TABLE 3.

Summary of articles about effect of ginger on knee AO

Author, year	Study design	Study population	Type of intervention	Results	Evidence level
Zahmatkash & Vafaeenasab, 2011	A double‐blind randomized controlled trial study.	Ninety‐two participates with the mean age of 52.2 (+/− 12.4) years, allocated to two groups: (a) Ginger, (b) Salicylate	Ginger versus salicylate: 2 g of topical ointment for three times a day, applied with massage for 1 min, for 6 weeks, twice a day. Treatment group applied herbal ointment and control group used salicylate ointment.	It seems that using this herbal combination is clinically effective for patients suffering from knee AO in order to decrease their pain, morning stiffness and limited motion; its effect is comparable with salicylate ointment. The severity of pain were measured using Visula analog pain scale.	Level IB
Niempoog, Siriarchavatana, & Kajsongkram, 2012	A double‐blind, randomized, controlled trial.	Fifty participates, male and female, allocated to two groups: (a) Treatment (Plygersic) gel, (b) Diclofenac gel	Zingiber officinale Zingiber cassumunar versus diclofenac: The combination of 4% ginger and plai extract in a gel (Plygersic gel) as compared with a 1% solution of diclofenac sodium gel.	Both Plygersic gel and diclofenac gel could significantly improve knee joint pain, symptoms, daily activities, sports activities and quality of life measured by KOOS following 6 weeks of treatment. In the ANOVA fo repeated measures, there were no differences in the results between the Plygersic and diclofenac gel groups.	Level IB
			Gels were applied as 1 g solution for four times a day for 2 months	The efficacy of the drugs was monitored by using KOOS (knee injury and AO outcome score) score.
Mozaffari‐Khosravi, Naderi, Dehghan, Nadjarzadeh, & Fallah Huseini, 2016	A randomized double‐blind placebo‐controlled trial	One hundred twenty participates, aged 50–70 years, allocated to two groups: (a) Ginger group (GG), (b) Placebo group (PG).	GG group: 500 mg of ginger powder, while PG participants received capsules filled with 500 mg starch.	At baseline proinflammatory cytokine (TNF‐alfa and IL‐1 g) concentrations did not differs in the groups. At 3 months, both cytokines decreased in the GG relative to the PG group.	Level IB
			Partecipants were treated twice daily for 3 months.	The results of this study indicate that ginger supplementation may have a promising benefits for knee AO.
Naderi, Mozaffari‐Khosravi, Dehghan, Nadjarzadeh, & Huseini, 2016	Double blind randomized placebo controlled clinical trial.	One hundred twenty patients with moderate painful knee OA, aged 50–70 years, Male and female, allocated to two groups: (a) Ginger, (b) Placebo	Two capsules of 500 mg per day for 3 months.	At the beginning of the study there were no significant difference between the two groups in terms of C‐reactive protein and nitric oxide. After 12 weeks the concentration of these markers declined more in the ginger group. Ginger supplementation at this dosage can reduce inflammatory markers in patients with knee AO	Level IB
			Capsules of ginger and placebo look the same and contains ginger and starch powder, respectly
Niempoog et al., 2012	A double‐blind randomized controlled trial.	Sixty patients, allocated to two groups: (a) Treatment group (n = 30), (b) Placebo group, aged 48.88 years (male); 49.09 years (female), allocated to two groups: (a) Ginger, (b) Placebo	Zingiber officinale (rhizome) versus placebo: 500 mg powered ginger in one capsule, twice a day for 2 months vs the same looking capsule of placebo twice a day.	The present study showed that 1 g per day of powdered ginger could not relieve joint pain and improve symptoms and the quality of life during 8 weeks of treatment of AO of the knee compared with the placebo.	Level IB
Nieman et al., 2013	Placebo‐controlled, randomized, double‐blind clinical trial.	One hundred men and women, ages 50–75 years with a history of join pain >3 months, allocated to two groups: (a) Instaflex, (b) Placebo	InstaflexTM is a joint pain supplement containing glucosamine sulfate, methylsufonlylmethane (MSM), white willow bark extract (15% salicin), ginger root concentrate, boswella serrata extract (65% boswellic acid), turmeric root extract, cayenne, and hyaluronic acid (4.0 mg).	Results from this support the use of the Instaflex dietary supplement in alleviating joint pain severity in middle‐aged and older adults, with mitigation of difficulty performing daily activities most apparent in subjects with knee pain.	Level IB
			Treatment: 1 gel capsule for three times a day for 8 weeks for INSTAFLEX and placebo.
Chopra et al., 2013	Randomized, double‐blind, parallel‐efficacy, four‐arm, multicentre equivalence drug trial.	Four hundred forty eligible patients suffering from symptomatic knee OA were enrolled and monitored as per protocol. Age > 55, four groups: Ayurvedic groups (two shunthi‐guduchi formulations, SGCG and SGC), vs glucosamine sulfate or celecoxib	Ayurvedic formulations SGCG and SGC (without Boswelia Serrata) are extracts of Tinospora cordifolia (73.33 mg), Zingiber officinale (33.33 mg), Emblica officinalis (166.66 mg), Boswellia serrata (100 mg). Two capsules for three times a day with palin water after a meal or snack.	Ayurvedic drugs were found equivalent to oral glucosamine sulfate and celecoxib in reducing knee pain and improving knee function.	Level IB
			Glucosamine sulphate (2 g daily) and celecoxib (200 mg daily) for 24 weeks.
Yip & Tam, 2008	Double‐blind, placebo‐controlled clinical trial	Of the 59 participants enrolled in this study, 53 (89.8%) participants completed both post 1‐week and 4‐week follow‐up. The majority of the 53 participants were women (79%) and the mean age was 73.59 years old (S.D. = 5.42 years). Their mean knee joint pain history was 9.71 years (S.D. = 7.05 years). Partecipants were allocated to groups: (a) Intervention group (IG), (b) Placebo control group (PG), (c) Control group (CG).	Ginger oil versus orange oil: Ginger essential oil (1% ginger and 0.5% Citrus sinensis oil in olive oil as the base lubricant) and conventional treatment. 0.5% orange essential oil (Citrus aurantium).	The intervention group reported a reduction in knee pain rating (at the 4‐week follow‐up period. No significant differences were reported in mean change in stiffness intensity for betweengroup comparison at thepost 1‐week follow‐up or post 4‐week follow‐up.	Level IB
			Sessions of 30–35 min of aroma massage on both lower imbs, six times witin 2–3 weeks.
Drozdov, Kim, Tkachenko, & Varvanina, 2012	Randomized clinical trial.	Forty‐three patients (35F, 8 M), aged 55.1–3.1 years, with an average disease duration of 7.1–1.3 years, were allocated to two groups: (a) Ginger, (b) Diclofenac	The ginger group received a specific ginger combination daily (340 mg EV.EXT 35 Zingiber officinalis extract) for 4 weeks. The diclofenac group received 100 mg diclofenac daily for the same period. Both groups also received 1,000 mg glucosamine daily.	The ginger group showed a slight but significantly decreased upper SODA pain intensity by the 28th day of treatment with p = .05. SODA dyspepsia did not change significantly during the treatment and the dyspepsia index remains the same with p = .6. EGDS showed significantly increased levels of PGE1, PGE2, and PGF2a in the stomach mucosa. The diclofenac group showed increased SODA pain and dyspepsia values with a corresponding significant decrease of stomach mucosa prostaglandins and general negative stomach mucosa degeneration.	Level IB
		The ginger group with 21 patients (17F, 4 M) and. The diclofenac group (positive control) of 22 patients (18F, 4 M)