DBP on Solid Bone

DBP stands for Vitamin D Binding Protein. For the better part of it's known life, DBP was just thought of as a vehicle to move all vitamin D forms in the body to target tissues for use. Now, that picture is changing. 

DBP is rapidly changing The Vitamin D story

While the function of vitamin D binding protein, DBP, has been observed for a long time, it is only quite recently that a few twists have emerged. One concerns the nature of the strength of these bounds and the real bio-active status of vitamin D. In the blood stream, about 85-90% of 25-OHD3 is strongly bound to DBP while 10-14% is weakly bound to the protein albumin and 1% of 25-OHD3 is free unbound. This now has new significance as vitamin D combined with DBP is so tightly bound that it is for all intensive purposes, not bio-available for body functions in that form. It just serves as a storage and delayed form for the Kidneys to convert into the hormone form when needed. Thus, it is only the 10-15% of 25-OHD3 bound to albumin or free form that is bio-active at any one time. It is this amount that shows an association with higher bone mineral density while the DBP bound 25OHD3 rarely reflects this influence. ref ref

Now, as if this is not enough to ponder, along comes another twist. The protein DBP also has other vital functions to perform either bound or not bound to vitamin D. ref  Following is a sentence copied from this reference: "Many studies have discussed the link between DBP-phenotypes and susceptibility or resistance to osteoporosis, Graves' disease, Hashimoto's thyroiditis, diabetes, COPD, AIDS, multiple sclerosis, sarcoidosis and rheumatic fever..."

Researchers now have to figure out how to best maximize all these different functions such as the vitally important one of preventing Actin polymerization. Actin forms necessary vital filaments to give cells their unique shape. But as cells naturally die, this released actin material needs to be quickly broken down and eliminated because it's rigid structure can damage surrounding tissues and cells. While there has never been found a deficiency of DBP, it's levels appear to be related somehow with the 25-OHD3 form of vitamin D. 

Over the years, DBP has readily changed into slightly different forms of Gc protein. While there are now over 120 forms, Gc1 and Gc2 dominate most as these these configurations: Gc1:1, Gc1:2, and Gc2:2. These different forms or SNPs modify the action level of DBP. People with more of Gc2:2 grow better bones than Gc1:1. Gc2 forms a weaker bond with DBP. The three are also listed as Gc1F, Gc1S, and Gc2 in some studies. Better bone growth exists without Gc1F. These types were discovered about 55 years ago.

DBP explains apparent controversial observations 

Dark skin people, who generally have lower levels of vitamin D as 25-OHD3, might also have lower DBP levels which means that the amount of bio-available free vitamin D might be the same as a light skin person with higher vitamin D. This would give them a higher bone mineral density than expected. This shouldn't happen given the current mainstream medicine bone building theories of higher calcium and vitamin D needed for stronger bones since they don't recognize the DBP bound part as mostly inert.

So, maybe it's time for another theory that better explains this situation. Along comes the DBP hormone theory. Below is the rest of the theory that helps explain the above given situation plus many other mysterious observational realities. Example: South Africans on their native diet consume daily about 300 mg of calcium while their relatives who move to the United States consume 750 mg or more but have a 9 times greater hip fracture rate.

DBP and 25-OHD3 are somehow linked. One may control the other and determine say how much 25-OHD3 the body should build and store given the amount of DBP present, or vice versa. But, the levles of DBP and vitamin D do vary in relationship to each other. And this changes health parameters. Thus, just increasing the intake of vitamin D (or calcium) supplements might not be enough to get to the proper bone health picture. Or it might negatively impact bone health by inadvertently hindering a natural balalnce. Some Nutritionists and other professionals who do not understand how this new theory works may be looking for and measuring the wrong parameters and thus giving faulty advice.

It is not necessarily how much vitamin D is present, but how much of it is bio-available to the body that is important as a percentage of the total vitamin D. Someone with lower vitamin D storage levels than another person could actually have more bio-active D form present. The DBP could be a rate limiting factor for how much vitamin D the body wants to optimally store. With sunlight production, the amount of vitamin D that is turned into storage form is limited, but with supplementation, this limiting pathway does not factor. The possibility to upset this body balance process is thus mostly from supplementation and the reason could be DBP.

The body adapting DBP levels could be the reason people survive the long winters with little sun to manufacture vitamin D. As vitamin D storage levels fall in the winter, the body may also reduce DBP to maintain a steady vitamin D action potential. Plus, vitamin D is also stored in fat which can be released. 

The DBP binding hormone theory explains more observed bone facts than any other theory, such as why studies of calcium with or without vitamin D are not always successful in building bone density or preventing fractures. Plus partly explain why lifetime milk drinkers can have more fractures, not less. The DBP research is still in early stages of discovery. Perhaps this is the reason that so many Doctors and Nutritionists are not yet aware of it and the Public is clearly in the dark.

SIDEBAR: Vitamin D exists in 2 main forms, and a number of secondary but still important ones too. One as 25-OHD3 is the storage form and the other as 1,25 OH2D3, the hormone form. The storage form is stable and lasts for 2-4 weeks while the hormone form is not stable and is destroyed in hours. These forms are mostly transported in the body attached to DBP. Once at their target tissues, they attach to VDR, vitamin D Receptor sites on cell membranes. At these receptors, the vitamin D directs the body to build certain structures needed to signal bone building and also to prevent the calcification of soft tissues and artery walls. Plus, these elements, one called osteocalcin, also participate in controlling blood sugar regulation. When vitamin D first produces osteocalcin, it is not active to work these functions. Vitamin K and a few minerals are needed to activate osteocalcin. The balance between the non-active and the active, or carboxylated osteocalcin, is what controls blood sugar.

