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      Vitamin K Status and Mobility Limitation and Disability in Older Adults: The Health, Aging, and Body Composition Study

      1 ,   2 , 3 , 1
      The Journals of Gerontology: Series A
      Oxford University Press (OUP)

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          Abstract

          Vitamin K has been implicated in chronic diseases associated with increased risk for mobility disability, such as osteoarthritis and cardiovascular disease. However, the association between vitamin K status and mobility disability is unknown. Therefore, we examined the association between vitamin K status and incident mobility disability in the Health, Aging, and Body Composition Study. Plasma phylloquinone (vitamin K1) was categorized as <0.5, 0.5–<1.0 and ≥1.0 nmol/L ( n = 1,323, 48% male). Plasma ucMGP, which increases when vitamin K status is low, was measured in 716 participants and categorized into tertiles. Mobility limitation and disability, defined as two consecutive semiannual reports of having any or a lot of difficulty walking a one-fourth mile or climbing 10 steps without resting, were assessed over a median 6–10 years of follow-up. Multivariate Cox proportional hazard models were used to evaluate the association between vitamin K status and incident mobility limitation and disability. Participants with plasma phylloquinone less than 0.5 nmol/L were more likely to develop mobility limitation and disability compared to those with at least 1.0 nmol/L (adjusted HR (95% CI) mobility limitation: 1.27 (1.05–1.53); disability: 1.34 (1.01–1.76)). After further adjustment for knee pain, the associations were partially attenuated (HR (95% CI) mobility limitation: 1.20 (0.99–1.45); disability: 1.26 (0.96–1.67)). Plasma ucMGP was not associated with incident mobility limitation, but was nonlinearly associated with incident mobility disability (HR (95% CI), compared to tertile 1: tertile 2 = 1.64 (1.19–2.27), tertile 3 = 1.17 (0.83–1.66), fully adjusted). Our results suggest vitamin K may be involved in the disablement process in older age. Future studies are needed to confirm our findings and clarify the underlying mechanism.

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          Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging?

          The triage theory posits that some functions of micronutrients (the approximately 40 essential vitamins, minerals, fatty acids, and amino acids) are restricted during shortage and that functions required for short-term survival take precedence over those that are less essential. Insidious changes accumulate as a consequence of restriction, which increases the risk of diseases of aging. For 16 known vitamin K-dependent (VKD) proteins, we evaluated the relative lethality of 11 known mouse knockout mutants to categorize essentiality. Results indicate that 5 VKD proteins that are required for coagulation had critical functions (knockouts were embryonic lethal), whereas the knockouts of 5 less critical VKD proteins [osteocalcin, matrix Gla protein (Mgp), growth arrest specific protein 6, transforming growth factor beta-inducible protein (Tgfbi or betaig-h3), and periostin] survived at least through weaning. The VKD gamma-carboxylation of the 5 essential VKD proteins in the liver and the 5 nonessential proteins in nonhepatic tissues sets up a dichotomy that takes advantage of the preferential distribution of dietary vitamin K1 to the liver to preserve coagulation function when vitamin K1 is limiting. Genetic loss of less critical VKD proteins, dietary vitamin K inadequacy, human polymorphisms or mutations, and vitamin K deficiency induced by chronic anticoagulant (warfarin/coumadin) therapy are all linked to age-associated conditions: bone fragility after estrogen loss (osteocalcin) and arterial calcification linked to cardiovascular disease (Mgp). There is increased spontaneous cancer in Tgfbi mouse knockouts, and knockdown of Tgfbi causes mitotic spindle abnormalities. A triage perspective reinforces recommendations of some experts that much of the population and warfarin/coumadin patients may not receive sufficient vitamin K for optimal function of VKD proteins that are important to maintain long-term health.
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            Concepts and Controversies in Evaluating Vitamin K Status in Population-Based Studies

            A better understanding of vitamin K’s role in health and disease requires the assessment of vitamin K nutritional status in population and clinical studies. This is primarily accomplished using dietary questionnaires and/or biomarkers. Because food composition databases in the US are most complete for phylloquinone (vitamin K1, the primary form in Western diets), emphasis has been on phylloquinone intakes and associations with chronic diseases. There is growing interest in menaquinone (vitamin K2) intakes for which the food composition databases need to be expanded. Phylloquinone is commonly measured in circulation, has robust quality control schemes and changes in response to phylloquinone intake. Conversely, menaquinones are generally not detected in circulation unless large quantities are consumed. The undercarboxylated fractions of three vitamin K-dependent proteins are measurable in circulation, change in response to vitamin K supplementation and are modestly correlated. Since different vitamin K dependent proteins are implicated in different diseases the appropriate vitamin K-dependent protein biomarker depends on the outcome under study. In contrast to other nutrients, there is no single biomarker that is considered a gold-standard measure of vitamin K status. Most studies have limited volume of specimens. Strategic decisions, guided by the research question, need to be made when deciding on choice of biomarkers.
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              The Role of Vitamin K in Chronic Aging Diseases: Inflammation, Cardiovascular Disease, and Osteoarthritis.

              Vitamin K is an enzyme cofactor required for the carboxylation of vitamin K dependent proteins, several of which have been implicated in diseases of aging. Inflammation is recognized as a crucial component of many chronic aging diseases and evidence suggests vitamin K has an anti-inflammatory action that is independent of its role as an enzyme co-factor. Vitamin K-dependent proteins and inflammation have been implicated in cardiovascular disease and osteoarthritis, which are leading causes of disability and mortality in older adults. The purpose of this review is to summarize observational studies and randomized trials focused on vitamin K status and inflammation, cardiovascular disease, and osteoarthritis. Although mechanistic evidence suggests a protective role for vitamin K in these age-related conditions, the benefit of vitamin K supplementation is controversial because observational data are equivocal and the number of randomized trials is few.
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                Author and article information

                Journal
                The Journals of Gerontology: Series A
                Oxford University Press (OUP)
                1079-5006
                1758-535X
                May 06 2019
                May 06 2019
                Affiliations
                [1 ]USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts
                [2 ]Sticht Center for Healthy Aging and Alzheimer’s Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina
                [3 ]Thurston Arthritis Research Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina
                Article
                10.1093/gerona/glz108
                7328196
                31056634
                3bcac8c5-5350-41fb-94cf-175f4af734a2
                © 2019

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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