Nopal (Prickly Pear Cactus), Fenugreek, Cinnamon, and Gymnema for Type 2 Diabetes: What Works? What Doesn't?

Case Presentation

Mr. Lopez is an English-speaking Latino patient whose parents are first-generation non-English-speaking immigrants from Mexico. He was born in the United States and graduated from high school. He is 40 years old, single, and overweight, with a body mass index of 28 kg/m². Six months ago, he was diagnosed with type 2 diabetes mellitus, a condition that several family members also have, including his father and uncles and his grandfather in Mexico. He is receiving glyburide at the maximum dose, but his glucose control has been less than optimal; his most recent glycated hemoglobin (A1c) level is 7.2%.He has also started atorvastatin for management of an elevated low-density lipoprotein (LDL) cholesterol level (200 mg/dL).

Mr. Lopez manages the family restaurant and reports that he eats a typical Mexican diet daily, which consists of whole milk, bread, and cereal for breakfast as well as refried beans, tortillas and beans with cheese and meat, or tamales or enchiladas for lunch, which he eats at work. He eats dinner at home with his parents, brother, and his brother's family; his mother cooks this meal each evening. Dinner is Mr. Lopez's heaviest meal of the day, and it includes lots of vegetables, fish or chicken, and rice and tortillas. He leads a sedentary lifestyle with little planned exercise other than walking 1 mile to and from work daily.

The patient is unhappy about the suggestion to add a second antidiabetic medication because he does not wish to be medication dependent. He shares with you that he has been advised by his family to use nopal (prickly pear cactus) and to add cinnamon and fenugreek to his food, which his mother is very happy to do for the evening meal because she also believes that these foods and spices will benefit his diabetes. He heard about Gymnema from an Asian Indian friend with diabetes and would like your advice about which of these supplements or herbals and spices to use, and in what daily dosages, before starting a new hypoglycemic agent. He has searched the Internet for more information on these herbals and spices, but what he found was confusing and difficult to assess. On further direct questioning, he does not currently use any herbals or supplements and is not seeing a curandera (Mexican healer).

Commentary

Diabetes now affects nearly 24 million people in the United States, and another 57 million people are estimated to have prediabetes. The prevalence of prediabetes and diabetes are higher in certain ethnic groups, including Latinos and American Indians.^[1] Diabetes causes substantial health impairments, such as kidney failure, heart disease, macrovascular and microvascular dysfunction, blindness, and death. Insulin-resistant, or type 2, diabetes is the predominant form.

A review of 18 studies from 9 countries found that 17%-78% of patients with diabetes use complementary and alternative medicine (CAM) therapies, including nutritional supplements; herbals; nutritional counseling; spices; plant foods; and such techniques as acupuncture, spiritual healing, Chinese medicine, and mindfulness, often concurrently with conventional healthcare.^[2]

A review of herbs and dietary supplements used for glycemic control in diabetes examined 108 trials of 36 herbs and 9 vitamins in 4565 patients with diabetes or impaired glucose tolerance. The researchers found 58 controlled trials.^[3] The studies were significantly heterogeneous in terms of quality. The supplements seemed to be generally safe but needed further study. The best evidence, in terms of study design and data from randomized controlled trials, was found for American ginseng and Coccinia indica; promising preliminary results were seen for Gymnema sylvestre, aloe vera, vanadium, Momordica charantia (bitter melon), and nopal. Since then, more randomized trials on other supplements and herbals have emerged.

Another review of herbals used in Mexico examined therapies preferred by 573 patients with type 2 diabetes in 9 clinics in Mexico City.^[4] The results found that 62% of this population reported using a CAM therapy; these patients were more likely than nonusers of CAM to be younger and female. Among this group, two thirds did not disclose their use of CAM to their physicians, and in 69% of patients, the decision originated in the family environment. Ninety-four percent of patients who used CAM therapies used herbals; nopal was used most often (73%).

