Table 3 Adverse events and dropout rate reported by 41 studies.

Reginster 2001¹⁷

34% (n = 73)

83 and 101 individuals reported adverse events in GS and placebo group, respectively. No difference was found between treatment and placebo group

Appelboom 2001¹⁸

13% (n = 35)

28, 24 and 23 individuals reported adverse events in ASU low dose, ASU high dose and placebo group, respectively. No difference was found between treatment and placebo group

Jung 2001¹⁹

3% (n = 3)

5, 6, 3 and 5 individuals reported adverse events in SKI 306X low dose, SKI 306X medium dose, SKI 306X high dose and placebo group, respectively. No difference was found between treatment and placebo group

Schmid 2001²⁰

0

16 and 16 individuals reported adverse events in Willow bark extract and placebo group, respectively. No difference was found between treatment and placebo group

Colker 2002²¹

22% (n = 9)

Adverse events have been supervised. No safety problems were recognized

Zenk 2002²²

17% (n = 7)

14, 14 and 14 individuals reported adverse events in MPC, GS and placebo group, respectively. No long-term adverse events of any treatment were reported. No difference was found between treatment and placebo group

Lequense 2002²³

41% (n = 67)

39 and 39 individuals reported adverse events in ASU and placebo group, respectively. No difference was found between treatment and placebo group

McAlindon 2004²⁴

9% (n = 19)

18 and 14 individuals reported adverse events in GS and placebo group, respectively. No difference was found between treatment and placebo group

Miller 2005²⁵

15% (n = 16)

Adverse events have been supervised. No serious safety problems were recognized

Kim 2006²⁶

20% (n = 10)

21 and 19 individuals reported adverse events in MSM and placebo group, respectively. No difference was found between treatment and placebo group

Pavelka 2007²⁷

9% (n = 16)

36 and 24 individuals reported adverse events in Diacerein and placebo group, respectively. No statistically significant difference was found between treatment and placebo group

Farid 2007²⁸

5% (n = 2)

Adverse events have been supervised. No safety problems were recognized

Mehta 2007²⁹

17% (n = 16)

4 and 3 individuals reported adverse events in GS and Reparagen group, respectively. No statistically significant difference was found between ASU groups and the placebo

Alishiri GH.H. 2007³⁰

4% (n = 5)

Not report

Sengupta 2008⁸

7% (n = 5)

24, 23 and 23 individuals reported adverse events in 5-Loxin 100, 5-Loxin 250 mg/day and placebo group, respectively. No difference was found between treatment and placebo group

Kalman 2008 ³¹

20% (n = 4)

1 and 2 individuals reported adverse events in Chicken comb extract and placebo group, respectively. No statistically significant difference was found between treatment and placebo group

Frestedt 2008³²

28% (n = 20)

12, 12, 13 and 140 individuals reported adverse events in Aquamin, GS, GS + Aquamin and placebo group, respectively. No statistically significant difference was found between treatment groups and placebo group

Jacquet 2009³³

6% (n = 5)

14 and 13 individuals reported adverse events in Phytalgic and placebo group, respectively. No statistically significant difference was found between treatment and placebo group. No statistically significant difference was found between treatment groups and placebo group

Frestedt 2009³⁴

36% (n = 8)

8 and 14 individuals reported adverse events in Aquamin and placebo group, respectively

Ruff 2009³⁵

37% (n = 22)

Adverse events have been supervised. No safety problems were recognized

Farid 2010³⁶

17% (n = 7)

Adverse events have been supervised. No safety problems were recognized

Sengupta 2010³⁷

5% (n = 3)

0, 1 and 1 individuals reported adverse events in 5 -Loxin, Aflapin and placebo group, respectively. No statistically significant difference was found between treatment groups and placebo group

Debbi 2011³⁸

0

Adverse events have been supervised. No safety problems were recognized

Notarnicola 2011³⁹

0

Adverse events have been supervised. No safety problems were recognized

Schauss 2012⁴⁰

15% (n = 12)

3 and 6 individuals reported adverse events in BioCell Collagen and placebo group, respectively. There was no significant difference between the two groups in the total number of adverse events

McAlindon 2013⁴¹

15% (n = 22)

31 and 23 individuals reported adverse events in Cholecalciferol and placebo group, respectively. There was no significant difference between the two groups in the total number of adverse events

Ebrahimi 2014⁴²

13% (n = 12)

Adverse events have been supervised. No safety problems were recognized

Kolahi 2015⁴³

4% (n = 3)

Adverse events have been supervised. No safety problems were recognized

Kumar 2015⁴⁴

7% (n = 2)

1 and 0 individuals reported adverse events in PCP and placebo group, respectively. There was no significant difference between the two groups in the total number of adverse events

Dehghan 2015⁴⁵

8% (n = 7)

Not reported

Jin 2016⁴⁶

0

56 and 37 individuals reported adverse events in Vitamin D3 and placebo group, respectively

Stebbings 2016⁴⁷

19% (n = 8)

6, 9 and 7 individuals reported adverse events in ART low dose, ART high dose and placebo group, respectively

Lugo 2016⁴⁸

12% (n = 22)

8, 28 and 9 individuals reported adverse events in UC-II, GC and placebo group, respectively

Lubis 2017⁴⁹

0

Not reported

Rafarf 2017⁵⁰

9% (n = 6)

Not reported

Lei 2017⁵¹

6% (n = 28)

Adverse events have been supervised. No safety problems were recognized

Shin 2018⁵²

17% (n = 10)

Not reported

Dehghani 2018⁵³

5% (n = 4)

Not reported

Salimzadeh 2018⁵⁴

5% (n = 4)

Not reported

Hancke 2019⁵⁵

5% (n = 5)

8, 1 and 2 individuals reported adverse events in ParActin low dose, ParActin high dose and placebo group, respectively. There was no significant difference between the ParActin groups and the placebo in the total number of adverse events

Majeed 2019⁵⁶

12% (n = 6)

Adverse events have been supervised. No safety problems were recognized

Rondanelli 2019⁵⁷

0

Adverse events have been supervised. No safety problems were recognized