Complementary and Alternative Medicine (CAM) Supplement Use in People with Diabetes: A Clinician's Guide. Laura Shane-McWhorter
and gas, or flatulence, which subside after a few days of use. A caution for women of childbearing age is that fenugreek consumption may cause uterine contractions and thus cause problems with pregnancy.75 Hypersensitivity reactions have occurred, including rhinorrhea, wheezing, and fainting after inhalation of the seed powder. Wheezing and facial angioedema were reported in a patient with chronic asthma after application of a topical fenugreekpaste.76
A theoretical adverse effect is an allergic reaction in people with a peanut allergy, since peanuts are also members of the Leguminosae family.76 However, this reaction has never been reported. All of these side effects may occur in the infants of nursing mothers who use fenugreek, since the fenugreek may be secreted in the milk.
Fenugreek contains some coumarin constituents, and thus may increase the effects of anticoagulant, or blood-thinning, drugs such as warfarin (Coumadin) or herbs with blood-thinning activity (such as ginkgo biloba, garlic, or ginger). A case report of an interaction between warfarin and a product containing the digestive agent boldo in combination with fenugreek resulted in an increase in international normalized ratio (INR).80 Fenugreek may also enhance the activity of diabetes medications; thus, when used in combination with insulin or oral diabetes agents, the patient may experience hypoglycemia.
Clinical Studies
There are only a few published studies using fenugreek. Most of these are short-term, involve very few patients, and do not adequately report details. In one study, 10 patients on insulin (with type 1 diabetes) were included in a 10-day evaluation.81 The patients were assigned to either placebo or twice-daily 50 g fenugreek defatted seed powder, used in unleavened bread. Fasting glucose decreased from an average of 272 mg/dl (15.1 mmol/l) at baseline to 196 mg/dl (10.9 mmol/l; P < 0.01). Total cholesterol decreased (P < 0.001), as did LDL and triglycerides (P < 0.01 for both).
A larger study involved a 6-month trial of fenugreek in 60 patients with inadequately controlled type 2 diabetes.82 Fenugreek seed powder, 25 g daily, was given in two equal doses at lunch and dinner. The average fasting glucose decreased from 151 mg/dl (8.4 mmol/l) to 112 mg/dl (6.2 mmol/l) after 6 months. Glucose values 1 and 2 hours after meals also declined. Mean baseline 1-hour glucose measured by oral glucose tolerance test (OGTT) was 245 mg/dl (13.6 mmol/l) at the start of the study and decreased to 196 mg/dl (10.9 mmol/l) after 6 months (P < 0.001). Mean 2-hour glucose decreased from 257 mg/dl (14.3 mmol/l) to 171 mg/dl (9.5 mmol/l; P < 0.001). Average A1C decreased from 9.6% to 8.4% after 8 weeks (P < 0.001).
In a different study, 25 newly diagnosed type 2 diabetes patients were given a hydroalcoholic fenugreek extract or placebo plus usual care of diet and exercise for 2 months.83 The group assigned to fenugreek was given 1 g/day of the seed extract. The fenugreek group did not differ from the placebo group in fasting or postprandial glucose, although they had improved area under the curve blood glucose and insulin levels (P < 0.001) and an improved lipid profile for triglycerides and HDL.
Summary
In the U.S., fenugreek has GRAS (generally recognized as safe) status84 and has been used in both type 1 and type 2 diabetes. However, there are few studies confirming its efficacy. It may have beneficial effects in pancreatic and other tissues and may affect glucose and carbohydrate absorption, as well as affect insulin resistance. Side effects are mostly uncomfortable gastrointestinal effects that may resolve in a few days. Pregnant women should not take fenugreek, since they may experience uterine contractions.75 Women who use fenugreek as a galactogogue should be aware that it may appear in breast milk, and their infant may experience the side effects of this botanical. Caution is warranted in those who have a peanut allergy or are allergic to chickpeas, soybeans, or green peas. Individuals who take antiplatelet agents, anti-inflammatory drugs, or herbs that have blood-thinning effects should not use fenugreek. Although the dose used is variable, a typical amount is 10–15 g/day, as a single dose or divided with meals, or 1 g of a hydroalcoholic extract.19 If fenugreek is combined with insulin or other diabetes medications, the patient may experience hypoglycemia; thus doses of diabetes medications may have to be adjusted.
