Reviewed: Vuksan V, Sung M, Sievenpiper J, et al. Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety. Nutr Metab Cardiovasc Dis. July 21, 2006 [E-pub ahead of print].

Diabetes is a growing epidemic around the world. Drug treatment is not completely successful in people with type 2 diabetes, and there is a compelling need for better prevention and treatment strategies. A survey of physicians revealed that about 75% of patients use some form of complementary and alternative medicine (CAM), even though physician knowledge, regulatory standards, and evidence of safety and benefit are often lacking.¹ Rigorous clinical testing is required to provide evidence of the safety and effectiveness of CAM therapies in people with diabetes and other chronic diseases.

The purpose of this study was to test the long-term safety and efficacy of a Korean red ginseng (Panax ginseng, Araliaceae) preparation selected from an acute clinical screening program in people with type 2 diabetes. (Korean red ginseng [KRG] is made from Korean white ginseng through a traditional steaming process which turns the fresh, steamed roots a dark reddish, auburn color and changes the chemistry of the roots. Korean ginseng is a synonym for Asian ginseng, denoting the geographical origin of the root.) This Canadian research group has previously published clinical trials demonstrating that American ginseng (P. quinquefolius) root can improve long-term glycemic control in patients with type 2 diabetes.^2,3

This study represents an “East-West” collaboration between Canadian and South Korean researchers that was supported by the Ministry of Agriculture, South Korea. There were two phases. The first phase, which was published previously,⁴ consisted of sequential acute preparation- and dose-finding studies with Korean red ginseng. This screening program identified the Korean red ginseng preparation, dose, and mode of administration with the greatest efficacy to be used for long-term testing. The second phase consisted of the present study, in which this information was applied using a longer term, randomized, double-blind, placebo-controlled, crossover design in people with type 2 diabetes.

The study was conducted at St. Michael’s Hospital and University of Toronto in Canada. Men and women aged 18 to 65 years were eligible for the study if they were diagnosed with type 2 diabetes more than 6 months prior to the study, had relatively stable blood sugar levels, and were not taking insulin, herbs, or dietary supplements.

Study treatments were determined based upon the previous acute clinical screening program. Powder made from ground, dried Korean red ginseng rootlets at a dose of 2 g in four 500 mg capsules administered as a preprandial agent taken 40 minutes before each meal was selected as the active treatment. Identical vanilla-flavored capsules containing cornstarch administered at the same dose and by the same mode of administration were selected for placebo. In addition, subjects were instructed to adhere to their underlying conventional diabetes treatment, which included a diet based on the Canadian Diabetes Association’s recommendations and/or oral hypoglycemic medications. The design of the study consisted of 4 parts. In the first part, all subjects took placebo capsules for 4 weeks to get accustomed to the regimen. In the second part, subjects were randomly assigned to take either placebo or the selected Korean red ginseng for 12 weeks. In the third part, all subjects took placebo during a 4-6 week washout period. In the fourth part, subjects who received placebo in the second part were crossed over to ginseng and subjects who received ginseng were crossed over to placebo for 12 weeks. Subjects took 4 capsules containing either cornstarch (placebo) or Korean red ginseng (Korea Ginseng Manufacturing Plant, National Agricultural Cooperative Federation, Chung-buk, Korea) 40 minutes before a meal 3 times a day, for a daily total of 6 g of ginseng. The subjects completed a baseline visit and returned for study visits every 6 weeks. At each visit, investigators examined the subjects and collected blood and urine samples. Subjects turned in 7-day dietary records and unused capsules to evaluate compliance, rated their symptoms, and reported any side effects. At the beginning and end of the two 12-week treatment periods, 2-hour oral glucose tolerance tests (OGTT) and 24-hour blood pressure monitoring were conducted. Thirty-nine subjects were enrolled in the study, but only 19 subjects completed the trial. Conventional diabetes treatment in these subjects included diet alone (n=5) or diet plus sulfonylurea (n=3), diet plus metformin (n=3), diet plus acarbose (n=1), diet plus sulfonylurea plus metformin (n=5), diet plus sulfonylurea plus rosiglitazone (n=1), or diet plus sulfonylurea plus metformin plusrosiglitazone (n=1). The main measure of clinical efficacy, HbA1c, did not change during the ginseng treatment or the placebo treatment. HbA1c is a measure of longer term glucose control, and all subjects remained well controlled during the study with a mean HbA1c of 6.5%. Fasting plasma insulin values decreased significantly by 34 nd fasting insulin sensitivity indices increased significantly by 33% when subjects took ginseng compared to placebo (P < 0.05). There was no significant difference in fasting plasma glucose between ginseng and placebo treatment. Six of the 7 OGTT glucose and insulin evaluations improved significantly during ginseng treatment compared with placebo treatment (P < 0.04). These improvements were reflected in a 33% increase in whole body insulin sensitivity assessed by an OGTT derived insulin sensitivity index during ginseng treatment compared with placebo treatment (P < 0.03). Blood pressure readings and measures of liver and kidney function did not change during eithertreatment. One adverse event was reported during ginseng treatment (hypoglycemia), and 2 adverse events were reported during placebo treatment (rapid heart beat and the combined symptoms of hypoglycemia, headache, blurry vision, irritability, and insomnia). Compliance with the study regimen was similar between the placebo and ginseng groups, based on the proportion of pills taken, analysis of dietary records, and changes in body weight. Differences in these efficacy, safety, and compliance outcomes were interpreted as being beyond those seen on their underlying conventional diabetes treatment (diet and/or medications).

