Oral/Dietary Supplements
The following supplements may be helpful in reducing pain and improving function for patients with mild to moderate knee osteoarthritis; however, the evidence is inconsistent/limited and additional research clarifying the efficacy of each supplement is needed.
a) Turmeric
b) Ginger extract
c) Glucosamine
d) Chondroitin
e) Vitamin D

Rationale

The Oral/ Dietary Supplements recommendation has been downgraded two levels because of inconsistency and need for additional clarity of efficacy.

The majority of 6 high quality trials (Reginster 2001, Cibere 2004, McAlindon 2004, Clegg 2006, Herrero-Beaumont 2007, Fransen 2015), the majority of 6 moderate quality trials (Noack 1994, Houpt 1999, Rindone 2000, Pavelka 2002, Giordano 2009, and Shahine 2014), and 1 low quality study that met inclusion criteria showed either improvement or no change in patient outcomes for those with osteoarthritis of the knee when taking glucosamine versus control.

The majority of 8 high quality trials (Fransen 2015, Clegg 2006, Uebelhart 2004, Reginster 2017, Morita 2018, Zegels 2013, Kahan 2009, Rondanelli 2019) and 6 moderate quality trials (Mazieres 2007, Moller 2010, Rondanelli 2019, Bourgeois 1998, Mazieres 2001, Bucsi 1998) that met inclusion criteria showed either improvement or no change in patient outcomes for those with osteoarthritis of the knee when taking chondroitin.

One high quality study (Srivastava 2016) that met inclusion criteria showed that Turmeric extract could be used over control to improve adverse events, function, and pain in patient with osteoarthritis of the knee.

One high study (Zakeri 2011) and one moderate quality study (Altman 2001) that met inclusion criteria showed that ginger extract may be used to improve pain in patients with osteoarthritis of the knee. However, there was no significant difference in function between ginger extract and control.

Three high quality studies (McAlindon 2013, Sanghi 2013, and Jin 2016) and 1 moderate quality study (Arden 2016) that met inclusion criteria showed either improvement or no significant difference in patient outcomes for those with osteoarthritis of the knee between Vitamin D and control.

Benefits/Harms of Implementation
The United States Food and Drug Administration does not hold dietary supplements to the same standards as prescription medication. As a result, variability can exist between producers of dietary supplements. The patient’s medications should be evaluated for potential drug-supplement interactions prior to initiating any dietary supplement.

Outcome Importance
Improvement in the predictability of the treatment effect for specific dietary supplements will either reduce an unnecessary out-of-pocket expense or provide patients with a relatively safe method for reducing pain and improving function in the treatment of mild to moderate osteoarthritis of the knee. Knowing which supplements have evidence-based support for effective treatment will reduce unnecessary out-of-pocket expenses and provide patients with a safe method for reducing pain and improving function in the treatment of mild to moderate osteoarthritis of the knee.

Cost Effectiveness/Resource Utilization
Dietary supplements are typically an out-of-pocket expense not covered by medical insurance. As a result, patients must individually consider the expense associated with utilization of dietary supplements. We did not have the analysis to comment on the cost-benefit ratio of dietary supplements compared to other over the counter or prescription medications.

Acceptability
The limited evidence supporting dietary supplements and out-of-pocket expense associated with their use will limit broader acceptance. For patients without a medication interaction, dietary supplements pose limited physical harm as it is typically difficult to consume a toxic quantity. Therefore, it is believed to be an acceptable means to potentially achieve benefit in the treatment of mild to moderate osteoarthritis of the knee.

Feasibility
Dietary supplements are widely available to patients. The associated out-of-pocket expense is the primary barrier to access.

Future Research
The most important future research will need to provide multiple investigations demonstrating reproducible results illustrating the effectiveness of dietary supplements. Additionally, future research is necessary to determine the appropriate dose, frequency, and duration of treatment with dietary supplements.