# VITamin D and OmegA-3 TriaL (VITAL): Interrelationship of Vitamin D and Vitamin K on Bone

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $648,358

## Abstract

ABSTRACT
Osteoporosis is the most common bone disease; 53.6 million Americans have a reduced bone mass, which
increases their risk of fragility fractures. In addition to the high prevalence of vitamin D deficiency, recent
studies show that approximately 60% of older men and 40% of older women have inadequate vitamin K
intakes. Growing evidence indicates that there are important interrelationships between vitamin D and vitamin
K on bone. Vitamin D increases intestinal calcium absorption and stimulates production of two proteins,
osteocalcin and matrix Gla protein. Vitamin K plays an essential role in activating these proteins so that
osteocalcin incorporates calcium in bone and matrix Gla protein inhibits calcification in soft tissues, including
the kidney. Both vitamins D and K are important for optimal function of these proteins. Although vitamin D
supplements are widely used to improve bone health, trials of supplemental vitamin D alone in reducing
fractures showed inconsistent results. Emerging evidence indicates that supplemental D in the context of low
vitamin K status is less effective on bone health measures. Therefore, low vitamin K status may account for
some of the inconsistencies of trials testing vitamin D and bone health and may contribute to toxicities
attributed to high-dose vitamin D such as kidney stones. No previous randomized controlled trials have been
adequately powered to test effects of vitamin K status on fracture risk or the interaction of vitamin K status with
high-dose, supplemental vitamin D on bone. To fill knowledge gaps, we propose an innovative, ancillary study
to the large, NIH-sponsored, VITamin D and OmegA-3 TriaL (VITAL). VITAL is testing effects of supplemental
vitamin D3 (cholecalciferol, 2000 IU/d), and/or omega-3 fatty acids (fish oil, 1 g/d) in the primary prevention of
cancer and cardiovascular disease in 25,871 U.S. men (aged ≥50) and women (aged ≥55), including 5,106
African Americans. In this competitive renewal application of “VITAL: Effects on Bone Structure and
Architecture,” we will determine whether low vitamin K status, assessed by 3 sensitive biomarkers, modifies
effects of supplemental vitamin D on fractures, bone mineral density (BMD) and structure, and secondarily on
increases in urine calcium excretion, a risk factor for low BMD and kidney stones. During the first cycle of this
grant, we surpassed recruitment goals and collected baseline and 2-yr post-randomization imaging studies for
bone density, structure and architecture that will be used in the proposed studies (n=771). In addition, other
key VITAL resources will be leveraged including: 16,953 baseline and 6,000 follow-up blood samples;
measures of vitamin D, calcium, creatinine and parathyroid hormone; and adjudicated fractures and kidney
stones. This proposal provides a unique opportunity to clarify in the largest study of supplemental vitamin D,
the interdependencies of vitamins D and K and their roles on fractures, bone health measu...

## Key facts

- **NIH application ID:** 9987515
- **Project number:** 5R01AR059775-07
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** MERYL Susan LEBOFF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $648,358
- **Award type:** 5
- **Project period:** 2012-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987515

## Citation

> US National Institutes of Health, RePORTER application 9987515, VITamin D and OmegA-3 TriaL (VITAL): Interrelationship of Vitamin D and Vitamin K on Bone (5R01AR059775-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9987515. Licensed CC0.

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