How is vitamin D absorbed and used in your body?
 
Vitamin D3 enters the body through sun exposure, diet or a supplement and goes into the blood stream where much of it binds to the vitamin D binding protein (VDBP) -- a protein that carries vitamin D compounds into circulation. From there, vitamin D3 functions within two systems in the human body - the endocrine system and the autocrine/paracrine system.
 
#1 - The Endrocrine System - for skeletal health

The endocrine system - this long studied system for action by vitamin D - is where calcium homeostasis and bone health are maintained. Vitamin D3, from UV exposure or diet, is delivered to the liver, converted to 25-hydroxyvitamin D, or 25(OH)D, and moved into circulation where it has a half life of approximately three weeks. As necessary, 25(OH)D is then transferred to the kidney where it is further converted to the active form of 1,25(OH)2D which has a half life of only a few hours. This active form can then help control calcium absorption and bone health. All the successful studies on vitamin D and bone health have benefited from the long half life and availability of 25(OH)D. For bone health, the important thing is the amount of 25(OH)D available, rather than direct intake of vitamin D.

#2 - The Autocrine/Paracrine System - for autoimmune health

What has not been appreciated until relatively recently is that in addition to being delivered to the liver for conversion to 25(OH)D, vitamin D is also delivered directly to all tissues of the body. Many of these tissues, such as breast, colon, prostate, and brain, can convert vitamin D to its active form within the tissue. It is through this process that vitamin D can help enable the cells to fight against infections, disease, and autoimmune disorders. Vitamin D has a half life in the autocrine system of roughly 24 hours, so in order for it to have a meaningful impact on cellular functions, you need a new supply of it every day. This new understanding means that frequency of dosing matters when testing for disease reduction and immune control - large monthly or quarterly doses that are effective for bone health will not show positive results for disease reduction. For disease prevention and treatment, daily dosing (food, sun, supplement) is very important!
 
Do nursing mothers need daily D3?
 
Without daily dosing, breast feeding mothers could have 50-60 ng/ml of measurable 25(OH)D in their blood but no measurable vitamin D3 in their breast milk. After vitamin D3 has been turned to 25(OH)D it cannot enter the breast milk. The only way to get vitamin D in breast milk is by dosing daily - either by sun, diet or supplementation. Dr. Hollis' research indicated that 6,400 IU/day was necessary for breast feeding mothers to attain sufficient vitamin D (to the value of 400 IU/day for the infant) in their breast milk.
 
Why does this matter for clinical trials?
 
Most of the clinical trials conducted in the past 40 years have focused on the endocrine system and have consistently shown the positive effects of vitamin D on bone health regardless of dosing regimen (from daily to quarterly). In the past 10 years, many new clinical trials have focused on non-skeletal outcomes such as autoimmune disorders, cancer, cardiovascular disease and infections. These new studies have also used various dosing regimens--but have yielded inconsistent results. Those with adequate daily vitamin D inputs have largely shown positive results while those with longer dosing intervals have shown no vitamin D effect. While 25(OH)D levels are maintained in these studies, it is the vitamin D3 levels that are essential to these systems. Therefore, it is necessary to design a clinical trial based on the physiology of the system of interest in order to accurately assess the effect of vitamin D in the body.
 
Conclusion
 
"Circulating vitamin D, the parent compound for tissue vitamin D activation, likely has an important direct physiological role beyond what was originally anticipated through the local tissue autocrine system." Schedules for vitamin D dosing could have profound effect on health outcomes.