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Vitamin K2 shows promise as rheumatoid arthritis treatment

Wednesday, December 23, 2015

The August 2015 issue of the European Journal of Pharmacology reports a positive outcome for treatment with menaquinone-7, a form of vitamin K2, among rheumatoid arthritis (RA) patients.

"Recently, menaquinone-4 (MK-4) was proven as a new potential agent for the treatment of rheumatoid arthritis," write authors Mahran S. Abdel-Rahman and colleagues. "However, menaquinone-7 (MK-7) has greater bioavailability and efficacy than MK-4 after oral administration. Yet, the therapeutic benefits of MK-7 in the management of patients with RA have never been addressed."

The current trial included 24 male and 60 female rheumatoid arthritis patients. Forty-two subjects received 100 micrograms MK-7 per day in addition to their rheumatoid arthritis medications for three months, while the remainder received only their normal therapeutic regimens. Clinical and biochemical markers, including undercarboxylated osteocalcin (ucOC, a bone metabolism marker that is elevated with low vitamin K status), erythrocyte sedimentation rate (ESR), disease activity score, C-reactive protein (CRP) and matrix metalloproteinase (MMP-3, an enzyme that degrades collagens and other tissue components, that is correlated with systemic inflammation of RA) levels were assessed before and after the treatment period.

Among those who received MK-7, ucOC, ESR, disease activity score, CRP and MMP-3 decreased from baseline levels. A significantly stronger decline in ucOC, ESR and disease activity score characterized moderate or good responders to MK-7, who demonstrated a greater increase in serum levels of the vitamin after treatment than the six-member group of nonresponders.

The authors remark that MK-7 is significantly less toxic than antirheumatic drugs and has the additional benefit of protecting against osteoporosis. The longer half-life of MK-7 compared to MK-4 enables the vitamin to be administered in a once-daily low dose.

The study is the first, to the authors' knowledge, to report the use of MK-7 for the treatment of rheumatoid arthritis. "It was suggested that MK-7 can improve disease activity score in RA patients, through changes in bone mineral metabolism and hence can be added to conventional antirheumatic therapy safely," they conclude. "Therefore, MK-7 represents a new promising agent for RA in combination therapy with other disease modifying antirheumatic drugs."

 
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Increased vitamin K intake associated with lower risk of dying over 4.8 year median
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A study reported in the May 2014 issue of the Journal of Nutrition links higher intake of vitamin K with a lower risk of dying from any cause over a median follow-up of 4.8 years.

The study included 7,216 participants in the PREDIMED study, which sought to evaluate the protective effect of a Mediterranean diet against the risk of cardiovascular disease in older men and women. Annual dietary questionnaire responses completed by the participants were analyzed for the intake of phylloquinone (vitamin K1) and menaquinone (vitamin K2). Over a 4.8 year median, there were 323 deaths, including 81 deaths from cardiovascular disease and 130 cancer deaths.

Adjusted analysis uncovered a 36% lower risk of dying from any cause and a 46% lower risk of dying from cancer over follow-up among those whose vitamin K1 intake was among the top 25% of participants in comparison with the lowest 25%. For those who increased their intake of vitamin K1 over follow-up, the risk of death was 43% lower and for vitamin K2, the risk was 45% less than subjects whose intake was reduced or unchanged. Improvement of vitamin K1 and K2 intake was also associated with a 36% and 59% lower risk of dying from cancer during the follow-up period.

"To our knowledge, this is the first study to evaluate the specific association of both active forms of vitamin K (vitamins K-1 and K-2), and their changes during the follow-up, with cancer mortality, cardiovascular mortality, or all-cause mortality in a prospective longitudinal study of Mediterranean individuals at high cardiovascular disease risk and using repeated measurements of dietary intake," the authors announce. "The results of the present study show, for the first time, an inverse association between an increased intake of both dietary phylloquinone and menaquinone, and cancer mortality or all-cause mortality."

 
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Health Concern

Rheumatoid arthritis

In RA, the immune system mistakenly attacks healthy cells and tissues — predominantly the synovium, the soft tissue between the articular capsule (joint capsule) and the joint cavity of synovial joints. This immune mediated assault leads to the development of pannus, a destructive fibrous tissue within affected joints that erodes cartilage and exacerbates joint dysfunction.

RA damage is engendered by multiple components of the immune system, including antibodies and killer T-cells.

Antibodies are proteins secreted by β-cells that normally recognize and bind to invading microbes such as bacteria and viruses. By attaching to the invading microbe, they activate other components of the immune system to launch an inflammatory response, which destroys the cells.

In RA, antibodies mistakenly recognize "self" cells as invaders. Once antibodies attach to synovial cells in the joint, they attract a variety of immune cells that launch a devastating inflammatory attack. The complex inflammatory process within joints is mediated in large by the cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). The inflammatory damage is not limited to the synovium, but spills over to the chondrocytes (cartilage cells that cushion joints). This process raises the level of dangerous inflammatory compounds throughout the body, including C-reactive protein (CRP), which is a marker of inflammation and can be evaluated via a high-sensitivity CRP (hs-CRP) test.

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