Complementary and Alternative Medicine (CAM) Supplement Use in People with Diabetes: A Clinician's Guide. Laura Shane-McWhorter
30 units for blood glucose >250 mg/dl [>13.9 mmol/l]). A control group consisted of six patients with type 1 diabetes and two patients with type 2 diabetes who did not receive any bitter melon. Fasting glucose was measured; then bitter melon was administered, and glucose was measured at 4, 6, 8, and 12 hours after injection. In patients with type 1 diabetes, mean fasting glucose decreased from 304 mg/dl (16.9 mmol/l) to 169 mg/dl (9.4 mmol/l) 4 hours after injection (P < 0.05). This effect was maintained at 6 and 8 hours after injection (176 mg/dl [9.87 mmol/l] and 172 mg/dl [9.6 mmol/l], respectively, P < 0.05 compared with baseline). In the patients with type 2 diabetes, there was no significant decline in blood glucose from baseline. However, glucose was different from that of the control group at 1 and 6 hours (P < 0.05).89
Summary
The evidence for bitter melon has come from mostly small studies with weak study design. One small trial indicated that bitter melon may decrease A1C after 7 weeks of use,90 but there are no long-term trials. Although some patients may benefit from using bitter melon, it may cause low blood glucose when combined with traditional diabetes medications. It should be used with caution by young women of childbearing age, since it may induce menstruation and inadvertently cause miscarriage. There is no information regarding use in lactating women, so it should be avoided in this population. Children should not use bitter melon, since serious adverse effects have occurred, including hypoglycemic coma. Individuals of Mediterranean or Middle-Eastern descent with known G6PDH deficiency or those who have allergies to the melon family should also avoid use. There is no traditional dose, since different forms have been used, including juice, powder, vegetable pulp suspensions, and injectable forms. One source indicated that the dose would be 1 small unripe melon eaten daily or 50–100 ml fresh juice drunk daily with food.85 However, tinctures and oral supplements are emerging as available sources. Overall bitter melon may be considered safe when eaten as a vegetable, but it is not consistently safe when used in supplement form.
ASIAN GINSENG (Panax ginseng C.A. Meyer) AND AMERICAN GINSENG (Panax quinquefolius L.)
Ginseng is a botanical product that has been used for medicinal purposes for centuries. Two different forms have been used for diabetes, Asian ginseng (Panax ginseng C.A. Meyer) and American ginseng (P. quinquefolius L.).91,92 The part used is the root.91
Both ginseng species are used as an “adaptogen” to deal with stress and to increase energy. Both species are also used in cosmetics and as flavoring ingredients. Although both Asian and American ginsengs have been used as sports performance enhancers, or “ergogenic aids” to help improve physical and athletic stamina, studies do not support this use. Asian ginseng has been used to enhance thinking and memory, to prevent cold or flu, and to prevent cancer. In a double-blind crossover trial, Korean red ginseng improved erectile dysfunction, a malady often found in men with diabetes.93
Chemical Constituents and Mechanism of Action
Ginseng contains many different chemical ingredients, but the most active ingredients are a family of steroidal saponins called ginsenosides. Some ginsenosides have opposing effects. For example, ginsenoside Rg1 has hypertensive and central nervous system–stimulant effects, while ginsenoside Rb1 has hypotensive and central nervous system–depressant effects.75,94 Some ginsenosides inhibit platelets and have analgesic and anti-inflammatory effects. Both Asian and American ginseng may boost the immune system.91,92 Although it is unknown how ginseng may benefit diabetes, animal research has shown that it may decrease the rate of carbohydrate absorption into the portal circulation,95 increase glucose transport and uptake,96 and modulate insulin secretion.97 American ginseng may help decrease postprandial glucose levels.92,98
Adverse Effects and Drug Interactions
Major side effects of ginseng include insomnia and restlessness. Worrisome side effects include increased blood pressure or heart rate. Headache is common, and ginseng may also cause mastalgia, mood changes, and nervousness. Ginseng is unsafe in infants and children, and may not be safe in pregnancy.91
Ginseng has been shown to decrease the effectiveness of the blood thinner warfarin (Coumadin),18 and protection against thromboembolic events is lost. Ginseng decreases the effects of diuretics and hypertension medications.19 In combination with certain antidepressants, ginseng has resulted in mania.19 With estrogens, ginseng may produce additive estrogenic effects.19 Ginseng may inhibit cytochrome P450 (CYP450) 2D6 isoenzymes involved in metabolism of drugs and result in increased effects of drugs such as certain analgesics and some antidepressants.19 When combined with insulin, sulfonylureas, or other secretagogues, ginseng may cause hypoglycemia.91
Clinical Studies
Ginseng has been frequently studied for physical performance or cognitive function as well as immune system effects, but there are few trials where it has been evaluated for diabetes. In one randomized, double-blind study of Asian ginseng in 36 newly diagnosed patients with type 2 diabetes, 12 people each were assigned to placebo, 100 mg/day, or 200 mg/day. Although baseline values were not reported, at the end of the 8-week study, fasting glucose for the three groups was 149 mg/dl (8.3 mmol/l), 139 mg/dl (7.7 mmol/l), and 133 mg/dl (7.4 mmol/l), respectively. (Results were significant only for the 100 mg/day group, P < 0.05.) Baseline values were not reported, and the average A1C levels at the end of the study were 6.5, 6.5, and 6%, respectively, for the three groups (P < 0.05 for the 200-mg group only).99 The accuracy of the diagnosis of diabetes or problems with study design may have been an issue.
American ginseng has been studied in people with and without type 2 diabetes. In a small study, subjects with and without diabetes were given a 25-g OGTT, with 3 g ginseng or placebo.92 Ginseng was given right before or 40 minutes before the OGTT. In subjects without diabetes, there was no difference in postprandial glucose when ginseng was taken right before the OGTT, but when it was taken 40 minutes before, there was a significant decrease in postprandial glucose (P < 0.05 vs. placebo). In the participants with diabetes, postprandial glucose decreased whether ginseng was given right before or 40 minutes before the OGTT. The same group of researchers tried the same and higher doses of American ginseng: 3, 6, or 9 g ginseng versus placebo. Glucose decreased in all groups, and there was no difference in effect between the 3-, 6-, and 9-g doses of ginseng.98
Summary
Ginseng is available in a variety of forms ranging from cosmetic ingredients to fresh or dried roots to solutions, sodas, and teas.19 Patients should be aware that there are different types of ginseng but two main types used for diabetes (Asian and American) and that the dose may vary. Both ginseng types have only been studied in type 2 diabetes. There may be inconsistencies in the manufacturing process. One study found that the amount of ginseng stated on the label did not reflect what was contained in the bottle; the ginseng content varied from less (12%) to more (137%) than was indicated on the bottle.100 Different products have been found to contain other substances, including mandrake root or phenylbutazone, and in one case, an athlete tested positive in a doping test.101 Ginseng may be safe if taken for 3 months or less. The most common side effect is insomnia, although some people may experience anxiety, headache, and increased blood pressure. It should not be used in children or in pregnant or lactating women. There are many potential drug interactions, so this is a product