Abstract
Background
Managing symptoms of chronic pancreatitis (CP) remains a significant challenge. Korean Red ginseng (KRG), a well-known herbal supplement, has shown potential benefits in various health conditions, prompting its investigation in CP patients.
Methods
We conducted a single-arm, prospective clinical trial to evaluate the effect of KRG on quality of life in CP patients exhibiting mild symptoms, as defined by a Clinical Global Impression (CGI) score of 0 or 1. 40 patients were enrolled and assessed at baseline, as well as at 30, 90, and 180 days. The primary outcome was an improvement in CGI scores, with secondary outcomes including changes in Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q) scores.
Results
A total of 40 patients were enrolled in this study, and 39 participants were analyzed. Results showed significant improvements in CGI scores at all examined intervals (days 0–30, 0–90, 0–180; p < 0.05). The PEI-Q score also significantly improved from day 0 to day 180 (p < 0.05). Two adverse events (AEs) probably related to KRG were reported, and all AEs were improved with conservative managements.
Conclusion
KRG supplementation significantly improves quality of life in CP patients with mild symptoms. These findings suggest that KRG may be a beneficial adjunct therapy in this patient population. Further research is needed to explore KRG’s pharmacological mechanisms, its use in combination with other treatments, and its effects in patients with more severe symptoms. (CRIS number: KCT0009681).
Keywords: Chronic pancreatitis, Korean Red ginseng, Clinical Global Impression, Prospective clinical trial
Graphical abstract
1. Introduction
Chronic pancreatitis (CP) affects approximately 20 patients per 100,000 annually worldwide [1]. Abdominal pain, a well-known symptom of CP, is driven by metabolic changes in the pancreas. The progression of CP and subsequent malabsorption also contribute to a decline in quality of life (QOL) [2]. Patients with CP often suffer from pancreaticolith and pancreatic duct stricture, requiring analgesics, including those containing opioids, which leads to dependency and other sideeffects [3]. Additionally, pancreatic enzyme replacement therapy (PERT) is recommended for CP patients with exocrine insufficiency and malnutrition. However, a meta-analysis has revealed inconsistencies among studies regarding the efficacies of this treatment, making it controversial [4]. Consequently, physicians face challenges in meeting the demands of CP patients suffering from these symptoms, and the scarcity of effective medications to alleviate symptoms that interfere with daily life remains a significant unmet need in the treatment of CP.
Korean Red ginseng (KRG) is a well-recognized health supplement known for enhancing immunity, reducing fatigue, improving blood flow and memory, and providing antioxidant benefits [5]. Its key active components are ginsenosides such as Rg1, Rb1, and Rg3 [6,7]. Various studies, including human trials and animal experiments, have confirmed the health benefits of KRG. Animal studies show its effectiveness in improving pancreatitis and protecting the gastrointestinal tract [8,9]. Moreover, KRG has been reported to alleviate arthritis pain and reduce reliance on opioid analgesics [10,11]. The safety and efficacy of KRG in improving patient fatigue have been recently confirmed through a double-blind randomized clinical trial (RCT) [12,13].
Based on the promising effects of KRG for symptom relief and anti-inflammation, we aim to evaluate the efficacy of KRG in the supportive care of CP patients in this clinical trial.
2. Methods
2.1. Study patients
We enrolled CP patients over the age of 18 with mild symptoms. Symptom analysis was based on the Clinical Global Impression (CGI) questionnaires, referencing a previous study that evaluated the efficacy of PERT in patients with pancreatic exocrine insufficiency (PEI), where investigators used CGI scores to assess symptom severity (mild symptom is defined as CGI score 0 and 1) [14]. Participants who visited outpatient clinics at our institution for diagnosis or treatment of CP were enrolled in this study.
Patients incapable of understanding consent form details, requiring addictive medication or invasive procedures for severe symptoms were excluded. Additionally, individuals with an allergy to KRG, a life expectancy less than 6 months, a history of drug abuse, or a current or possible pregnancy were also excluded for safety reasons.
