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Table 4 Summary of trials on ingredients having at least a limited evidence of efficacy

From: Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence

Lead author and date [Reference] Inclusion criteria Duration of intervention, study design, sample size and treatment (dosage) Sample size and dropout rate (percentage) at the end of treatment ITT results at the end of treatment (baseline and final values or percentage change, intergroup p value)
ASUs
Blotman 1997 [24] Knee and hip OA
Mean age = 64.1 years
Mean wt = 70.2 kg
Mean ht = 166 cm
F/M: 108/55
3 months
Parallel study (n = 164)
1. Placebo (n = 83)
2. ASU (n = 81) (300 mg × 1/day)
Placebo (n = 76)
ASU (n = 77)
Dropout = 6.7%
Number of patients who resumed NSAID intake
Placebo (n = 53) (69.7%)
ASU (n = 33) (43.4%)
p < 0.001
Maheu 1998 [26] Knee and hip OA
Mean age = 64.1 years
Mean BMI = 26.8
F/M: 118/46
6 months
Parallel study (n = 164)
1. Placebo (n = 79)
2. ASU (n = 84) (300 mg × 1/day)
Placebo (n = 69)
ASU (n = 75)
Dropout = 12%
LFI score:
Placebo (9.3 to 9.9, +6%)
ASU (9.7 to 6.8, -30%)
p < 0.001
Appelboom 2001 [25] Knee OA
Mean age = 65 years
Mean wt = 76.5 kg
Mean ht = 164 cm
F/M: 205/55
3 months
Parallel study (n = 260)
1. diclofenac (n = 88)
2. ASU (n = 86) (300 mg × 1/day)
3. ASU (n = 86) (600 mg × 1/day)
Placebo (n = 76)
ASU 300 mg (n = 74)
ASU 600 mg (n = 75)
Dropout = 13.5%
Intake of NSAID and analgesics intake (mg/diclofenac per day)
Placebo (130 to 81, -38%)
ASU 300 mg (133.8 to 45.2, -66%)
ASU 600 mg (123.7 to 52.5, -58%)
p < 0.01 for each ASU group vs. placebo
ASU 300 vs. ASU 600: NS
Lequesne 2002 [27] Hip OA
Mean age = 63.2 years
Mean wt = 70.5 kg
Mean ht = 165 cm
F/M: 61/102
2 years
Parallel study (n = 163)
1. Placebo (n = 78)
2. ASU (300 mg × 1/day) (n = 85)
Placebo (n = 45)
ASU (n = 51)
Dropout = 41.1%
Joint space width mm:
Placebo: 2.50 to 1.90, -24%
ASU: 2.35 to 1.87, -20%
NS between groups
MSM
Usha 2004 [130] Knee OA
Mean age = 51 years
Mean wt = 66 kg
Mean ht = 160.5 cm
F/M: 76/42
12 weeks
Parallel study
Double dummy (n = 118)
1. Placebo (n = 28)
2. Glu (500 mg × 3/day) (n = 30)
3. MSM (500 mg × 3/day) (n = 30)
4. Glu (500 mg × 3/day) + MSM (500 mg × 3/day) (n = 30)
Placebo (n = 24)
Glu (n = 27) MSM (n = 27)
Glu + MSM (n = 28)
Dropout = 10.2%
Likert scale pain index (0 to 3)
Placebo (1.57 to 1.16, -26%)
Glu (1.74 to 0.65, -63%)
p < 0.001 vs. placebo
MSM (1.53 to 0.74, -52%)
p not reported
Glu + MSM (1.7 to 0.36, -79%)
p < 0.05 vs. Glu and MSM alone
LFI
Placebo: NS decrease
Glu: 13 to 8.85, -32%
MSM: 12.48 to 8.48, -32%
Glu + MSM: 13 to 8.65, -33%
p between groups not reported
Kim 2006 [131] Knee OA
Mean age = 56 years
F/M: 25/15
12 weeks
Parallel study (n = 50)
1. MSM (n = 25) (6 g/day)
2. Placebo (n = 25)
Placebo (n = 19)
MSM (n = 21)
Dropout = 20%
WOMAC pain:
Placebo (55.1 to 47.9, -13.2%)
