Study of Efficacy and Safety of Ginseng Seed Oil in Heathy Subjects Who Have Mild Liver Dysfunction: A Randomized, Double Blinded, Placebo-Controlled Study

Article information

J Korean Med. 2018;39(2):36-55

Publication date (electronic) : 2018 June 30

doi : https://doi.org/10.13048/jkm.18014

Young-Ji Kim ¹

, Jung-Yeon Kwon ¹

, Ho-Yeon Go ¹

, Dong-Nyung Lee ², Sung-Kwon Ko ³, Kyung-Hwan Kong ¹

¹Dep. of Korean Internal Medicine, College of Korean Medicine, Semyung University

²Dep. of Korean Gynecology, College of Korean Medicine, Semyung University

³Dept. of Oriental Medical Food & Nutrition, Semyung University

⁴Ginseng Research Center, Koyeon

Correspondence to: 공경환(Kyung-Hwan Kong), 충북 충주시 상방4길 63 세명대학교충주한방병원 한방내과 Tel: +82-43-841-1732, Fax: +82-43-856-1731, E-mail: kong124@hanmail.net

Received 2018 May 28; Revised 2018 June 8; Accepted 2018 June 8.

Abstract

Objectives

The purpose of this study was to investigate the effectiveness and safety of ginseng seed oil in healthy subjects who have mild liver dysfunction.

Methods

A randomized, double blinded, placebo-controlled trial was conducted. A total of 167 subjects visited Semyung University Hospital from July 1st, 2016 to June 10th 2017. Except for the 103 excluded subjects, 64 subjects were randomized into one of the two groups: an treatment group(n=33) and control group(n=31). Subjects were randomly given either ginseng oil seed capsules or indistinguishable placebo capsules(2 capsules per dose, twice per day). Laboratory tests(aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase, triglyceride, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol) were performed to evaluate the effectiveness after 6, 12 weeks of treatment. Vital sign, laboratory test were performed to assess safety at every visit.

Results

There were no significant differences in efficacy between treatment group and control group. There were some adverse events with no significant difference in symptoms and frequency between treatment group and control group.

Conclusions

Although the efficacy of ginseng seed oil was not proved, ginseng seed oil did not worsen liver function and proved its safety. More study of ginseng seed oil and clinical trials are necessary to increase the usefulness of above-ground parts of ginseng.

Keywords: Ginseng seed oil; Mild liver dysfunction; RCT

Fig. 1

Experimental design

Fig. 2

Disposition of subjects, enrolled in the study

Table 1

The Composition of GSO

Table 2

Characteristics of the Subjects

Table 3

Change of Lab

Table 4

Change of Lab in the Subject Except for People with Excessive Drinking

Table 5

Comparisons of Adverse Event Between Treatment Group and Control Group

Vital Sign

Hematology

Blood Chemistry

Comparative Analysis of Normal and Abnormal Urinalysis

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Article information Continued

Fig. 1

Experimental design

Fig. 2

Disposition of subjects, enrolled in the study

Table 1

The Composition of GSO

	%	750 mg
Ginseng seed oil	66.7	500
Pigskin gelatin	26.5	199
Glycerin	3.33	25
D-Sorbitol	3.33	25
Cochineal extract	0.07	0.5
Caramel color	0.07	0.5

Table 2

Characteristics of the Subjects

Characteristics	Treatment(N=26) n(%) or Mean±SD	Control(N=27) n(%) or Mean±SD	p*
Age(year)	50.73±9.489	51.67±8.440	0.564
Gender
Male	15(57.7)	13(48.1)	0.487
Female	11(42.3)	14(51.9)
Height(cm)	165.731±10.7240	161.593±9.9817	0.442
Body weight(kg)	74.173±13.1612	69.607±12.7435	0.944
Smoking status
Never	17(65.4)	18(66.7)	0.634
Past	4(15.4)	6(22.2)
Current	5(19.2)	3(11.1)
Alcohol intake
Never or past	12(46.2)	16(59.3)	0.628
Moderate	8(30.8)	6(22.2)
Excessive	6(23.1)	5(18.5)
Meal
Regular	25(96.2)	24(88.9)	0.317
Irregular	1(3.8)	3(11.1)
Exercise
Never	7(26.9)	6(22.2)	0.604
Irregular	9(34.6)	13(48.1)
Regular	10(38.5)	8(29.6)

