Glucosamine-containing supplement improves locomotor functions in subjects with knee pain: a randomized, double-blind, placebo-controlled study

Figures & data

Table 1 The baseline characteristics of the study population

Variables	GCQID groupa (n=50)	Placebo groupa (n=50)	P-value
Age (years)	51.9±1.2	51.6±1.1	0.852
Sex (male/female)	22/28	22/28	1.000
Height (cm)	162.0±1.0	163.0±1.2	0.507
Body weight (kg)	60.3±1.3	62.3±1.3	0.397
Body mass index (kg/m^2)	22.9±0.5	23.3±0.5	0.500
Systolic blood pressure (mmHg)	129.7±2.1	125.7±2.2	0.198
Diastolic blood pressure (mmHg)	81.1±1.5	80.2±1.5	0.704
Heart rate (beats/min)	71.8±1.6	75.4±1.7	0.131
Normal walking speed (m/s)	1.28±0.02	1.29±0.02	0.912
Knee-extensor strength (% body weight)b	100.0±5.2	93.1±5.3	0.360
JOA criteria aggregate scores (points)	180.4±1.3	177.9±2.0	0.919
VAS score for pain on walking (mm)	25.5±3.0	21.3±2.7	0.297
Average daily steps walked in a week (steps)	6,511±465	6,192±446	0.622
K–L grades (0, I, II)	14, 25, 11	16, 23, 11	0.897

Notes:

a All values except sex and K–L grade are expressed as mean ± standard error.

b Knee-extensor strength was measured in both knees and expressed as total strength of both knees.

Abbreviations: GCQID, glucosamine hydrochloride, chondroitin sulfate, type II collagen peptides, quercetin glycosides, imidazole peptides, and vitamin D; JOA, Japanese Orthopaedic Association; K–L, Kellgren–Lawrence; VAS, visual analog scale.

Table 2 Changes in knee-joint functions and locomotor functions in subjects eligible for efficacy assessmenta

Variables	Values at each time pointb					Two-way ANOVA (group × time) P-value
	Baseline	Week 4	Week 8	Week 12	Week 16
JKOM
(I) VAS score for knee pain (mm)
GCQID	27.0±3.4	24.2±3.1	17.1±2.5*	14.0±3.0**	9.8±2.3**	0.939
Placebo	28.5±3.0	24.2±3.3	18.7±3.2*	13.0±2.5**	11.4±2.1**
(II–V) Total score (points)
GCQID	14.0±1.6	11.8±1.5	9.2±1.0*	9.1±1.2**	8.5±1.1**	0.362
Placebo	13.0±1.0	12.6±1.1	11.0±1.1	10.5±1.2	9.3±0.9*
VAS score for pain on walking (mm)
GCQID	23.7±3.3	16.2±2.8	12.5±2.5**	9.6±2.3**	7.1±2.2**	0.216
Placebo	18.6±2.2	16.1±2.9	15.0±3.1	11.6±2.3*	7.3±1.6**
Normal walking speed (m/s)
GCQID	1.28±0.03		1.32±0.03*		1.35±0.02**	0.524
Placebo	1.28±0.02		1.32±0.02*		1.33±0.02**
Knee-extensor strength (% body weight)c
GCQID	95.9±5.0		104.6±5.0*		104.5±4.9*	0.546
Placebo	88.1±5.8		92.3±5.5		92.6±5.6

Notes:

a GCQID group (n=41) and placebo group (n=41).

b Values expressed as mean ± standard error.

c Knee-extensor strength was measured in both knees and expressed as the total strength of both knees.

* P<0.05 and

** P<0.01 compared with baseline value.

Abbreviations: ANOVA, analysis of variance; GCQID, glucosamine hydrochloride, chondroitin sulfate, type II collagen peptides, quercetin glycosides, imidazole peptides, and vitamin D; JKOM, Japanese Knee Osteoarthritis Measure; VAS, visual analog scale.

