Low levels of circulating vitamin K are linked to increased risk of mobility limitation and disability in older adults

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Low levels of circulating vitamin K are linked to increased risk of mobility limitation and disability in older adults, identifying a new factor to consider for maintaining mobility and independence in older age, according to a study led by researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University.

The study, published online in May in advance of print in the Journal of Gerontology: Medical Sciences, is the first to evaluate the association between biomarkers of vitamin K status and the onset of mobility limitation and disability in older adults.

“Because of our growing population of older people, it’s important for us to understand the variety of risk factors for mobility disability,” said Kyla Shea, first and corresponding author and a nutrition scientist in the Vitamin K Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University.

“Low vitamin K status has been associated with the onset of chronic diseases that lead to disability, but the work to understand this connection is in its infancy.

Here, we’re building on previous studies that found that low levels of circulating vitamin K are associated with slower gait speed and a higher risk of osteoarthritis,” she continued.

The new study examined two biomarkers: circulating levels of vitamin K (phylloquinone) and a functional measure of vitamin K (plasma ucMGP).

Using participant data from the Health, Aging, and Body Composition Study (Health ABC), the study found that older adults with low levels of circulating vitamin K were more likely to develop mobility limitation and disability.

The other biomarker, plasma ucMGP, did not show clear associations with mobility limitation and disability.

Specifically, older adults with low circulating vitamin K levels were nearly 1.5 times more likely to develop mobility limitation and nearly twice as likely to develop mobility disability compared to those with sufficient levels.

This was true for both men and women.

“The connection we saw with low levels of circulating vitamin K further supports vitamin K’s association with mobility disability,” said senior author Sarah Booth, a vitamin K and nutrition researcher, and director of the HNRCA.

“Although the two biomarkers we looked at are known to reflect vitamin K status, biomarker levels can also be affected by additional known or unknown factors.

Further experiments to understand the mechanisms of biomarkers and vitamin K and their role in mobility are needed.”

The study used data from 635 men and 688 women ages 70-79 years old, approximately 40 percent of whom were black, who participated in Health ABC.

In Health ABC, mobility was assessed every six months for six to ten years through annual clinic visits and phone interviews in the intervening time.

For the present analysis, the researchers defined mobility limitation as two consecutive semi-annual reports of having any amount of difficulty either with walking a quarter of a mile or climbing 10 steps without resting, and mobility disability as two consecutive semi-annual reports of having a lot of difficulty or inability to walk or climb the same amount.

Circulating vitamin K levels reflect the amount of vitamin K in the diet.

The best food sources of vitamin K include leafy greens such as spinach, kale and broccoli and some dairy products.

For an average adult, one cup of raw spinach provides 145 micrograms (mcg) of vitamin K1, or 181 percent of the Daily Value; one cup of raw kale provides 113 mcg, or 141 percent; and half of a cup of chopped boiled broccoli provides 110 mcg, or 138 percent.


Osteoarthritis (OA) has been found to affect the whole joint as pathological abnormalities are not only confined to cartilage destruction and bone remodeling but also include low grade synovitis, lax ligaments, periarticular muscle weakness and neurosensory system affection [1].

These features lead to development of manifestations such as pain, muscle weakness, and limited mobility and may progress over time to functional disability [2].

In Egyptian patients with knee OA (KOA) many factors play a role in the disease pathogenesis including cytokines [3], oxidative stress [4].

Vascular endothelial growth factor was remarkably associated with the radiological changes of KOA [5] and osteopontin served as another biomarker of disease severity and was predictive of the disease [6] and radiological progression [7].

Vitamin K represents a family of related molecules that have a common structure and carboxylation activity.

This family includes three compounds: vitamin K1 (Phylloquinone) that is found in food from plant origin, vitamin K2 (Menaquinone) that is of a bacterial by-product origin and is found in fermented products and vitamin K3 (Menadione) that is a synthetic compound found only in dietary supplements [8].

About 17 vitamin K-dependent proteins or γ-carboxyglutamate (Gla) proteins are known and their activation is carried out by gamma carboxylation of their glutamate residue mediated by vitamin K [9].

Most of vitamin K dependent proteins are involved in the coagulation cascade and the function of some of them is still unknown [10].

However, some are constituents of bone and extracellular matrix such as osteocalcin (OC), matrix Gla protein (MGP) and growth arrest specific gene 6 protein (Gas 6) and they act as a regulator of bone mineralization and calcification of soft tissues as well as stimulation of cell proliferation [8], [11].

Deficiency of vitamin K leads to decrease in the functional forms of vitamin K dependent proteins that can affect chondrocyte differentiation and endochondral bone formation, a possible underlying mechanism of osteophyte formation [12], [13].

Thus, vitamin K deficiency may play a potential role in the pathophysiology of OA [14].

Plain radiography has been used as the initial imaging modality for assessment of OA; it is considered a helpful tool for evaluation of narrowing of the joint space, osteophytes and sclerosis [15].

But on the other hand, there are limitations in direct visualization of the hyaline cartilage, menisci and involvement of periarticular soft tissue. The changes detected by plain radiography are not only specific to OA but may be found also in asymptomatic elderly people [16].

Musculoskeletal ultrasound (MSUS) is now considered an important imaging modality for assessment of various joint pathologies as it has the ability for direct visualization of the hyaline articular cartilage, menisci, synovial membrane, bursa and the bone cortex [17].

In OA, it is used to demonstrate many pathological changes that occur due to structural damage and inflammation. Synovial inflammation appears in the form of joint effusion and synovial hypertrophy and structural damage appears in the form of cartilage lesions and osteophytes [18].

So, MSUS is considered a cheap, non-invasive, fast imaging modality that is ideal for early diagnosis and monitoring of disease progression of OA especially in joints with wide acoustic window such as the knee [19], [20].

This study aimed to assess plasma vitamin K1 (phylloquinone) concentrations in primary KOA patients and to correlate these levels with clinical parameters and radiological progression of OA using plain radiography and MSUS.

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More information: M Kyla Shea et al, Vitamin K Status and Mobility Limitation and Disability in Older Adults: The Health, Aging, and Body Composition Study, The Journals of Gerontology: Series A (2019). DOI: 10.1093/gerona/glz108

Provided by Tufts University

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