DOES D-DEFICIENCY DRIVE DISEASE?

Vitamin-D, that is…

Several weeks ago there was a newspaper report that a specific change (technically called a polymorphism) in the gene for the vitamin-D receptor (VDR) was almost twice as common in women at high risk for breast cancer who live in Marin County.  Without specifically stating it, the article implied that these women were less responsive to vitamin-D because they had a less effective receptor.  The authors then suggested that this might explain breast cancer in Marin and it might be a rationale to give high-risk women supplemental vitamin-D.  Interesting idea.  Where do we go with this?

For years it has been known that “sunshine vitamin-D” was a vitamin because it was necessary for our bodies to absorb calcium to make our bones healthy.  Without adequate vitamin-D, we will not absorb calcium. If this happens to a growing child, the child’s bones will be weak, and the child’s legs will grow with a curve from being bent under their own weight.  This is called rickets. 

More recently, it has been found that vitamin-D levels are lower in persons with breast and colon cancer when compared to persons without these cancers. It is not known, however, whether the lower level of vitamin-D caused the cancer, or if the low level of vitamin-D and cancer coexist by chance, or if they are both caused by some unknown, third factor.  The possibility of a relation is supported, but not proved, by research showing that vitamin-D has its own pathway by which it can control cell growth.  [For a discussion of how “pathways” work, see my post, “Whither breast cancer in 2013?”.]

In this context, it is interesting that Marin County women at higher risk of breast cancer are more likely to have an abnormal vitamin-D receptor gene (called A2/A2).  At first thought, one might assume this explains more breast cancer in Marin.  However, on further consideration, this inherited change in the VDR is not likely to explain breast cancer in Marin for two reasons. 

Marin County is a diverse group of persons.  It is difficult to believe that somehow a selected group of women with this specific mutation selectively moved to Marin.  It is more likely that any woman living anywhere with breast cancer would be more likely to have an abnormal VDR. Such a general association of vitamin-D receptor changes and breast cancer is supported by a 1999 study that found changes in the VDR in Australian women with breast cancer.

The other limitation is that the difference reported in Marin was found by comparing women believed to be at high risk by a theoretical model to women thought to be at low risk by the same model.  What the authors did not emphasize was that when they looked at women who actually had breast cancer 62 percent had the A2/A2 change in the VDR gene, but so did 58 percent of women without cancer. Not a big difference.

Despite these limitations, the possible role of vitamin-D and vitamin-D receptors is an exciting new area of research.  We just don’t know what to do with it yet. 

One might argue to put everyone on high doses of vitamin-D – just to be safe – but that is untested, and it might have adverse consequences.  Remember the excitement that so-called “antioxidants” such as vitamin-E were going to prevent cancer? Epidemiology and laboratory work showed how this was certain to work.  But when it was tested, vitamin-E not only did not decrease cancer, it may have increased lung cancer in smokers and prostate cancer.  High doses of vitamin-E did the opposite of what was hoped.

So how does one decide what to do about vitamin-D in 2012? 

Answering this question is made especially difficult because different studies gather information different ways so we can’t easily compare one study to another.  For example, one study found no relationship of vitamin-D level to developing breast cancer, but three-quarters of their subjects were vitamin-D deficient.  It is not easy to look for a benefit of vitamin-D if most of the subjects are deficient.  In another study, researchers found a benefit of very high levels compared to anything lower, but they did not evaluate mid range levels that might be safer (see below). 

Until we know more about using vitamin-D to prevent cancer, our best guide is research on osteoporosis.  Low levels of vitamin-D are associated with more fractures, and giving vitamin-D reduces the risk of fractures. 

The most practical way to address this is to start with a blood test to find out what your vitamin-D level is.  For example, when I first encountered research on vitamin-D and cancer in 2006, doctors were already recommending calcium with vitamin-D, but the researchers presented data that a lot of women were vitamin-D deficient.  I started testing whether my patients had adequate vitamin-D levels and a quarter of them were deficient.  My own blood level was the third from the lowest I have ever seen.  Why?  I’m indoors all day long, and I use sunscreen when I’m outside.

What vitamin-D level to aim for?  Less than 20 nanograms per milliliter of blood (< 20 ng/ml) is clearly too low.  Between 20 and 30 ng/ml used to be considered low – but not terrible – but now the lowest acceptable level is greater than 30 ng/ml.  How much higher is still debated.

A recent report in the New England Journal of Medicine observed fewer fractures when a woman started out with a vitamin-D level that was over 30 ng/ml.  There was a possible added benefit going from 30 to 60 ng/ml, but no benefit being over 60 ng/ml. 

Some doctors take a more-the-merrier attitude and push vitamin-D levels above 60 ng/ml, but there is not a lot known about what level of vitamin-D might be toxic.  For example, one study in 2010 suggested that levels above 50 ng/ml might be associated with increases in otherwise rare cancers (recall how vitamin-E increased some cancers).

For this reason, at this time – and for the foreseeable future – I suggest that the wise choice is to start by finding out your own vitamin-D blood level.  If it is over 40 ng/ml, that is probably sufficient.  If it is 30 to 40 ng/ml, I would try to boost that to at least 40 ng/ml.  If it is anything under 30 ng/ml, you definitely need to correct that.   Sunshine can help, but beware of sun damage to your skin.  Furthermore, sunscreen blocks the UV light that usually makes vitamin-D in our skin, so sunscreen makes it so that sunlight cannot always make our own vitamin-D.

If you take a vitamin-D supplement, remember it is a fat-soluble vitamin.  That means it must dissolve in fat (or oil) so it can be absorbed into your body with the fat. If you take a solid vitamin-D pill with water and there is no fat in your stomach – for example, on an empty stomach or after a non-fat meal – the vitamin-D is poorly absorbed.  If you are trying to boost a low vitamin-D blood level, I suggest using a gel cap in which the vitamin-D is already dissolved in a drop of oil and thus ready to be absorbed from your intestine (with the oil) to your blood where it can help you.

This is an area of active research, and there will be more information as current studies are completed.  For example, today I read a study from July 2012 Archives of Pediatrics and Adolescent Medicine that looked at stress fractures in adolescent young women who played high-impact sports.  The amount of calcium they had in their diet did not affect their rate of stress fractures, but those who had more vitamin-D in their diet had significantly fewer broken bones from stress fractures.  This seems to reinforce the importance of vitamin-D intake.

As I said, there is new information all the time. 

Please stay tuned.

This website is for educational purposes only. Your personal situation may vary. Consult your physician before making your healthcare decisions.

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