Treatment : group taking GSO, Control : group taking placebo, N : number

p: p-value between groups by independent t-test or chi-square test

Table 3

Change of Lab

		Treatment(N=26)		Control(N=27)		p†
						p†
		Mean±SD	p*	Mean±SD	p*
AST (IU/L)	Baseline	33.88±5.750		31.41±5.970		0.130
	6weeks	32.500±8.3391	0.263	28.889±7.4902	0.020	0.103
	12weeks	36.885±21.8711	0.746	29.222±8.0734	0.071	0.094

ALT (IU/L)	Baseline	38.885±17.1891		34.074±11.2760		0.232
	6weeks	35.538±19.5576	0.179	35.222±15.6262	0.942	0.948
	12weeks	42.077±28.0170	0.989	31.407±12.8998	0.140	0.079

γ-GTP (IU/L)	Baseline	55.423±49.6823		48.704±48.2739		0.620
	6weeks	48.731±41.0410	0.017	47.370±51.9824	0.439	0.916
	12weeks	49.038±44.0958	0.012	43.111±42.5869	0.002	0.621

TG (mg/dL)	Baseline	178.654±110.7025		179.074±146.9262		0.991
	6weeks	197.692±132.2751	0.211	166.889±153.9076	0.210	0.439
	12weeks	193.192±152.8105	0.657	182.148±190.5243	0.943	0.817

t.Chol (mg/dL)	Baseline	192.077±33.5296		199.111±35.1342		0.460
	6weeks	202.385±32.9740	0.042	211.000±33.6109	0.034	0.351
	12weeks	207.462±38.7889	0.005	207.296±33.1045	0.100	0.987

HDL (mg/dL)	Baseline	49.154±11.2452		50.778±13.9127		0.643
	6weeks	49.885±11.6218	0.647	53.481±13.4718	0.173	0.304
	12weeks	47.308±12.6262	0.567	53.148±14.0239	0.095	0.118

LDL (mg/dL)	Baseline	116.450±40.6234		134.955±35.6671		0.124
	6weeks	124.254±36.8828	0.369	133.562±33.6150	0.573	0.346
	12weeks	124.654±39.2621	0.795	121.077±27.4079	0.024	0.705

Treatment: group taking GSO, Control: group taking placebo, N: number

AST: aspartate aminotransferase. ALT: alanine aminotransferase, γ-GTP: gamma glutamyl transpeptidase, TG: triglyceride, t.Chol: total cholesterol, HDL: high-density lipoprotein-cholesterol, LDL: low-density lipoprotein-cholesterol

p: p-value for baseline vs post(6weeks, 12weeks) by paired t-test or Wilcoxon’s signed rank test

^†

p: p-value between groups by independent t-test

Table 4

Change of Lab in the Subject Except for People with Excessive Drinking

		Treatment(N=20)		Control(N=22)		p†

		Mean±SD	p*	Mean±SD	p*
AST (IU/L)	Baseline	32.85±5.650		30.59±5.152		0.183
AST (IU/L)	12weeks	32.350±10.7178	0.812	27.864±7.1200	0.041	0.115

ALT (IU/L)	Baseline	36.900±16.7329		32.636±10.7062		0.327
ALT (IU/L)	12weeks	35.450±15.0909	0.481	29.545±12.1370	0.121	0.168

γ-GTP (IU/L)	Baseline	37.000±16.9923		33.091±19.2920		0.492
γ-GTP (IU/L)	12weeks	33.100±14.8391	0.111	30.545±24.2600	0.009	0.686

TG (mg/dL)	Baseline	167.000±120.1411		148.045±102.3204		0.584
TG (mg/dL)	12weeks	157.450±130.4097	0.471	135.727±56.0715	0.987	0.480

t.Chol (mg/dL)	Baseline	195.550±32.2775		196.818±37.7456		0.908
t.Chol (mg/dL)	12weeks	207.550±40.8688	0.116	202.318±32.7143	0.317	0.648

HDL (mg/dL)	Baseline	49.100±11.6750		51.000±13.3880		0.628
HDL (mg/dL)	12weeks	48.650±3.2159	0.784	53.955±13.6538	0.077	0.209

LDL (mg/dL)	Baseline	120.786±37.4005		139.824±38.4939		0.176
LDL (mg/dL)	12weeks	124.143±34.2634	0.889	127.941±29.7373	0.042	0.474

Treatment: group taking GSO, Control: group taking placebo, N: number

p: p-value for baseline vs post(12weeks) by paired t-test or Wilcoxon’s signed rank test

