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Journal of the American College of Nutrition, Vol. 25, No. 2, 100-107 (2006)
Published by the American College of Nutrition

Korean Red Ginseng Rootlets Decrease Acute Postprandial Glycemia: Results from Sequential Preparation- and Dose-Finding Studies

John L. Sievenpiper, PhD, Mi-Kyung Sung, PhD, Marco Di Buono, PhD, Kwang Seung-Lee, PhD, Ki Yeul Nam, PhD, John T. Arnason, PhD, Lawrence A. Leiter, MD and Vladimir Vuksan, PhD

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto (J.L.S., L.A.L., V.V.)
Risk Factor Modification Centre, St. Michael’s Hospital (J.L.S., M.D., L.A.L., V.V.), Toronto
Department of Biology, Faculty of Science, University of Ottawa, Ottawa (J.T.A.), CANADA
Department of Food and Nutrition, Sookmyung Women’s University, Seoul (M.S.)
Korea Ginseng Manufacturing Plant, National Agricultural Cooperative Federation, Chung-buk (K.S.L.)
Korean Ginseng and Tobacco Research Institute, Daejeon (K.Y.N.), KOREA

Address reprint requests to: Vladimir Vuksan, PhD, Clinical Nutrition and Risk Factor Modification Centre, St. Michael’s Hospital, #6 138-61 Queen Street East, Toronto, Ontario, M5C 2T2, CANADA. E-mail: v.vuksan{at}utoronto.ca


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 ACKNOWLEDGMENTS
 REFERENCES
 
Background: Fractionation of a ginseng source to produce differences in the ginsenoside profile might influence its effect on postprandial glycemia. To explore this possibility and identify an efficacious ginseng for a longterm study, we conducted a preparation-finding study of different Korean red ginseng (KRG) root fractions followed by a dose-finding study of the most efficacious fraction.

Methods: A double-blind, randomized, within-subject design was used in both studies. In the preparation-finding study, 7 healthy subjects (sex: 3m:4f, age: 32 ± 4 y, BMI: 24 ± 2 kg/m2) received 6 g placebo and KRG-rootlets, -body, and -H2O extract 40 min before a 50 g-OGTT with finger-prick blood samples at –40-, 0-, 15-, 30-, 45-, 60-, 90-, 120-min. In the dose-finding study, 12 healthy subjects (sex: 9M,3F, age: 29 ± 3 y, BMI: 22.5 ± 1 kg/m2) received 0 g (placebo), 2 g, 4 g, and 6 g of the most efficacious root fraction following the same protocol. Ginsenosides were analyzed using HPLC-UV.

Results: In the preparation-finding study, a wide variation in the ginsenoside profiles was achieved across the 3 KRG fractions. This variation coincided with differential effects. The main effects of KRG-rootlets (p = 0.050) and time (p < 0.001) and their interaction (p < 0.1) were significant. This was reflected in a 29% reduction in area under the curve (AUC) by KRG-rootlets compared with placebo (p = 0.052). Conversely, neither KRG-H2O extract nor KRG-body affected glycemia. Stepwise-multiple regression models identified Rg1 as the sole predictor of mean- and AUC postprandial blood glucose. In the dose-finding study, KRG-rootlets were tested as the most efficacious fraction. A significant effect of KRG-rootlets treatment (mean of 3 doses) but not dose was found. The mean of 3 doses decreased AUC by 17% compared with placebo (p = 0.057).

Conclusions: Together the studies indicate 2 g KRG-rootlets is sufficient to achieve reproducible reductions in postprandial glycemia. But the longterm sustainability of KRG selected using this approach remains to be tested.

Key words: Complementary and Alternative medicine, ginseng, ginsenosides, postprandial glycemia, OGTT


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 ACKNOWLEDGMENTS
 REFERENCES
 
Evidence for the efficacy of ginseng has serious limitations. We recently demonstrated that the ginsenoside composition of ginseng is highly variable [1]. This may contribute to equally high variability in its efficacy. Recent human studies from our clinic have demonstrated that the glycemic effects of ginseng are secondary to different ginseng source parameters in humans. We showed that while a first [2–6] and second [7] batch of American ginseng consistently decreased acute postprandial glycemia, a third batch of American ginseng [6] and Japanese-rhizome, Sanchi, Vietnamese-wild, and Korean red ginsengs [7] had null effects, and Asian [7, 8], Siberian, and American-wild ginsengs [7] significantly raised acute postprandial glycemia. The protopanaxadiol (PPD):protopanaxatriol (PPT) ginsenoside ratio was implicated as the sole independent predictor of these effects [7]. But the variance explained by this ginsenoside ratio was very small, bringing into question its utility as a marker for standardization. Taken together, this demonstrated high variability across different batches, preparations, and species and the continued lack of adequate standardization criteria has highlighted the need to develop clinical screening techniques to identify batches with reproducible and sustainable glycemic lowering efficacy.