BITTER MELON (Momordica charantia)
Bitter melon is a plant product also known as bitter gourd, bitter cucumber, and karela. It is a member of the Cucurbitaceae family and is related to honeydew and Persian melon, cantaloupe, muskmelon, and casaba. Although used for diabetes, bitter melon is cultivated in various parts of the world, including India, Asia, Africa, and South America, for consumption as a vegetable. Bitter melon grows as a vine with green leaves and yellow flowers. The fruit is green with a bumpy exterior, resembling a cucumber, and the interior is yellow-orange. The fruit and seeds are thought to be useful for diabetes.75,85
Bitter melon has also been used for psoriasis, gastrointestinal disorders, kidney stones, and fever, and as a topical agent for wounds and abscesses. Women have used bitter melon to help induce menstruation and as an abortifacient. Recently it has also been used to treat cancer and HIV.75,85,86
Chemical Constituents and Mechanism of Action
Bitter melon contains several chemical ingredients, including the glycosides momordin and charantin. Polypeptide P, charantin, and vicine are the specific components thought to produce hypoglycemic effects.75,85 Other possible mechanisms in diabetes include increased tissue glucose uptake, increased liver/muscle glycogen synthesis, inhibition of enzymes involved in glucose production (glucose-6-phosphatase, fructose-1, and 6-bisphosphatase), and enhanced glucose oxidation (by the glucose-6-phosphate dehydrogenase, or G6PDH, pathway).75,85
Adverse Effects and Drug Interactions
The major side effect of bitter melon is gastrointestinal discomfort. However, some very serious, isolated events have occurred, including hypoglycemic coma from a tea containing bitter melon. Another syndrome called favism, or hemolytic anemia, has occurred; it is characterized by headache, fever, abdominal pain, and coma. Individuals of Mediterranean or Middle-Eastern ancestry, who may have a G6PDH deficiency, may be prone to the hemolytic anemia. The red arils around the seeds have been reported to cause vomiting, diarrhea, and death in one child. Certain ingredients, α-momorcharin and β-momorcharin, are known abortifacients.75,85,86
When bitter melon is combined with sulfonylureas such as chlorpropamide (Diabinese), hypoglycemia may occur, and this has been reported.87
Clinical Studies
Few studies have evaluated bitter melon in diabetes, and most do not have adequate study design. The largest study used an aqueous suspension of bitter melon vegetable pulp in 100 patients with type 2 diabetes. The authors did not state the amount of bitter melon used, but stated it was based on body weight. On the first day, mean fasting blood glucose was 152 mg/dl (8.4 mmol/l); and after a 75-g OGTT, mean 2-hour postprandial glucose was 257 mg/dl (14.3 mmol/l). On day 2, mean fasting glucose was 160 mg/dl (8.9 mmol/l); then bitter melon extract was given, and mean blood glucose 1 hour later was 131 mg/dl (7.3 mmol/l; P < 0.001 vs. fasting value). A 75-g OGTT was then given, and mean 2-hour blood glucose was 222 mg/dl (12.3 mmol/l) (lower than the previous day’s 2-hour value of 257 mg/dl [14.3 mmol/l], but not significant).88
In another study, bitter melon was prepared as an injectable “plant insulin” and injected in five patients with type 1 diabetes and six patients with type 2 diabetes. The dose used was based on blood glucose levels (10 units for blood glucose <180 mg/dl [<10.0 mmol/l], 20 units for blood glucose 180–250 mg/dl [10.0–13.9