Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial

J Am Coll Nutr. 2016 Jul;35(5):392-8. doi: 10.1080/07315724.2015.1026004. Epub 2015 Jul 9.


Objectives: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an increase in some autoantibodies and proteolytic enzymes, leading to joint destruction. Although recent investigations have considered vitamin K as an anti-inflammatory nutrient with an important role in bone metabolism, there is currently limited information on its efficacy in RA. We aimed to examine the effects of vitamin K1 (phylloquinone) on the biomarker of joint destruction and autoantibody in patients with RA.

Materials and methods: This was a randomized clinical trial in which 64 women with RA who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Vitamin K1 or placebo was administered to the participants for 8 weeks. Baseline characteristics and anthropometric measures were obtained. Clinical status using disease activity score in 28 joints (DAS-28), serum levels of matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF) were assessed before and after the intervention.

Results: The serum level of MMP-3 compared with the baseline values did not change significantly in the groups. However, the serum concentration of RF decreased significantly in the vitamin K1 group (p = 0.041). Intergroup comparison showed no significant change in RF serum level after adjusting for relevant confounders (p > 0.05).

Conclusions: Vitamin K1 supplementation at 10 mg/day for 8 weeks did not alter joint destruction and immune status in the patients with RA compared with the controls.

Keywords: matrix metalloproteinase-3; phylloquinone; rheumatoid arthritis; rheumatoid factor; vitamin K.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Biomarkers / blood
  • Double-Blind Method
  • Female
  • Humans
  • Joints / physiopathology
  • Matrix Metalloproteinase 3 / blood*
  • Middle Aged
  • Placebos
  • Rheumatoid Factor / blood*
  • Vitamin K 1 / administration & dosage
  • Vitamin K 1 / therapeutic use*


  • Biomarkers
  • Placebos
  • Vitamin K 1
  • Rheumatoid Factor
  • MMP3 protein, human
  • Matrix Metalloproteinase 3