Vitamin D Deficiency
Conditions
Keywords
Vitamin D, Immune function
Brief summary
Hypothesis: Volunteers with vitamin D insufficiency (serum 25(OH)D 25-50 nmol/L) given intermediate or high dose vitamin D supplements (2,000 or 5,000 IU per day) will have increased production of anti-bacterial peptides and interleukin-1, decreased production of other pro-inflammatory cytokines, increased production of regulatory cytokines and an enhanced T- and B-cell response to a tetanus vaccine compared to vitamin D insufficient subjects given low dose vitamin D supplements (400 IU per day).
Detailed description
Specific Aim 1: Determine if high dose vitamin D supplements decrease the production of proinflammatory and increase the production of regulatory cytokines and chemokines by innate immune cells stimulated ex vivo. Specific Aim 2: Determine if high dose vitamin D supplements decrease serum markers of inflammation and increase serum and cellular levels of defensive molecules (e.g., cathelicidin). Specific Aim 3: Determine if high dose vitamin D supplements decrease blood levels of proinflammatory T-helper type 1 (Th1) and Th17 cells and increase levels of anti-inflammatory T-regulatory (Treg) and Th2 cells. Specific Aim 4: Determine if high dose vitamin D supplements increase antigen specific T cell and B cell responses after tetanus vaccination.
Interventions
DIETARY_SUPPLEMENTVitamin D - Treatment 1
Volunteers will take a 400 IU/day dose of Vitamin D for 12 weeks.
DIETARY_SUPPLEMENTVitamin D - Treatment 2
Volunteers will take a 2,000 IU/day dose of Vitamin D for 12 weeks.
DIETARY_SUPPLEMENTVitamin D - Treatment 3
Volunteers will take a 5,000 IU/day dose of Vitamin D for 12 weeks.
Sponsors
USDA, Western Human Nutrition Research Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 20-49 (men) and 20-45 (women) * BMI 18.5-30 * Serum 25OH Vitamin D 25-50 nmol/L
Exclusion criteria
* Pregnant or nursing women * Daily smoker * Anemia (Hgb\<12 mg/dL for women and \<13 mg/dL for men) determined at initial visit * Any report or diagnosis of disease or chronic condition that may affect vitamin D absorption such as cystic fibrosis, celiac disease, surgical removal of part of the stomach or intestines, and some forms of liver disease * Diagnosis of hyper parathyroidism and chronic granulomatous disease, which increases risk of hypercalcemia. * Planned to travel to a location at which either altitude or latitude would result in significant vitamin D synthesis during the study period. * Not previously vaccinated with TT, or vaccinated within five years * Use of steroids or antibiotics within the past 4 weeks * Current use of nutritional supplements that may alter immune function such as omega 3 fatty acid supplements * Current use of anti-inflammatory or anti-convulsion medications * Self reported history of significant adverse response to previous vaccinations
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in urinary calcium-to-creatinine ratio | 0, 2, 4, 6, 8 and 10 weeks | — |
| Change in markers of response to tetanus vaccination | 0, 8, 9, 10 and 12 weeks | Markers of response to tetanus vaccine include tetanus-specific proliferation and production of cytokines by CD4 T-helper cells. |
| Change in serum 25OH Vitamin D | 0, 4, 8, and 12 weeks | — |
| Change in Cathelicidin levels in granulocytes | 0, 8, and 12 weeks | — |
| Change in cytokine levels from stimulated Periferal Blood Mononuclear Cells | 0, 8 and 12 weeks | — |
| Change in serum cytokines and acute phase proteins | 0, 8 and 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in production of leukotrienes in granulocytes | 0, 8, and 12 weeks |
| Change in level of 5-lipoxygenase protein in granulocytes | 0, 8 and 12 weeks |
Countries
United States
Outcome results
None listed