A combination of hydroxytyrosol, omega-3 fatty acids and curcumin improves pain and inflammation among early stage breast cancer patients receiving adjuvant hormonal therapy: results of a pilot study

Clin Transl Oncol. 2019 Apr;21(4):489-498. doi: 10.1007/s12094-018-1950-0. Epub 2018 Oct 6.


Purpose: Breast cancer patients receiving hormonal therapies face risks of relapse, increased rates of cardiovascular events, and toxicities of therapy such as aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS). C-reactive protein (CRP), a marker for inflammation, is associated with breast cancer outcomes. We evaluated whether the olive-derived polyphenol hydroxytyrosol combined with omega-3 fatty acids and curcumin would reduce CRP and musculoskeletal symptoms in breast cancer patients receiving adjuvant hormonal therapies.

Experimental design: This prospective, multicenter, open-label, single arm, clinical trial enrolled post-menopausal breast cancer patients (n = 45) with elevated C-reactive protein (CRP) taking predominantly aromatase inhibitors to receive a combination of hydroxytyrosol, omega-3 fatty acids, and curcumin for 1 month. CRP, other inflammation-associated cytokines, and pain scores on the Brief Pain Inventory were measured before therapy, at the end of therapy and 1 month after completion of therapy.

Results: CRP levels declined during the therapy [from 8.2 ± 6.4 mg/L at baseline to 5.3 ± 3.2 mg/L (p = 0.014) at 30 days of treatment], and remained decreased during the additional 1 month off therapy. Subjects with the highest baseline CRP levels had the greatest decrease with the therapy. Pain scores also decreased during the therapy. There were no significant adverse events.

Conclusions: The combination of hydroxytyrosol, omega-3 fatty acids, and curcumin reduced inflammation as indicated by a reduction in CRP and reduced pain in patients with aromatase-induced musculoskeletal symptoms. Longer studies comparing this combination to other anti-inflammatories in larger groups of patients with clinical outcome endpoints are warranted.

Keywords: AI-musculoskeletal syndrome; Brief pain index; CRP.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aromatase Inhibitors / adverse effects*
  • Aromatase Inhibitors / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • C-Reactive Protein / metabolism
  • Chemotherapy, Adjuvant / adverse effects
  • Curcumin / administration & dosage*
  • Curcumin / adverse effects
  • Drug Combinations
  • Fatty Acids, Omega-3 / administration & dosage*
  • Fatty Acids, Omega-3 / adverse effects
  • Female
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Middle Aged
  • Musculoskeletal Pain / chemically induced
  • Musculoskeletal Pain / drug therapy*
  • Musculoskeletal Pain / pathology
  • Phenylethyl Alcohol / administration & dosage
  • Phenylethyl Alcohol / adverse effects
  • Phenylethyl Alcohol / analogs & derivatives*
  • Pilot Projects
  • Postmenopause
  • Prospective Studies


  • Aromatase Inhibitors
  • Drug Combinations
  • Fatty Acids, Omega-3
  • 3,4-dihydroxyphenylethanol
  • C-Reactive Protein
  • Curcumin
  • Phenylethyl Alcohol