Korean red ginseng (KRG) represents a good candidate for efficacy screening. KRG is the only other species that has been reported to decrease glycemia in humans [9]. It also shares a similar PPD:PPT ratio with our original efficacious batches of American ginseng [1]. We hypothesized that a preparation selected to have a close PPD:PPT ratio will lower postprandial glycemia. One way to select different ginsenoside profiles is fractionation and extraction. Rootlets, for example, have been shown to contain >3-fold higher total ginsenoside concentrations and >2-fold higher PPD:PPT ratio than the main root body [1]. Water extracts of whole root have also been shown to have higher total ginsenoside concentrations and PPD:PPT ratio than non-extracts of whole-root [1]. We used these approaches to produce different preparations from the same root source with a range of PPD:PPT ratios. These included 3 KRG preparations: rootlets, body, and whole-root water extract. Sequential clinical preparation- and dose-finding studies were then conducted using these 3 preparations to identify the most efficacious KRG fraction and its most efficacious dose on acute postprandial glycemia with the intention of investigating their longterm efficacy and safety in a randomized, double-blind, placebo-controlled trial in type 2 diabetes. The two acute clinical screening studies are reported here.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
ACKNOWLEDGMENTS
 REFERENCES
 
Participants
The methods for the present studies have been described previously [10]. Briefly, both studies were approved by the St. Michael’s Hospital ethics review board. Healthy adult participants were recruited for the two acute studies from print advertisements, our outpatient database, and postings. Inclusion criteria included euglycemic (FPG 4–6 mmol/L), nonpregnant, 18–65 years of age, clinically euthyroid, normal renal and hepatic function, no major illness/disease, no gastro-intestinal disorders, normo-tensive, not taking herbs or supplements known to affect glycemia, and not using alcohol or cigarettes heavily. Those candidates who met the inclusion criteria and gave informed consent were enrolled in the study. Seven healthy participants (sex: 3m:4f, age: 32 ± 4 y, BMI: 24 ± 2 kg/m2) were enrolled in and completed the first study and 12 healthy participants (sex: 9M:3F, age: 29 ± 3 y, BMI: 22.5 ± 0.9 kg/m2) were enrolled in and completed the second study.

Treatments
Two treatment sets derived from a single batch of Korean red ginseng were investigated. The ginseng was selected by the Korean Ginseng and Tobacco Research Institute (Daejeon, South Korea). The selection process included proper botanical identification and the safekeeping of voucher specimens. In the first acute preparation-finding study, the following 3 derived fractions were tested at a high dose of 6 g: (1) whole root water extract, (2) root body, and (3) rootlets. The whole root water extract fraction was prepared by extraction of ground whole root by distilled water at a ratio of 1:10 at 85°C 3 times, followed by cooling, centrifuging at 1500 rpm, and spray drying. The root body and rootlets fractions were prepared mechanically by separating the lateral roots and root hairs from the main body of the root. These fractions were selected to provide a wide range of composition that would allow for a partitioning of effects. The 6 g dose was decided upon, as it was intermediate with respect to the 1–9 g dose range investigated in our previous studies [2–8]. In the second acute dose-finding study, 3 scaled-down doses of the most efficacious fraction identified in the preceding study were tested: 2 g, 4 g, and 6 g. These doses were determined based on a 3-fold dose range that included the 6 g from the preparation-finding study. A broader dose range was not considered out of concern that the selected KRG-fraction might exhibit a narrow therapeutic range. The treatments in both studies were administered in the form of dried ground powder encapsulated in 500 mg capsules, taken with 300 ml of water, 40 min before a 50 g-Glucodex (TechniLab, Rougier, Quebec). The time of administration was based on the protocol from our previous studies [2–8]. The placebo treatments consisted of identical placebo capsules containing cornstarch. These capsules were matched with the active treatments for appearance, energy, and carbohydrate content. The number of capsules was also kept equal among the doses in the second acute trial by adding placebo capsules to the lower doses to keep the capsule count at 12 for each treatment.