Prickly pear cactus or nopal. Nopal includes plants of the genus Opuntia, including Opuntia ficus-indica (the most common culinary species), Opuntia fuliginosa (purified extract), Opuntia streptacantha, and other species. Nopal is native to arid areas of North America (including the southwestern United States) and South America. It is traditionally used among Mexicans as a food, for instance in salads. It is also used medicinally as an anti-inflammatory, a laxative, or a hypoglycemic agent for diabetes and to treat gastritis. The exact mode of action is not known, although nopal has high fiber and mucilage content and may have an insulin-sensitizing effect, as demonstrated in a rat model.^[5] An intake of 500 g of prickly pear provides 4.3 g carbohydrate, 8.25 g protein, 1.05 g lipids, 18.85 g cellulose, and 100 kcal of energy.^[6] The broiled stems are traditionally used for their hypoglycemic effect, which is seen 3-4 hours after ingestion and can persist for up to 6 hours. Extracts of nopal seeds increased muscle and liver glycogen and reduced blood glucose levels in the rat diabetes model.^[5] In studies, the hypoglycemic effect of 500 g of broiled nopal stems in diabetic patients peaked 180 minutes after ingestion.^[7,8]

When 85 g of nopal was added to typical Mexican breakfasts, it reduced glucose levels for several hours and favorably altered the glycemic index of 3 different test breakfasts among 36 patients with type 2 diabetes who were receiving glibenclamide, metformin, or both. The breakfasts consisted of chilaquiles (a casserole made with corn tortilla, vegetable oil, and pinto beans), burritos (made with eggs, vegetable oil, and pinto beans), or quesadillas (made with flour tortillas, low-fat Monterey cheese, avocado, and pinto beans).^[9] The researchers of the breakfast trial proposed that nopal be used to supplement dietary approaches to diabetes care in a culturally effective way for Mexicans.

Studies exploring other forms of nopal, such as capsules or juice, did not demonstrate any significant changes in serum glucose.^[6]

The usual single dose of nopal is 500 g of broiled stems. Reported side effects include:

• Mild diarrhea;

• Nausea;

• Abdominal fullness; and

• Headache.

The theoretical concern with use of nopal is interaction with antidiabetic medication, with consequent hypoglycemia. Patients who use nopal regularly should be advised to monitor blood glucose closely.

Gymnema sylvestre.Gymnema, or gurmar, is a woody climbing plant found in central and southern India, tropical Africa, and Australia that it is used in Ayurvedic medicine. The active components are present in the leaves of the plant^[10] and are used as digestive, diuretic, hypoglycemic, hypolipidemic, and weight-loss agents, as well as for diabetes and the metabolic syndrome.^[6,11,12] The main constituent of Gymnema is believed to be gymnemic acid, consisting of different saponins. Other important constituents that contribute to the hypoglycemic effect of the plant include polypeptides (gurmarin) alkaloids (conduritol, gymnamine, gypenoside), and other saponins.^[6] Some of these components are thought to block the ability to taste sweets, which may contribute to decreased sugar intake. Laboratory studies also suggest that Gymnema may decrease the uptake of glucose from the small intestine and improve glycogen synthesis and hepatic and muscle glucose uptake.

A systematic review of randomized controlled trials identified only 2 efficacy studies, both of poor methodological quality.^[12] Significant reductions in blood glucose (P < .001), A1c (P < .001), and glycosylated plasma proteins (P < .001) were observed in 22 patients with type 2 diabetes who were receiving a combination of 400 mg of Gymnema extract and conventional antihyperglycemic agents daily over 18 months.^[13] Similar results were seen for 27 patients with type 1 diabetes given 400 mg of Gymnema extract, who experienced reduced A1c and increased C-peptide levels.^[14] However, overall, evidence is insufficient for its efficacy in diabetes treatment.^[6] The dose used in extract form is generally 200-400 mg twice daily.

Like nopal, Gymnema may interact with oral hypoglycemic agents and increase the risk for hypoglycemia. Therefore, Gymnema should be used with caution in diabetic patients. Gymnema may also cause the loss of ability to taste sweets.

