A role for vitamin K in the treatment of osteoarthritis

Posted on January 7, 2011 by Dr. Jonathan

The importance of vitamin K for normal blood clotting and bone integrity in the prevention of osteoporosis is well known. There is also evidence for the importance of of vitamin K in the treatment of osteoarthritis. Consider research published in the journal Arthritis & Rheumatism in which the authors state:

“Poor intake of vitamin K is common. Insufficient vitamin K can result in abnormal cartilage and bone mineralization. Furthermore, osteophyte growth, seen in osteoarthritis (OA), may be a vitamin K–dependent process. We undertook this study to determine whether vitamin K deficiency is associated with radiographic features of OA.”

They correlated radiographic (x-ray) findings with levels of phylloquinone (vitamin K) in 672 subjects, taking into consideration the degree of degenerative joint pathologies by prevalence ratios (PR) and variables such as vitamin D, bone mineral density, body mass index, age, etc. What did their data show?

“The PRs for OA, osteophytes, and JSN [joint space narrowing] and adjusted mean number of joints with all 3 features in the hand decreased significantly with increasing plasma phylloquinone level…For the knee, only the PR for osteophytes and the adjusted mean number of knee joints with osteophytes decreased significantly with increasing plasma phylloquinone levels.”

Thus their conclusion:

“These observational data support the hypothesis of an association between low plasma levels of vitamin K and increased prevalence of OA manifestations in the hand and knee.”

A clinical trial reported in the Annals of the Rheumatic Diseases highlights the practical importance of using objective laboratory tests to discriminate when may expect to see meaningful improvements from taking vitamin K (or any other intervention). The authors state:

“Vitamin K has bone and cartilage effects, and previously shown to be associated with radiographic osteoarthritis. We evaluated vitamin K’s effect on hand osteoarthritis in a randomised controlled trial.”

They observed the effects of vitamin K supplementation versus placebo on hand x-ray features of osteoarthritis regardless of their initial vitamin K status. Then they further examined a subgroup restricted to those that were vitamin K insufficient at baseline. Not surprisingly…

“There were no effects of randomisation to vitamin K for radiographic osteoarthritis outcomes.” BUT…”Those with insufficient vitamin K at baseline who attained sufficient concentrations at follow-up had trends towards 47% less joint space narrowing.“

Another study published in the Journal of Orthopaedic Science takes a closer look at vitamin K intake associated with knee osteoarthritis:

“The present study sought to identify dietary nutrients associated with the prevalence of radiographic knee osteoarthritis (OA) in the Japanese elderly of a population-based cohort of the Research on Osteoarthritis Against Disability (ROAD) study.”

The authors analyzed a number of dietary factors and correlated them with the severity of radiographic (x-ray) osteoarthritic degenerative changes in the knees among 719 subjects. The association with vitamin K stood out in the data:

“Among the dietary factors, only vitamin K intake was shown to be inversely associated with the prevalence of radiographic knee OA by multivariate logistic regression analysis. The presence of joint space narrowing of the knee was also inversely associated with vitamin K intake. The prevalence of radiographic knee OA for each dietary vitamin K intake quartile decreased with the increased intake.”

We can also appreciate a paper published in the journal Osteoarthritis and Cartilage that examines a mechanism by which vitamin K deficiency contributes to degenerative joint disease (osteoarthritis). The authors observe:

“Mineralization has been observed in osteoarthritic cartilage but the mechanisms are incompletely understood. Vitamin K is an essential cofactor in post-translational modification of proteins where specific Glu residues become modified to Ca++ binding γ-carboxyglutamic acid residues (Gla). One such protein, matrix Gla protein (MGP), is a known mineralization inhibitor. This study determined if synthesis of MGP and formation of a fetuin–MGP protein complex was altered in chondrocytes and vesicles from osteoarthritis (OA) cartilage.”

They examined cartilage cells from osteoarthritic and normal joints to determine the presence of the fully γ-carboxylated form of MGP (cMGP) and non-γ-carboxylated MGP (ucMGP) as well as fetuin and MGP–fetuin complexes. This is significant because vitamin K is necessary for the production of cMGP and of the cMGP–fetuin complex, the absence of which results in the abnormal mineralization of cartilage. What did their data reveal?

“Chondrocytes and vesicles from osteoarthritic tissue produced significantly less cMGP compared to those from normal cartilage. This correlated with significantly less vitamin K-dependent γ-carboxylase enzyme activity in OA chondrocytes…A fetuin–MGP complex was identified in normal chondrocytes and in vesicles shed from these cells but not in OA cells or vesicles.”

Thus their conclusion puts the spotlight on an important vitamin K dependent mechanism for maintaining joint cartilage:

“The absence of cMGP and of the cMGP–fetuin complex in OA cells and OA vesicles may be an important mechanism for increased mineralization of osteoarthritic cartilage.”

Clinicians and patients alike may ask the questions: Who will benefit from vitamin K supplementation and for whom will it not make a significant difference. How do we know, for each individual, what is the right amount? Measure it.

Yeast growth in the gut aggravates arthritis and allergies

Posted on September 20, 2010 by Dr. Jonathan

It is a cardinal principle in functional medicine to examine the gut in any case of autoimmune or allergic disease. No wonder, considering that 60-80% of the immune system tissue in the body is the lymphoid tissue packed around the intestines. This principle is illustrated by an interesting study recently published in the journal Medical Mycology:

“We examined whether Candida albicans gut colonization aggravates immune diseases in mice.”