Protocol
The protocol was designed to follow the World Health Organization (WHO) [11] guidelines for the oral glucose tolerance test (OGTT) (Figure 3). Participants attended St. Michael’s hospital (Toronto, ON, Canada) following a 10–12 h overnight fast. They were instructed to maintain the same dietary and exercise patterns the evening before each test and consume a minimum of 150 g of carbohydrate per day for the 3 days prior to the test. Compliance was assessed by a questionnaire. A minimum 3-day "washout" separated visits. At the start of each test, subjects provided an approximately 250 µL fasting finger-prick capillary blood sample (–40-min). One of the randomly selected treatments was then administered with 300 ml of water. Another blood sample was collected 40 min later (0-min). A 50 g-Glucodex was then consumed over exactly 5 min. Additional blood samples were drawn at 15-, 30-, 45-, 60-, 90-, and 120-min after the start of the test. Participants also indicated any adverse symptoms during each test and the intervening "washout" days between clinic visits using visual analogue 7-point bipolar scales.


Figure 3
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  		Fig. 3. Effect of overall Korean red ginseng (KRG) rootlets treatment (mean of 2 g, 4 g, 6 g doses) on postprandial glycemia. The line plots and bars in the represent the incremental change and area under the curve (AUC) for placebo (•) or the mean of the 3 KRG-rootlets doses ({square}) administered 40-min before a 50 g-OGTT in 12 healthy nondiabetic subjects (sex: 9M:3F, age: 29 ± 3 y, BMI: 22.5 ± 1 kg/m2). P-values reported in the base of the plot area are for the main effects of treatment and time and their interactions from repeated measures two-way ANOVA. Data are mean ± SEM.

 
Ginsenoside Analyses
Analysis of 8 common ginsenosides (Rb1, Rb2, Rc, Rd, Rg3 Rg1, Rf, Re) in each of the 3 fractions were done in quadruplicate using standard HPLC-UV techniques [12]. The HPLC conditions included: chromatograph—Beckman HPLC system; column—a reverse-phase Beckman ultrasphere C-18, 5 µm octadecylsilane, 250 x 4.6 mm column; mobile phase—de-ionized water and acetonitrile; flow rate—1.3 ml/min; UV detection—a module 168 diode-array detector set at 203 nm.

Blood Glucose Analyses
All samples were frozen immediately and analyzed within three days of collection. The glucose concentration of each was determined by the glucose oxidase method using an YSI 2300 Stat glucose/L-lactate analyzer, model 115 (Yellow Springs, Ohio, U.S.). The inter-assay coefficient of variation of this method for two sample pools was 3.3% (n = 91, 3.99 ± 0.13 mmol/L) and 1.8% (n = 89, 14.35 ± 0.26 mmol/L).

Data Analyses
Blood glucose curves were plotted as the incremental change over time and the positive incremental area under each curve (AUC) was calculated geometrically for each participant, ignoring areas below the fasting value [13]. Incremental blood glucose was used to control for baseline differences. Statistical analyses were then performed using the Number Cruncher Statistical System (NCSS) 2000 software (NCSS statistical software, Kaysville, Utah). Planned comparisons were with placebo. Repeated measures two-way ANOVA assessed the interactive and independent effects of preparation or dose and sampling time on incremental changes in blood glucose for each comparison with placebo. If the interaction terms were significant, then pairwise comparisons with placebo were done at individual time points using repeated measures one-way ANOVA adjusted by the Tukey-Kramer test for multiple pairwise comparisons. Stepwise multiple regression models assessed the ginsenoside predictors of blood glucose indices. All results were expressed as mean ± SEM and significant at p < 0.05 for main effects and P < 0.01 for interactive effects.

RESULTS
Both study protocols were followed safely and without difficulty by the respective groups of participants. A minimum of 150 g of carbohydrate was consumed over the 3 days prior to each test. Baseline anthropometry and fasting plasma glucose were maintained. The participants consumed the placebo and KRG treatments in the self-standardized amount of time and the 50 g oral glucose load in the allotted 5 min for each test. There were also no differences among the placebo and KRG treatments in the frequency or intensity of self-rated symptoms that included bloating, belching, nausea, dizziness, headache, diarrhea, flatulence polyuria, insomnia, anxiety, numbness, light-headedness, or drowsiness during the clinic visits or intervening washout periods (data not shown).