This study is one of the first well-controlled, randomized clinical studies to examine the safety and effectiveness of Korean red ginseng in people with type 2 diabetes. The authors explain that clinical efficacy (as assessed by HbA1c) was not demonstrated for the selected Korean red ginseng in this study. However, supplementation with the selected Korean red ginseng improved the regulation of plasma glucose and insulin beyond that achieved on their conventional treatment (diet and/or medications) in people with well-controlled type 2 diabetes. The study demonstrated the safety of the selected Korean red ginseng in this population, despite previous warnings about the potential for blood pressure elevation and impaired blood clotting function with ginseng supplementation.

Mechanisms by which the selected KRG treatment improved glycemic control were unclear. The authors propose an insulin-sparing mechanism coupled with increased glucose transport. This was seen in the increases in the fasting and OGTT-derived indices of insulin sensitivity. A growing database of animal and in vitro studies was also cited by the authors to support this mechanism. They stressed, however, that this mechanism needs to be tested directly by more rigorous techniques.

The authors provide a balanced discussion of the limitations of the study. This included the high number of dropouts. The more than 50 ttrition rate in the study was greater than the 35-40xpected. Exclusions resulted largely from protocol violations related to changes in patients’ antidiabetic medications. The changes were necessitated by the ethical prohibition of maintaining the study protocol in participants who developed uncontrolled glycemia. Other limitations discussed included the possibility that the results might not be generalizable to patients whose diabetes is not well controlled and the possibility that other sources or formulations of KRG may not yield the same results. Additional studies with larger groups of subjects, including those with poorer diabetes control, are needed to further evaluate the clinical effectiveness and safety of Asian ginseng in type 2 diabetes.

—Heather S. Oliff, PhD, and Mark Blumenthal

References

1. Wolsko PM, Eisenberg DM, Davis RB, Ettner SL, Phillips RS. Insurance coverage, medical conditions, and visits to alternative medicine providers: results of a national survey. Arch Intern Med. 2002;162(3):281-287.
2. Vuksan V, Xu Z, Jenkins AL, et al. American Ginseng improves long-term glycemic control in Type 2 diabetes: double-blind placebo controlled crossover trial. American Diabetes Association Annual Meeting. Diabetes. 2000;49(Suppl 1):A95.
3. Vuksan V, Sievenpiper JL, Xu Z, et al. Konjac-mannan and American ginseng: Emerging alternative therapies for type 2 diabetes. J Am Coll Nutr. 2001;20:370S-380S.
4. Sievenpiper JL, Sung MK, Di Buono M, et al. Korean red ginseng rootlets decrease acute postprandial glycemia: results from sequential preparation-and dose-finding studies. J Am Coll Nutr. 2006;25(2):100 107.