2.2. Study design
This investigator -initiated, single-arm, prospective clinical trial evaluated whether CP patients with mild symptoms experienced an improvement in their QOLs after taking KRG.
Initially, participants were screened, selecting those who met the inclusion and exclusion criteria. Others who experienced severe events necessitating trial suspension, who withdrew or violated the study's main schedule, or were deemed unsuitable to continue by investigators were excluded. Both full analysis set and per protocol analysis set were implemented to minimize the risk of loss-to-follow-up bias. Enrolled patients were scheduled to visit the clinics at 30, 90, and 180 days post-enrollment for assessment regarding study outcomes (Fig. 1).
Fig. 1.
Scheme of the study design.
This trial adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines to ensure logical validity. This trial has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the institutional review boards (IRB) of our institution. (IRB number: H-2210-151-1373), and registered with The Clinical Research Information Service (CRIS number: KCT0009681).
2.3. Interventions
Enrolled participants received KRG tablets containing Ginsenoside Rb1, Rg1, and Rg3. Each tablet was 500 mg, with dosing instructions to take two tablets orally twice daily for 180 days. The estimated daily intake of Ginsenoside was 8 mg. Tablets were packaged in bottles, with 120 tablets per bottle and 6 bottles dispensed, totaling 720 tablets per participant. Patient-specific numbers were labeled on the bottles post-screening to prevent mismatches. No official guidelines on serious drug-drug interactions with KRG exist, but caution was advised regarding the potential for allergic reactions, risk of tooth injury if chewed, and interactions with other medications such as oral hypoglycemic agents and anticoagulants regarding known drug interaction data of other herbal medicines including an increased bleeding risk with Ginko biloba if taken with Warfarin [15].
2.4. Evaluations of study outcomes and definitions
The primary outcome of this trial is the CGI score, which assesses the severity of CP symptoms. Additionally, the PEI-Q score, safety, and adverse events (AEs) are considered secondary outcomes.
On the first day, demographic profiles including age, sex, social history, comorbidities, and the Charlson Comorbidity Index (CCI) were documented. The date of diagnosis, diagnostic modality, and combined symptom related to CP as described by the CGI and PEI-Q scores were also collected.
At each follow-up, the number of residual tablets for assessing compliance, discarded on Day 180, along with CGI and PEI-Q scores for symptom assessment, and any clinical events including death, admission, and operation were documented.
The CGI score is categorized into five levels: 0 indicates no symptoms present, 1 indicates symptoms are present but not bothersome, 2 indicates symptoms are bothersome, 3 indicates symptoms interfere with normal activities, and 4 indicates symptoms prevent the subject from continuing normal activities.
The PEI-Q score, developed to diagnose and assess the severity of PEI, is defined by a daily fat excretion exceeding 15 g due to malabsorption. It includes three categories: Abdominal symptoms (A), Bowel movement symptoms (B), and Impacts (C). The diagnosis and severity of PEI are determined based on the score [16].
AEs during this trial are defined as any undesired medical incident in a patient after consuming dietary supplement or during the associated clinical trial, regardless of its link to the treatment. Each AE is documented in a case report regardless of severity, comorbidity, or potential drug association. Event symptoms are standardized and grouped, and each event's occurrence date, maximum severity, concomitant treatments, outcomes, and the investigator's opinion on the association with the clinical study are noted. Severity is categorized by the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE), Version 5, which has been applied in other randomized controlled trials assessing KRG's effect on non-oncologic morbidities [17]. If an event does not fit any example provided by the NCI-CTCAE, the investigator may choose from four severity classifications: mild, moderate, severe, and life-threatening.
Blood samples of each participant were collected on initial visit and day 180. Laboratory tests included complete blood count (CBC) consisting of serum white blood cell (WBC) count, serum hemoglobin (Hb), and serum platelet (PLT), blood urea nitrogen (BUN), serum creatinine (Cr), serum albumin (Alb), serum aspartate aminotransferase (AST), serum alanine transaminase (ALT), serum total bilirubin (Bil), serum amylase, serum lipase, serum C-reactive protein (CRP), serum carcinoembryonic antigen (CEA), and serum cancer antigen 19-9 (CA 19-9).
