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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.

Does vitamin D testing misdiagnose African-Americans?

On November 21 the New England Journal of Medicine published an article that led to press headlines (NPR) such as How a vitamin D test misdiagnosed African-Americans and summaries (ConsumerLab.com) such as:

Lower Vitamin D in Blacks May Be Adequate – The traditional method of assessing vitamin D levels may not be appropriate for most black people, according to a new study. Due to a genetic variant, this approach classifies many black individuals as “deficient” in vitamin D although their levels may be adequate.

Here’s the study:

Powe CE, Evans MK, Wenger J, et al. Vitamin D-binding protein and vitamin D status of black Americans and white Americans. N Engl J Med. Nov 21 2013;369(21):1991-2000.

Bioavailable vitamin D is 25(OH)D in the blood that’s not attached to vitamin D binding protein (DBP), a molecule that can bind to the fat-soluble vitamin D-related compounds and carry them in the bloodstream. Another blood protein, albumin, which is closely related to DBP but 15 times more abundant, can also bind vitamin D compounds, but the “affinity” or strength of this bond is lower. About 1% of a human’s 25(OH)D  circulates unattached to anything while 10% to 15% is bound to albumin – it’s this combined fraction of vitamin D that’s considered bioavailable, or “free 25(OH)D.”

There’s another recent article that theorizes that this bioavailable form of vitamin D is important for the modern, autocrine/paracrine multi-disease understanding of vitamin D,  but not for the classic endocrine bone-health understanding.

Chun RF, Peercy BE, Orwoll ES, Nielson CM, Adams JS, Hewison M. Vitamin D and DBP: The free hormone hypothesis revisited. The Journal of steroid biochemistry and molecular biology. Oct 3 2013.

“While the association between 25(OH)D and DBP is pivotal for renal handling of 25(OH)D and endocrine synthesis of 1,25(OH)2D… we hypothesize that binding to DBP impairs delivery of 25(OH)D… that drives many of the non-classical actions of vitamin D. Levels of “free” 25OHD are dependent on the concentration of DBP and alternative serum binding proteins such as albumin, but will also be influenced by variations in DBP binding affinity for specific vitamin D metabolites.”

It’s important to note that these concepts are still theoretical at this point. Moreover, both sets of researchers imply that DBP and albumin levels and affinities aren’t related to 25(OH)D levels. If that’s the case, then higher total 25(OH)D levels in any particular individual will always result in higher bioavailable 25(OH)D levels, so which one is more clinically significant is pretty murky. If that’s not the case, on the other hand, then those of African decent would have lower DBP levels at least in part because they have lower 25(OH)D levels, not only because of mutations in the DBP gene.

In any case, what I take issue with in the New England Journal of Medicine paper is the conclusion that since those of African decent have bioavailable 25(OH)D levels similar to those in Caucasians, the well-known difference in 25(OH)D levels between the two races is inconsequential to the health disparities between the two groups.

Here is the core of their argument:

Low total 25-hydroxyvitamin D levels do not uniformly indicate vitamin D deficiency and call into question routine supplementation in persons with low levels of both total 25-hydroxyvitamin D and vitamin D-binding protein who lack other traditional manifestations of this condition.

By “traditional manifestations” they mean bone mineral density (BMD), calcium levels, and parathyroid hormone levels. They say,

“We studied a community-dwelling population, in which overt vitamin D deficiency was rare; in fact, few participants had parathyroid hormone levels outside the normal range.…Labeling the majority of the black participants as vitamin D-deficient would be inconsistent with the observation that they had higher BMD, higher calcium levels, and only slightly higher parathyroid hormone levels than their white counterparts.”

In other words, we shouldn’t label the majority of the black participants as vitamin D-deficient because of the BMD paradox, which, incidentally, the authors themselves can’t explain. They report bioavailable vitamin D is the same in blacks and whites, which doesn’t address why BMD, calcium, or parathyroid hormone is higher in blacks. Moreover, there is a serious conflict between the two articles in that the other implies bioavailable vitamin D isn’t relevant to bone health, while this one doesn’t even acknowledge that vitamin D has an impact on anything other than bone health.

Next note the reliance on “parathyroid hormone levels outside the normal range.” The Vitamin D Council and many researchers are convinced that optimal vitamin levels occur only when parathyroid hormone levels are maximally suppressed, which is at the low extreme of the normal range.

We know that vitamin D levels in traditionally-living people in Africa are much higher than in either those of African decent or Caucasians in the U.S. We know that vitamin D deficiency and health disparities are associated with many of the same diseases (see here and here). My own research supports the theory that vitamin D status is a determinant of health disparities. There is far too little new evidence in this paper to call into question much of anything, including the relationship between vitamin D status and skin-color based health disparities.

  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 Does vitamin D testing misdiagnose African-Americans?

  1. Jim Larsen says:

    BMD varies as a function of 20+ nutrients, impact exercise, and smoking history.

    BMD by itself is not a strong predictor of bone strength or fracture risk. Bone geometry is the gold standard.

    If you look at the NASA bone research done in space, you can see the interaction of D, calcium, and exercise. And that’s just 3 of the 20+ variables.

    Drawing a straight line between BMD and D levels without controlling for diet, exercise, and lifestyle is simply overly reductionistic. Look at Kleges et al re basketball players….. Low calcium intake exacerbated by calcium sweat losses meant poor bone status despite high levels of impact exercise.

    A hypothesis is not a finding.

  2. Jan says:

    My first question on reading the article last week was, “why then, is the incidence of rickets so much higher in African American babies than it is in Caucasian babies?

  3. Rita and Misty says:

    I think that autism risk is also higher among African Americans, as well as other diseases–Colon cancer, for example:

    “African Americans have the highest colorectal cancer incidence and mortality rates of all racial groups in the United States.”

    http://www.exactsciences.com/blog/prevalence-colon-cancer-among-african-americans/

    Agreed–A hypothesis is not a finding.

    Furthermore….

    Bone disease is not the only health condition to consider.

    (Be well)

  4. dyvik1@gmail.com says:

    In a lecture on vitamin D in the Chicago-meeting in American Congress of Rheumatology a few years ago, I learned that in blacks/africans, PTH is not responsive to low vitamin D-levels. These are not “coupled” in the way it is in homo sapiens out of Africa. I think the explanation was that there was no VBR on parathryeoid cells. That made sense, knowing that Africans in Norway, where I live, do not get osteoporotic the way Norwegians do, despite low VitD. This little piece of information made the whole meeting worthwile for me, as the osteoporosis paradox has puzzeled me a lot.