Efficacy and safety of plant-derived products for the treatment of osteoarthritis

Figures & data

Table 1 Details of the herbal medicinal products used for the treatment of OA in randomized controlled double-blind studies

Study, duration	n	Mean age (years) Sex (M:F)	OA site	Formulation (daily dose)	Comparator	Route	Pain and function outcomes	Adverse events^#	Comments
AIF
Park et al^Citation45 6 weeks	57	69 5 M:52 F	Knee	AIF (Panax notoginseng Rehmannia glutinosa Libosch, Eleutherococcus senticosus), 200 mg	Placebo	Oral	VAS pain, WOMAC	Dyspepsia
Arnica
Widrig et al^Citation57 3 weeks	198	64 51 M: 147 F	Hand	Arnica gel (Arnica montana, 50 g/100 g gel)	Ibuprofen gel 5%	Topical	Pain VAS, hand function (hand algofunctional index)	–
Articulin–F
Kulkarni et al^Citation81 12 weeks	42	48 10 M:32 F	Knee, hip	Articulin–F (Withania somnifera, 900 mg; Boswellia serrata, 200 mg; Curcuma longa, 100 mg; zinc, 50 mg)	Placebo	Oral	NRS pain	Dermatitis, abdominal pain, nausea		Case–crossover trial
Aquamin F
Frestedt et al^Citation47 4 weeks	22	62 7 M: 5 F	Knee	Aquamin F (seaweed)	Placebo	Oral	WOMAC	Increased pain		Trial was 12 weeks, but only 4 weeks’ pain data included
Frestedt et al^Citation55 12 weeks	39	58 17 M: 19 F	Knee	Aquamin F (seaweed)	Placebo	Oral	WOMAC	Musculoskeletal complaints
ASU
Pavelka et al^Citation40 6 months	364	62 62 M:299 F	Knee	ASU, 300 mg	Chondroitin sulfate, 1,200 mg	Oral	WOMAC, Lequesne’s functional index, VAS pain	Allergic reactions, GI symptoms
Lequesne et al^Citation65 1 year	163	63 102 M:61 F	Hip	ASU, 300 mg	Placebo	Oral	VAS pain, Lequesne’s functional index	GI symptoms, neurologic, cutaneous, epigastric
Appelboom et al^Citation75 3 months	260	65 55 M:205 F	Knee	ASU, 300 mg or 600 mg	Placebo	Oral	VAS pain, Lequesne’s functional index	–		Dose–finding study
Maheu et al^Citation75 6 months	164	64 46 Μ: 118 F	Knee, hip	ASU, 300 mg	Placebo	Oral	VAS pain, Lequesne’s functional index	–
Blotman et al^Citation80 3 months	163	64 55 M: 108 F	Knee, hip	ASU, 300 mg	Placebo	Oral	VAS pain, Lequesne’s functional index	–
Ayurved Siriraj Wattana recipe
Pengkhum et al^Citation30 12 weeks	60	63 8 M:52 F	Knee	Ayurved Siriraj Wattana recipe, 900 mg (see Notes for ingredients)	Diclofenac, 75 mg	Oral	VAS pain (0–100), Oxford knee scores	Edema, diarrhea		Open label
Boswellia serrata
Sengupta et al^Citation38 12 weeks	38	52 12 M:26 F	Knee	Boswellia serrata extract (5–Loxin®; Aflapin®)	Placebo	Oral	WOMAC, Lequesne’s functional index, VAS pain	Acidity
Sengupta et al^Citation54 90 days	75	53 20 M:50 F	Knee	5–Loxin® (Boswellia serrata extract, 100 mg and 250 mg)	Placebo	Oral	WOMAC, VAS, Lequesne’s index	–		Only total n of adverse events reported
Sontakke et al^Citation59 6 months	66	Not stated	Knee	Boswellia serrata, 1 g	Valdecoxib, 10 mg	Oral	WOMAC	GI symptoms, inadequate pain control		Open label; dropouts reported, not adverse events
Usha and Naidu^Citation60 6 weeks	40	55 13 M:F 27	Knee	EazMov Plus: Picrorbiza kurroa (270 mg); Boswellia serrata (200 mg); Cyperus rotundus(100 mg); Tinospora cordifolia (100 mg); Glycyrrhiza glabra (60 mg); Zingiber officinale (50 mg); Tracbyspermum am mi (100 mg)	Ibu profen, 1,200 mg	Oral	Likert pain, VAS pain, Lequesne’s index	GI symptoms		Total n of patients with adverse events not reported
