Antidiabetic Effects of Ginseng Extract

Park SH, Oh MR, Choi EK, et al. An 8-week, randomized, double-blind, placebo-controlled clinical trial for the antidiabetic effects of hydrolyzed ginseng extract. J Ginseng Res. Epub 26 May 2014.

 

Randomized, double-blind, placebo-controlled clinical trial for patients with impaired fasting glucose

 

Adults with impaired fasting glucose measurements between 5.6 and 6.9 mmol/L (101-124 mg/dL) and without a diagnosis of another disease were selected to be included in the trial. One hundred patients were screened for inclusion, and 77 were excluded. Exclusion criteria included other abnormal laboratory tests; cardiovascular, gastrointestinal, or renal disease; a history of antipsychotic medication use; corticosteroid or lipid-lowering medication use; alcohol or substance abuse; acute or chronic inflammation; allergy or hypersensitivity to any of the ingredients in the test products; pregnancy or breastfeeding. Twenty-three remaining participants were randomized to either a hydrolyzed ginseng extract or placebo. Three participants dropped out for personal reasons, leaving 20 people to finish the trial. 

 

Hydrolyzed ginseng extract (HGE; Ilhwa Co Ltd, Guri, South Korea) was used. The ginseng was hydrolyzed by pectinase and contained 7.54 mg/g of the ginsenoside Rg1; 1.87 mg/g of Re; 5.42 mg/g of Rb1; 0.29 mg/g of Rc; 0.36 mg/g of Rb2; and 0.70 mg/g of Rd. The compound K (another ginsenoside metabolite) content in the HGE was 6.3 mg/g. Both the placebo and the ginseng supplement contained pumpkin seed oil, refined palm oil, and a yellow wax. It was administered as a capsule (480 mg/cap 2x/d). 

 

Assessment parameters included fasting plasma glucose (FPG), postprandial glucose (PPG; also known as the oral glucose tolerance test [OGTT]), fasting plasma insulin (FPI), and postprandial insulin (PPI). Using the homeostasis model, insulin resistance (homeostatic model assessment [HOMA]-IR) and beta-cell sensitivity (HOMA-β) were also tracked. Measurements for circulating endproducts of glycosylation included glycated albumin, fructosamine, and hemoglobin A1c (HbA1c). Lastly, kinetics of glucose and insulin changes were assessed using incremental area under the curve (iAUC) and maximum concentration (C_max) of each.

 

Assessed in this trial were FPG, plasma glucose during PPG/OGTT, glucose iAUC, and glucose C_max, insulin [fasting plasma insulin (FPI), plasma insulin during OGTT (PPI), insulin iAUC, and insulin C_max], HOMA-IR, HOMA-β, glycated albumin, fructosamine, HbA1c, and safety evaluation tests including such as complete blood count, comprehensive metabolic pane, and electrocardiogram. 

 

After the 8-week intervention of 480 mg twice daily, statistically significant differences were found in FPG (P=0.017) and PPG60min (P=0.01). PPG30min (P=0.059), FPI (P=0.063), and PPI60min (P=0.077) showed a tendency to improve slightly more than placebo group, although the results did not reach statistical significance. 

 

The health impact associated with poor glucose control has grown, especially the incidence of non–insulin dependent diabetes and cardiovascular disease. The World Health Organization has estimated that 347 million people worldwide have diabetes, and by 2030 diabetes will be the 7th leading cause of death.¹ While it is essential to address the many determining factors that are implicated in this insidious illness, researchers are also continuing to seek out different types of medications, including more botanical extracts. 

Panax ginseng is possibly one of the most familiar and researched botanical medicines in the world. It has long been used for qi tonification and respiratory and digestive support in China, and it has increased popularity in North America as an adaptogen. Recent preclinical investigations have supported the use of ginseng in abnormal metabolic parameters such as glucose intolerance, metabolic syndrome, and non–insulin dependent diabetes mellitus (NIDDM). However, human intervention trials are still in the early stages and have mixed results. While this recent study has shown some modest improvement in FPG and PPG, the researchers did not provide detail on randomization or blinding, which means this study cannot be included in a systematic analysis. Neither did they give specific outcomes at 8 weeks regarding fasting lab results. Instead, the study relies on a graphic representation of standard deviation of the iAUC, and while that is becoming standard, it is the opinion of this author that more detail should be included to truly assess the validity of this study. 

 

A 2011 systematic review of red ginseng and NIDDM analyzed 4 randomized clinical trials and revealed that bias was most likely present in at least 3 of the studies.² One type of bias is location bias; many of the smaller studies, such as this one, are from Korea, where the majority of red ginseng is grown and most likely subsidized by the government. Another problem discussed in the 2011 review, also present in our example, is the small number of participants. 

 

A particular factor that may be important when evaluating the literature and considering whether to use ginseng in patients is the type of ginseng product. Korean red ginseng has specific parameters for processing: It must be harvested when the root is 6 years old and steamed or heated properly to increase the saponin content. According to Chen and Chen in their book Chinese Medical Herbology and Pharmacology, red ginseng is warmer when unprocessed and is best used for qi and yang deficiencies. Wild-crafted red ginseng is the most expensive resource, reserved for severe cases of qi deficiency.³

 

In this particular study, the ginseng was hydrolyzed using pectinase. Hydrolyzation alters the composition of the ginsenosides to produce more active metabolites. Ginsenosides have been the subject of a significant amount of preclinical research. In vivo studies with ginsenosides RB2, Rg1, Rh2, and Re showed activation of adenosine monophosphate kinase (AMPK), which has been shown to improve insulin sensitivity, reduce hepatic glucose production, and have an antiobesity effect.^4,5

 

Another way to process ginseng is fermentation using β glucosidase–producing microorganisms⁶ or the gypenoside pathway in the human gut.⁷ The types and amounts of ginsenosides vary by processing technique. For example, the ginsenoside protopanaxadiols Rb1, Rb2, and Rc, are converted via deglycosylation reactions by intestinal bacteria into compound K,^7,8  which has been shown to suppress NF-κB activation⁹ and induce autophagy and apoptosis.¹⁰ (Rb1 is also found in Panax quinquefolius, American ginseng, in significant amounts.¹¹

 

There are other secondary factors that may support a clinician’s use of Panax ginseng. One example is use in those patients who need support to correct a hypothalamic–pituitary-adrenal axis that has been imbalanced by stress. Another may be to lessen inflammation. Yet another reason is to improve energy so that the patient can start or increase an exercise plan. Panax ginseng may be used to tonify a system, and yet it can be used safely for very specific purposes, like the stimulation of the AMPK and NF-κB pathways. 

 

The evidence in this study adds to a large body of research on Panax ginseng. While research continues on the nuances of which ginsenosides are best and at which dosages, clinicians can feel comfortable recommending ginseng as an adaptogen and to improve physical stamina, a use in keeping with its traditional role for millennia.

 

This article was a part of the August 2014 special Natural Medicine Journal issue on endocrinology. To see the rest of the special issue, click here.