The relationship between vitamin D levels and lack of response to supplementation
The machinery of our body is made up of several components that are essential for it to function properly. Among these components are vitamins, which ensure that certain reactions take place correctly. One of the most important—if not the most important—is vitamin D, widely known since the beginning of the pandemic due to its immunomodulatory effects. However, it also plays many other roles related to our health, especially bone health.
However, in our country a large proportion of the population presents a deficiency associated with this vitamin. Specifically, up to 51.8% of the population shows this deficiency in summer, while in winter prevalence can reach up to 76.5%.
If it is so important, why do so many people have a vitamin D deficiency?
This has essentially happened due to the major change in our routines during the 21st century. Changes in working habits—such as working on computers, spending time indoors without sun exposure, or even working night shifts—make vitamin D synthesis considerably more difficult, since according to experts up to 90–95% of vitamin D reserves come from sun exposure. The remaining percentage comes from diet, which is the second source of vitamin D, from which we can absorb up to 80% of the vitamin D content in foods.
Nevertheless, there are people who may have good daily sun exposure and still fail to reach normal levels. How is that possible? Wasn’t sun exposure enough? This is where we need to start talking about genetics.
The metabolism of vitamin D within our body goes through several reactions until it reaches the optimal form and site where it can act. Until then, vitamin D and its blood levels are influenced by proteins responsible for managing this vitamin in its absorption, transport and even its conversion into the active form. These proteins are strongly influenced by genetics, which determines their structure. A small change in the DNA sequence that defines how a protein is built can permanently affect its function. This is exactly what happens when we talk about polymorphisms related to vitamin D metabolism—small mutations capable of conditioning these proteins and therefore the final vitamin D levels in our blood.
What are these mutations?
Regarding vitamin D receptors, there are genetic variants of great interest located in a gene called VDR. This gene encodes the specific receptor for vitamin D, which allows the vitamin to act within cells. However, there are certain variants within this gene—present in a relatively high proportion of the population (33–43%)—that can influence blood levels of this vitamin. Given the high frequency of these variants and lifestyle habits with limited sun exposure, it is logical that a large part of the population presents this deficiency. But does it end here?
The answer is no. There are additional variants located in genes related to vitamin D transport (GC gene) or its conversion into the active form (CYP2R1 gene), with frequencies of 27–43% and up to 69% respectively. These variants also influence blood levels of vitamin D due to less efficient transport or impaired conversion into its active form.
Essentially, it could be said that we have not had enough time to adapt and evolve towards a more efficient management of this vitamin, and therefore today we are experiencing the consequences. For this reason, many people—especially during the winter months—choose to use supplementation to cover these needs more efficiently. But is that enough for everyone? Does genetics have something to say about this?
Indeed, a very recent study has shown that not all of us respond with the same efficiency to vitamin D supplementation. Not only that, but the study also highlights the genetic variants involved in vitamin D metabolism—and yes, we can confirm that they are quite common in the population. This is extremely valuable information that every healthcare professional should consider in order to prescribe the exact dose each person needs to adequately cover their vitamin D requirements through supplementation.
Do you think you have good vitamin D metabolism?
Do you respond well to vitamin D supplementation? Do you currently have good vitamin D levels thanks to excellent habits? There is only one way to find out: by studying the genetic variants that may affect your vitamin D levels and by checking your current blood vitamin D levels.
References
- Usategui-Martín R, De Luis-Román DA, Fernández-Gómez JM, Ruiz-Mambrilla M, Pérez-Castrillón JL. Vitamin D Receptor (VDR) Gene Polymorphisms Modify the Response to Vitamin D Supplementation: A Systematic Review and Meta-Analysis. Nutrients. 2022;14(2):360. doi:10.3390/nu14020360
- Fakhoury HMA, El Shamieh S, Rifai A, Tamim H, Fakhoury R. Vitamin D Related Gene Polymorphisms and Cholesterol Levels in a Mediterranean Population. J Cardiovasc Dev Dis. 2022;9(4):102. doi:10.3390/jcdd9040102
- Akter R, Afrose A, Sharmin S, Rezwan R, Rahman MR, Neelotpol S. A comprehensive look into the association of vitamin D levels and vitamin D receptor gene polymorphism with obesity in children. Biomed Pharmacother. 2022;153:113285. doi:10.1016/j.biopha.2022.113285
- Ammar M, Heni S, Tira MS, et al. Variability in response to vitamin D supplementation according to vitamin D metabolism related gene polymorphisms in healthy adults. Eur J Clin Nutr. 2022. doi:10.1038/s41430-022-01218-y
- Mimpen M, Rolf L, Poelmans G, et al. Vitamin D related genetic polymorphisms affect serological response to high-dose vitamin D supplementation in multiple sclerosis. PLoS One. 2021;16(12):e0261097. doi:10.1371/journal.pone.0261097
- Xenos K, Papasavva M, Raptis A, Katsarou MS, Drakoulis N. Vitamin D Supplementation and Genetic Polymorphisms Impact on Weight Loss Diet Outcomes in Caucasians. Front Med (Lausanne). 2022;9:811326. doi:10.3389/fmed.2022.811326
- Díaz-López A, Paz-Graniel I, Alonso-Sanz R, Marqués Baldero C, Mateos Gil C, Arija Val V. Vitamin D deficiency in primary health care users at risk in Spain. Nutr Hosp. 2021;38(5):1058-1067. doi:10.20960/nh.03565
- Valero Zanuy MÁ, Hawkins Carranza F. Metabolism, endogenous and exogenous sources of vitamin D. REEMO. 2007;16(4):63–70. doi:10.1016/S1132-8460(07)73506-7
