Pam Lutsey smiling

Lutsey finds flaw in vitamin D test, debunks previous study

Charlie Plain | September 25, 2015

For the past few years, Vitamin D has been a hot health topic and it’s become one of the most commonly used health screening tests in many parts of the world.

Pam Lutsey smiling
SPH epidemiologist Pam Lutsey

“You’re constantly hearing about the potential health benefits of vitamin D in the news. This has caused a dramatic increase in vitamin D supplement use,” says School of Public Health epidemiologist Pam Lutsey. “Thirty-six percent of U.S. adults report taking a vitamin D supplement either as a prescription or in a multivitamin.”

The reason so many people are taking supplements is a lot Americans are chronically low in blood vitamin D concentrations.

According to data from the National Health and Nutrition Examination Survey, 28 percent of whites are thought to have inadequate vitamin D. That number skyrockets to 81 percent for blacks.

In 2013, the New England Journal of Medicine published a study that seemed to prove there are racial differences in the amount of specific types of vitamin D present in our bodies, and that blacks have greater concentrations of its most biologically useable form.

The results were a revelation for vitamin D researchers as they try to sort out how our bodies use vitamin D and what levels are best for good health.

That same journal has now published a letter co-authored by Lutsey and colleagues that disproves the 2013 study and highlights how the vitamin D binding protein test used in the 2013 article is seriously flawed.

The vitamin D paradox

Vitamin D is known to be important for good bone and cardiovascular health. It’s naturally produced in the body through skin synthesis triggered by exposure to sunlight.

Blacks are thought to have lower concentrations of vitamin D because the melanin in their skin blocks sunlight and reduces the amount of skin synthesis that takes place.

With reduced concentrations of vitamin D, the expectation is that blacks should have increased health issues, such as bone fractures.

But they don’t.

In fact, despite their low vitamin D concentrations, research shows that blacks actually have higher bone mineral density and suffer fewer fractures than whites.

The paper published in the New England Journal of Medicine in 2013 attempted to explain this apparent paradox.

The paper’s lead-author Camille Powe said the reason why blacks have low concentrations of vitamin D yet don’t seem so badly affected by the deficiency is that a racial difference in their genome results in higher concentrations of the nutrient’s most usable form roaming around their bodies.

“The Powe paper was really transformative in the way everyone was thinking about vitamin D,” says Lutsey. “It offered an explanation — a beautiful explanation — for why we’re seeing these unexpected race interactions — but it was wrong.”

Bound to be wrong

Powe’s explanation hinged on the fact that there are actually two primary forms of vitamin D found in the body: “bound” and “bioavailable.”

Bound is a type of vitamin D that is attached to blood “binding” proteins. Binding proteins assist in transporting vitamin D throughout the body, and hold onto it until it is released into the tissues.

Bioavailable vitamin D is the other form and found floating around the circulatory system ready for immediate use in physiologic processes, like bone mineralization.

The Powe study concluded that racial differences in concentrations of bioavailable vitamin D were the answer after running a test that measures vitamin D binding protein concentrations called a monoclonal sandwich immunoassay.

Their results showed blacks actually have lower concentrations of vitamin D binding protein than whites. That meant that a greater proportion of their overall vitamin D exists in the free, bioavailable form, which explains why they have stronger bones and a lower prevalence of deficiency problems.

As for why blacks have unusually low amounts of binding protein, Powe said two simple genetic variations, called polymorphisms, accounted for 80 percent of the reason.

Lutsey agreed with Powe’s reasoning right up until this point.

Despite Powe’s elegant explanation, Lutsey couldn’t accept that so much was determined by something so little.

“That didn’t seem realistic; it just didn’t make sense that two polymorphisms explain 80 percent of the variability,” says Lutsey.

Lutsey consulted with her long-time collaborator, John Eckfeldt, from the Department of Lab Medicine and Pathology, and together they couldn’t think of any other instances where two polymorphisms have so much influence on anything similar.

Lutsey and Eckfeldt decided they wanted to do some testing of their own, and got in touch with Andy Hoofnagle at the University of Washington.

They’d learned that Hoofnagle was in the late stages of developing a new blood test for measuring vitamin D binding protein concentrations. The test employs a method known as a liquid chromatography mass spectrometry, and they wanted to use his test.

“It’s a different approach — a better approach,” says Lutsey.

Lutsey and her collaborators tested the new and old methods on blood samples from a previous study. The results showed that blacks do not have especially low binding protein concentrations as Powe has asserted.

A testing flaw

Lutsey says the real reason why blacks in the Powe study measured low is because of a flaw in the test that was used.

The issue is binding proteins come in different genetic variations, and the test Powe used doesn’t measure well for a type of protein that is common in blacks. The test’s poor sensitivity to this type of protein led to the erroneously low results.

With the debunking of Powe’s claim, Lutsey says the question is still open about why low vitamin D isn’t associated with disease risk in blacks like it is in whites.

On top of that, she says researchers still don’t know, particularly in blacks, what are the right blood concentrations of vitamin D for good health.

And finally, as Lutsey has shown, there’s still uncertainty as to what’s the best way to measure vitamin D in people.

“So much is yet unknown. People are being prescribed vitamin D right and left, and the big question is what is the right blood concentration for optimal health — we need to figure that out,” says Lutsey.


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