An interventional study of Vitamin Arm 1 and Vitamin Arm 2 in Hypovitaminosis D and Hypovitaminosis, sponsored by Madigan Army Medical Center. Recruiting at 1 site in United States. Open to participants aged 18 Years to 69 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-09-30.
Sponsored by Madigan Army Medical Center · Not applicable, Interventional, and Treatment
The main purpose of this research study is to learn about the effects of supplemental vitamin D3 and vitamin K2 on blood levels and the gut microbial community, called the gut microbiome. There are many influences on blood levels of vitamin D and K to include your dietary intake, lifestyle behaviors (physical activity, sleep), genetic alterations in metabolism of these vitamins, and the gut microbial abundance and diversity. You will be asked to take one capsule containing vitamin D3 (125 mcg), vitamin K2 (180 mcg), a combination of vitamins D3 and K2 (same doses as previous), or a placebo powder for 90 days. You will also be asked to complete questionnaires, undergo body composition and blood pressure measurements, provide blood samples and a stool swab, all on 2 occasions about 3 - 4 months apart. By conducting this study, we aim to identify the frequency of common genetic alterations in vitamins D and K metabolism and establish the impact on the gut microbiome for the first time. Your participation in this study will last about 4 - 6 months and include up to 3 visits.
Health promotion efforts for all branches of Service aim to ensure the health and readiness of the Force. This timely, relevant study supports this effort as well as the TriService Nursing Research Program priorities of Fit and Ready Force, Care for the Caregiver, and Translate Research into Practice. In 2023, the Defense Health Agency unveiled its strategic plan through 2028 which included these two priorities, 1) 'achieving new levels of excellence by fully leveraging emerging scientific and technological advancements to optimize the health and care experience of our beneficiaries', and 2) 'creating a workplace where people are the primary focus, and the principles of high reliability nurture and energize each individual'. The previous nutrigenomics work by this research team, the expertise and enthusiasm of our new members, and the choice of diverse cohorts for this study, presents an exciting and potentially impactful extension of nutrigenomics with metagenomics of the gut microbiome to provide insight into complex nutrient pathways and specifically, the response of the gut microbial community to select micronutrients. Vitamin D and vitamin K2 are vital micronutrients that support immune, bone, gut, and cardiometabolic health with insufficiencies contributing to musculoskeletal injuries (MSKi), metabolic syndrome, cardiovascular disease, and gut dysbiosis. This Follow-On research application advances the science linking vitamin D, lifestyle behaviors, and chronic disease prevention in healthy adults by probing unexplored areas such as a key symbiotic nutrient, vitamin K2, with vitamin D3, next generation sequencing (NGS) of polymorphisms involved in vitamin metabolism pathways as well as metagenomics to assess the response of the gut microbial community to dietary and supplemental nutrients. The Specific Aims and research questions for our study include:
Specific Aim 1. Evaluate effect of vitamin D3 and K2 dietary intake and supplementation groups vs placebo group on the gut microbiome; Research Question (RQ)1.a. Will gut microbiome composition, diversity, and richness respond differently to each treatment group - vitamin D3, vitamin K2, D3+K2 versus the control group? RQ1.b. What effect will vitamin D3 and/or K2 metabolism pathway single nucleotide polymorphisms (SNPs) have on gut microbiome response?
Specific Aim 2. Assess response to vitamin supplementation with serum 25-hydroxyvitamin D [25(OH)D] and osteocalcin levels pre and post supplement; RQ2. Will selected doses, based on clinical experience and published data, achieve designated endpoints for sufficiency; serum 25(OH)D greater than 30 ng/mL and undercarboxylated osteocalcin (ucOC) within normal limits?
Specific Aim 3. Assess the influence of vitamin D and K metabolism pathway SNPs on serum 25(OH)D and osteocalcin to determine vitamin D3, K2, and D3 + K2 supplementation efficacy; RQ3. To what extent does the presence of vitamin D and/or K metabolism pathway SNPs affect supplement efficacy when comparing treatment vs control group response measured by serum biomarkers?
Specific Aim 4. Explore relationships between diet/Dietary Inflammatory Index (DII), lifestyle behaviors (steps and sleep), body composition, metabolic and inflammatory biomarkers, SNPs, and the gut microbiome from Baseline to 3 months; RQ4.a. What factors need consideration when exploring genetic and non-genetic contributions to the gut microbiome in the treatment vs control group? RQ4.b. What role do age, gender, body mass index, inflammation status, and lipid profile play in the gut microbiome composition?
Hypothesis 1: Genotypic alterations in vitamin D3 and/or K2 metabolism pathways will influence gut microbiome composition in response to supplementation.
Hypothesis 2: Genotypic alterations in vitamin D3 and/or K2 metabolism pathways will influence serum response to supplementation.
801 studies on the registry are indexed under Vitamin D Deficiency; 60 are open to participants now.
This study's planned enrollment of 96 is above the median of 78 across 590 interventional studies indexed under Vitamin D Deficiency.
Browse Vitamin D Deficiency studies →Madigan Army Medical Center is the lead sponsor of 26 studies on the registry; 4 are open to participants now.
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Exclusion Criteria:
Vitamin D3 125 mcg taken orally once daily for 90 days
Dietary Supplement: Vitamin Arm 1
Vitamin K2 180 mcg taken orally once daily for 90 days
Dietary Supplement: Vitamin Arm 2
Vitamin D3 125 mcg combined with vitamin K2 180 mcg taken orally once daily for 90 days
Dietary Supplement: Vitamin Arm 3
Inert capsule taken orally once daily for 90 days
Other: Placebo
Subject receives dietary supplement for 90 days
Subject receives dietary supplement for 90 days
Subject receives dietary supplement for 90 days
Subject receives placebo for 90 days
Gut microbiome composition
Evaluate effect of vitamin D3 and K2 dietary intake, and assigned vitamin supplementation group versus placebo group, on the gut microbiome composition
Time frame: 90 days
Gut microbiome richness
Will use Operational Taxonomic Units, Simpson Index and /or Chao1 index to evaluate gut microbiome richness before and after vitamin supplementation vs placebo
Time frame: 90 days
Gut microbiome diversity
Will use Operational Taxonomic Units, Simpson Index and /or Chao1 index to evaluate gut microbiome diversity before and after vitamin supplementation vs placebo
Time frame: 90 days
Serum 25OHD
Response to vitamin supplementation with serum 25(OH)D level pre and post supplement
Time frame: 90 days
Serum Osteocalcin level
Response to vitamin supplementation with serum osteocalcin level pre and post supplement
Time frame: 90 days
Vitamin D3 and K2 metabolic pathway variants on supplementation efficacy
Examine vitamin D3 and K2 metabolism pathway single nucleotide polymorphisms for effect on serum 25(OH)D and osteocalcin levels
Time frame: 90 days
Genetic and non-genetic factor contributions to gut microbiome composition
Explore relationships between diet, lifestyle behaviors (steps and sleep), body composition, metabolic and inflammatory serum biomarkers, and single nucleotide polymorphisms, and the gut microbiome
Time frame: 90 days
Plan to share: Yes — A data sharing agreement has been developed and submitted to the Defense Health Agency; approval has been received.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Supporting information will be available upon request after completion of protocol, for the following 2 years.
Access criteria: Contact principal investigator at mary.s.mccarthy1.civ@health.mil
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Madigan Army Medical Center