Comparative Effectiveness of Vitamin D and Repletion Strategies

VitD has numerous hormonal effects, including regulation of Ca2+ and Mg2+, as well as effects on numerous genes, including insulin and androgens. Mounting literature demonstrates associations between VitD insufficiency and cancer, diabetes and heart disease. VitD insufficiency, defined by concentration of serum 25-hydroxycholecalciferol (25-OHD) <33ng/ml (82.5 nmol/ml), is common at all latitudes; the prevalence is estimated at ~35% in "healthy" populations. VitD testing and replacement is gaining popularity in clinical practice. It is not known whether there is a difference in the effect of equivalent doses of emulsified vs. non-emulsified cholecalciferol (VitD3) supplementation, reflected by quantitative changes in serum 25-OHD. However, clinical observations revealed that in an average of 4.4 months, subjects taking 4000 iu daily of the emulsified form of cholecalciferol improved their 25-OHD levels by 6.76 ng/mL more than those taking 5,000 iu daily of the non-emulsified form. The safety of taking 10,000 IU/day has been confirmed. Taking this dose for 12 weeks should cause a robust increase in serum 25-OHD. This study will provide preliminary data comparing three high quality VitD3 supplements, one a powdered capsule, one a chewable tablet, and the other a lipid-emulsified liquid. Future studies will compare the "better" supplement to conventional VitD replacement using VitD2.

Inclusion criteria

• Provision of informed consent
• Between18-65 years of age; there is an age-related decline in the absorption, transport or liver hydroxylation of orally-consumed VitD (Harris, 1999) therefore adults older than 65 will be excluded. This population is also at greater risk of being on medications with potential medication interactions, e.g. anticoagulants.
• Willingness to perform baseline screening tests: serum 25-OHD, CBC, Comprehensive metabolic chemistry panel (electrolytes, hepatic and renal function tests, lipids, HgA1C, insulin and glucose)
• Screening serum 25-OHD <33ng/ml (82.5 nmol/ml). If >=33ng/ml (82.5 nmol/ml), subjects will participate in the research study as baseline controls for the nested studies of Klotho and TLR-4.
• Ability to read and speak English
• Willingness to be randomized to one of three active treatments for 3 months

Exclusion criteria

• Subjects who have a serum baseline 25-OHD >=33ng/ml (82.5 nmol/ml) will be excluded once the VitD sufficient baseline control recruitment goal is met
• Subjects who have historical or current use of extra-dietary VitD, other than what is in a multivitamin, for the previous 3 months.
• LFTs: AST>60 U/L; ALT>65 U/L; Alkaline phosphatase >120 U/L. Total bilirubin>1.5 mg/dL
• Serum creatinine>1.4 mg/dL; BUN >25 mg/dL5. Subjects who are pregnant, or could become pregnant, unless they are using regular birth control (OCPs, condoms, IUD).
• Subjects who have established osteoporosis.
• Subjects who have history or symptoms of a parathyroid disorder.
• Subjects who have difficulty swallowing pills.
• Subjects who are unwilling to use sunscreen.
• Subjects who have had a past adverse reaction to sunscreen.
• Subjects who are taking medications over the previous 3 months that interfere with the metabolism of VitD (anti-convulsants, anti-coagulants, oral corticosteroids, or barbiturates).
• Subjects with any psychological conditions or substance abuse that may make the subject non- adherent, such as history of bipolar disorder, mania, untreated anxiety or other mood disorder, as determined by the site PI.
• Other severe illness or mental incapacity that, in the opinion of the site PI, would render the potential subject incapable of participating in the study.
• Allergy to sesame oil base
• Heart arrhythmia