Summary
Research is currently underway to evaluate the effects of cinnamon in type 2 diabetes. The active ingredient is thought to be hydroxychalcone, which may enhance insulin sensitivity. Cinnamon decreases fasting glucose,65,66 and in one study total cholesterol, triglycerides, and LDL were also decreased.65 A more recent study showed that in subjects with lower fasting glucose there was a significant decline, but there were no changes in A1C or lipids.66 Differences in the two studies that are available seem to indicate that cinnamon may be more effective in individuals who have higher glucose values. Side effects are benign, and there are no known interactions, although doses of secretagogues may have to be adjusted to prevent hypoglycemia. Doses used in one study of subjects with high baseline glucose included 1, 3, or 6 g/day in divided doses.65 Another study used 1 g three times a day of an aqueous cinnamon extract.66 The amount used in studies is equivalent to about a half teaspoonful of ground cinnamon per day, which may be used in cereals, in beverages, on breads, and in other foods.
GYMNEMA (Gymnema sylvestre R. Br.)
Gymnema is a unique botanical product that has been used for centuries in Ayurvedic medicine. It is also known as gurmar, the “sugar destroyer,” because it dulls the ability to taste “sweetness.”67 In India, gymnema has been traditionally used to treat madhu meha, “honey urine,” or diabetes.68 This woody climbing plant grows in tropical forests in central and southern India. The leaves are the part used for medicinal purposes.69 Gymnema has been used in both type 1 and type 2 diabetes.
Chemical Constituents and Mechanism of Action
The constituents include a variety of chemicals, including saponins, stigmasterol, quercitol, the gymnemosides, and the amino acid derivatives betaine, choline, and trimethylamine.70 Although the exact mechanism of action is unknown, varying effects from animal and in vitro cell research have shed light on how it may work. Gymnema appears to increase enzyme activity responsible for glucose uptake and use.71 Gymnema may also stimulate pancreatic β-cell function, increase numbers of pancreatic β-cells, and possibly increase insulin release by increasing cell permeability to insulin.68,69,72 For Gymnema to produce its pharmacological effects, some residual pancreatic function may be required, since in pancreatectomized animals it does not produce a hypoglycemic effect.73 Work is continuing to elucidate more specific information on its pharmacological activity.
Adverse Effects and Drug Interactions
No adverse effects have been reported for gymnema, although in theory it may cause hypoglycemia. Gymnema may enhance the blood glucose lowering effects of certain drugs used to treat diabetes. These drugs include insulin, sulfonylureas, or the nonsulfonylurea secretagogues.
Clinical Studies
Gymnema has been researched since the 1930s.68 In a study of 27 patients with type 1 diabetes, gymnema was administered at a dose of 200 mg twice a day for 6–30 months.69 The researchers tracked A1C, fasting blood glucose, and insulin dose. Average A1C declined from 12.8% at baseline to 9.5% after 6–8 months (P < 0.001), and after 16–18 months 22 individuals continuing to take gymnema had a mean A1C of 9% (P values not stated). At the end of 26–30 months, six patients remaining on gymnema had a further decline to 8.2% (P values not stated). Average fasting glucose declined from 232 mg/dl (12.9 mmol/l) at baseline to 177 mg/dl (9.8 mmol/l) after 6–8 months, 150 mg/dl (8.2 mmol/l) after 16–18 months, and 152 mg/dl (8.4 mmol/l) after 20–24 months (P values not stated). Average insulin dose decreased from 60 units/day to 45 units/day after 6–8 months and declined further to 30 units/day after 26–30 months (P values not stated). A control group of 37 patients who took only insulin was also followed for 10–12 months, and these individuals had no change in blood glucose or A1C.
In a different study, 22 patients with type 2 diabetes took gymnema at a dose of 400 mg daily for 18–20 months in addition to a sufonylurea.74 A1C declined from an average baseline of 11.9% to 8.5% (P < 0.001), and average fasting glucose decreased from 174 mg/dl (9.7 mmol/l) at baseline to 124 mg/dl (6.9 mmol/l) after 18–20 months (P < 0.001). Notably, five individuals were able to discontinue sulfonylurea treatment. Lipids also significantly declined in this study. A control group of 25 patients on sulfonylureas plus placebo had no significant changes in A1C, fasting glucose, or lipids.
Summary
Gymnema has been studied for up to 2 years in both type 1 and type 2 diabetes. Target goals for A1C and fasting glucose have not been achieved in published studies. Gymnema has a variety of actions that may stimulate glucose uptake and utilization as well as stimulate β-cell function. If gymnema is used, a standardized extract should be chosen. This product has not been studied in pregnant or lactating women, children, or elderly and therefore should not be used in these populations. The main potential adverse effect is hypoglycemia; hence it is important that medical providers supervise their patients’ use of this product and possibly consider decreasing the dose of concomitant secretagogues. A standardized gymnema extract is being studied in the U.S. A typical dose is 400 mg/day, standardized to contain 24% gymnemic acids.19
FENUGREEK (Trigonella foenum-graecum L.)
Fenugreek is a member of the Leguminosae, or Fabaceae, family and grows well in India, Egypt, and other parts of the Middle East.75 The leaves are ingested as a vegetable in India.76 The part used medicinally is the seed.
Not only has fenugreek been used to treat diabetes, but since it tastes and smells like maple syrup, it has also been used as a cooking spice and flavoring agent in foods and tobacco. It has been used to mask the taste of medicines.75 Other uses include treatment of constipation and hyperlipidemia, and postpregnancy use to promote lactation.75 There are no studies supporting its use in lactation.
Chemical Constituents and Mechanism of Action
Fenugreek contains many different chemical components, including saponins and several glycosides.75 The seeds contain alkaloids, including trigonelline, gentianine, and carpaine compounds. Fiber, 4-hydroxyisoleucine, and fenugreekine, components that may have hypoglycemic activity, are also found in the seeds. The mechanism is thought to involve delay of gastric emptying, slowing carbohydrate absorption, and inhibition of glucose transport.77 Fenugreek may also increase the number of insulin receptors in red blood cells and improve glucose utilization in peripheral tissues; thus demonstrating potential antidiabetic effects in both the pancreas and other sites.78 A constituent of the seeds, 4-hydroxyisoleucine, may directly stimulate insulin secretion.79
Adverse Effects and Drug Interactions
The main side effects include