New research now believes that the 85% of storage form vitamin D attached to DBP is non active and only the free or loosely bound to albumin vitamin D is the active part.  It is of interest to understand that the storage form vitamin D has a 1000 times stronger affinity to attach to DBP than the hormone form of D while the hormone form has a 1000 times stronger attachment to vitamin D receptors on cell membranes. It can be deducted as to why these different attractions exist when one understands the new DBP theory. With the knowledge from the DBP hormone theory, a greater measure of vitamin D sufficiency can be determined using "bioavailable 25-OHD levels" for better treatment protocols to target "the relationship between vitamin D and a wide range of outcomes including fracture, infections, cancer, and cardiovascular disease." 

The Free-Hormone Hypothesis

The DBP hormone theory fails under the scientific term for Free-Hormone Hypothesis. ref This hypothesis says that free unbound hormone is highly active and readily passes into cells. And it is responsible for most of the nutrient or vitamin-like action. For vitamin D, this also includes the loosely bound vitamin D with the abundant albumin protein. BUT, also with vitamin D, this free hormone theory may not be entirely universal to all body tissues or cells. There are about 11 tissue types, such as breast, prostate, and colon to name a few, where storage vitamin D is converted in the celll to the hormone form which then acts to protect that cell and tissue. What is not completely known yet is if the vitamin D bound to DBP also be used for this purpose or just the "free" bio-available D. The cells in these tissues contain an enzyme that performs this conversion process. It is the same one the Kidneys use when the hormone form of D is needed directed by PTH from the parathyroid gland to correct a low blood calcium level.

This new free-hormone hypothesis for vitamin D research is still in a very early stage according to scientific years, maybe only 6. It takes about 10 years before there is general acceptance by the scientific community and the Public finally finds this out. The internet should shorten this somewhat.

This type of research is very lab technique intensive, expensive, and easily subject to errors. That is one reason a longer time frame is needed to verify.

Wrap Up

This information is presented mainly to let the reader become aware that all the facts for bone health are not completely known yet. And also that numerous elements are involved in bone health with some of the obvious observations and resulting assumptions are not always correct. One could measure lower vitamin D levels but still have strong bones. DBP is very likely one of the failsafe systems the body incorporates to control rates for vitamin D functions and to extend vitamin D life in the body. Look at this study on Breast Cancer prevention and 25-OHD levels. ref A U-shaped curve indicates more cancers at both lower and higher vitamin D levels.** The middle levels are the healthiest, yet some Doctors and Nutritionists are promoting higher and higher levels. Can you guess why mother nature uses DBP to control 24-OHD levels and extend their availablity?

How and if there are any other lifestyle patterns or supplemental nutrients that can impact DBP functions, it is too early to tell. Obviously, there probably is an optimal level for 25-OHD and DBP, plus vital information concerning who is at greater risk from certain DBP gene patterns and needs appropriate treatment protocols.

**The safest level exhibiting the lowest breast cancer rate was for vitamin D between 76-99 nmol/L (or 30-40 ng/ml) (Strange, this is really close to the level recommended by the new vitamin criteria.) Below 75 the cancer rate was 1.88-2.46 (double the rate of women between 76-99) and if over 100 it was again about 1.75 - 2 times greater. To arrive at the safe vitamin D levels, one may need to be in the sun for 2 hours a day*** (as the Hawaiian surfer study showed very moderate D levels from many sun hours) or take supplemental vitamin D3 at 1500 -2000 IUs. Once one starts on a higher vitamin D amount, it takes 3 months to reach a plateau. After that, the supplemented vitamin D amount can be reduced by about half to maintain. This level assumes that most people are low as research has discovered. CAUTION: Sun exposure needs to be gradually increased. The amount of skin showing determines the length of sun exposure needed. Only 20 minutes with a bathing suit while 2 hours wearing a short sleeve shirt and pants.

To get to a detrimental reading for vitamin D over a 100 nmol/L, if starting at 50 nmol/L, slightly higher than average for women in the US, would require 4000 IUs or more for 3 months. DBP levels and gene types might knock this down a little and require slightly higher dosages to get over the 100 reading. The ideal level appears to be closer to the middle, say 85 nmol/L or 33 ng/ml.

This correlates almost exactly with a study showing the lowest mortality from cardiovascular disease is exhibited with vitamin D levels of 28 ng/ml, (70 nmol/L) ref

***A study showed 20 minutes in a tanning booth was equal to taking 10,000 units of vitamin D2. But, the Hawaiian surfer study did not show levels anywhere near this high from surfers in the sun daily for 3 hours. Did the study not factor in the sun feedback process that limits how high vitamin D blood levels rise? Another study Hollis co-authored acknowledged that many people do not produce high enough vitamin D levels just from sun exposure. Check it out here. 51% under 31ng/mL from lots of sun time.

WHAT TO DO

To test or not to test for vitamin D levels and just increase with sun exposure and/ or vitamin D pills. ref This reference says not to test since testing is expensive and it is not known what levels are healthiest. PLUS, unless one also knows their DBP gene types, the tested level has less meaning. The safest approach is to get some sun exposure without burning plus take a moderate dosage supplement of vitamin D3, 600-1000.

With the results from a yearly physical examination, your Doctor can better analyze  information your status and health condition for proper amounts to supplement or get sun exposure. Sun exposure has a built in failsafe process while supplements do not. Best to not rely on supplements only.