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Do supplements help aromatase inhibitor joint pain?

No supplement has clearly helped. In the largest trial, omega-3 eased aromatase inhibitor joint pain no more than a placebo oil in 249 women, though pain fell by half in both groups, and vitamin D trials mostly found no clear benefit. Grade B. Exercise and acupuncture have better trial support. Keep taking your aromatase inhibitor unless your oncologist changes it, and tell your cancer team about any supplement.

Last reviewed

How we grade evidenceEditorial policy

What the studies found

  • Grade B. Omega-3: no better than placebo. In 249 women on an aromatase inhibitor with moderate to severe joint pain, 3.3 g of omega-3 a day for 24 weeks did not ease pain more than a soybean and corn oil placebo. Pain improved by more than half in both groups. (Hershman 2015)
  • Grade B. Vitamin D: mostly no clear benefit. In 113 women with joint symptoms, 4,000 IU a day for 6 months did no better than 600 IU. In 160 women starting letrozole, a weekly high dose missed its main goal, with only a later re-analysis favoring it, and a third trial stopped early when high and standard doses looked the same. (Shapiro 2016; Khan 2017; Niravath 2019)
  • Grade C. Across all pills, the evidence is thin. A Cochrane review of 17 trials (2,034 women) of medicines, supplements and herbal products found every result low or very low certainty and called the findings inconclusive. (Roberts 2022)
  • Grade D. Glucosamine with chondroitin: in a single study with no placebo group, 46% of the 39 women who finished 24 weeks reported less pain and stiffness. (Greenlee 2013)

Who should be careful

  • Don't stop or skip your aromatase inhibitor because of joint pain without talking to your oncologist. Joint symptoms lead many women to stop, which may weaken cancer protection (Roberts 2022).
  • Tell your cancer team about every supplement. In one trial, 4,000 IU of vitamin D did not change anastrozole or letrozole blood levels (Shapiro 2016); for other supplements, no interaction studies with aromatase inhibitors were found.
  • The adult upper limit for vitamin D is 4,000 IU a day (NIH ODS). Glucosamine with chondroitin caused headache, indigestion and nausea in some women (Greenlee 2013).
  • Duloxetine, a prescription medicine, lowered joint pain modestly more than placebo but caused more side effects (78% versus 50%) (Henry 2018). It is an option to discuss with your oncologist, not to start on your own.
  • Call your cancer team promptly for a hot or swollen joint, fever, new pain in one bone that won't go away, or pain that stops you from working or sleeping.

Try first

  • Exercise. In a year-long trial of 121 inactive women, 150 minutes a week of aerobic exercise plus supervised strength training twice a week cut worst joint pain by 29%, while pain rose slightly with usual care (Irwin 2015).
  • Acupuncture. In 226 women, 6 weeks of twice-weekly acupuncture lowered worst joint pain about 1 point more than sham acupuncture or waiting, a gain of uncertain size in daily life (Hershman 2018).

Sources

  1. Hershman DL, et al. Randomized Multicenter Placebo-Controlled Trial of Omega-3 Fatty Acids for the Control of Aromatase Inhibitor-Induced Musculoskeletal Pain: SWOG S0927. J Clin Oncol. 2015. PubMed 25940724 · doi:10.1200/JCO.2014.59.5595
  2. Shapiro AC, et al. Randomized, blinded trial of vitamin D3 for treating aromatase inhibitor-associated musculoskeletal symptoms (AIMSS). Breast Cancer Res Treat. 2016. PubMed 26868123 · doi:10.1007/s10549-016-3710-6
  3. Khan QJ, et al. Randomized trial of vitamin D3 to prevent worsening of musculoskeletal symptoms in women with breast cancer receiving adjuvant letrozole. The VITAL trial. Breast Cancer Res Treat. 2017. PubMed 28770449 · doi:10.1007/s10549-017-4429-8
  4. Niravath P, et al. Randomized controlled trial of high-dose versus standard-dose vitamin D3 for prevention of aromatase inhibitor-induced arthralgia. Breast Cancer Res Treat. 2019. PubMed 31218477 · doi:10.1007/s10549-019-05319-4
  5. Roberts KE, et al. Systemic therapies for preventing or treating aromatase inhibitor-induced musculoskeletal symptoms in early breast cancer. Cochrane Database Syst Rev. 2022. PubMed 35005781 · doi:10.1002/14651858.CD013167.pub2
  6. Greenlee H, et al. Phase II study of glucosamine with chondroitin on aromatase inhibitor-associated joint symptoms in women with breast cancer. Support Care Cancer. 2013. PubMed 23111941 · doi:10.1007/s00520-012-1628-z
  7. Henry NL, et al. Randomized, Multicenter, Placebo-Controlled Clinical Trial of Duloxetine Versus Placebo for Aromatase Inhibitor-Associated Arthralgias in Early-Stage Breast Cancer: SWOG S1202. J Clin Oncol. 2018. PubMed 29136387 · doi:10.1200/JCO.2017.74.6651
  8. Irwin ML, et al. Randomized exercise trial of aromatase inhibitor-induced arthralgia in breast cancer survivors. J Clin Oncol. 2015. PubMed 25452437 · doi:10.1200/JCO.2014.57.1547
  9. Hershman DL, et al. Effect of Acupuncture vs Sham Acupuncture or Waitlist Control on Joint Pain Related to Aromatase Inhibitors Among Women With Early-Stage Breast Cancer: A Randomized Clinical Trial. JAMA. 2018. PubMed 29998338 · doi:10.1001/jama.2018.8907