Dietary supplementation with vitamin D or fish oil failed to alleviate chronic knee pain in older adults, a secondary analysis of data from the large randomized VITAL trial found.
At baseline, pain scores on the 100-point Western Ontario and McMaster Universities (WOMAC) Arthritis Index were 35.4 among patients receiving vitamin D and 36.5 for those given placebo. At the time of last follow-up, after more than 5 years, mean WOMAC pain scores in the two groups were 32.7 and 34.6, respectively, and at no time throughout the trial was there a statistically significant difference in pain scores between the vitamin D and placebo groups, reported Lindsey Adair MacFarlane, MD, of Brigham and Women’s Hospital in Boston, and colleagues.
As shown in their study online in Arthritis & Rheumatology, among patients randomized to receive marine omega-3 fatty acids or placebo, WOMAC pain scores at baseline were 36.5 and 35.4. At the final follow-up visit, pain scores were 33.6 in the fish oil group and 33.7 in the placebo group, and once again, there were no significant differences in pain scores between the two groups at any time point.
“Over the mean of 5.3 years of follow-up, a small decrease in reported knee pain was observed, but this occurred in both the treatment and placebo groups and may reflect regression to the mean and some loss of participants to total knee replacement,” the researchers wrote.
An estimated one-quarter of older adults experience knee pain, usually related to osteoarthritis, but current management options include only exercise, weight loss, and analgesics that often are associated with adverse effects, MacFarlane and co-authors explained. “Identifying safe and inexpensive therapies that reduce pain could vastly improve management of chronic knee pain.”
Two promising candidates have been vitamin D, because of its anti-inflammatory effects and role in muscle strength and bone resorption, and fish oils, which also have anti-inflammatory properties and protect against cartilage loss. Previous studies, however, have shown conflicting and confusing results.
For example, in one 2-year study of patients with symptomatic knee osteoarthritis and low vitamin D levels, there was no difference between vitamin D supplementation or placebo on WOMAC pain scores, but a post-hoc analysis found benefits on the WOMAC function subscale.
Another study compared high-dose versus low-dose fish oil for symptomatic knee osteoarthritis over 24 months and found improvements on WOMAC pain and function scores for the low-dose group, but the fish oil supplement used also contained sunola oil, potentially confounding the results.
Therefore, to more fully address the question of the potential utility of these treatments, MacFarlane’s group analyzed data from VITAL (VITamin D and OmegA-3 Trial), which was a large population-based trial that evaluated the effects of vitamin D and omega-3 fatty acids in the primary prevention of cancer and cardiovascular disease.
VITAL enrolled more than 25,000 U.S. adults age 50 and older beginning in 2011, randomizing them to receive vitamin D3, 2,000 IU/day; omega-3 fatty acids (Omacor), 1 g/day; or placebo. The study was completed at the end of 2017, with primary results reported in late 2018.
Within the larger cohort was a subgroup of 1,398 participants who reported frequent, chronic knee pain at baseline and were considered “highly likely” to have knee osteoarthritis and who filled out a knee pain questionnaire at baseline and annually thereafter.
In addition to pain scores, participants also rated stiffness and function on those WOMAC subscales and reported on the type and frequency of medications used.
At baseline, participants’ mean age was 68, two-thirds were women, and mean body mass index (BMI) was 31.8. The majority reported daily knee pain, unilateral symptoms, and daily or occasional use of nonsteroidal anti-inflammatory drugs (NSAIDs). About 15% also occasionally or daily used analgesics, including opioids.
As with the pain scores, no differences were seen throughout follow-up on WOMAC stiffness or function scores for either vitamin D or fish oil. Moreover, on a secondary outcome of incident total knee replacement, suggesting severe and progressive osteoarthritis, the hazard ratios compared with placebo were 0.97 (95% CI 0.78-1.22) for vitamin D and 0.99 (95% CI 0.79-1.24) for fish oil. There also was no change in analgesic or NSAID use throughout the study.
Subgroup analyses by baseline vitamin D level and omega-3 fatty acid index did not influence the effect of either treatment on knee pain, nor did race, BMI, or baseline fish consumption.
This analysis suggests “that supplementation with vitamin D or omega-3 fatty acids does not have a role in the management of symptomatic knee pain due to osteoarthritis,” the authors concluded.
A limitation of the study, they said, was the lack of radiographic data.
Last Updated June 26, 2020
The authors reported financial relationships with Flexion Therapeutics, Samumed, Amgen, Janssen, Pharmavite, and the Swedish Rheumatism Foundation.