2.5. Sample size calculation
We calculated the sample size based on a previous study regarding the efficacy of a 6-month pancreatic enzyme replacement therapy in participants with PEI. The study results indicated increases in the proportions of participants with baseline CGI scores of 0 and 1 (10 percent and 40 percent, respectively) by 20 percent and 10 percent respectively [14]. Considering the 10 percent of participants whose symptoms worsened after treatment, regardless of baseline CGI, we concluded that the net change includes 35 percent improvement and 5 percent exacerbation. Consequently, we estimated the sample size, setting alpha at 0.05 and beta at 0.20, which required 33 patients. Given the poor compliance noted in CP patients, we anticipated a 20 percent dropout rate. Thus, the final estimated sample size was 40 patients.
2.6. Statistical analysis
We applied both the full analysis set and the per-protocol set for our data analysis approach. Under the former standard, participants who violated inclusion or exclusion criteria, failed to take any of the provided tablets, or lacked data for the primary outcome were excluded. In the latter case, all participants who adhered to the treatment as per the study design were included, except those who took less than 80 percent of the provided tablets.
For efficacy assessment, we collected data on CGI and PEI-Q scores at each visit. Descriptive statistics were generated based on the data. We conducted a Shapiro-Wilk test to assess the normality of score differences, followed by either a paired t-test or Wilcoxon signed rank test depending on whether the data showed normal distribution. Statistical significance was set at a p-value below 0.05.
Subgroup analyses based on demographics, comorbidities, social history, and initial scores have been proceeded by comparing odds ratio of achieving CGI improvement. Odds ratios, 95 percent confidence intervals (CI) of odds ratio for each variable and p-values were calculated by Fisher’s exact test and the results was presented by a forest plot.
Statistical analyses were performed, independently checked, and replicated with the use of RStudio software, version 4.4.0.
3. Results
3.1. Study patients and their baseline characteristics
We enrolled 40 CP patients. Four patients dropped out before or on Day 30, one due to poor compliance and the others due to AEs. Additionally, four patients dropped out between Day 30 and Day 90 or on Day 90, with one lost to follow-up and the others due to AEs (Fig. 2).
Fig. 2.
Flowchart of the study.
Table 1 displayed the baseline characteristics of the study patients. Males predominated at 77.5 % (N = 31), and the median age was 61 (Interquartile range (IQR), 14). The primary cause of CP was alcohol at 57.5 % (N = 23), followed by unknown etiology, stone, recurrent pancreatitis, IgG4-related disease, and pancreas divisum, which accounted for 15 % (N = 6), 12.5 % (N = 5), 10 % (N = 4), 2.5 % (N = 1), and 2.5 % (N = 1), respectively. One participant reported dyspepsia, while others did not. Among the initially assessed CGI scores, “0”, “1”, and “2” constituted 37.5 % (N = 15), 60.0 % (N = 24), and 2.5 % (N = 1) respectively. The median initial PEI-Q score was 0.47 (IQR, 0.42). A total of 46.3 % (N = 19) of study patients were diagnosed with diabetes mellitus (DM), followed by hypertension (30.0 %), a history of any operation (25.0 %), dyslipidemia (12.5 %), solid tumor (10.0 %), hepatobiliary disease (7.5 %), and respiratory disease (2.5 %). The median value of CCI was 2 (IQR, 2). Patients with a family history of disease, including a single case of liver cancer and another of gastric cancer, constituted 4.9 % (N = 2). Moreover, enrolled participants identified as current smokers and ex-smokers were 20.0 % (N = 8) and 47.5 % (N = 19), respectively. The proportions of current drinkers and ex-drinkers were 35.0 % (N = 14) and 40.0 % (N = 16), respectively.
Table 1.