Preparation-Finding Study
The preparation-finding study was conducted first to identify the most efficacious root fraction. Fig. 1 shows the effect of batch (KRG-rootlets, -body, and -H2O extract of whole root), time, and their interaction on incremental postprandial glycemia for each comparison with placebo. Two-way repeated measures ANOVA applied to these data showed that the main effect time on incremental glycemia was significant for all three comparisons (p < 0.0001), while the main effect of KRG fraction on incremental glycemia was only significant for the comparison between KRG-rootlets and placebo (p = 0.050) with a time interaction (p < 0.1). The interaction was explored with one-way repeated measures ANOVA, in which KRG-rootlets and placebo were compared at each level of time (–40-, 0-, 15-, 30-, 45-, 60-, 90-, 120-min). A significant effect of KRG-rootlets was observed at 90-min (p = 0.022), in which KRG-rootlets lowered incremental glycemia by 71% from 0.35 versus 1.22 mmol/L compared with placebo. This was reflected in the AUC. KRG rootlets significantly decreased the AUC by 29% from 170.4 to 121.7 mmol/L compared with placebo (p = 0.052).


Figure 1
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  		Fig. 1. Differential effects of 3 Korean red ginseng (KRG) fractions derived from the same root source on postprandial glycemia in a preparation-finding study. The line plots and bars in the array represent the incremental change and area under the curve (AUC) for placebo (•) or one of 3 KRG-fractions—KRG-rootlets ({square}), KRG-body ({triangleup}), KRG-H2O extract of whole root ({lozenge})—administered at a dose of 6 g 40-min before a 50 g-OGTT in 7 healthy nondiabetic subjects (sex: 3m:4f, age: 32 ± 4 y, BMI: 24 ± 2 kg/m2). P-values reported in the base of each plot area are for the main effects of treatment and time and their interactions from repeated measures two-way ANOVA. The significant interaction between treatment and time (treatment x time) on glycemia in the case of KRG-rootlets was explored with repeated measures one-way ANOVA at each level of time. Asterisks indicate that points or bars for KRG fraction are significantly different from placebo (p ≤ 0.05, repeated measures one-way ANOVA). Data are mean ± SEM.

 
Dose-Finding Study
The most efficacious root fraction from the preparation-finding study, KRG-rootlets, was advanced to the dose-finding study. The effects of KRG-rootlets dose and treatment (the mean of all doses) were assessed on incremental postprandial glycemia over time.

Fig. 2 shows the effects of dose, time, and their interaction on incremental postprandial glycemia for each comparison with placebo. Two-way repeated measures ANOVA showed that the main effect of time on incremental glycemia was significant for all 3 comparisons between the doses and placebo (p < 0.0001). But the main effect of dose and its interaction with time were not significant for any of the comparisons. Re-performing the analysis with the data expressed as change from placebo did not yield a significant dose response (data not shown).


Figure 2
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  		Fig. 2. Differential effects of 3 doses of Korean red ginseng (KRG) rootlets on postprandial glycemia in a dose-finding study. The line plots and bars in the array represent the incremental change and area under the curve (AUC) for placebo (•) or one of 3 doses of KRG-rootlets—2 g ({lozenge}), 4 g ({square}), 6 g ({triangleup})—administered 40-min before a 50 g-OGTT in 12 healthy nondiabetic subjects (sex: 9M:3F, age: 29 ± 3 y, BMI: 22.5 ± 1 kg/m2). P-values reported in the base of each plot area are for the main effects of treatment and time and their interactions from repeated measures two-way ANOVA. Data are mean ± SEM.

 
Fig. 3 shows the effect of treatment and its interaction with time on incremental postprandial glycemia. Two-way repeated measures ANOVA showed that the main effect of time (p < 0.0001) and treatment were significant (p = 0.057) without an interaction. The mean of all 3 doses decreased mean postprandial incremental glycemia by 17% from 1.54 to 1.37 mmol/L compared with placebo. This was reflected in the AUC. There was a tendency (p = 0.094) for the mean of all 3 doses of KRG rootlets to decrease the AUC by 14% from 233.4 to 201.9 min.mmol/L compared with placebo.

