The reason for doing this study is to learn whether raising a person's vitamin D level from
below normal to normal levels will improve his or her body's ability to use sugar. Vitamin D
is well known to be an important vitamin for the development and maintenance of bones.
Recently, scientists have learned that vitamin D may have a role in the prevention of cancer,
diabetes, and autoimmune diseases. The investigators are specifically interested in studying
this question in the overweight/obese population as they are at greater risk for both vitamin
D deficiency and impaired ability to metabolize sugar (glucose intolerance).
Vitamin D repletion (increasing the serum 25(OH)D level from ≤ 20 ng/ml to ≥ 30 ng/ml) will
improve insulin sensitivity in individuals who are overweight/obese and insulin resistant.
1. Vitamin D repletion will improve biomarkers of cardiovascular risk and inflammation
(directly altering macrophage cytokine production and/or indirectly as a result of
improvement in insulin sensitivity.) 2. 30,000 IU (0. 25 mg) weekly of cholecalciferol (vitamin
D3) will raise serum 25(OH)D levels from ≤ 20 ng/ml to ≥ 30 ng/ml overweight/obese
population.
Inclusion Criteria:
- Nonsmoking men and women, ages 18-65
- Body mass index (BMI) ≥ 28 kg/m² and within 10% of maximum weight
- Serum 25(OH)D level ≤ 20 ng/ml
- Serum insulin level ≥ 7. 2 mU/l
- Willingness to maintain current body weight for the duration of the study
- Willingness to maintain baseline lifestyle activities and routines for the duration of
the study
- Willingness to avoid the use of non-steroidal anti-inflammatory drugs (NSAIDS),
including low-dose daily aspirin, for at least ten days prior to each admission (due
to the potential effects of these agents on inflammatory markers.)
- Willingness to avoid the use of all over-the-counter or prescription vitamins, dietary
supplements, and herbal products during the study, with the exception of a basic
multivitamin supplement.
- If of childbearing potential, willingness to use highly effective contraception for
the duration of the study.
Exclusion Criteria:
- Current tobacco smoking
- History of bleeding or coagulation disorders
- Gastrointestinal disease resulting in significant gastrointestinal dysfunction or
malabsorption
- History of diabetes, or diagnosed during screening OGTT
- Current treatment with hypertensive medications
- History of cardiovascular disease
- Renal disease, as evidenced by a serum creatinine above the upper limit of normal on
more than one screening visit
- History of kidney stones
- History of chronic hepatitis, or liver enzymes (AST or ALT) more than 2. 5 times the
upper limit of normal
- Primary hyperparathyroidism or baseline hypercalcemia from any cause
- Current treatment with over-the-counter or prescription weight loss medications, such
as orlistat or sibutramine
- History of bariatric surgery
- Current treatment with any cholesterol-lowering medications, such as statins, niacin,
fibrates, or ezetimibe
- Blood pressure ≥ 145/90 after ten minutes of rest on more than one screen visit
- Hyperthyroidism or untreated hypothyroidism. Subjects with chronic, treated, stable
hypothyroidism may be included in the study at the discretion of the Principal
Investigator.
- Pregnancy, desired pregnancy, or lactation within the study period.
- HIV, Hepatitis B and C
- Medical conditions requiring daily calcium supplementation or antacid use
- Use of medications known to interact with calcium or vitamin D metabolism
(bisphosphonates, corticosteroids, thiazide diuretics, cholestyramine, colestipol,
mineral oil, phenytoin, barbituates, dititalis glycosides, antacids)
- Subjects with known hypersensitivity to cholecalciferol
- Participation in an investigational drug study within one month of screening
- History, physical, or laboratory findings suggestive of any other medical or
psychological condition that would, in the opinion of the principal investigator, make
the candidate ineligible for the study