Chopra et al^Citation66 32 weeks	90	57 23 M:67 F	Knee	RA–11: Witbania somnifera; Boswellia serrata; Zingiber officinale; Curcuma longa; (amounts not stated); four capsules daily	Placebo	Oral	VAS pain, WOMAC	Skin rash
Kimmatkar et al^Citation68 8 weeks	30	59 12 M: 18 F	Knee	Boswellia serrata extract (333 mg)	Placebo	Oral		GI symptoms		Case–crossover trial
Capsaicin
Kosuwon et al^Citation41 4 weeks	100	61 0 M:99 F	Knee	Capsaicin, 0.0125%	Placebo	Topical	Pain VAS, WOMAC	Application site burning		Case–crossover
McCleane^Citation78 5 weeks	80	48 39 M:4I F	Knee, hip, shoulder, hand	Capsaicin, 0.025%	Placebo	Topical	Pain VAS			No info on adverse events
Altman et al^Citation83 12 weeks	113	62 41 M:72 F	Knee, ankle, elbow, wrist, shoulder	Capsaicin, 0.025%	Placebo	Topical	Pain VAS	Application site burning
Schnitzer et al^Citation84 3 weeks + extension to 9 weeks	59	67 29 M:40 F	Hand	Capsaicin, 0.025%	Placebo	Topical	Pain VAS	Application site burning		Total n of adverse events not given
Cat’s claw (Uncaria tomentosa, Uncaria guianensis)
Piscoya et al^Citation72 4 weeks	45	60 45 M:0 F	Knee	Cat’s claw (Uncaria tomentosa, Uncaria guianensis), 100 mg	Placebo	Oral	Likert pain scale (pain at rest)	Headache
Curcumin (Curcuma domestica)
Madhu et al^Citation24	42	120 56 37 M:83 F	Knee	Curcuma domestica extract, 1000 g (NR–INF–02)	Placebo, glucosamine	Oral	VAS pain	Body pain, cough, dyspepsia
Kuptniratsaikul et al^Citation45 6 weeks	107	61 21 M:86 F	Knee	Curcuma domestica extract, 2 g	Ibuprofen, 800 mg	Oral	WOMAC pain subscales	–
Castor oil
Medhi et al^Citation43 4 weeks	100	55 32 M:68 F	Knee	Castor oil, 2.7 ml_	Diclofenac sodium, 150 mg	Oral	VAS pain	–		No info on SD
Comfrey
Laslett et al^Citation25 12 weeks	133	64.8 54 M:79 F	Knee	4Jointz, 3.5 mg: Comfrey extract Symphytum officinale (200 mg/g); tannic acid (100 mg/g); aloe vera (300 mg/g); eucalyptus oil (40 mg/g); frankincense oil (1.0 mg/g)	Placebo	Topical	VAS pain, KOOS pain and stiffness	Rash
Grube et al^Citation58 3 weeks	220	58 67 Μ: 153 F	Knee	Kytta–Salbe F (comfrey root liquid, Symphytum officinale, 35%) 6 cm	Placebo	Topical	Pain VAS	Not stated
Derris scandens
Kuptniratsaikul et al^Citation35 4 weeks	125	60 18 M:89 F	Knee	Derris scandens	Naproxen, 500 mg	Oral	WOMAC	–
Duhuo Jisheng Wan (Radix Angelicae Pubescentis, Loranthus parasiticus)
Teekachunhatean et al^Citation62 4 weeks	200	62 41 M: 159 F	Knee	Duhuo Jisheng Wan (DJW)^a 3 g	Diclofenac, 75 mg	Oral	WOMAC, Lequesne’s functional index	–
E–OA–07
Kulkarni et al^Citation34 12 weeks	16	55 3 Μ: 13 F	Knee	E–OA–07 (shyonak [Oroxylum indicum], ashwagandha [Withania somnifera], shunthi [Zingiber officinale], guggul [Commiphora wightii], chopchini [Smilax china], rasana [Pluchea lanceolata], shallaki [Bowellia serrata]); amounts not stated	Placebo	Oral	VAS pain score, WOMAC	Fracture
Flavocoxid