Ginsenoside Composition
Table 1 shows the ginsenoside profiles for the KRG-rootlets, -body, and -H2O extract. The profiles were distinct. A wide variation was seen across the 3 fractions with KRG-H2O extract and -rootlets having the highest concentrations of ginsenosides. The KRG-rootlets fraction had 240% higher total ginsenosides, a 98% higher PPD: PPT ratio, and a 34% higher Rb1:Rg1 ratio than the KRG-body fraction. The KRG H2O extract had even higher values with 440% higher total ginsenosides, a 220% higher PPD:PPT ratio, and a 350% higher Rb1:Rg1 ratio than KRG-body fraction. These large differences in the ginsenoside profiles produced overlap in various authentication criteria. For example, the <3 Rb1:Rg1 ratio indicative for Panax ginseng C.A. Meyer [14–16] was not met by the KRG-H2O extract. The >1 Rg1:Re and Rb2:Rc ratios indicative for Panax ginseng C.A. Meyer [17] were also not met by the KRG-H2O extract or rootlets. As these criteria apply to whole-root sources and not fractions, this lack of agreement with the authentication criteria serves only to confirm that botanically significant differences were achieved by the fractionation process.


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  		Table 1. Ginsenoside Profiles of the 3 Korean Red Ginseng (KRG)

 
Some differences in composition were tied to differences in glycemic effects. Stepwise-multiple regression models including all of the measured ginsenoside concentrations and ratios identified Rg1 as the sole predictor of the change in mean- (ß = 0.1624, partial-r2 = 0.026, p = 0.026) and AUC- (ß = 0.028, partial-r2 = 0.23, p = 0.028) postprandial blood glucose from placebo in the preparation-finding study.


   DISCUSSION
 
The present sequential KRG preparation- and dose-finding studies were successful in identifying an efficacious batch and dose of KRG from a single root source. In the preparation-finding study, a wide range in the ginsenoside profiles was achieved among the 3 KRG root fractions, which coincided with an equally wide range in glycemic effects. KRG-rootlets decreased postprandial glycemia compared with placebo, while KRG-H2O extract of whole root and KRG-body did not. These data identified KRG-rootlets as the most efficacious preparation to be advanced through the screening model. In the dose-finding study, KRG-rootlets over a 3-fold dose range from 2–6 g decreased postprandial glycemia. Although no effect of dose was observed, the mean of all 3 doses decreased postprandial glycemia compared with placebo. The implication was that the 3 doses were equally efficacious. Taken together, these data indicated that 2 g KRG-rootlets was sufficient to achieve reductions in postprandial glycemia.

Although a wide range in the PPD:PPT ratio was achieved, it did not correspond to the differences in postprandial glycemia among the 3 fractions. The preparation with the highest PPD:PPT ratio, the KRG-H2O extract, did not exhibit the greatest glycemia lowering efficacy. On the contrary, the KRG-rootlets with a 60% lower PPD:PPT ratio was the only fraction that significantly lowered postprandial glycemia compared with placebo. This is in contrast to our previous findings using a similar acute postprandial protocol, in which we consistently demonstrated an inverse relationship between the PPD:PPT ratio and postprandial glycemic response across different batches, preparations, and species of ginseng [7].

Reasons for this disagreement are unclear. Other ginsenoside and/or non-ginsenoside component(s) might have had a greater influence on blood glucose outcomes. In this regard, the sole predictor of effects identified from the stepwise-multiple regression models was Rg1. It explained 23% of the variance in the change in mean- and AUC-postprandial blood glucose from placebo. This represents a 3-fold improvement over the predictive value of the PPD:PPT ratio reported previously. Although the PPD:PPT was the sole independent predictor of 4 of the 7 acute plasma glucose and insulin indices in our previous study comparing 8 of the most common types of ginseng [7], this ratio explained <7% of the variation. Additional candidates also deserve consideration. Re [18, 19], Rb2 [19–21], and panaxan B [22, 23] represent components for which there is consistent data across different models, species, doses, and investigator groups. In addition to Rg1, these components individually or together might have influenced glycemic outcomes in the present study. Although it was not identified by our stepwise models, Re followed the direction of the glycemic effects for KRG-rootlets. Another possibility is the presence of an opposing factor in the KRG-H2O extract that confounded effects. A saturation effect is also possible. The PPD:PPT ratio of the KRG-H2O extract (3.721) may have been above the efficacy threshold. In this regard, the PPD:PPT ratios of the two batches of American ginseng that previously exhibited acute glycemic lowering efficacy were between 35 and 43% lower (2.13 and 2.44) than that of the KRG-H2O extract. Clearly, more specific extraction of ginsenosides are needed to disentangle the relative contributions of different ginsenosides to glycemic effects.