Table 3 Baseline characteristics of subjects selected for stratified analyses

Variables	GCQID groupa (n=23)	Placebo groupa (n=25)	P-value
Age (years)	51.5±1.7	50.6±1.4	0.702
Sex (male/female)	9/14	12/13	0.536
Height (cm)	162.3±1.7	163.8±1.7	0.527
Body weight (kg)	63.1±2.8	62.9±2.3	0.956
Body mass index (kg/m^2)	23.8±0.7	23.4±0.7	0.696
Systolic blood pressure (mmHg)	131.1±3.6	126.6±3.2	0.352
Diastolic blood pressure (mmHg)	82.7±2.5	82.4±2.5	0.924
Heart rate (beats/min)	72.0±2.3	76.7±2.3	0.153
Normal walking speed (m/s)	1.26±0.04	1.25±0.03	0.957
Knee-extensor strength (% body weight)b	93.4±6.7	81.5±7.6	0.248
JOA criteria aggregate scores (points)	178.9±2.0	175.4±2.9	0.522
VAS score for pain on walking (mm)	33.3±4.3	24.5±3.0	0.103
Average daily steps walked in a week (steps)	6,221±510	6,386±599	0.837
K–L grades (0, I, II)	6, 14, 3	7, 12, 6	0.563

Notes:

a All values except sex and K–L grade are expressed as mean ± standard error.

b Knee-extensor strength was measured in both knees and expressed as total strength of both knees.

Abbreviations: GCQID, glucosamine hydrochloride, chondroitin sulfate, type II collagen peptides, quercetin glycosides, imidazole peptides, and vitamin D; JOA, Japanese Orthopaedic Association; K–L, Kellgren–Lawrence; VAS, visual analog scale.

Table 4 Changes in knee-joint functions and locomotor functions at each time point in subjects with mild-to-severe knee pain at baselinea

Variables	Values at each time pointb					Two-way ANOVA (group × time) P-value
	Baseline	Week 4	Week 8	Week 12	Week 16
JKOM
(I) VAS score for knee pain (mm)
GCQID	41.5±4.0	31.2±4.3	19.9±2.9**	15.4±4.4**	9.9±3.4**	0.490
Placebo	40.0±3.1	28.6±3.9*	22.4±3.5**	18.5±3.7**	16.4±3.0**
(II–V) Total score (points)
GCQID	17.6±2.5	14.3±2.5	10.3±1.5*	10.7±2.0**	9.2±1.7**	0.169
Placebo	15.2±1.3	13.7±1.6	13.3±1.6	12.2±1.7	10.6±1.2
VAS score for pain on walking (mm)
GCQID	33.3±4.3	22.2±4.3*	14.3±3.4**	12.0±3.9**	8.7±3.8**	0.067
Placebo	24.5±3.0	20.0±3.7	17.9±3.4*	16.6±3.4*	9.6±2.4**
Normal walking speed (m/s)
GCQID	1.26±0.04		1.32±0.04*		1.37±0.04**	0.095
Placebo	1.25±0.03		1.28±0.03		1.30±0.03*
Knee extensor strength (% body weight)c
GCQID	93.4±6.7		108.4±5.3^**,§		109.8±5.6**	0.330
Placebo	81.5±7.6		88.0±7.3		92.0±7.8**

Notes:

a GCQID group (n=23) and placebo group (n=25).

b Values are expressed as mean ± standard error.

c Knee-extensor strength was measured in both knees and expressed as total strength of both knees.

* P<0.05 and

** P<0.01 compared with values at baseline.

§ P<0.05 compared with placebo.

Abbreviations: ANOVA, analysis of variance; GCQID, glucosamine hydrochloride, chondroitin sulfate, type II collagen peptides, quercetin glycosides, imidazole peptides, and vitamin D; JKOM, Japanese Knee Osteoarthritis Measure; VAS, visual analog scale.

Figure 1 Changes in magnitude of (A) JKOM total score (items II–V) and (B) normal walking speed.