MSM (58 to 43.4, -25%)
p = 0.041
WOMAC stiffness
Placebo (55.2 to 48.7, -12%)
MSM (51.2 to 41.1, -19.7%)
p = 0.32
WOMAC physical function
Placebo (52.9 to 44.1, -16.6%)
MSM (51.5 to 35.8, -30.4%)
p = 0.045
WOMAC total
Placebo (54.4 to 46.9, -13.8%)
MSM (53.6 to 40.1, -25%)
p = 0.054
SKI306X
Jung 2001 [125] Knee OA
Mean age = 58 years
Mean wt = 62.2 kg
Mean ht = 157.1 cm
F/M: 84/9
4 weeks
Parallel study (n = 96)
1. Placebo (n = 24)
2. SKI (200 mg × 3/day) (n = 24)
3. SKI (400 mg × 3/day) (n = 24)
4. SKI (600 mg × 3/day) (n = 24)
Placebo (n = 23)
SKI (200 mg) (n = 24)
SKI (400 mg) (n = 23)
SKI (600 mg) (n = 23)
Dropout = 3%
VAS of pain (only absolute change reported)
Placebo: -7.5 mm
200 mg: -23.6 mm
400 mg: -22.0 mm
600 mg: -29.8 mm
p < 0.001 for each SKI306X group vs. placebo
Jung 2004 [126] Knee OA
Mean age = 60 years
F/M: 231/18
4 weeks
Parallel study
Double dummy (n = 249)
1. diclofenac (n = 124)
2. SKI (200 mg × 3/day) (n = 125)
Diclofenac (n = 109)
SKI (n = 105)
Dropout = 14.1%
VAS of pain (only absolute change reported)
Diclofenac -15.49 mm
SKI -14.18 mm
NS between groups
Vitamin B 3
Jonas 1996 [79] OA of at least two joints
Mean age = 65 years
Mean wt = 163 kg
F/M 38/22 (PP)
12 weeks (N = 72)
1. Placebo
2. Vit B3 (n = 500 mg/day × 6/day)
Placebo (n = 29)
Vit B3 (n = 31)
Dropout = 17%
Global AIMS score (only change reported)
Placebo: +2.7, -10%
Vit B3: -5.9, +29%
p = 0.036
NSAIDs intake (pill/month) (only change reported)
Placebo: +0.25
Vit B3: -6.7, -13%
p = 0.014
VAS pain (only change reported)
Placebo: +1 mm
Vit B3: +8.2 mm
NS between groups
Vitamin C
Jensen 2003 [58] OA hip and/or knee
Mean age = 63 years
All female
14 days
Crossover study
7 days washout (n = 136)
1. Placebo
2. Calcium ascorbate (Vit C) (1,000 mg × 2/day)
Placebo (n = 71)
Vit C (n = 62)
Dropout = 2.2%
VAS pain:
Average difference between gps before and after crossover: 4.6 mm (starting levels 45–50 mm)
p = 0.0078
Duhuo Jisheng Wan
Teekachunhatean 2004 [129] Knee OA
Mean age = 62.5 years
Mean BMI = 26
F/M: 159/41
4 weeks
Parallel study
Double dummy (n = 200)
1. Diclofenac (25 mg × 3/day) (n = 100)
2. DJW (3 g × 3/day) (n = 100)
Diclofenac (n = 94)
DJW (n = 94)
Dropout = 6%
VAS total pain mm (sum of 5 VAS)
DJW (269 to 70, -73.93%)
Diclofenac (267 to 58, -78.15%)
VAS total stiffness cm (sum of 3 VASs)
DJW (122 to 32, -73.81%),
Diclofenac (129 to 32, -75.30%)
LFI
DJW (14.20 to 8.92, -37.18%)
Diclofenac (14.80 to 8.64, -41.62%)
NS between groups for all
Cetyl myristoleate
Hesslink 2002 [50] Knee OA
Mean age = 56.8 years
Mean wt = 76.4 kg
Mean ht = 164.7 cm
F/M: 39/25
68 days
Single-blind parallel study (n = 66)
1. Placebo: (soy lecithin 500 mg)
2. Cetyl myristoleate (350 mg, 50 mg soy, 75 mg fish oil)
Placebo (n = 31)
Cetyl myristoleate (n = 33)
Dropout 3%
Knee flexion
Cetyl myristoleate: +10.1 degree
Placebo: +1.1 degree
p < 0.001.
