Table 4.
Summary of trials on ingredients having at least a limited evidence of efficacy
| 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 B3 | ||||
| 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 |
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.