Levy et al^Citation46 4 weeks	103	58 13 M:90 F	Knee	Flavocoxid, 1,000 mg (Scutellaria baicalensis; Acacia catechu)	Naproxen, 1,000 mg	Oral	Total WOMAC score	–
Fufang Nanxing Zhitong Gao, Shangshi Jietong Gao
Wang^Citation31 1 week	150	59 13 M: 136 F	Knee	FNZG; SJG (see notes for ingredients)	Placebo	Patch	Pain VAS (walking on flat surface); WOMAC score (Likert scale)	Patch site reaction
GBT
Tao et al^Citation42 8 weeks	90	63 52 M:38 F	Knee	GBT, 400 mL:drynaris rhizoma, 18–20 g; eucommia bark, 20–30 g; cibot rhizome (Rhizoma Cibotii) 25–30 g; psoralea fruit, 10–15 g;tubeimu tuber (Bolbostemma paniculatum) 15–20 g; orientvine (Caulis Sinomenii) 20–30 g; spatholobus stem (Spatholobus suberectus), 20–30 g; epimedium herb, 10–15 g	Glucosamine sulfate 1,500 mg	Oral	VAS pain	Abdominal distension, mild diarrhea
Ginger¥
Drozdov et al^Citation27 4 weeks	43	55 8 M:35 F	Knee, hip	Ginger + glucosamine (Zinaxin® glucosamine: 200 mg, ginger extract; 1,000 mg, glucosamine)	Diclofenac + glucosamine (100 mg diclofenac; 100 mg glucosamine)	Oral	VAS pain on standing (0–100)	–
Zahmatkash and Vafaeenasab^Citation33 6 weeks	92	52.2 2 M:90 F	Knee	Ginger (Zingiber officinale), mastic, sesame oil, 6 g	Salicylate (dose not stated) 6 g	Topical	VAS pain, stiffness	–		Adverse events not reported
Zakeri et al^Citation37 6 weeks	204	47 40 Μ: 164 F	Knee	Ginger (Zintoma: Zingiber officinale) 250 mg	Placebo	Oral	VAS pain (standing, walking), WOMAC	–
Yip and Tam^Citation53 4 weeks	59	74 11 M:42 F	Knee	Massage + 1 % ginger essential oil, 0.5% orange essential oil	Massage + no essential oils; conventional treatment only	Topical, massage	WOMAC	–
Wigler et al^Citation67 12 weeks	29	62 6 M:23 F	Knee	Ginger extract (Zingiber officinale, Zintona EC) 1,000 mg	Placebo	Oral	VAS pain on movement	–		Case–crossover trial
Altman and Marcussen^Citation71 6 weeks	261	65 98 Μ: 163 F	Knee	Ginger extract EV.EXT 77 (Zingiber officinale, Alpinia galanga) 255 mg	Placebo	Oral	VAS pain on standing (0–100), WOMAC	GI events
Harpagophytum procumbens
Chantre et al^Citation77 16 weeks	122	61 45 M:77 F	Knee, hip	Devil’s claw, Harpadol, 2,610 mg (Harpagophytum procumbens)	Diacerein, 100 mg	Oral	VAS pain, Lequesne’s functional index	–
Individualized herbal treatment
Hamblin et al^Citation51 10 weeks	20	67 6 M: 14 F	Knee	Individualized herbal treatment + multivitamins	Placebo + multivitamins	Oral	WOMAC	Not reported		Adverse events not reported
Individualized traditional Chinese medicine
Lechner et al^Citation32 20 weeks	102	59 29 M:63 F	Hip or knee	Individualized traditional Chinese medicine prescription	Nonspecific herbal treatment	Oral, as tea	WOMAC, SF–36	–
Olive oil
Bohlooli et al^Citation29 4 weeks	71	40–80 0 M:7I F	Knee	Virgin olive oil	0.5% piroxicam (amount not stated)	Topical	WOMAC	–
Passion fruit peel
Farid et al^Citation39 90 days	33	53 8 M:25 F	Knee	Passion fruit peel extract (Passiflora edulis), 150 mg	Placebo	Oral	WOMAC	–
Phellodendron amurense
Oben et al^Citation44 8 weeks	80	–	Knee	Phellodendron amurense tree bank, Citrus sinensis extract (NP 06–1, 1.5 g)	Placebo	Oral	Lequesne’s functional index	Hepatitis, nausea		Limited demographic information, stratified by BMI