Notes: GCQID group (n=23) and placebo group (n=25). ^§P<0.05 compared with placebo group. Values are expressed as mean ± standard error.
Abbreviations: GCQID, glucosamine hydrochloride, chondroitin sulfate, type II collagen peptides, quercetin glycosides, imidazole peptides, and vitamin D; JKOM, Japanese Knee Osteoarthritis Measure.

Table 5 Changes in JKOM total score (items II–V) and normal walking speed at each time point in subjects with mild-to-severe knee pain and baseline K–L grade ≥II or ≤Ia

Variables	K–L grades ≥II				K–L grades ≤ I
	JKOM total score (points)		Normal walking speed (m/s)		JKOM total score (points)		Normal walking speed (m/s)
Values at each time pointb	GCQID	Placebo	GCQID	Placebo	GCQID	Placebo	GCQID	Placebo
Baseline	29.7±14.8	13.7±2.6	1.16±0.07	1.28±0.04	15.8±1.8	15.7±1.5	1.27±0.04	1.25±0.04
Week 4	24.3±14.9	12.0±3.4			12.9±2.0	14.3±2.0
Week 8	9.3±2.4	14.2±3.8	1.31±0.13	1.30±0.05	10.5±1.7	13.1±1.8	1.33±0.05	1.28±0.04
Week 12	9.3±1.5	13.0±5.3			10.9±2.3	11.9±1.6
Week 16	8.0±2.6	9.3±2.8	1.35±0.08	1.35±0.06*	9.4±1.9*	11.0±1.4	1.37±0.04**	1.28±0.04
Two-way ANOVA (group × time) P-value	0.082		0.064		0.634		0.193

Notes:

a GCQID group (n=3), placebo group (n=6) for K–L grade ≥II. GCQID group (n=20), placebo group (n=19) for K–L grade ≤I.

b Values expressed as mean ± standard error.

* P<0.05 and

** P<0.01 compared with baseline values.

Abbreviations: ANOVA, analysis of variance; GCQID, glucosamine hydrochloride, chondroitin sulfate, type II collagen peptides, quercetin glycosides, imidazole peptides, and vitamin D; JKOM, Japanese Knee Osteoarthritis Measure; K–L, Kellgren–Lawrence.

