Vitamin D, the vitamin that is not really a vitamin…
A prohormone that is synthesized in the skin using cholesterol in a chemical reaction with UVB radiation from the sun, vitamin D is essential to many processes in the body. Vitamins are defined as substances that are necessary to obtain from the diet; vitamin D doesn’t meet that definition because we need can obtain all that we need by adequate sun exposure. In addition to our body’s production from sunlight, there are a few food sources of vitamin D, as well as supplements of D2 (ergocalciferol) or D3 (cholecalciferol).
Importance of Vitamin D:
There are a lot of articles that lay out the importance of adequate vitamin D levels. Vitamin D affects everything from mood to cancer risk to immunity to bone density. Here are just a few articles that outline the importance of adequate vitamin D:
On the other hand…
There is also some controversy on whether supplemental vitamin D3 is beneficial, so do some research before jumping into supplementing with vitamin D. Here are a few studies that have found little benefit from supplementing with vitamin D3 :
- The impact of cholecalciferol supplementation on the systemic inflammatory profile: a systematic review and meta-analysis of high-quality randomized controlled trials.
- Vitamin D and Cancer Risk and Mortality: State of the Science, Gaps, and Challenges.
- The effect of vitamin D supplementation on glucose metabolism in type 2 diabetes mellitus: A systematic review and meta-analysis of intervention studies.
- Vitamin D Status and the Host Resistance to Infections: What It Is Currently (Not) Understood.
Conversion of vitamin D to the active form:
The form of vitamin D produced in our skin is the biologically inactive form, cholecalciferol, and it must be converted to the active form that our body uses. The first step in the conversion takes place in the liver, where cholecalciferol is hydroxylated in the liver into calcifediol (25(OH)D), which can then be converted in the kidneys or macrophages into calcitriol, the biologically active form of vitamin D also known as 1,25(OH)2D.
Vitamin D and genetics:
Genetics can play a role in vitamin D levels in several ways, which makes sense when looking at the different steps involved in converting it to the active form which then acts on the vitamin D receptors in a cell.
CYP2R1 is the gene that codes for the enzyme that converts cholecalciferol into calcifediol in the liver. A common polymorphism is associated with decreased vitamin D levels.
|Check your 23andMe results for rs2060793 – CYP2R1 gene:
AA: Lower vitamin D levels [study]
AG: Normal vitamin D levels
GG: Higher vitamin D levels
|Check your 23andMe results for rs1562902 – CYP2R1 gene:
TT: Higher vitamin D levels [study]
CC: Normal vitamin D levels
The second step in the conversion to the active form of vitamin D involves CYP27B1 as a catalyst for the conversion of calcifediol to calcitriol. While there are several common polymorphisms in CYP27B1 that have been studied in regards to vitamin D related conditions, none of the common polymorphisms have been definitively shown to have an effect. A couple of rare mutations of CYP27B1 do affect the conversion to the active form of vitamin D, and these mutations are linked to rickets, a disease caused by the lack of vitamin D in childhood.
|Check your 23andMe results for rs28934607 – CYP27B1 gene:
AA: Pathogenic for Vitamin D related rickets [ClinVar]
|Check your 23andMe results for rs28934605 – CYP27B1 gene:
TT: Pathogenic for Vitamin D related rickets [ClinVar]
|Check your 23andMe results for rs28934604 – CYP27B1 gene:
TT: Pathogenic for Vitamin D related rickets [ClinVar]
The most common way to test vitamin D levels is to measure the serum 25(OH)D levels. This gives a snapshot of total 25(OH)D but doesn’t differentiate between free and bound 25(OH)D. One study explains: “In the circulation close to 90% of total 25(OH)D are bound to vitamin D-binding protein (DBP) with high affinity, about 10% are more loosely bound to albumin and <0.1% are in an unbound, or free,form”. The vitamin D binding protein is coded for by the GC gene, and polymorphisms in the gene affect the total serum levels of 25(OH)D. While those with the polymorphisms listed below may test lower on a serum vitamin D test, this doesn’t necessarily mean that their levels of available free 25(OH)D are low. It may be better to run the more expensive blood test to check the active form, 11,25(OH)2D. Many of the polymorphisms in the GC gene vary in different ethnic groups, and this is thought to be a big part of the difference in vitamin D levels among populations. You can read more in the introduction of this study.
|Check your 23andMe results for rs2282679 on the GC gene:
TT: Normal vitamin D levels [study]
GT: Somewhat lower total serum vitamin D levels
GG: Lower serum vitamin D levels
|Check your 23andMe results for rs7041 on the GC
CC: Normal Vitamin D levels [study]
AA: Lower Vitamin D levels [study]
After vitamin D (from sunlight, food or supplements) has gone through the conversion steps, the active form, calcitriol, can act on cells through the vitamin D receptor (VDR) which is a transcription factor that regulates gene transcription either positively or negatively. One study explains this interaction: “Activation of the VDR through direct interaction with 1,25(OH)2D3 prompts the receptor’s rapid binding to regulatory regions of target genes, where it acts to nucleate the formation of large protein complexes whose functional activities are essential for directed changes in transcription (2). In most target cells, these actions trigger the expression of networks of target genes whose functional activities combine to orchestrate specific biological responses. These responses are tissue-specific and range from highly complex actions essential for homeostatic control of mineral metabolism to focal actions that control the growth, differentiation and functional activity of numerous cell types including those of the immune system, skin, the pancreas and bone as well as many other targets that are described in this issue devoted to vitamin D.”
There are several polymorphisms for the Vitamin D Receptor (VDR) gene that affect the response to vitamin D:
|Check your 23andMe results for rs731236 – VDR TaqI
GG: Normal [study]
AA: Increased risk of low bone mineral density, lower vitamin D levels [study]
|Check your 23andMe results for rs1544410 – VDR BsmI
CC: Normal bone mineral density [study]
AA: Increased risk of low bone mineral density, lower vitamin D levels [study] [study]
|Check your 23andMe results for rs2228570 – VDR FokI (previously rs10735810)
GG: Decreased vitamin D levels, increased risk of fractures [study] [study] [study]
|Check your 23andMe results for rs7975232 – VDR gene
CC: Half the risk of dengue fever [study]
Testing Vitamin D levels:
If you haven’t recently tested your vitamin D level, it is an easy and fairly inexpensive blood test. If you are in the US, there are lots of online sites where you can order lab tests without doctor’srs order. If you are close to a LabCorp testing site, Walk In Lab usually offers the Vitamin D test for around $50 (check for specials and coupons), as does Direct Labs. Accesa Labs uses Quest for their blood draws if that is closer to you. For all of these online lab companies, be sure to shop around and check for coupons; they all run specials fairly often.
Diet and Supplements:
Currently, in the US and Canada, vitamin D is added to milk. Fatty fish, such as salmon, tuna, and mackerel, are also good sources of vitamin D. Some types of mushrooms, when exposed to UV light, also contain vitamin D (as D2).
There are many vitamin D supplements available at stores and online. Keep in mind that vitamin D is fat soluble and supplements usually contain oil such as soybean oil, which you may want to avoid. One that I like is this one with coconut oil on Amazon. Again, the jury seems to still be out when it comes to a definitive recommendation on how much vitamin D is needed. You may find that your sun exposure is enough to keep your levels high enough.
More to Read:
- Vitamin D: Production, Metabolism, and Mechanisms of Action
- Vitamin D: Fact Sheet For Health Professionals (NIH)
- This is just the tip of the iceberg — if you are interested in more details on any of these polymorphisms, do a search on PubMed: http://www.ncbi.nlm.nih.gov/pubmed