Similar mechanisms may also explain the absence of a dose-response to the KRG-rootlets in our second study. Opposing factors may have exerted themselves at higher doses. It is also possible that the dose range studied may have been above the dose-response threshold. A broader dose range may be needed to observe differences. This interpretation is consistent with our findings with American ginseng using a similar acute postprandial protocol. Doses over a 3-fold dose range from 1–3 g and 3–9 g showed were equally efficacious in lowering postprandial glycemia in normal subjects. The same was true for doses from 3–9 g in subjects with type 2 diabetes. The suggestion is that the dose response range may lie below 2 g for KRG-rootlets. A dose-finding study using less than 2 g is needed to answer this practical question. Nevertheless, the most likely explanation for the lack of significance in the main effect of dose was an insufficient sample size to detect the weaker than expected dose response.

That different fractions and parts of ginseng with distinct compositional profiles produce differential glycemic effects is not a novel observation. There are numerous examples in animal models. In a stepwise-fractionation study, the water-soluble DPG series fractions of Asian ginseng root significantly lowered acute glycemia in alloxan diabetic mice, while the fat-soluble fractions, D-8151, D-81513, had null effects and the fat-soluble fraction, D-81516, had increasing effects. A specific water extracted fraction, DPG-4 containing ginsenosides identified as Rb and Rc also had increasing effects on acute blood glucose [24]. In another study, although aqueous extracts of Asian ginseng root body and rootlets each decreased fasting blood glucose by ~40% and ~37% with a concomitant decrease in insulin of ~76% and 52% in KKAy diabetic mice, the mechanisms appeared to be different. KRG-rootlets increased the peroxisome proliferator activated receptor-{gamma} (PPAR-{gamma}) protein, the target of the thiazolidinedione class of antihyperglycemic oral agents, while the KRG-body did not [25]. Finally, an Asian ginseng berry extract produced marked improvements in indices of glucose, insulin, and body-weight control, while an Asian ginseng root extract prepared from the same plant source showed null or only modest potency in ob/ob mice [18, 26, 27]. In other studies from the same group, American ginseng berry [28] and leaf [29] extracts were able to replicate the improvements in glucose, insulin, and body-weight control in ob/ob mice. Taken together, variability in glycemic effects has been shown secondary to differences in root fractions and plant parts.

In conclusion, acute postprandial glycemia varied across the three KRG fractions derived from the same root source. Although this variation was not tied directly to the PPD:PPT ratio as hypothesized, it allowed us to identify an efficacious preparation (rootlets) and dose (2 g) of KRG. In the absence of definitive ginsenoside standardization criteria for antihyperglycemic indications, acute clinical screening represents the only viable basis for identifying a batch with reproducible efficacy in humans. Nevertheless, whether the effects seen with KRG-rootlets are sustainable over the longterm remains speculative. To test this question, our clinic is undertaking a randomized, double-blind, placebo-controlled trial in type 2 diabetes using the same 2 g KRG-rootlets as an oral prandial agent [10]. Further efforts are still required to elucidate a basis for ginseng standardization criteria.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 ACKNOWLEDGMENTS
REFERENCES
 
The funding for these two studies was provided by the Korean Ministry of Agriculture and Forestry. This work was presented in part at the 22nd International Symposium on Diabetes and Nutrition held in Brugge, Belgium from June 19–22, 2003 [30]; American Diabetes Association annual conference held in New Orleans, LA, June 13–17, 2003 [31]; the 8th International Symposium on Ginseng held in Seoul, South Korea, October, Oct 28–31, 2002 [32]; and the Federation of American Societies for Experimental Biology (FASEB) conference held in New Orleans, LA from April 20–24, 2002 [33].

Received February 18, 2005. Accepted September 15, 2005.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 ACKNOWLEDGMENTS
 REFERENCES
 

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