Baseline characteristics of study patients.
| Characteristic | N = 40 |
|
|---|---|---|
| Median [IQR, 25–75 percentile] or % | ||
| Demographics | ||
| Sex | Female | 9 (22.5 %) |
| Male | 31 (77.5 %) | |
| Age (years) | 61 [54–68] | |
| History of surgery | 10 (25.0 %) | |
| Smoking | Never smoker | 13 (32.5 %) |
| Ex-smoker | 19 (47.5 %) | |
| Current Smoker | 8 (20.0 %) | |
| Alcohol Consumption | Never Drinker | 10 (25.0 %) |
| Ex-Drinker | 16 (40.0 %) | |
| Current Drinker | 14 (35.0 %) | |
| CCI | 2 [1–3] | |
| CP Related Feature | ||
| Age of Diagnosis (years) | 56.5 [48.75–62] | |
| Etiology | Alcohol | 23 (57.5 %) |
| Stone | 5 (12.5 %) | |
| Recurrent Pancreatitis | 4 (10.0 %) | |
| IgG4-Related Disease | 1 (2.5 %) | |
| Pancreas Divisum | 1 (2.5 %) | |
| Unknown | 6 (15.0 %) | |
| CP-related symptoms | Abdominal discomfort | 2 (5.0 %) |
| Abdominal pain | 2 (5.0 %) | |
| Dyspepsia | 1 (2.5 %) | |
| Flank pain | 1 (2.5 %) | |
| Fever | 0 | |
| Jaundice | 0 | |
| Steatorrhea | 0 | |
| CGI | 0 | 15 (37.5 %) |
| 1 | 24 (60.0 %) | |
| 2 | 1 (2.5 %) | |
| PEI-Q | 0.47 [0.2525–0.6725] | |
| Comorbidity | ||
| DM | 18 (45.0 %) | |
| HTN | 12 (30.0 %) | |
| Dyslipidemia | 5 (12.5 %) | |
| Respiratory | 1 (2.5 %) | |
| Hepatobiliary | 3 (7.5 %) | |
| Solid tumor | 4 (10.0 %) | |
IQR Interquartile Range, CCI Charlson Comorbidity Index, CP Chronic Pancreatitis, CGI Clinical Global Impression, PEI-Q Pancreatic Exocrine Insufficiency Questionnaire, DM Diabetes Mellitus, HTN Hypertension.
3.2. Study outcomes
The test results over three intervals (day 0 to day 30, day 0 to day 90, day 0 to day 180) demonstrated statistical significance (p < 0.05), with Wilcoxon signed rank statistics (V) of 112, 161.5, and 161.5 respectively. No significant statistical differences were observed between the other intervals. (P = 0.1294, 0.1294, 1. V = 17.5, 17.5, 1, respectively for day 30 to day 90, day 30 to day 180, day 90 to day 180) (Table 2).
Table 2.
Changes in CGI score and PEI-Q score of study patients.
| Primary outcome: CGI score | ||||||||
|---|---|---|---|---|---|---|---|---|
| Interval | Pre (A) |
Post (B) |
Difference (B-A) |
Wilcoxon signed-rank test |
||||
| Score | No. (%) | Score | No. (%) | Score | No. (%) | V | P | |
| Day 0 - Day 30 | 0 | 13 (36.1 %) | 0 | 26 (72.2 %) | −1 | 14 (38.9 %) | 112 | <0.001∗∗ |
| 1 | 23 (63.9 %) | 1 | 10 (27.8 %) | 0 | 21 (58.3 %) | |||
| 2 | 0 (0 %) | 2 | 0 (0 %) | 1 | 1 (2.8 %) | |||
| Day 0 - Day 90 | 0 | 10 (31.2 %) | 0 | 26 (81.2 %) | −1 | 17 (53.1 %) | 161.5 | <0.001∗∗ |
| 1 | 22 (68.7 %) | 1 | 6 (18.8 %) | 0 | 14 (43.8 %) | |||
| 2 | 0 (0 %) | 2 | 0 (0 %) | 1 | 1 (3.1 %) | |||
| Day 0 - Day 180 |
0 | 10 (31.2 %) | 0 | 26 (81.2 %) | −1 | 17 (53.1 %) | 161.5 |
<0.001∗∗ |
| 1 | 22 (68.7 %) | 1 | 6 (18.8 %) | 0 | 14 (43.8 %) | |||
| 2 |
0 (0 %) |
2 |
0 (0 %) |
1 |
1 (3.1 %) |
|||
| Secondary outcome: PEI-Q score | ||||||||
|
Interval |
Pre (A) | Post (B) | Difference (B–A) | Wilcoxon Signed Rank Test | ||||
| (Mean ± SD) |
V |
P |
||||||
| Day 0 toDay 180 | 0.5 ± 0.3 | 0.3 ± 0.4 | −0.3 ± 0.3 | 423 | <0.001∗∗ | |||
CGI Clinical Global Impression, PEI-Q Pancreatic Exocrine Insufficiency Questionnaire, SD Standard Deviation.
