American Ginseng Extract Used with Conventional Therapy Enhances Management of Type 2 Diabetes Mellitus

Several herbal supplements are used to help manage type 2 diabetes mellitus (T2DM). Among them is American ginseng (AG, Panax quinquefolius, Araliaceae), which has been evaluated in randomized, controlled trials for its effects on glycemic control. These authors conducted a double-blind, placebo-controlled, randomized, crossover, clinical trial to investigate the effects of AG on glycemic control and diabetes-related risk factors when used as adjunctive therapy to conventional T2DM treatment.

The primary objective was to determine whether an AG extract used as add-on therapy would significantly affect glycated hemoglobin (HbA1c) values compared with the standard treatment. Secondary endpoints were changes in fasting blood glucose, insulin, systolic and diastolic blood pressures, plasma lipids, markers of nitric oxide generation, and plasminogen-activating factor-1 (PAI-1) concentration. Safety parameters included markers of hepatic and renal function.

The study was conducted at the Risk Factor Modification Centre at St. Michael’s Hospital at the University of Toronto, Canada. Eligible patients, recruited through local newspaper notices, were between 45 and 75 years old, had been diagnosed with T2DM for one year or longer, had a body mass index (BMI) of 25-35 kg/m2, and HbA1c between 6.5% and 8.5%. Patients who changed oral antihyperglycemic, blood pressure or lipid-lowering medication during the intervention were dropped from the study. The study included two eight-week treatment periods separated by a washout period of four weeks. The patients attended the clinic at baseline and at weeks four and eight of each treatment period during the 20-week study.

At each visit, the patients provided a three-day diet history and underwent anthropometric, laboratory, and clinical measurements. At the beginning, middle, and end of the study, patients reported adverse effects. Patients were instructed to take two 500 mg capsules of either Canada Corn (Zea mays, Poaceae) Starch as the placebo or AG extract 40 minutes before each meal for eight weeks, for a total of 3 grams daily.

The AG used was from three-year-old ginseng (Ontario Ginseng Growers Association; Simcoe, Ontario, Canada) grown in Ontario, Canada. Dried whole AG root was repeatedly extracted using a ~70% ethanol solution to reach the targeted ginsenoside composition. The extraction liquid was dried, milled into a fine powder, and placed into capsules. The final extract included the following major ginsenosides: Rb1 (5.86%), Rb2 (0.09%), Rc (0.59%), Rd (0.73%), Re (2.15%), and Rg1 (0.25%).

Of the 459 interested patients, 38 were eligible to enroll in the study. Of those, 24 completed the study. Dropout reasons included: a change in oral antihyperglycemic medication (n=5), a change in lipid-lowering medication (n=3), a change in antihypertensive medication (n=2), strong headaches during AG treatment (n=1), diarrhea during placebo treatment (n=1), and scheduling conflicts (n=2). The 13 males and 11 females who completed the study had an average age of 64 ± 7 years; their mean BMI was 27.8 ± 4.6 kg/m2, and their HbA1c was 7.1 ± 1.2%. To control their T2DM, eight patients were being treated with dietary modifications only and 16 were taking oral antihyperglycemic agents.

At the end of the study, HbA1c values were 0.29 ± 0.1% lower with the AG treatment compared with placebo (P=0.041). This level of reduction may seem small; however, the authors say, the clinical relevance in the standards for antihyperglycemic agents required by the Food and Drug Administration is an absolute change in HbA1c by ≥0.3%. Fasting blood glucose was significantly lower (by 0.71 ± 0.34 mmol/L, or 12.78 ± 6.12 mg/dL) with the AG intervention compared with placebo (P=0.008). Serum insulin increased by 33 ± 21% with AG compared with placebo; however, the between-group difference was not significant (P=0.127). Systolic blood pressure was 5.6 ± 2.7 mm Hg lower with AG compared with placebo at the end of the study (P=0.001); no significant difference in diastolic blood pressure was observed (P=0.12). The improvement in systolic blood pressure with the AG treatment is important, say the authors, as approximately 70% of patients with diabetes also have hypertension.

At the end of the study, the following plasma lipid levels were significantly lower with AG treatment compared with placebo: low-density lipoprotein cholesterol (LDL-C, P=0.003), total cholesterol (TC, P=0.002), TC/LDL-C ratio (P=0.016), and LDL-C/high-density lipoprotein cholesterol ratio (P=0.009). The AG treatment improved endothelial function as demonstrated by an increase in serum nitric oxide compared with placebo (P=0.03). PAI-1 was significantly reduced compared with baseline (P=0.007), but not compared with placebo (P=0.057). No differences were seen in hepatic or renal function safety parameters within each treatment or between treatments.

The patients maintained their body weight, and no significant differences were seen in energy and macronutrient intake during the placebo or AG interventions. Compliance rates were 90% with the AG treatment and 91% with the placebo.

“Some caution must be taken when drawing conclusions from the results of the present study and its implications for efficacy and safety,” write the authors, particularly the consideration of possible methodological confounders related to the study’s design and protocol. A longer study period may provide a better estimate of changes in HbA1c levels; however, HbA1c is an exponentially weighted three-month average of mean blood glucose levels for which the first two months contribute a major portion. The small sample size, another limitation of the study, was due to a high dropout rate, as more patients than expected were advised to change medications during the study following findings from a large randomized, controlled trial advocating more stringent diabetes control. The results from this study may not be applicable to other types of ginseng or processing methods because the composition of ginseng varies widely among commercial products and extraction methods.

These results suggest the use of AG as an adjunct to conventional T2DM treatment may be safe and effective in managing the disease and its associated cardiovascular disease risk factors. It is important to encourage T2DM patients to consult with their doctor before taking AG in addition to their standard treatment.

This study was funded by the Ontario Ministry of Agriculture, Food and Rural Affairs, Agriculture and Agri-Food Canada, and by Chai-Na-Ta Corp. of Langley, British Columbia, Canada (which also provided the study materials). The authors declare several conflicts of interest.


Vuksan V, Xu ZZ, Jovanovski E, et al. Efficacy and safety of American ginseng (Panax quinquefolius L.) extract on glycemic control and cardiovascular risk factors in individuals with type 2 diabetes: a double-blind, randomized, cross-over clinical trial. [published online February 24, 2018]. Eur J Nutr.  doi: 10.1007/s00394-018-1642-0.