The authors colonized the guts of the study animals and measured changes in contact hypersensitivity and immunoreactive arthritis. Their observations correspond to what we see in our patients:

“C. albicans gut colonization increased the incidence of allergic diarrhea, which was accompanied by gut hyperpermeability, as well as increased infiltration of inflammatory cells in the colon. Contact hypersensitivity was also exacerbated by C. albicans gut colonization, as demonstrated by increased swelling, myeloperoxidase activity, and proinflammatory cytokines in ear auricles. Furthermore, C. albicans gut colonization promoted limb joint inflammation in collagen-induced arthritis, in an animal model of rheumatoid arthritis.”

These results add to the large body of evidence for the key importance of immune regulation by microbes in the gut and the far-reaching impact of disruptions of the intestinal microbial ecology. The authors’ concluding comments apply to other gut pathogens as well:

“These findings suggest that C. albicans gut colonization in mice aggravates inflammation in allergic and autoimmune diseases, not only in the gut but also in the extra-gut tissues and underscores the necessity of investigating the pathogenic role of C. albicans gut colonization in immune diseases in humans.“

The most reliable way to investigate the microbial environment in the gut (now being used for pioneering studies of the human microbiome as well as for examination in clinical practices like ours) is DNA analysis.

Laser therapy reduces inflammatory cytokines

Posted on June 14, 2010 by Dr. Jonathan

Photomedicine and Laser Surgery The therapeutic use of non-invasive, low level (cold) laser and and infrared has not crossed the gap into clinical practice to the degree that the rich body of scientific research justifies. The laser and infrared therapies we use here appear to help even though you can’t feel them (at the time of application); but what evidence is there that they really do anything? And by what mechanisms? Consider this study published in the journal Photomedicine and Laser Surgery a few years ago that documents the effect of visible and infrared light on inflammatory cytokines (immune system messenger molecules). The authors state:

“The aim of this randomized, placebo-controlled, double-blind trial was to investigate changes in the content of 10 cytokines in the human peripheral blood after transcutaneous [through the skin] and in vitro [to blood removed from the body] irradiation with polychromatic visible and infrared (IR) polarized light…”

The magnitude of the effect that they observed by just applying the light to the sacral area of the study subjects is surprising:

“A dramatic decrease in the level of pro-inflammatory cytokines TNF-α, IL-6, and IFN-γ was revealed: at 0.5 h after exposure of volunteers (with the initial parameters exceeding the norm), the cytokine contents fell, on average, 34, 12, and 1.5 times. The reduced concentrations of TNF-α and IL-6 were preserved after four daily exposures, whereas levels of IFN-γ and IL-12 decreased five and 15 times. At 0.5 h and at later times, the amount of anti-inflammatory cytokines was found to rise: that of IL-10 rose 2.7–3.5 times (in subjects with normal initial parameters) and of TGF-β1 1.4–1.5 times.”

But if you expose just the area over the sacrum, what happens when that blood mixes with the rest of the circulation?

“Similar regularities of the light effects were recorded after in vitro irradiation of blood, as well as on mixing the irradiated and non-irradiated autologous blood at a volume ratio 1:10 (i.e., at modeling the events in a vascular bed of the exposed person when a small amount of the transcutaneously photomodified blood contacts its main circulating volume).”

In other words, a small limited application causes system-wide effects. Considering how much we need therapies that physiologically modulate the inflammatory response without side effects, the authors’ conclusion is extremely compelling:

“Exposure of a small area of the human body to light leads to a fast decrease in the elevated pro-inflammatory cytokine plasma content and to an increase in the the anti-inflammatory factor concentration, which may be an important mechanism of the anti-inflammatory effect of phototherapy. These changes result from transcutaneous photomodification of a small volume of blood and a fast transfer of the light-induced changes to the entire pool of circulating blood [!].”

Here’s a little more from the large body of research published in the same journal:

By the way, this is interesting in connection with the earlier post on the infrared treatment of depression.

The importance of testing cytokines: rheumatoid arthritis

Posted on February 5, 2010 by Dr. Jonathan

It has come to my attention that many doctors remain unfamiliar with the clinical value and importance of testing (blood) cytokines. Cytokines are ‘messenger molecules’ of the immune system involved in the regulation of inflammation. Knowledge of their levels helps not just with early diagnosis and prognosis, but can profile immune system imbalance allowing functional treatment to be precisely targeted and bad reactions avoided (even Echinacea can push some people’s immune system in the wrong direction). There are thousands of studies on clinical conditions for which this is important. Here ‘s one for rheumatoid arthritis:

Arthritis & Rheumatism Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis

This study recently published in the journal Arthritis & Rheumatism (the journal of the American College of Rheumatology) set out to “identify whether cytokines, cytokine-related factors, and chemokines are up-regulated prior to the development of rheumatoid arthritis (RA).” Their conclusion was in line with findings of other investigators: “Individuals in whom RA later developed had significantly increased levels of several cytokines, cytokine-related factors, and chemokines representing the adaptive immune system (Th1, Th2, and Treg cell-related factors.”