Lipids from Perna canaliculus
Gibson 1980 [46] OA hip and knee
Mean age = 55 years
F/M: 22/8
3 months
Parallel study (n = 38)
1. Lipid extract (210 mg/day) (n = 22)
2. Mussel powder (1,150 mg/day) (n = 16)
Dropout = 13% VAS pain:
Placebo: 13% improved
Mussel powder 40% improved
Audeval 1986 [45] Knee OA
Mean age = 66 years
F/M: 37/16
6 months
Parallel study (n = 53)
1. Placebo
2. Mussel powder (dose not stated)
Dropout = 0% VAS pain mm
Placebo (59 to 68, +15%)
Mussel powder (54 to 27, -50%)
p < 0.001
Gibson 1998 [47] OA hip and knee
Mean age = 69 years
F/M: 37/1
3 months
Parallel study (n = 30)
1. Lipid extract (210 mg/day) (n = 15)
2. Mussel powder (1,150 mg/day) (n = 15)
Lipid (n = 13)
Mussel powder (n = 13)
Dropout = 13%
VAS pain (absolute values not reported)
Difference between groups not reported
p < 0.05 vs. baseline for both groups
Harpagophytum procumbens
Lecomte 1992 [99] OA spine and knee
55 to 75 years old
F/M: 50/39
2 months
Parallel study (n = 89)
1. Placebo (n = 44)
2. H. procumbens (670 mg × 3/day) (n = 45)
Not reported VAS pain mm
Placebo (68 to 50,-26%)
H. procumbens (73 to 45, -38%)
p = 0.012
Chantre 2000 [100] OA hip and knee
Mean age = 62 years
Mean wt = 75 kg
F/M: 77/55
4 months
Parallel study
Double dummy (n = 112)
1. Diacerhein (50 mg × 2/day) (n = 60)
2. H. procumbens (Harpado) (435 mg × 6) (n = 62)
Diacerhein (n = 42)
H. Procumbens (n = 50)
Dropout = 27%
VAS pain cm
Diacerhein (62 to 36, -42%), H. procumbens (64 to 31, -51%)
NS between groups
Bromelain
Singer 1996 [92] Knee OA
Mean age = 53 years
F/M 37/43
28 days
Parallel study
Double dummy (n = 63)
1. Diclofenac (50 mg × 2/day) (n = 40)
2. Phlogenzym (Bromelain 90 mg × 2/day) (n = 40)
Diclofenac (n = 36)
Phlogenzym (n = 32)
Dropout rate = 15%
Morning pain (score 1–5)
Diclofenac (2.5 to 1.2, -52%)
Phlogenzym (2.3 to 1.4, -39%)
NS between groups
Pain walking (score 1–5)
Diclofenac (3.1 to 1.4, -55%)
Phlogenzym (2.9 to 1.7, -41%)
NS between groups
Singer 2001 [142] Knee OA
19–75 years
21 days
Parallel study
Double dummy (n = 63)
1. Diclofenac (50 mg × 2/day) (n = 32)
2. Phlogenzym (Bromelain 90 mg × 2/day) (n = 31)
Dropout rate = 0% VAS pain at rest mm
Diclofenac: 31 to 14, -54%
Phlogenzym: 35 to 15, -58%
NS between groups
VAS pain on movement cm
Diclofenac: 54 to 27, -49%
Phlogenzym: 60 to 30, -56%
NS between groups
LFI:
Diclofenac: 15.81 to 12.77, -19%
Phlogenzym 15.48 to 9.81, -37%
p = 0.0165
Klein 2000 [91] Knee OA
Mean age = 52 years
F/M: 37/36
3 weeks
Parallel study
Double dummy (n = 73)
1. Diclofenac (50 mg × 2/day) (n = 37)
2. Phlogenzym (Bromelain 90 mg × 2/day) (n = 36)
Diclofenac (n = 34)
Phlogenzym (n = 35)
Dropout = 5.5%
LFI:
Diclofenac: 14.04 to 3.50, -75%
Bromelain 13.56 to 3.10, -77%
NS between groups
Tilwe 2001 [89] Knee OA
Mean age = 57 years
F/M: 31/19
3 weeks
Parallel study
Single-blind study (n = 50)
1. Phlogenzym (45 mg bromelain × 2/day) (n = 25)
2. Diclofenac (50 mg × 2/day) (n = 25)
Not reported Joint tenderness (4-pt scores)
Diclofenac 1.44 to 1.16, -19.4%
bromelain 1.64 to 0.80, -51.2%,
p < 0.05
Pain at rest (4-pt scores)
Diclofenac 1.24 to 0.92, -25.8%
bromelain 1.12 to 0.64, -42.9%,
NS difference between groups
Pain on movement (4-pt scores)
Diclofenac 2.04 to 1.32, -35.3%
bromelain 1.92 to 1.16, -39.6%,
NS difference between groups
Akhtar 2004 [90] Knee OA
Mean age = 57 years
Mean wt = 76 kg
Mean ht = 163 cm
F/M: 70/28
6 weeks
Parallel study
Double dummy (n = 98)
1. Phylogenzym (90 mg bromelain × 3/day) (n = 46)
2. Diclofenac (50 mg × 2/day) (n = 52)
Diclofenac (n = 42)
Phylogenzym (n = 36)
Dropout = 20%
LFI
Diclofenac 12.5 to 9.4, -23.6%,
Phlogenzym 13.0 to 9.4, -26.3%
NS difference between groups
  1. ASU = avocado soybean unsaponifiable; BMI = body mass index; DJW = Duhuo Jisheng Wan; F = female; Glu = glucosamine; ht = height; ITT = intention-to-treat; LFI = Lequesne functional index; M = male; MSM = methylsulfonyl methane; N = total sample size; NS = not significant; NSAID = nonsteroidal anti-inflammatory drug; OA = osteoarthritis; PP = per protocol; SKI = SKI 306X; VAS = visual analog scale; Vit = vitamin; WOMAC = Western Ontario and McMaster universities [index]; wt = weight.