^†

p: p-value between groups by independent t-test

Table 5

Comparisons of Adverse Event Between Treatment Group and Control Group

	Treatment(N=32)		Control(N=31)		p†

	n* (%)	n†	n* (%)	n†
Treatment Emergent Adverse Events (TEAE)	8(25.00)	10	7(22.58)	9	0.8217
Adverse drug reaction(ADR)	2(6.25)	2	2(6.45)	3	1.0000
Unexpected adverse drug reaction(UADR)	2(6.25)	2	2(6.45)	2	1.0000
Serious adverse event(SAE)	0(0.00)	0	1(3.23)	1	0.4921
Adverse event influencing participant dropout	2(6.25)	2	3(9.68)	3	0.6719

Treatment : group taking GSO, Control : group taking placebo, N : number

n: number of subjects,

^†

n: number of events

^‡

p: p-value between groups by chi-square test or Fisher’s exact test

Table 6

Vital Sign

Vital sign		Treatment (N=32)		Control (N=31)		p†

		Mean±SD	p*	Mean±SD	p*
SBP (mmHg)	Baseline	126.09±13.72		122.39±11.80		0.2183
SBP (mmHg)	Final visit	124.14±14.02	0.0993	123.79±11.15	0.4465	1.0000

DBP (mmHg)	Baseline	80.16±7.67		79.68±7.52		0.8532
DBP (mmHg)	Final visit	78.62±7.89	0.2668	80.34±7.78	0.8145	0.4184

Pulse (beats/min)	Baseline	71.84±9.78		73.45±11.16		0.5450
Pulse (beats/min)	Final visit	69.28±7.38	0.2026	70.38±8.65	0.0600	0.6032

BT(°C)	Baseline	36.44±0.14		36.51±0.19		0.2313
BT(°C)	Final visit	36.55±0.23	0.0442	36.49±0.18	0.4103	0.1584

Treatment: group taking GSO, Control: group taking placebo, N: number

SBP: systolic blood pressure, DBP: diastolic blood pressure, BT: body temperature

p: p-value for baseline vs final visit by paired t-test or Wilcoxon’s signed rank test

^†

p: p-value between groups by independent t-test or Mann-Whitney test

Table 7

Hematology

Hematology		Treatment (N=32)		Control (N=31)		p†

		Mean±SD	p*	Mean±SD	p*
WBC (10³/μl)	Baseline	5.96±1.43		6.00±1.56		0.9233
WBC (10³/μl)	Final visit	5.98±1.79	0.8933	6.33±1.70	0.1803	0.3417

RBC (10⁶/μl)	Baseline	4.35±0.29		4.49±0.37		0.1021
RBC (10⁶/μl)	Final visit	4.39±0.35	0.7236	4.36±0.40	0.0309	0.7765

Hgb (mg/dL)	Baseline	13.78±1.49		14.22±1.38		0.3391
Hgb (mg/dL)	Final visit	13.97±1.47	0.9808	13.86±1.54	0.0205	0.9935

Hct (%)	Baseline	39.45±3.49		40.74±3.33		0.1393
Hct (%)	Final visit	39.86±3.51	0.9727	39.78±3.73	0.0385	0.9385

Platelets (10³/μl)	Baseline	241.25±48.35		236.19±53.47		0.6950
Platelets (10³/μl)	Final visit	229.71±49.21	0.3534	239.07±56.29	0.7242	0.4708

Treatment: group taking GSO, Control: group taking placebo, N: number

RBC: red blood cell, WBC: white blood cell, Hgb: Hemoglobine, Hct: Hematocrit

p: p-value for baseline vs final visit by paired t-test or Wilcoxon’s signed rank test

^†

p: p-value between groups by independent t-test or Mann-Whitney test

Table 8

Blood Chemistry

Blood chemistry		Treatment (N=32)		Control (N=31)		p†

		Mean±SD	p*	Mean±SD	p*
ALP (IU/L)	Baseline	74.44±25.17		71.71±16.26		0.6104
ALP (IU/L)	Final visit	81.00±23.53	0.0665	79.04±18.44	0.0109	0.7294

T.Bili (mg/dL)	Baseline	0.23±0.12		0.22±0.11		0.7350
T.Bili (mg/dL)	Final visit	0.22±0.10	0.5449	0.23±0.09	0.3060	0.5849

Total protein (mg/dL)	Baseline	7.53±0.34		7.49±0.39		0.6584
Total protein (mg/dL)	Final visit	7.60±0.37	0.7057	7.5±0.34	0.9179	0.2814

Albumin (g/dL)	Baseline	4.61±0.25		4.65±0.25		0.5737
Albumin (g/dL)	Final visit	4.70±0.23	0.2858	4.69±0.22	0.6329	0.8596