The PEI-Q score on day 0 and day 180 showed significant statistical differences (Wilcoxon signed rank test, p < 0.05). (Table 2).
Statistical analyses previously mentioned yielded consistent results across both the full analysis set and the per protocol analysis set.
3.3. Safety and adverse events
During the trial, seven AEs occurred, each representing a different category. Detailed manifestations included abdominal distension (Grade 2), abdominal pain (Grade 1), constipation (Grade 1), diarrhea (Grade 1), headache, steatorrhea (Grade 2) and liver function test abnormalities. Abdominal distension and constipation were documented as 'probably related' to the KRG therapy. In contrast, the connections for the other AEs were classified as 'unknown.' Six participants who experienced AEs withdrew due to the corresponding events (Table 3). There were no fatalities associated with these events, and the patients recovered fully through conservative management.
Table 3.
Safety and adverse events in the study.
| No AEs |
Detailed AEs | Severity | Relationship | No. of Events (%) |
|---|---|---|---|---|
| N = 34 (85) | ||||
| Any AEs | N = 6 (15) | |||
| Abdominal Distension ∗ | G2 | Probably Related | 1 (2.5) | |
| Abdominal Pain | G1 | Unrelated | 1 (2.5) | |
| Constipation † | G1 | Probably related | 1 (2.5) | |
| Diarrhea | G1 | Not related | 1 (2.5) | |
| Headache | G1 | Not related | 1 (2.5) | |
| Steatorrhea | G2 | Not related | 1 (2.5) | |
| LFT abnormality | G1 | Not related | 1 (2.5) |
∗, †: Corresponding events occurred in the same participant.
LFT Liver Function Test.
3.4. Subgroup analysis
The participants were grouped by variables such as demographics, comorbidities, social history, and initial scores, which were collected during the initial visits (Fig. 3). The CGI score differences between baseline and day 180 of each group were compared with the opposing groups. Participants with DM showed statistically significant improvement in CGI scores compared to those without the comorbidity (95 % CI: 1.120742–51.566943, p < 0.05).
Fig. 3.
Subgroup analyses of CGI improvement by baseline factors.
3.5. Laboratory test
Laboratory test results from blood samples collected on initial and the last visit have been analyzed (Table 4). Though Cr and ALT showed statistically significant decrease and increase, respectively, the values were found to be in normal ranges.
Table 4.
Laboratory test result from blood sample before and after treatment.
| Lab | Day 0 | Day 180 | P-value |
|---|---|---|---|
| WBC | 6.869 ± 1.925 | 6.742 ± 1.774 | 0.679 |
| Hb | 13.986 ± 0.922 | 14.10 ± 1.034 | 0.367 |
| PLT | 238.448 ± 58.424 | 241.448 ± 65.540 | 0.609 |
| BUN | 15.000 ± 4.706 | 14.379 ± 3.499 | 0.471 |
| Cr | 0.863 ± 0.153 | 0.835 ± 0.139 | 0.026 |
| Alb | 4.513 ± 0.249 | 4.500 ± 0.215 | 0.762 |
| AST | 24.033 ± 6.795 | 26.867 ± 10.034 | 0.136 |
| ALT | 22.833 ± 9.774 | 26.033 ± 14.922 | 0.014 |
| Bil | 0.887 ± 0.406 | 0.917 ± 0.497 | 0.616 |
| Amylase | 75.833 ± 27.534 | 78.882 ± 26.014 | 0.379 |
| Lipase | 29.333 ± 23.485 | 29.889 ± 27.808 | 0.887 |
| CRP | 0.242 ± 0.499 | 0.181 ± 0.280 | 0.447 |
| CEA | 2.080 ± 0.600 | 2.200 ± 0.442 | 0.460 |
| CA19-9 | 18.364 ± 26.447 | 28.409 ± 48.805 | 0.677 |
SD Standard deviation, WBC White blood cell, Hb Hemoglobin, PLT Platelet, BUN Blood urea nitrogen, Cr Creatinine, Alb Albumin, AST Aspartate aminotransferase, ALT Alanine transaminase, Bil Total bilirubin, CRP C-reactive protein, CEA Carcinoembryonic antigen, CA19-9 Cancer antigen 19-9.
