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Information on the latest vitamin D news and research.

Find out more information on deficiency, supplementation, sun exposure, and how vitamin D relates to your health.

Direct measurement technique suggests calculated bioavailable vitamin D levels are inaccurate

Within the last year I’ve blogged on three studies that presented results based on bioavailable vitamin D levels, the Powe  and Chun studies and the Ponda RCT. Bioavailable or free vitamin D refers to circulating vitamin D compounds that aren’t attached to vitamin D binding protein (DBP), a blood protein related to albumin but more than 100 times less abundant.

About 85% of vitamin D compounds in the blood attach to DBP. Consequently, this vitamin D is available only to cells that can absorb DBP. Many types of cells don’t have the appropriate receptors, which are called megalin and cubilin and are found on many of the cells involved in the classic bone health understanding of vitamin D. The remaining vitamin D compounds attach to albumin and tiny amounts circulate unattached to anything. The albumin-bound and totally free vitamin D compounds are considered to be bioavailable.

This leads to the hypothesis that free 25(OH)D may be more important for many of the non-classical actions of vitamin D than total 25(OH)D, which in turn has led to research on the association between bioavailable vitamin D and various markers of health.

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  About: Tom Weishaar

After a career writing about computers and personal finance, Tom Weishaar is a doctoral student in the health education program at Teachers College, Columbia University.

4 Responses to Direct measurement technique suggests calculated bioavailable vitamin D levels are inaccurate

  1. mbuck says:


    So, it’s a little confusing—are you talking about the D3 levels in the blood, as found by blood-spot tests from, for example, ZRT labs?

    On one hand you write, “..even if the free vitamin D hypothesis is confirmed, total 25(OH)D would still be a valid biomarker of vitamin D status.” and on the other, “These findings favor the use of the direct measurement of free 25(OH)D over calculated estimates of free 25(OH)D…”

    Define direct measurement, and define calculated measurement, how are these arrived at, and how do these relate to blood-spot test, please.


  2. Tom Weishaar says:

    MBuck – The blood-spot test measures total 25(OH)D, which is the currently accepted biomarker of vitamin D status.

    However, there are some scientists who argue that a better biomarker of vitamin D status would be free or bioavailable 25(OH)D (rather than total).

    The problem is that those scientists didn’t actually measure free 25(OH)D in their studies, they calculated it.

    In this paper, the researchers are comparing measured free-25(OH)D with calculated free-25(OH)D. And they found that calculating it doesn’t provide accurate results.

    At the same time, they also found a high correlation between total 25(OH)D and measured free-25(OH)D. This suggests that total 25(OH)D, what the blood-spot test measures, is the only biomarker of vitamin D status we need.


  3. IAW says:

    This would probably not be an “apples to apples” comparison but I am going to say it anyway.

    Many, many years ago science decided that the gold standard for diagnosing thyroid disease would be the TSH test (Thyroid Stimulating Hormone). If you fall within the acceptable blood test range you are OK and too high and you probably have hypothyroidism. Then to treat someone you give them T4 medicine, check their TSH levels again and when they are within the “range” again, call the patient “well” even if they still have symptoms. Only problem is until you would then perform a Free T4 lab test and a Free T3 lab test would you then be able to actually see if you really are giving the patient enough of the correct medicine and if they are “converting” it properly for use in the body.

    My point is for the most part a 25OHD might work out just fine as a measurement. Then again maybe a “free” level will also have a place, at some point, in order to diagnose. As we have seen (case point Vitamin D) once medical science seems to make a decision, it takes a whole lot to undue a wrong! (As a side note some doctors have been battling since the 1950’s to show the problems that are inherent in only using a TSH test to diagnose and treat hypothyroidism. So Dr. Cannell is not alone in trying to right some of the wrongs made in medical science.) So we should all “tread carefully” before we decide “free” levels are not useful!

  4. My takeaway from this is that if it is true that the optimal value for “vitamin d” is not a specific number but rather an approximation or a range, such as 50 ng/ml + or – 10 ng/ml and varies substantially based on genetic variation, skin type, etc., there is little empiric significance in getting “precise” measurements. Kind of like multiplying 2 x 2, and stating that the results are 4.0000 – it may be true but it’s clinically insignificant to append the “.0000” :)