Having adequate serum levels of both nutrients was variously linked to better function, faster gait, and faster chair stand times at baseline and over time, suggesting that dual supplementation may benefit some KOA patients, whereas vitamin D supplements alone have not.

“These findings merit confirmation in vitamin K and D co-supplementation trials,” wrote M. Kyla Shea, PhD, of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston, and colleagues.

While epidemiologic data have suggested that low vitamin D is associated with more radiographic OA and progression, most trials of KOA vitamin D supplementation alone have not shown improved structural or functional outcomes. Last year, for example, Nigel Arden et al reported that vitamin D supplementation did not slow the rate of KOA joint space narrowing or produce reductions in pain, stiffness, and functional loss over a 3-year period, leading the authors to conclude that vitamin D supplementation has no role in managing KOA.

Randomized controlled clinical trials of co-supplementation might alter that view, said Shea and colleagues. Using a single measurement, they evaluated baseline K and D sufficiency (as circulating phylloquinone/25-hydroxy vitamin D) and lower-extremity function in the Health, Aging Body Composition Knee OA Sub-study (Health ABC) cohort and then replicated the analysis in the Osteoarthritis Initiative (OAI). These two nutrients are mechanistically linked, because the expression of vitamin K-dependent proteins in joint tissues requires the 25(OH)D, active form of vitamin D.

The 1,069 participants in Health ABC had a mean age of approximately 75, and more than 60% were female. Patients’ function was based on the Short Physical Performance Battery (SPPB) and their usual 20-meter gait speed.

Dietary intakes of both vitamins were assessed by the Block Brief 2000 Food Frequency Questionnaire. Sufficient vitamin K intake was defined according to the Institute of Medicine recommendations of ≥90 mcg/day for women and ≥120 mcg/day for men. Sufficient vitamin D intake was defined as ≥600 IU/day for men and women younger than 70 and ≥800 IU/day for men and women 70 and over. The vitamin D included was that from both food and supplements, while vitamin K was restricted to food sources.

In Health ABC, participants with adequate levels of both vitamins were more likely to be male and/or white. In the 4,475 participants in the OAI cohort, those reporting sufficient intakes of both nutrients were more likely to be female and/or Caucasian. In OAI participants with the lowest levels of both nutrients, the mean Healthy Eating Index score was 66, rising to 71 in those with the highest combined levels.

In terms of education, 24% of those with less than a high school education were in the top level of the combined vitamins, whereas 44% in that category had a college education or higher.

Health ABC participants with sufficient plasma vitamin K (≥1.0 nmol/L) and serum 5(OH)D (≥50 nmol/ L) generally had better SPPB and Health ABC-PPB scores and faster 20-meter gait speed at baseline and over 4-5 years of follow-up (P≤0.002) . In the OAI analysis, sufficient combined intake correlated with overall faster usual gait speed and chair stand completion time over follow-up (P≤0.029).

The effect of higher combined nutrient status on lower-extremity function was additive, the team found. For example, in Health ABC those with circulating phylloquinone ≥1.0 nmol/L combined with 25(OH)D ≥50 nmol/L had, on average, a 0.04-0.07 meter per second (m/s) faster 20-meter gait speed (adjusted for confounders) than those with phylloquinone <1.0 nmol/L or 25(OH)D <50 nmol/L.

In the Health ABC 400-meter walk test, circulating combined levels were not significantly associated either with completion time in those who completed the walk or with the ability to complete the walk at baseline.

Analyzing each nutrient separately, the investigators also observed a slight positive difference in 20-meter gait speed. The difference in participants with < or ≥ 1.0 nmol/L plasma phylloquinone was 0.02-0.03 m/s (17), and the difference between participants with < or ≥ 50 nmol/L serum 25(OH)D was also, on average, 0.02-0.03 m/s. (A 0.05 m/s difference is considered clinically meaningful.)

In the OAI cohort, sufficient combined K/D intake at baseline was associated with overall faster 20-meter gait speed, chair stand completion time, and 400-meter walk time among completers of the walk.

Asked for his perspective on the findings, Brett L. Smith, DO, of the East Tennessee Medical Group in Alcoa and not a participant in the study, told MedPage Today: “I think the findings are very intriguing because the vitamin D studies have typically failed. This is one of the first positive studies of adequate circulating vitamin D and K repletion where we actually see an improvement in lower-extremity function in the very common problem of KOA. Clinical trials should be done, because the observational data is very suggestive.”

Smith said he does not currently test for vitamin K levels in KOA patients or suggest an increase in intake because of the lack of supporting data and the absence of an established standard of care for vitamin K consumption. But he would consider conducting a small observational study in his practice to see if the nutrient improves function: “If I can get enough results, I could perhaps use them to propose a clinical trial.”

Shea and colleagues noted that limitations to their study are its observational design, which cannot determine causality; the one-time-only measurement of circulating vitamins, which could not capture nutritional changes over time; and patient self-reporting of dietary intakes. Other drawbacks were the lack of an established clinical measure of vitamin K status and the confounding potential that adequate serum levels of these vitamins might reflect just a generally healthy lifestyle.

• Reviewed by F. Perry Wilson, MD, MSCEAssistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner

LAST UPDATED 10.30.2017