4. Discussion
The current treatment regimen for CP, including PERT, leaves some needs unmet [4] and is associated with side effects such as those from opioid analgesics [3]. In light of this, we focused on addressing these unmet needs by introducing supplementary materials alongside conventional treatments. Furthermore, KRG has been increasingly supported by evidence of its positive effects on various morbidities [[8], [9], [10], [11], [12], [13]].
This study demonstrated the benefit of KRG in improving the QOL of CP patients with mild symptoms. Given the lack of curative or therapeutic effects of the current treatments for CP, our trial highlights the clinical significance of using dietary supplements like KRG as supportive care.
Regardless of their design, whether preclinical or clinical, various studies have examined the benefits of KRG, using objective data such as laboratory results as primary outcomes [9]. In contrast, others have focused on subjective data, such as pain extracted from self-report questionnaires [10]. Similarly, the primary outcomes of this study are principally based on trends in participants' subjective experiences. Considering that CP is not curable due to its progressive nature, and core treatment strategies focus on alleviating symptoms, managing complications, and delaying progression [18], the results of this study are significant in developing new approaches targeting a primary focus of the current treatment regimen. Additionally, although a preclinical study on the efficacy of KRG in improving pancreatitis [8] was conducted earlier, there has been no clinical trial assessing the benefits of KRG in patients with CP, thus emphasizing the originality of our study.
The physiological hypothesis that KRG improves symptoms of CP can be attributed to its antioxidative activity. KRG is known to exhibit antioxidative potency in various organs, as demonstrated in studies with animal models [19]. Additionally, CP may involve an inflammatory cascade and cellular injury, both directly or indirectly precipitated by oxidative stress [18]. Although further evaluation of detailed mediators is necessary, the accumulation of oxidative stress, which leads to cellular injury and inflammatory progression, can be mitigated by KRG, thereby alleviating associated manifestations. Detailed antioxidative potency of KRG has been evaluated by its contribution to increasing activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and decreasing malondialdehyde (MDA), a lipid oxidation marker [19]. Corresponding biomarkers were proved to be representative of increased oxidative stress injury on CP patient [20,21]. Further studies are required for elucidating association between changes of corresponding biomarkers and KRG when applied to CP patients.
Better improvement of CGI score of participants with DM compared to those without DM described by the subgroup analysis is remarkable. A randomized placebo-controlled study with well-controlled type 2 DM published in 2008 proved that KRG improves plasma glucose and plasma insulin regulation [22]. Given the fact that one of the core strategies to treat diabetic neuropathic pain is glucose control [23], better improvement of CGI might be a sum of improvement of both pain by CP and DM neuropathy. But evidence is limited because this study lacks of glucose data including hemoglobin A1C, preprandial and postprandial plasma glucose, which shall be included in subsequent studies for better evidence.
Changes in laboratory test result from participants’ blood samples were found. But the results either from before or after taking KRG were found in normal ranges. Considering that we had not anticipated that KRG functions as a cure for CP, rather a supplementary agent, the results are not out of our expectation.
