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

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