Research Reviews

Research Review: Vitamin D and your genes

by Helen Kollias

We’re starting to hear more about how vitamin D is an important nutrient. But are our vitamin D levels affected by our genes?

For a while now we’ve been told to stay out of the sun, and that if we do wander out we should wear protection: sun block, a hat, long-sleeved shirts, a tarp…

All of this is supposed to prevent skin cancer.

Don’t get me wrong — I do all these things, but I’m starting to wonder if we’ve gone overboard.

You see, sunlight is one of the best sources for vitamin D. Low levels of vitamin D have been linked to cancers, inflammatory disorders, autoimmune diseases, psychiatric diseases, abdominal obesity, high blood pressure and raised triglycerides with low HDL levels [1-5].

Wow, it’s like low vitamin D gives you a disease of the everything.

Vitamin D in our bodies

In figure 1 you can see how your body makes vitamin D.

  1. It starts by absorbing UVB rays (from the sun) via the skin.
  2. Through a series of biochemical reactions, your body converts vitamin D into 25-hydroxyvitamin D [25(OH)D] and then into 1 a,25-dihydroxyvitamin D or [a-25(OH)D].
  3. After that, it goes off to the intestines, bones and immune system (to name a few) to keep everything working properly.

It turns out that 1 a,25-dihydroxyvitamin D is important in preventing cancer. It suppresses cancer tumor growth and cancers like prostate, colon, breast cancer to name a few [6-9].

Fig 1 Vit D 1024x838 Research Review: Vitamin D and your genes
Vitamin D metabolism

Research question

Great, just as us northerners enter into winter with the days getting shorter and getting even less sun exposure, I tell you sunlight is good.

But is there more to the story than just how much vitamin D you make from the sun or eat in your diet?

For example, is there a genetic component to our vitamin D status?

Some studies have found the skin color affects how much vitamin D someone can make.

People with darker skin make less vitamin D. The theory is that people with darker skin traditionally lived in areas that were sunny year round. Thus, they didn’t need to be so efficient at converting sunlight to vitamin D. Their bodies had to worry more about absorbing too much solar radiation, thus they produced more melanin (skin pigment) to protect themselves.

On the other hand, people with lighter skin lived in areas with less sun year round, so they needed to be more efficient at making vitamin D from the little sun they got.

But let’s say we’re not comparing dark to light skin, or Ethiopians to Scandinavians, but people with the same geographic-ethnic background and skin tone. Is there a gene that helps people have more vitamin D?

This week’s review look at how genetic differences change vitamin D levels in the body.

Sinotte M, Diorio C, Bérubé S, Pollak M, Brisson J. Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women. Am J Clin Nutr. 2009 Feb;89(2):634-40

Methods

Blood samples and anthropometric measurements were taken from 783 premenopausal women during their routine mammogram (mammography) screening. Of the 783 women, 741 of them approved genetic tests that checked for a vitamin D metabolite.

Average age of these volunteers was 46.8 years old, their BMI was 25.2 (falling in the overweight category) and their physical activity levels were 27.1 MET-hour/week.

What is a MET?

MET stands for metabolic equivalent task.

One MET is your resting metabolic rate that you get when you sit quietly. When you’re sleeping, your MET is 0.9 and if you’re running at 17.5km/h (10.9 mph) then your MET is 18.

One MET-hour is the equivalent of the energy expended by the body during one hour of rest. You can accumulate several MET hours of exercise during one actual hour. For example:

  • 5 MET hours per week vigorous exercise is the equivalent of 45 minutes per week.
  • 5 MET hours per week walking is the equivalent of 1.5 hours brisk walking per week.[10]

Geographic location

All this testing happened in Quebec City, Canada between February and December 2001, which is important because the amount of vitamin D metabolite (and vitamin D) in the blood samples would vary as the daylight lengthens (from February to June 21) and shortens (from June 21 to December).

Since Quebec City is at a latitude of 46.8°North (according to Google Maps) then the longest day would have 16 hours of daylight and the shortest day would have under 9 hours of daylight. June 21 is the longest day and December 21 is the shortest (in the northern hemisphere). At this latitude, there is a good 7 hours of difference in daylight between the longest and the shortest day!

If you go far enough North — or South for that matter — you can go for months without sunlight, or conversely with the sun blazing at all hours.

While it’s pretty obvious that not seeing the sun for a few months is going to make your vitamin D levels plummet (unless you’re supplementing or eating vitamin D-rich foods like cod liver) less significant changes also impact vitamin D levels.

quebec city winter Research Review: Vitamin D and your genes
Quebec City in winter — hardly a sunny tropical paradise.

Vitamin D metabolite

The researchers tested for the vitamin D metabolite 25(OH)D. Why not test for vitamin D? Well, vitamin D is quickly converted into 25(OH)D in the liver; thus testing for 25(OH)D gives you a better idea of how much vitamin D was absorbed by the body.

DNA testing

Researchers also tested for the Vitamin D binding protein (DBP) gene .

DBP attaches to vitamin D in the circulation and transports vitamin D (see Figure 1, above). What exactly DBP does with vitamin D is a bit foggy, but we do know that about 90% of vitamin D is attached to DBP.

Basically, the researchers had a hunch that different versions of DBP would change how much vitamin D would be floating around in the blood.

The researchers isolated DNA from the blood collected and checked to see what “flavour” (technically, SNPs — single nucleotide polymorphisms) of DBP each participant had, if any. The two flavours were rs7041 and rs4588 (both are rare).

Results

Vitamin D levels and the seasons

Blood samples collected in the summer and winter had the highest and lowest 25(OH)D levels respectively.

Women’s blood samples from the summer were 21.7 nmol/L or 38% higher than those in the winter!

Women with SNPs rs7041 and rs4588 have lower vitamin D

Yup, the researchers’ hunch was right, but only partially. The women with one of the two SNPs had lower levels of vitamin D (actually 25(OH)D) in the summer.

These SNPs explained 25 (OH)D levels more than vitamin D intake (from diet and supplementation)… but only from May to October. From November to April, when 25(OH)D levels are lowest, these SNPs weren’t correlated to 25(OH)D levels.

Conclusion

Vitamin D levels  fluctuate seasonally. Months with little sunlight (winter in northern latitudes) have the lowest levels of vitamin D.

There is a least one genetic component to vitamin D metabolism: DBP genetic mutations (SNPs rs7041 and rs4588).

Both mutations are correlated to lower levels of the vitamin D metabolite 25(OH)D in the summer months. But these mutations didn’t correlate to vitamin D metabolism in the winter – when vitamin D levels are already low.

Bottom line

Years of lower vitamin D levels because of genetic mutation may increase the chance of getting certain cancers.

Supplementing with vitamin D or increasing sun exposure could be helpful for people with these mutations.

By boosting vitamin D with supplementation, carriers of the mutation could reduce the risks associated with low vitamin D.

But — and this is a big but — this is one study and the differences in vitamin D were only in the summer when there was the most sunlight and vitamin D. If the differences were year-round or in the winter when vitamin D levels are already low, then I could see this as more of a problem.

So regardless of whether you have a genetic mutation in your DBP gene, I’d suggest you get more sunlight or supplement in the winter.

One thing is clear – vitamin D levels drop in the winter and vitamin D is good for more than just bone health.

References

Click here to view the information sources referenced in this article.

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