Phytalgic
Jacquet et al^Citation48 4 weeks	81	57 26 M:55 F	Knee or hip	Phytalgic (fish oils, Urtica dioica, zinc, vitamin E)	Placebo	Oral	WOMAC	Fishy belching, increased pain, infection, falls, muscle pains
Pycnogenol
Cisár et al^Citation52 15 weeks	100	54 32 M:68 F	Knee	Pycnogenol (French maritime pine Pinus maritima), 150 mg	Placebo	Oral	VAS, WOMAC
Farid et al^Citation22 90 days	37	48 3 M:35 F	Knee	Pycnogenol (French maritime pine, Pinus maritima), 150 mg	Placebo	Oral	WOMAC	–
Reparagen
Mehta et al^Citation56 8 weeks	95	53 24 M:71 F	Knee	Reparagen (Uncaria guianensis, 300 mg; Lepidium meyenii, 1,500 mg), 1,800 mg	Glucosamine sulfate, 1,500 mg	Oral	WOMAC, Pain VAS	–
Rosehip
Winther et al^Citation61 3 months	94	65 40 M:54 F	Knee or hip	Rosehip (Rosa canina), 5 g	Placebo	Oral	WOMAC	–		Case–crossover trial
Rein et al^Citation64 3 months	112	67 41 M:71 F	Various	Hyben Vita (Rosa canina fruits), 5 g	Placebo	Oral	Likert pain	Micturition, waterbrash, diarrhea, cancer		Case–crossover trial
Warholm et al^Citation85 4 months	100	65 35 M:65 F	Knee or hip	Standardized rosehip powder (Rosa canina), 5 mg	Placebo	Oral	Likert pain score for symptom improvement (0–4)	–
Scutellaria baicalensis
Sampalis and Brownell^Citation28 12 weeks	60	57.6 22 M:38 F	Knee or hip	UP446 (extracts of Scutellaria baicalensis and Acacia catechu), 250 mg or 500 mg	Placebo or celecoxib, 200 mg daily	Oral	WOMAC, SF–36	–
Shu Feng Huo Luo Pian
Wu and Zhou^Citation70 4 weeks	50	63 13 M:37 F	Not stated	Shu Feng Huo Luo Pian, 1.2 g	Sulindac, 0.4 g	Oral	Arthralgia and joint dysfunction indexes	Feverish sensation in limbs, stomach burning		Open label
SKI306X
Jung et al^Citation65 4 weeks	249	63 18 M:23 1 F	Knee	SK1306X (600 mg): Clematis Radix; Trichosanthes root; Prunella spike	Diclofenac, 100 mg	Oral	Pain VAS, Lequesne’s functional index	–
Jung et al^Citation74 4 weeks	72	59 9 M:84 F	Knee	SK1306X (600 mg, 1,200 mg, 1,800 mg); Clematis mandshurica; Trichosanthes kirilowii; Prunella vulgaris	Placebo	Oral	VAS pain, Lequesne index	–		Dose–finding study
Stinging nettle (Urtica dioica)^f
Randall et al^Citation50 16 weeks	42	66 24 M: 18 F	Knee	Stinging nettle (Urtica dioica)	Placebo (Urtica galeopsifolia)	Topical	VAS pain, WOMAC	Localized skin rash
Randall et al^Citation76 1 week	27	60 4 M:23 F	Base of thumb	Stinging nettle (Urtica dioica)	Placebo	Topical	VAS pain	Localized skin rash		Case–crossover trial; some patients with RA and AS
Tipi tea (Petiveria alliacea)
Ferraz et al^Citation82 1 week	20	62 2 M: 20 F	Knee, hip	Tipi tea (Petiveria alliacea), 9 g in 600 mL water	Placebo tea (Imperata exaltata [sape])	Oral, as tea	Pain subscales (pain at rest, pain on motion, pain at night)	Not reported		Case–crossover trial; AE not reported
Willow bark (Salix daphnoides)
Biegert et al^Citation63 42 days	127	62 53 M:74 F	Knee or hip	Willow bark (Salix daphnoides), 240 mg	Diclofenac 100 mg or placebo	Oral	WOMAC	–
Schmid et al^Citation73 2 weeks	78	52 59 M: 19 F	Knee or hip	Willow bark (Salix daphnoides), 340 mg	Placebo	Oral	WOMAC, VAS pain	–

