American ginseng (Panax quiquefolius), and Japanese ginseng (Panax japonicus). Most clinical trials have used American ginseng to examine the herb's short-term effects on patients with type 2 diabetes after a standard oral glucose tolerance test.¹² Two longer-term trials administered American ginseng for eight weeks.¹² Both studies reported decreases in fasting blood glucose and A1c. Studies of American ginseng in diabetes suggest a possible hypoglycemic effect. However, the trials are small (24 to 36 subjects) and longer-term studies are needed.

Bauhinia forficata and Myrcia uniflora: In Brazilian herbal medicine, Bauhinia forficata has been referred to as "vegetable insulin." Another commonly used South American herb is Myrcia uniflora. These two products were used in small studies that were a part of a Brazilian national effort to identify promising plant products for glucose control.⁹ Teas of these two products were compared to a placebo tea with no known or suspected hypoglycemic effect. No difference was seen in any of the products.¹² Allium species, Allium sativum (garlic) and Allium cepum (onion) have been studied in small clinical trials. The available data provide conflicting evidence for glycemic control.¹²

Ocimum sanctum (holy basil): In one clinical trial using 40 subjects, Ocimum sanctum showed positive effects on both fasting and postprandial glucose in patients with type 2 diabetes who used a preparation of fresh leaf powder mixed in water for four weeks.¹² Ocimum sanctum warrants further study for its glucose-lowering properties.

Ficus carica (fig leaf): Ficus carica is popular with patients with diabetes in Spain and southwestern Europe. Animal studies of Ficus carica have shown both short-term and long-term hypoglycemic effects, but there are no trials in humans.¹² More information is needed to assess this natural product.

Silibum marianum (milk thistle): Silibum marianum is used to treat alcoholic and viral hepatitis liver damage. Because some insulin resistance is secondary to liver damage, it has been proposed that milk thistle be studied for glycemic control. One clinical trial of 60 subjects studied patients with type 2 diabetes and cirrhosis. Patients were given 600 mg/day of an Italian milk thistle product for 12 months.¹² Subjects showed significant improvement in glucose control when compared to controls receiving no treatment. Higher quality trials may provide more information about the usefulness of milk thistle for type 2 diabetes.

Opuntia streptacantha (nopal or prickly pear cactus): Opuntia streptacantha is commonly used by people of Mexican descent for glucose control. Animal studies have demonstrated decreases in postprandial glucose and A1c.¹² Two controlled short-term studies of 14 and 32 subjects, respectively, reported decreased fasting glucose and insulin levels in patients with type 2 diabetes. Longer-term clinical trials are needed to confirm these findings.

Trigonella foenum (fenugreek): Trigonella foenum is a legume and commonly used herb in Ayurvedic medicine which has been described in early Greek and Latin pharmacopoeias for hyperglycemia. Several uncontrolled trials have studied the use of fenugreek in type 2 diabetes.¹² Some studies have followed patients taking fenugreek for up to six months and reported benefits of the legume in glycemic control.⁹ Evidence for the efficacy of fenugreek suggests that further studies may be warranted.

Gymnema sylvestre (gurmar): Gymnema sylvestre is another commonly used herb in Ayurveda. The popular Hindi name of the plant gurmar means "destroyer of sugar," because of its purported ability to cause a loss of sweet taste. The evidence for the effect of Gymnema sylvestre in diabetes is suggestive of benefit and warrants further study.

Momordica charantia (bitter melon): There is very limited data for bitter melon that suggests a potential use in diabetes.

Conclusion
Diabetes is a chronic metabolic disorder with devastating long-term consequences. The disease cannot be cured and may only be moderately controlled with conventional treatment. Dietary supplements may offer an alternative to help control blood glucose and are used by people with diabetes worldwide. Many dietary supplements have traditionally been used as part of folk medicine. Some herbal supplements have been withdrawn from the market and linked to several deaths. The products described herein have been shown to be largely safe with little adverse effects.^8,12 Although many supplements show promise for managing diabetes, clinical studies of dietary supplements have been mostly small and uncontrolled. More research is needed to establish the efficacy of natural products for the treatment of diabetes.

As incidence of diabetes in the U.S. continues to increase at an alarming rate, so does public interest in the use of nutritional supplements and natural products for diabetes. The pharmacist is the health care provider best positioned to monitor the use of dietary supplements by patients with diabetes. Pharmacists should be aware of the safety and efficacy of natural products that their patients may be using and can be assured that most of the products mentioned in this article have been used safely. Patients should be monitored for adverse effects from supplements, since some of these products may have hypoglycemic effects that may warrant the reduction of oral medication and insulin doses. Any changes in diabetes therapy, including the addition of dietary supplements and changes in medication doses, should involve the primary care provider. As always, optimal care involves the patient-physician-pharmacist triad.

REFERENCES
1. U.S. Centers for Disease Control and Prevention. Diabetes: Disabling, Deadly, and on the Rise. Available at: www.cdc.gov/nccdphp/aag/aag_ddt.htm. Accessed October 18, 2005.
2. Conquering Diabetes: A Strategic Plan for the 21st Century, A Report of the Congressionally-Established Diabetes Research Working Group; 1999.
3. American Diabetes Association Clinical Education Series. Medical Management of Type 2 Diabetes. 4th ed. 1998.
4. Symlin Product Information.
5. Byetta Product Information.
6. Nutrition Principles and Recommendations in Diabetes. American Diabetes Association: Clinical Practice Recommendations 2004. Diabetes Care. 2004;27:(suppl 1).
7. Egede LE, Ye X, Zheng D, Silverstein MD. The prevalence and pattern of complementary and alternative medicine use in individuals with diabetes. Diabetes Care. 2002;25:324-329.
8. Yeh GY, Eisenberg DM, Davis RB, Phillips RS. Complementary and alternative medicine use among patients with diabetes mellitus: results of a national survey. Am J Public Health. 2002;92:1648-1652.
9. National Center for Complementary and Alternative Medicine Research Report. Treating Type 2 Diabetes with Dietary Supplements. Available at: nccam.nih.gov/health/diabetes. Accessed October 18, 2005.
10. Jacob S, Ruus P, Hermann R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Radic Biol Med. 1999;27:309-314.
11. Konrad T, Vicini P, Kusterer K, et al. Alpha-lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes. Diabetes Care. 1999;22:280-287.
12. Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care. 2003;26:1277-1294.
13. O'Connell B. Select vitamins and minerals in the management of diabetes. Diabetes Spectrum. 2001;14:133-148.
14. Lopez-Ridaura R, Willett WC, Rimm EB, et al. Magnesium intake and risk of type 2 diabetes in men and women. Diabetes Care. 2004;27:134-140.
15. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747-2757.

US Pharm., Vol. No: 30:11 Posted: 11/15/2005

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