AST (IU/L)	Baseline	34.69±6.14		31.55±6.03		0.0326
AST (IU/L)	Final visit	38.57±21.95	0.7432	29.46±8.03	0.1696	0.0411

ALT (IU/L)	Baseline	38.66±16.55		34.90±11.27		0.2961
ALT (IU/L)	Final visit	42.71±27.11	0.6376	32.00±13.04	0.2923	0.0794

γ-GTP (IU/L)	Baseline	53.09±46.84		50.94±48.77		0.6401
γ-GTP (IU/L)	Final visit	48.39±42.69	0.0065	43.79±41.94	0.0052	0.3458

BUN (mg/dL)	Baseline	16.22±3.70		14.97±3.72		0.2064
BUN (mg/dL)	Final visit	15.68±3.58	0.3994	13.93±3.30	0.1235	0.0625

Creatinine (mg/dL)	Baseline	1.00±0.21		0.90±0.19		0.0496
Creatinine (mg/dL)	Final visit	1.04±0.19	0.3835	1.00±0.20	0.0148	0.5420

Glucose (mg/dL)	Baseline	99.47±19.02		101.74±21.81		0.8365
Glucose (mg/dL)	Final visit	97.71±29.41	0.0857	93.21±21.01	0.0785	0.7805

Uric acid (mg/dL)	Baseline	5.14±1.55		5.03±1.91		0.5869
Uric acid (mg/dL)	Final visit	5.59±1.42	0.0160	5.01±1.80	0.8401	0.1881

TG (mg/dL)	Baseline	171.09±101.72		180.52±147.93		0.6255
TG (mg/dL)	Final visit	192.00±147.56	0.6571	181.50±186.99	0.7393	0.6820

t.Chol (mg/dL)	Baseline	189.63±32.82		203.68±35.69		0.0605
t.Chol (mg/dL)	Final visit	206.04±39.05	0.0019	208.29±32.90	0.0769	0.8165

LDL (mg/dL)	Baseline	116.00±38.39		140.20±36.95		0.0277
LDL (mg/dL)	Final visit	123.82±38.56	0.5640	122.48±27.85	0.0136	0.8835

HDL (mg/dL)	Baseline	49.63±11.07		50.55±13.81		0.7703
HDL (mg/dL)	Final visit	48.07±13.40	0.9311	53.96±15.89	0.0338	0.1813

Treatment : group taking GSO, Control : group taking placebo, N : number

AST: aspartate aminotransferase. ALT: alanine aminotransferase, γ-GTP: gamma glutamyl transpeptidase, ALP: alkaline phosphatase, TG: triglyceride, t.Chol : total cholesterol, HDL: high-density lipoprotein-cholesterol, LDL: low-density lipoprotein-cholesterol

p: p-value for baseline vs final visit by paired t-test or Wilcoxon’s signed rank test

^†

p: p-value between groups by independent t-test or Mann-Whitney test

Table 9

Comparative Analysis of Normal and Abnormal Urinalysis

Final visit		Treatment (N=27)		Control (N=27)		p*

Baseline		Normal n(%)	Abnormal n(%)	Normal n(%)	Abnormal n(%)
pH	Normal	27(100.0)	0(0.00)	27(100.0)	0(0.00)
pH	Anormal	0(0.00)	0(0.00)	0(0.00)	0(0.00)

RBC	Normal	19(70.37)	2(7.41)	23(85.19)	0(0.00)	0.4889
RBC	Anormal	4(14.81)	2(7.41)	2(7.41)	2(7.41)	0.4889

WBC	Normal	25(92.59)	1(3.70)	20(74.07)	3(11.11)	0.3507
WBC	Anormal	0(0.00)	1(3.70)	3(11.11)	1(3.70)	0.3507

Protein	Normal	27(100.0)	0(0.00)	26(96.30)	0(0.00)
Protein	Anormal	0(0.00)	0(0.00)	1(3.70)	0(0.00)

Glucose	Normal	26(96.30)	1(3.70)	26(96.30)	1(3.70)	1.0000
Glucose	Anormal	0(0.00)	0(0.00)	0(0.00)	0(0.00)	1.0000

Specific gravity	Normal	26(96.30)	0(0.00)	27(100.0)	0(0.00)
Specific gravity	Anormal	0(0.00)	0(0.00)	0(0.00)	0(0.00)

Treatment: group taking GSO, Control: group taking placebo, N: number

RBC: red blood cell, WBC: white blood cell

p: p-value between groups by Fisher’s exact test