Notes:

a Duhuo Jisheng Wan (DJW): 7.75% each of Radix Angelicae Pubescentis (Duhuo), Radix Gentianae Macrophyllae (Qinjiao), Cortex Eucommiae (Duzhong), Radix Achyranthis Bidentatae (Niuxi), Radix Angelicae Sinensis (Danggui), Herba Taxilli (Sangjisheng), Radix Rehmanniae Preparata (Shudihuang), Rhizoma Chuanxiong (Chuanxiong), Cortex Cinnamomi (Rougui) and Radix Ledebouriellae (Fangfeng), 5% each of Radix Paeoniae Alba (Baishao), Radix Codonopsis (Dangshen), Radix Glycyrrhizae (Gancao) and Poria (Fuling), as well as 2.5% of Herba Asari (Xixin). FNZG, hypaconitine and eugenol (Rhizoma Arisaematis, Radix Aconiti, Flos Caryophylli), Cortex Cinnamomi, Radix Angelicae Dahuricae, Herba Asari, Rhizoma Chuanxiong, Radix Cynanchi Panicuclati, Olibanum, myrrah, camphora, Borneolum Syntheticum). SJG, 17 different herbs, including Rhizoma Arisaematis, Radix Aconiti, Radix Angelicae Dahuricae, Cortex Cinnamomi, camphora, Borneolum Syntheticum, Radix Angelicae Pubescentis, Cortex Acanthopanacis, Rhizoma Curcuma Longae, Flos Carthami, Folium Artemisiae, argyi, Rhizoma Atractylodis, Rhizoma Pinelliae, Semen Sinapis, Semen Vaccariae, Radix Aconiti Kusnezoffi, and Herba Menthae.

