Reviewed: Mucalo I, Jovanovski E, Vuksan V, Božikov V, Romić Ž, Rahelić D. American ginseng extract (Panax quinquefolius L.) is safe in long-term use in type 2 diabetic patients [published online May 7, 2014]. Evid Based Complement Alternat Med. doi: 10.1155/2014/969168.

For patients with type 2 diabetes mellitus (T2DM), managing the condition is complicated by a growing number of hypoglycemic pharmaceutical agents used in various combinations and by concerns about the agents’ potential interactions and associated adverse effects. Common among patients with T2DM is an interest in so-called complementary and alternative medicine, particularly the use of American ginseng (AG; Panax quinquefolius, Araliaceae), which reportedly is well tolerated by most users. Because of a lack of randomized clinical studies on the long-term use of ginseng in patients with T2DM, the authors conducted a double-blind, randomized, placebo-controlled, parallel study to determine the safety of 12 weeks of supplementation with AG when used as adjunctive therapy in patients with T2DM.

Seventy-four patients (mean age: 63 ± 9.5 years) with T2DM recruited from a diabetes outpatient clinic completed the study. From the original group of patients screened, five participants dropped out because of changes in medication therapy, and two were unwilling to continue the study. Included participants had well-controlled T2DM for more than six months without complications, metabolic stability (average glycated hemoglobin A1c [HbA1c] between 6.5% and 8.1%), and were on diet modifications and/or conventional diabetes medications. Nine of the patients used diet only to treat T2DM; others used diet plus oral agents such as metformin (n=48), sulfonylurea (n=43), dipeptidyl peptidase-4 inhibitors (n=11), glucagon-like peptide-1 agonists (n=1), acarbose (n=4), and metformin with pioglitazone (n=1).

The patients were randomly assigned to receive either two 500 mg capsules of AG root extract (containing 10% ginsenosides) before meals three times daily (n=35) — a daily dosage recommended in traditional Chinese medicine¹ — or two 500 mg identical-appearing placebo capsules containing corn (Zea mays, Poaceae) starch (n=39). AG root was supplied by Ontario Ginseng Growers (Simcoe, Ontario, Canada) and extracted with ethanol. Treatment or placebo was taken along with any antihypertensive or hypoglycemic medications used by the patients. At baseline, body mass index and fasting plasma glucose levels were significantly higher in the AG group compared with the placebo group; all other demographic and clinical parameters were similar.

The patients visited the clinic at baseline and at weeks six and 12 to have biochemical and anthropometric measurements taken. During these visits, participants also completed the International Quality of Life Assessment SF-36v2 questionnaire, received a new supply of capsules, returned unused capsules, and were interviewed by a dietitian. Patients were instructed to maintain body weight, follow their usual dietary and physical activity habits throughout the study, and refrain from all medications, including AG or placebo, for 12 hours before each study visit.

Safety was assessed by measuring markers of hepatic (aspartate aminotransferase and alanine aminotransferase), renal (serum urates and serum creatinine), and hemostatic (prothrombin time and international normalized ratio) functions.

The authors report that AG had no significant dependent or independent effects on any of the safety parameters. All hepatic, renal, and hemostatic function values were within normal limits. Regarding adverse events, stomach heaviness was reported in one patient in the AG group during the first six weeks, but the patient continued the treatment.

Safety concerns surrounding the use of ginseng followed a now widely discredited, uncontrolled, observational study by Siegel2 in 1979, in which 12 weeks of ginseng supplementation was associated with elevated blood pressure and several other adverse effects (e.g., gastrointestinal disturbances, insomnia, and nervousness).* The ginseng dose assigned in the Siegel trial was much higher than the usually recommended dose, and “the validity of these side effects is questionable due to a lack of a control group in the study and the fact that subjects were not controlled for dose, duration, route of administration, type of ginseng, or other concurrent bioactive substances intake,” write the authors of the study reported here, who previously found that three grams of AG taken daily for 12 weeks compared with placebo was associated with decreased blood pressure in persons with hypertension and T2DM³.

The authors point out that the results of this current study may not be generalizable to other AG ingredients, including the unprocessed root or other ginseng extracts, but they conclude that the AG treatment in this study demonstrated “rather convincing long-term clinical safety when administered as an adjunct to conventional antihypertensive and antidiabetic therapy.”

—Shari Henson

*The adverse effects mentioned in the Siegel study were reported in 10% of a group of persons claiming to use products containing “ginseng” in which such products were consumed at relatively high levels with concomitant high levels of coffee.⁴ Notably, there was no control or analysis of the “ginseng” products’ contents in the study.

References

1. Dharmananda S. The nature of ginseng: traditional use, modern research, and the question of dosage. HerbalGram. 2002;(54):34-51.
2. Siegel RK. Ginseng abuse syndrome: problems with the panacea. JAMA. 1979;241(15):1614-1615.
3. Mucalo I, Jovanovski E, Rahelić D, Božikov V, Romić Ž, Vuksan V. Effect of American ginseng (Panax quinquefolius L.) on arterial stiffness in subjects with type-2 diabetes and concomitant hypertension. J Ethnopharmacol. 2013;150(1):148-153.
4. Blumenthal M. Debunking the “Ginseng Abuse Syndrome.” Whole Foods. 1991;89-91.