Shea MK, Kritchevsky SB, Loeser RF, Booth SL. Vitamin K status and mobility limitation and disability in older adults: The Health, Aging, and Body Composition Study [published online ahead of print May 6, 2019]. J Gerontol A Biol Sci Med Sci.
To determine whether vitamin K (as phylloquinone) deficiency may be a risk factor for impaired mobility and disability in older adults.
Prospective, longitudinal cohort study
The study included 1,323 participants (635 men, 688 women), mean age 74.6±2.8. Forty percent were African American, 60% were Caucasian.
Study Parameters Assessed
1. Objective parameters:
a. Baseline plasma phylloquinone (vitamin K) and undercarboxylated matrix glycoprotein (ucMGP; levels inversely correlate with vitamin K status)
b. Serum triglycerides
c. Interleukin-6 (IL-6)
d. Glomerular filtration rate (GFR)
2. Subjective parameters:
a. Healthy Eating Index (HEA)
b. Mobility limitation: defined as 2 consecutive semiannual reports of having any difficulty either walking ¼ mile or climbing 10 steps without resting.
c. Mobility disability: defined as 2 consecutive semiannual reports of having a lot of difficulty or inability walking ¼ mile or climbing 10 steps without resting.
Primary Outcome Measures
- Mobility limitation
- Mobility disability
Plasma phylloquinone (vitamin K1) was positively associated with triglycerides and the HEI and inversely associated with IL-6 and knee pain.
In keeping, plasma ucMGP was positively associated with triglycerides and IL-6. Separately, ucMGP was inversely associated with estimated GFR. African American participants were more likely to have lower ucMGP.
When analyses of plasma phylloquinone and mobility were limited to the subset of participants who had ucMGP measured (n=716), the association between plasma phylloquinone and mobility limitation was similar, but the association with mobility disability was attenuated.
When analyzed cross-sectionally, participants with less than 0.5 nmol/L plasma phylloquinone were 1.49 times more likely to have mobility limitation (odds ratio [OR]: 1.49; 95% confidence interval [CI]: 1.04-2.13, fully adjusted) and nearly twice as likely to have mobility disability (OR: 1.95; 95% CI: 1.08-3.54, fully adjusted) compared to those with at least 1.0 nmol/L.
According to data from the 2011-2012 National Health and Nutrition Examination Survey (NHANES), on average 57% of men and 37.5% of women do not consume even the minimum AI of vitamin K per day.1
The odds for mobility limitation and disability did not differ significantly between those with 0.5-1.0 nmol/L phylloquinone and those with at least 1.0 nmol/L (OR: 1.19; 95% CI: 0.87-1.63 for mobility limitation; OR: 1.65; 95% CI: 0.97-2.81 for mobility disability, both fully adjusted).
The odds of having mobility limitation or disability did not differ significantly across ucMGP tertiles. Compared to tertile 1, ORs for mobility limitation were 1.16 for tertile 2 (95% CI: 0.77-1.74) and 1.42 for tertile 3 (95% CI: 0.93-2.17). Odds for mobility disability (also compared to tertile 1) were 0.88 for tertile 2 (95% CI: 0.44-1.74) and 1.62 for tertile 3 (95% CI: 0.84-3.13), all fully adjusted.
This study is 1 of 2 studies to date that looked at vitamin K status and frailty in older adults. An earlier, 2016 study evaluated the association between nonphosphorylated-uncarboxylated isoform of MGP (dp-ucMGP), another marker for vitamin K status, and frailty.1
Nutritional deficiencies are known risk factors for chronic disease, functional impairment, and mortality. Therefore, understanding how nutrients affect disease onset and progression is important for informing public health policy, teaching clinicians how to identify and properly screen at-risk patients, and creating treatments that address and reverse potential underlying nutritional deficiencies.
In this study the researchers found that older adults 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. However, after adjustment for knee pain, the hazard for mobility disability did not significantly differ between those with plasma phylloquinone less than 0.5 nmol/L and those with at least 1.0 nmol/L.
Plasma ucMGP was not associated with incident mobility limitation. However, plasma ucMGP was associated with mobility disability such that those in the middle ucMGP tertile were more likely to develop mobility disability compared to those in the lowest tertile, but there was no difference in incident mobility disability between those in the highest and lowest tertiles.
There are several challenges with interpreting and applying these results clinically. First, association does not mean causation. Mobility is a complex mechanical process under neurological, musculoskeletal, and hormonal control. Reducing it to a single nutrient may miss more fundamental reasons as to why a patient is struggling.
Second, vitamin K status as measured by surrogate markers such as ucMGP is not a straightforward estimation. An abnormal lipid profile may affect the results, as indicated in the present study. While ucMGP decreases with vitamin K consumption, the production of MGP is independent of vitamin K. The researchers did not measure MGP or provide a ucMGP-to-MGP ratio, which would have been more instructive.