# Adverse events listed are events that are more frequent in participants receiving plant-based therapy. Adverse events of active comparators are not listed. Adverse events are not listed if similar patterns were observed in both groups. Ayurved Siriraj Wattana recipe: Piper nigrum, Boesenbergia pandurata, Tinospora cordifolia, Terminalia chebula, Cladogynos orientalis, Ferula asafoetida, Saussurea lappa, Cyperus rotundus, Derris scandens, Anamirta cocculus, Drypetes roxburghii, Cinnamomum siamense, Aegle marmelos, Conioselinum univitatum, and Cryptolepis buchanani. Individual amounts not stated;³⁰

β Boswellia serrata: also see Kulkarni⁸¹ and Kulkarni (E-OA-07);³⁴

¥ Ginger (Zingiber officinale): also see EazMov Plus,⁶⁰ E-OA-07,³⁴ and RA–11, Chopra;⁶⁶

f Stinging nettle, see also Phytalgic (Jacquet).⁴⁸

Abbreviations: n, number of study participants; M, male; F, female; OA, osteoarthritis; AE, adverse event; AIF, anti-inflammatory factor; VAS, visual analog scale; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index; NRS, numeric rating scale; ASU, avocado/soybean unsaponifiables; GI, gastrointestinal; SD, standard deviation; KOOS, Knee injury and Osteoarthritis Outcome Score; FNZG, Fufang Nanxing Zhitong Gao; SJG, Shangshi Jietong Gao; GBT, Gubitong Recipe; BMI, body mass index; RA, rheumatoid arthritis; AS, ankylosing spondylitis.