Cinnamon. Cassia cinnamon, or Cinnamomum aromaticum, is a popular spice used in cooking worldwide. Animal and in vitro studies have indicated that cinnamon may mimic the effects of insulin, act as an insulin sensitizer, and improve cellular glucose uptake and glycogen synthesis.^[15,16] Clinical studies are small and have produced contradictory results. For example, improved plasma glucose after a glucose tolerance test was seen in one study of healthy athletes who took a single 5 g dose of cinnamon.^[17] In a another study, however, postmenopausal diabetic women given cinnamon did not experience improvement in their glucose tolerance tests.^[18]

A systematic review conducted in 2008 found 5 prospective randomized trials (n = 282) that examined the effect of cinnamon supplementation on A1c, lipid profile and blood glucose; overall no beneficial effect was found.^[19] In the most recent randomized controlled trial, of 109 patients with type 2 diabetes from 3 primary care clinics whose A1c levels were 7 or higher at baseline, cinnamon capsules at a dose of 1 g daily for 90 days lowered A1c by 0.83% (95% confidence interval [CI], 0.46%-1.20%; P < .001), from 8.47% +/- 1.8% at baseline to 7.64% +/- 1.7% after 2 months; in contrast, usual care only lowered A1c by 0.37%(95% CI, 0.15%-0.59%; P = 0.16), from 8.28% +/- 1.3% at baseline to 7.91% +/-1.5%.^[20] The investigators recommended cinnamon as an adjunct to diabetes care for patients with an A1c level greater than 7.0%.

The dose of cinnamon for type 2 diabetes is typically 1 to 6 g daily; 1 teaspoon contains 4.75 g. This dose is considered to be safe for up to 4 months.^[6]

Of note, cinnamon contains coumarin; ingestion of large amounts is therefore not recommended. Liver toxicity in animal models has also been reported, and reversible hepatotoxicity has been reported in humans at daily doses of 50-7000 mg.^[6] As for the other supplements discussed in this article, hypoglycemia is a potential adverse effect when used with antidiabetic drugs. Because there are no known data on use of cinnamon during pregnancy and lactation, it is not recommended during those periods.

Fenugreek.Trigonella foenum-graecum is an annual herb native to western Asia and southeastern Europe. Fenugreek has several components, including saponins, alkaloids, and high fiber content, which comprise 50% of the seed. Its seed is traditionally used to treat constipation, slow gastric emptying, and delay absorption of glucose from the gastrointestinal tract. Animal studies indicate that fenugreek increases the rate of insulin release.^[21,22]

Few clinical trials on fenugreek are available. In one study, 10 patients with insulin-dependent type 1 diabetes were randomly assigned to 10 days of either 50 g of fenugreek seed powder twice daily or placebo, plus usual therapy.^[23] The fenugreek diet significantly reduced fasting blood glucose and improved glucose tolerance test results. The serum glucose level was reduced by 29%, and serum total, LDL, and very low-density lipoprotein cholesterol and triglyceride levels were also significantly reduced. Adjunct use of fenugreek seeds also improved glycemic control and decreased insulin resistance in another study of 25 patients with newly diagnosed type 2 diabetes mellitus who were randomly assigned to receive either 1 g of hydroalcoholic extract of fenugreek seeds daily or usual care and placebo for 2 months.^[24]

Additional larger and high-quality studies are needed to confirm these findings. The recommended dose of fenugreek for diabetes is 10 to 15 g daily, as a single dose or in divided doses. Side effects include hypoglycemia (especially when used with hypoglycemic agents), diarrhea, dyspepsia, and flatulence at high doses^[6]; there is also a theoretical risk for interaction with warfarin, which entails risk for bleeding. Fenugreek can cause a maple syrup odor in urine (similar to the smell of maple syrup urine disease, an autosomal recessive metabolic disorder generally diagnosed in infants).

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Cite this: Désirée Lie. Nopal (Prickly Pear Cactus), Fenugreek, Cinnamon, and Gymnema for Type 2 Diabetes: What Works? What Doesn't? - Medscape - Jun 30, 2010.