Table S1 Changes in laboratory values between baseline and week 16

Variablesa	Group	Values at time point
		Baseline	Week 16
AST (IU/L)	GCQID	21.3±0.8	20.6±0.9
	Placebo	22.1±1.1	19.5±0.8*
ALT (IU/L)	GCQID	20.7±1.5	19.7±2.0
	Placebo	22.0±1.8	20.2±1.7
ALP (IU/L)	GCQID	204.9±8.5	201.3±8.4
	Placebo	204.8±8.2	208.8±7.6
LDH (IU/L)	GCQID	185.3±3.9	190.9±3.8*
	Placebo	184.6±5.4	187.1±3.8
γ-GTP (IU/L)	GCQID	30.8±4.3	29.1±4.0
	Placebo	30.1±3.4	28.1±3.4
T-Bil (mg/dL)	GCQID	0.75±0.05	0.82±0.05*
	Placebo	0.72±0.05	0.74±0.06
TP (g/dL)	GCQID	7.33±0.05	7.19±0.05*
	Placebo	7.26±0.06	7.15±0.05*
Alb (g/dL)	GCQID	4.29±0.03	4.31±0.03
	Placebo	4.27±0.04	4.29±0.03
CPK (IU/L)	GCQID	124.5±12.6	121.3±9.9
	Placebo	103.0±6.3	112.7±7.3
Triglyceride (mg/dL)	GCQID	105.2±8.0	97.5±8.4
	Placebo	109.2±9.0	120.0±11.9
TC (mg/dL)	GCQID	220.7±4.7	214.3±4.4
	Placebo	223.3±5.0	213.4±5.2**
HDL-C (mg/dL)	GCQID	68.7±2.9	65.0±2.7**
	Placebo	68.2±2.7	62.5±2.3**
LDL-C (mg/dL)	GCQID	128.3±3.5	126.0±3.7
	Placebo	130.5±4.5	125.1±4.6*
BUN (mg/dL)	GCQID	14.0±0.5	13.3±0.6*
	Placebo	13.4±0.4	13.1±0.4
UA (mg/dL)	GCQID	4.53±0.18	4.95±0.19**
	Placebo	4.82±0.16	5.13±0.17**
Cr (mg/dL)	GCQID	0.69±0.02	0.70±0.02
	Placebo	0.66±0.02	0.68±0.02*
Na (mEq/L)	GCQID	140.1±0.2	139.9±0.2
	Placebo	140.0±0.2	140.5±0.3
K (mEq/L)	GCQID	4.45±0.05	4.28±0.05**
	Placebo	4.48±0.05	4.26±0.05**
Cl (mEq/L)	GCQID	103.2±0.3	103.9±0.2*
	Placebo	103.3±0.3	104.2±0.3**
Glucose (mg/dL)	GCQID	91.3±1.5	90.5±1.8
	Placebo	91.4±1.2	91.3±1.4
HbA1c (%)	GCQID	5.00±0.05	4.97±0.05
	Placebo	5.07±0.04	5.06±0.04
CRP (mg/dL)b	GCQID	0.10±0.02	0.10±0.02
	Placebo	0.10±0.02	0.07±0.01
Insulin (μU/mL)b	GCQID	5.83±0.58	5.92±0.69
	Placebo	5.55±0.65	7.23±0.84
WBC (×10^3/μL)	GCQID	5.74±0.17	5.60±0.16
	Placebo	5.94±0.20	5.80±0.19
RBC (×10^4/μL)	GCQID	463.1±4.3	449.0±4.6**
	Placebo	466.1±5.4	454.7±5.3**
Hb (g/dL)	GCQID	13.9±0.2	13.5±0.2**
	Placebo	14.0±0.2	13.7±0.2**
Hct (%)	GCQID	42.4±0.4	41.1±0.4**
	Placebo	42.8±0.5	41.5±0.5**
Plt (×10^4/μL)	GCQID	25.1±0.9	24.2±0.9*
	Placebo	25.6±0.9	24.2±0.8**

Notes: All values are expressed as mean ± standard error for GCQID group (n=48) and placebo group (n=49).

a Of the 100 subjects eligible for safety assessment, three (two in the GCQID group and one in the placebo group) dropped out of the study and did not undergo laboratory examinations at week 16.

b Values below the detectable limit for CRP and insulin are calculated as 0.05 mg/dL and 2.0 μU/mL, respectively.

* P<0.05 and

** P<0.01 compared with baseline.

Abbreviations: Alb, albumin; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; Cl, chloride; CPK, creatinine phosphokinase; Cr, creatinine; CRP, C-reactive protein; GCQID, glucosamine hydrochloride, chondroitin sulfate, quercetin glycosides, imidazole peptides, and vitamin D; γ-GTP, gamma-glutamyl transpeptidase; Hb, hemoglobin; HbA_1c, hemoglobin A1c; Hct, hematocrit; HDL-C, high-density lipoprotein cholesterol; K, potassium; LDH, lactate dehydrogenase; LDL-C, low-density lipoprotein cholesterol; Na, sodium; Plt, platelet; RBC, red blood cell; T-Bil, total bilirubin; TC, total cholesterol; TP, total protein; UA, uric acid; WBC, white blood cell.

Table S2 Incidence of adverse eventsa

Variables	GCQID group	Placebo group	P-value
Number of subjects eligible for safety assessment	50	50
Number of subjects with adverse events	10	10	1.000
Incidence of adverse eventsa (%)	20	20	1.000
Number of adverse events	14	14	1.000

Note:

a Incidence of adverse events (%) =100× number of subjects with adverse events/number of subjects eligible for safety assessment.

Abbreviation: GCQID, glucosamine hydrochloride, chondroitin sulfate, quercetin glycosides, imidazole peptides, and vitamin D.