Table 2 Risk of bias assessment for individual randomized controlled trials of botanical therapy versus placebo or active comparator

Study	Treatment	Random sequence generation	Allocation concealment	Blinding: participants	Blinding: outcome assessment	Incomplete outcome data	Selective reporting	Other
Madhu et al^Citation24	Curcumin	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Bohlooli et al^Citation29	Olive oil	Low risk	Low risk	Low risk	Low risk	Risk unclear	Low risk	Risk unclear
Drozdov et al^Citation27	Ginger	High risk	Risk unclear	Risk unclear	Risk unclear	Low risk	Low risk	Low risk
Laslett et al^Citation25	4Jointz	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Niempoog et al^Citation26	Ginger	Risk unclear	Risk unclear	Low risk	Low risk	Risk unclear	Low risk	Low risk
Pengkhum et al^Citation30	Ayurved Siriraj Wattana	Low risk	Risk unclear	High risk	High risk	Low risk	Low risk	Low risk
Sampalis and Brownell^Citation28	UP446	Risk unclear	Risk unclear	Risk unclear	Risk unclear	Risk unclear	Low risk	Low risk
Wang et al^Citation31	FNZG, SJG	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Kosuwon et al^Citation41	Capsaicin	Low risk	High risk	Risk unclear	Risk unclear	Low risk	Low risk	Low risk
Kulkarni, 2011^34	E–OA–07	Risk unclear	Low risk	Risk unclear	Risk unclear	High risk	Low risk	Low risk
Kuptniratsaikul et al^Citation35	Derris scandens	Low risk	Low risk	High risk	Risk unclear	Risk unclear	Low risk	Low risk
Lechner et al^Citation32	TCM	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Vishal et al^Citation36	Boswellia serrata	Low risk	Low risk	Low risk	Low risk	Risk unclear	Low risk	Low risk
Zahmatkash and Vafaeenasab^Citation33	Ginger	Low risk	Risk unclear	Risk unclear	Risk unclear	Risk unclear	Low risk	Low risk
Zakeri et al^Citation37	Ginger	Risk unclear	Risk unclear	Low risk	Low risk	Risk unclear	Low risk	Low risk
Farid et al^Citation39	Passion fruit peel	Risk unclear	Risk unclear	Low risk	Low risk	Risk unclear	Low risk	Low risk
Pavelka et al^Citation40	ASU	Low risk	Risk unclear	Low risk	Low risk	Low risk	Low risk	Low risk
Sengupta et al^Citation38	Boswellia serrata	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Frestedt et al^Citation47	Aquamin F	Low risk	Low risk	Low risk	Low risk	High risk	Low risk	Risk unclear
Jacquet et al^Citation48	Phytalgic	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Kuptniratsaikul et al^Citation45	Curcumin	Low risk	Low risk	High risk	High risk	Risk unclear	Low risk	Low risk
Levy et al^Citation46	Flavocoxid	Risk unclear	Risk unclear	Risk unclear	Risk unclear	Low risk	Low risk	Low risk
Medhi et al^Citation43	Castor oil	Risk unclear	Risk unclear	Risk unclear	Risk unclear	Risk unclear	Low risk	Low risk
Oben et al^Citation44	Phellodendron amurense	Low risk	Risk unclear	Low risk	Low risk	Risk unclear	Low risk	Low risk
Park et al^Citation49	AIF	Risk unclear	Low risk	Low risk	Low risk	High risk	Low risk	Low risk
Tao et al^Citation42	GBT	High risk	Risk unclear	High risk	High risk	Low risk	Low risk	Low risk
Cisar et al^Citation52	Pycnogenol	Risk unclear	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Frestedt et al^Citation55	Aquamin F	Low risk	Low risk	Low risk	Low risk	High risk	Low risk	Low risk
Hamblin et al^Citation51	Individualized herbal treatment	Risk unclear	Low risk	Risk unclear	Risk unclear	Low risk	Low risk	Low risk
Randall et al^Citation50	Stinging nettle	Low risk	Low risk	Low risk	Low risk	Risk unclear	Low risk	Low risk
Sengupta et al^Citation54	Boswellia serrata	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Yip and Tam^Citation53	Massage + essential oils	High risk	High risk	High risk	High risk	Low risk	Low risk	Low risk
Grube et al^Citation58	Comfrey	Risk unclear	Risk unclear	Risk unclear	Risk unclear	Risk unclear	Low risk	Low risk
Mehta et al^Citation56	Reparagen	Low risk	Low risk	Low risk	Low risk	Risk unclear	Low risk	Low risk
Sontakke et al^Citation59	Boswellia serrata	Low risk	Risk unclear	High risk	High risk	Risk unclear	Risk unclear	Low risk
Widrig et al^Citation57	Arnica gel	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Farid et al^Citation22	Pine bark	Risk unclear	Risk unclear	Low risk	Low risk	Low risk	Low risk	Low risk
Usha and Naidu^Citation60	EazMov Plus	Low risk	Risk unclear	High risk	High risk	Low risk	Low risk	Low risk
Winther et al^Citation61	Rosehip	Low risk	Low risk	Low risk	Low risk	Risk unclear	Low risk	Low risk
Biegert et al^Citation63	Willow bark	Low risk	Low risk	Low risk	Low risk	Risk unclear	Low risk	Low risk
Chopra et al^Citation66	RA–11	Low risk	Low risk	Low risk	Low risk	Risk unclear	Low risk	Low risk
Jung et al^Citation65	SKI306X	Low risk	Low risk	High risk	High risk	Risk unclear	Low risk	Low risk
Rein et al^Citation64	Rosehip	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Teekachunhatean et al^Citation62	DJW	Risk unclear	Risk unclear	Low risk	Low risk	Risk unclear	Low risk	Low risk
Kimmatkar et al^Citation68	Boswellia serrata	Low risk	Risk unclear	Low risk	Low risk	Risk unclear	Low risk	Low risk
Wigler et al^Citation67	Ginger	Low risk	Low risk	Low risk	Low risk	Risk unclear	Low risk	Low risk
Lequesne et al^Citation69	ASU	Low risk	Low risk	Low risk	Low risk	Risk unclear	Low risk	Low risk
Wu and Zhou^Citation70	Shu Feng Huo Luo Pian	Risk unclear	Risk unclear	Risk unclear	Risk unclear	High risk	Risk unclear	Risk unclear
Altman and Marcussen^Citation71	Ginger	Low risk	Low risk	Low risk	Low risk	High risk	Low risk	Low risk
Appelboom et al^Citation75	ASU	Risk unclear	Risk unclear	Risk unclear	Risk unclear	Low risk	Low risk	Low risk
Jung and Roh^Citation74	SKI306X	Risk unclear	Risk unclear	Low risk	Low risk	Risk unclear	Low risk	Low risk
Piscoya et al^Citation72	Cat’s claw	Risk unclear	Risk unclear	Low risk	Low risk	Low risk	Low risk	Low risk
Schmid et al^Citation73	Willow bark	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Chantre et al^Citation77	Devil’s claw	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk	Low risk
Randall et al^Citation76	Stinging nettle	Risk unclear	Risk unclear	Low risk	Low risk	Low risk	Low risk	Low risk
McCleane^Citation78	Capsaicin	Low risk	Low risk	Low risk	Low risk	High risk	Low risk	Low risk
Maheu et al^Citation79	ASU	Low risk	Low risk	Low risk	Low risk	Risk unclear	Low risk	Low risk
Blotman et al^Citation80	ASU	Risk unclear	Risk unclear	Low risk	Low risk	Risk unclear	Low risk	Low risk
Altman et al^Citation83	Capsaicin	Risk unclear	Risk unclear	Risk unclear	Risk unclear	High risk	Low risk	Low risk
Schnitzer et al^Citation84	Capsaicin	Risk unclear	Risk unclear	Risk unclear	Low risk	High risk	Low risk	Low risk
Ferraz et al^Citation82	Tipi tea	Risk unclear	High risk	Risk unclear	Risk unclear	Risk unclear	Risk unclear	Risk unclear
Kulkarni et al^Citation81	Articulin–F	Risk unclear	Risk unclear	Low risk	Low risk	Risk unclear	Low risk	Low risk