The strengths of our study are manifold. Firstly, this is the initial clinical trial to reveal the efficacy of KRG in CP patients using real-world data. Moreover, the quantified dosage of KRG administered to each participant during the study provided a sufficient basis for clinical benefit. Additionally, the improvement in CGI scores for participants with DM, as shown by subgroup analysis, is promising and underscores the need for specific target recommendations, although the exact pharmacological mechanism behind this enhanced responsiveness remains to be determined. However, the study has several limitations. Firstly, it is based on a small population and lacks a placebo-controlled group, though it is significant in terms of its controlled processes and circumstances compared to retrospective studies. The reasons for designing the trial as single-armed are that there were insufficient former studies as references to initiate RCT, and that this study is basically established on a hypothesis that KRG acts as a beneficial supplement, not a clinical treatment. Regarding the latter reason it is likely to be controversial to set a RCT with placebo group, though the evidence of the trial would be preserved by the sample size calculation based on a statistically logical hypothesis according to previous clinical trials and possible drop-out population despite single-arm design. Furthermore, designing RCT in the future could be more feasible referring to the results of this study. Secondly, since KRG is classified as a dietary supplement, it is debatable whether the results indicate its effectiveness as a clinical treatment for CP, thus making it controversial to compare KRG’s efficacy with other medical treatment including PERT. However, considering the scarcity of effective treatments for CP in the real-world, the findings that KRG, as a dietary supplement, improved symptoms of chronic disease are noteworthy, by which designing further trials for evaluating KRG’s potency as a clinical treatment possibly be stimulated. Furthermore, absence of integration of sex and gender-based analyses (SGBA) into our research would hinder generalizability of the result due to a lack of clarification of gender dimension. Lastly, as the most frequently used statistical modalities are non-parametric, low statistical power is another limitation of the trial. This issue could be addressed in subsequent trials with increased sample sizes to ensure normality.
5. Conclusions
In conclusion, KRG has been found to effectively improve the quality of life for CP patients with mild symptoms. It is therefore likely beneficial to apply KRG to individuals with the corresponding condition in the real world. Further research on combined treatment with other medications, the exact pharmacological mechanism of KRG, and broader objectives, including patients with severe manifestations, is imperative.
Author contribution
Conceptualization, Sang Hyub Lee; Data Curation, Joongyu Kang and Jin Ho Choi; Formal Analysis, Joongyu Kang and Jin Ho Choi; Funding Acquisition, Sang Hyub Lee; Investigation, Joongyu Kang, Jin Ho Choi, Junyeol Kim, Tae Seung Lee, Sung Hoon Chang, Yong Soo Song, In Rae Cho and Woo Hyun Paik; Methodology, Sang Hyub Lee; Project Administration, Sang Hyub Lee; Resources, Sang Hyub Lee; Software, Joongyu Kang and Jin Ho Choi; Supervision, Ji Kon Ryu; Validation, Sang Hyub Lee, In Rae Cho, Woo Hyun Paik and Ji Kon Ryu; Visualization, Joongyu Kang, Jin Ho Choi, Junyeol Kim, Tae Seung Lee, Sung Hoon Chang and Yong Soo Song; Writing – Original Draft Preparation, Joongyu Kang and Jin Ho Choi; Writing – Review & Editing, Joongyu Kang, Jin Ho Choi and Sang Hyub Lee.
Declaration of generative artificial intelligence (AI) and AI-assisted technologies in the writing process
Neither AI nor AI-assisted technologies has not been used in the writing process.
Declaration of competing interest
none.
Acknowledgment
This work was supported by a grant from the Korean Society of Ginseng (2023–2025). This work is based on a master's thesis of Joongyu Kang.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Contributor Information
Joongyu Kang, Email: jgkang94@gmail.com.
Jin Ho Choi, Email: jinhchoi@snu.ac.kr.
Sang Hyub Lee, Email: gidoctor@snu.ac.kr.
Junyeol Kim, Email: kimjun16@gmail.com.
Tae Seung Lee, Email: rhytksa@snu.ac.kr.
Sung Hoon Chang, Email: smartsarge@gmail.com.
Yong Soo Song, Email: yongsoono1@naver.com.
In Rae Cho, Email: inrae0428@snu.ac.kr.
Woo Hyun Paik, Email: iatrus@snu.ac.kr.
Ji Kon Ryu, Email: jkryu@snu.ac.kr.
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