The challenge with surrogate markers is important for clinicians to understand, since we frequently discuss, recommend, or test surrogate markers. The most common vitamin K–dependent surrogate marker tested clinically is undercarboxylated osteocalcin (ucOC).
This marker has been inversely associated with osteoporosis; however, as the authors of the present study point out, we don’t yet have a clinical definition for vitamin K deficiency based on surrogate markers because the relevance of different thresholds to clinical endpoints has not been studied extensively. Additionally, according to a 2016 review by Shea and Booth published in the journal Nutrients, “In contrast to other nutrients, there is no single biomarker that is considered a gold-standard measure of vitamin K status.”2
The present study falls short in that it did not measure serial ucMGP and plasma vitamin K, which would have given a better estimate of vitamin K status. Nor did the study participants complete a food frequency questionnaire to estimate their vitamin K intake from diet.
As an essential nutrient, vitamin K (as phylloquinone, which was what was measured in this study), can only be consumed through diet or dietary supplements. Importantly, a concentration less than 0.5 nmol/L, which the researchers found was associated with decreased mobility, corresponds to a dietary vitamin K intake less than half of the recommended Adequate Intake (AI). The AI for vitamin K for adults is 90 micrograms for women and 120 micrograms for men.3
How common is it that people aren’t consuming the AI for vitamin K? According to data from the 2011-2012 National Health and Nutrition Examination Survey (NHANES), on average 57% of men and 37.5% of women do not consume even the minimum AI of vitamin K per day.4
Therefore, vitamin K status, like the status of other essential nutrients, should be evaluated in the context of a person’s overall dietary pattern. Plants, specifically green leafy vegetables, are the main source of dietary vitamin K (phylloquinone) in the United States.
Given the prevalence of poor nutrition in the United States, controlling for nutritional status is important when trying to correlate one clinical endpoint with a single nutrient. An estimated 56% of US adults don’t consume the minimum requirement for magnesium,5 15% consume less than half the Recommended Daily Amount (RDA) for vitamin C, 10% consume less than half the RDA for vitamin E, and 18% consume less than half the RDA for zinc.6
In addition to not correcting for dietary patterns, the researchers did not evaluate or correct for other potential nutritional deficiencies known to affect mobility, such as vitamin D. Vitamin D deficiency is associated with loss of muscle mass,7,8 weakness,9 and decreased lower extremity function.10 Finally, they did not evaluate patients for sarcopenia, which can also decrease mobility.11
Since biochemistry involves a network of interactions between biochemical pathways, controlling for overall nutritional status is important.
Researching how nutrients may correlate with disease is important for advancing how diet influences health and for advancing the field of medicine. For research in this field to have the greatest clinical impact, future studies should correct for dietary status, evaluate nutritional status using laboratory testing, and control for variables we already know contribute to decreased mobility and impairment.
- Mayer O, Jr., Seidlerova J, Wohlfahrt P, et al. Desphospho-uncarboxylated matrix Gla protein is associated with increased aortic stiffness in a general population. J Hum Hypertens. 2016;30(7):418-423.
- Shea MK, Booth SL. Concepts and controversies in evaluating vitamin K status in population-based studies. Nutrients. 2016;8(1).
- Vitamin K: Fact Sheet for Health Professionals. National Institutes of Health. https://ods.od.nih.gov/factsheets/vitaminK-HealthProfessional/. Published 2018. Accessed August 4, 2019.
- Harshman SG, Finnan EG, Barger KJ, et al. Vegetables and mixed dishes are top contributors to phylloquinone intake in us adults: data from the 2011-2012 NHANES. J Nutr. 2017;147(7):1308-1313.
- Ames BN. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc Natl Acad Sci U S A. 2006;103(47):17589-17594.
- Ames BN. DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res. 2001;475(1-2):7-20.
- Ko MJ, Yun S, Oh K, Kim K. Relation of serum 25-hydroxyvitamin D status with skeletal muscle mass by sex and age group among Korean adults. Br J Nutr. 2015;114(11):1838-1844.
- Visser M, Deeg DJ, Lips P. Longitudinal Aging Study Amsterdam. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab. 2003;88(12):5766-5772.
- Al-Shoha A, Qiu S, Palnitkar S, Rao DS. Osteomalacia with bone marrow fibrosis due to severe vitamin D deficiency after a gastrointestinal bypass operation for severe obesity. Endocr Pract. 2009;15(6):528-533.
- Bischoff-Ferrari HA, Dietrich T, Orav EJ, et al. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or =60 y. Am J Clin Nutr. 2004;80(3):752-758.
- Mathieu SV, Fischer K, Dawson-Hughes B, et al. Association between 25-hydroxyvitamin D status and components of body composition and glucose metabolism in older men and women. Nutrients. 2018;10(12).