Abbreviations: FNZG, Fufang Nanxing Zhitong Gao; SJG, Shangshi Jietong Gao; TCM, traditional Chinese medicine; ASU, avocado/soybean unsaponifiables; AIF, anti-inflammatory factor; GBT, Gubitong Recipe; DJW, Duhuo Jisheng Wan.

Figure 1 Efficacy of plant-derived therapies compared to placebo on VAS and NRS pain scores.

Note: Weights are from random effects analysis.
Abbreviations: n, number of study participants; SMD, standardized mean difference; CI, confidence interval; VAS, visual analog scale; NRS, numeric rating scale; AIF, anti-inflammatory factor; ASU, avocado/soybean unsaponifiables.

Table 3 Summary of efficacy findings of plant-based therapy compared to placebo, by therapy class

Class of plant–based therapy	VAS/NRS pain score	WOMAC/ KOOS pain	WOMAC/ KOOS function
ASU^Citation65,Citation75,Citation75,Citation80	No	–	Yes
Boswellia serrate^Citation36,Citation38,Citation54,Citation55,Citation60,Citation66,Citation68,Citation81	Yes	Yes	Yes
Capsaicin^Citation41,Citation78,Citation83,Citation84	Yes	Yes	Yes
Comfrey^Citation25,Citation58	No	(No)	(No)
Ginger^Citation37,Citation53,Citation71	–	Yes	No
Pycnogenol^Citation22,Citation52	(Yes)	No	(Yes)
Other treatments
Rosehip^Citation61,Citation64	(No)	(No)	–
Stinging nettle^Citation50,Citation76	(No)	(No)	(No)
Willow bark^Citation63,Citation73	(Yes)	(No)	No
NR–INF–02^24	Yes	–	–
UP446 250 mg^Citation28	–	No	Yes
UP446 500 mg^Citation28	–	Yes	Yes
FNZG/SJG^Citation31	–	No	–
Individualized TCM/nonspecific herbal treatment^Citation32	–	No	–
E–OA–07^34	Yes	Yes	Yes
Passion fruit peel^Citation39	–	Yes
Phellodendron and citrus extracts (NP 06–1)^Citation44	–	–	No
Phytalgic^Citation48	–	Yes	Yes
AIF^Citation49	No	–	No
Individualized herbal treatment^Citation51	–	No	No
Aquamin F^Citation47,Citation55	–	Yes	No
SKI306X^Citation74	Yes	–	Yes

Notes: Status in brackets indicates that data are only available for one trial within the class. Rosehip, stinging nettle, and willow bark were all trialed in two studies, but they are not directly comparable on the same outcome measure.

Abbreviations: VAS, visual analog scale; NRS, numeric rating scale; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index; KOOS, Knee injury and Osteoarthritis Outcome Score; ASU, avocado/soybean unsaponifiables; FNZG, Fufang Nanxing Zhitong Gao; SJG, Shangshi Jietong Gao; TCM, traditional Chinese medicine; AIF, anti-inflammatory factor.

Figure 2 Efficacy of plant-derived therapies compared to placebo on pain WOMAC and KOOS pain scores.

Note: Weights are from random effects analysis.
Abbreviations: AIF, anti-inflammatory factor; n, number of study participants; SMD, standardized mean difference; CI, confidence interval; FNZG, Fufang Nanxing Zhitong Gao; SJG, Shangshi Jietong Gao; AIF, anti-inflammatory factor; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index; KOOS, Knee injury and Osteoarthritis Outcome Score; TCM, traditional Chinese medicine.

Figure 3 Efficacy of plant-derived therapies compared to active comparator on VAS and NRS pain scores.

Note: Weights are from random effects analysis.
Abbreviations: ASU, avocado/soybean unsaponifiables; n, number of study participants; SMD, standardized mean differences; CI, confidence interval; VAS, visual analog scale; NRS, numeric rating scale.

Figure 4 Efficacy of plant-derived therapies compared to active comparator on WOMAC and KOOS pain scores.

Note: Weights are from random effects analysis.
Abbreviations: ASU, avocado/soybean unsaponifiables; n, number of study participants; SMD, standardized mean differences; CI, confidence interval; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index; KOOS, Knee injury and Osteoarthritis Outcome Score.

Figure 5 Safety of plant-derived therapies compared to placebo: incidence of one or more adverse events.

Abbreviations: n, number of study participants; FNZG, Fufang Nanxing Zhitong Gao; SJG, Shangshi Jietong Gao; RR, relative risk; CI, confidence interval; AIF, anti-inflammatory factor; TCM, traditional Chinese medicine; M-H, effect size for the risk ratio using a fixed effect model using the method of Mantel and Haenszel; D+L, effect size for the risk ratio using a random effects model using the method of DerSimonian and Laird.

Figure 6 Safety of botanical therapy compared to active comparator: incidence of one or more adverse events.

Abbreviations: n, number of study participants; RR, relative risk; CI, confidence interval; ASU, avocado/soybean unsaponifiables; TCM, traditional Chinese medicine.

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