The troubling thing is some people have a genetic defect of their intracellular metabolic machinery handling vitamin D or its receptor in cells. Thus, some of you who are taking Optimal doses of vitamin D3 and who have obtained Optimal blood levels may not notice any difference or a lessened effect. 

No or lessened improvement in sleep. Immune system or metabolism, or any of the other affects I have written about! Why? Well up 30% of people have genetic defects that result in a poor response to vitamin D3. These defects often result in a poor quality vitamin D receptor (VDR). 

Additionally, others may have genetic issues with proteins that bind and activate vitamin D in the cells. Both VDR and metabolic machinery genetic issues can cause many different health issues, more on this in a bit. If you are afflicted with one of these genetic defects you probably had no idea.

So, are you out of luck? No. As the way our enzymatic system works it is often a cascade of different enzymes to carry out action. Perhaps due to a genetic defect you are deficient in one of the enzymes involved in the cell metabolic pathway used to activate vitamin D in the cell. 

So often by boosting the efficacy of the other enzymes in the cascade you can at overcome the genetic defect. The same with defects in the VDR receptor. First you can optimize your results you have by taking optimal doses and obtaining optimal blood levels of vitamin D3. 

None of us are perfect such that we all may suffer from if not a major at least a minor genetic defect in the VDR or metabolic machinery involving vitamin D in the cell. A deficiency that compromises our ability to make the most of the vitamin D3 we take. To optimize our health.

With a VDR genetic defect alone as documented by vitamin D researcher and founder of vitaminDwiki result in 55 health issues and double the risk of 44 health conditions. For example, a VDR issue is found in 40% of those obese. 1 Perhaps the most striking and for so many is Lyme disease.

For Lyme disease your risk is increased by 50 fold. Though it is not mentioned on his site I would expect the risk for the other tick related diseases like rocky mountain spotted fever and meat allergy (Alpha-Gal allergy) to name a few to be significantly increased.

Other diseases that show significant increase due to VDR issues are Crohn’s disease (11 fold increase), sepsis (13 fold increase), and Chronic heart failure (15 fold increase). 2 Though all diseases are significant, especially if it affects you.

Other illnesses with significant risk increases include metabolic syndrome, obesity and breast cancer. So why wouldn’t you do something to protect yourself knowing this? Perhaps because information overload especially false and/or deceptive information is causing you to throw up their hands and quit. Don’t! There is help.

So, if you have some of the following signs and symptoms: depression, obesity, diabetic neuropathy, keloids, tooth decay, hypertension, skin issues (for example vitiligo), and others. 3,4,5,6,7,8 It could be either a lack of vitamin D3, a VDR issue, a metabolic vitamin D machinery issue or all. There are possible solutions.

First as almost everyone in my opinion is vitamin D3 deficient, this lack of adequate blood levels of vitamin D3 can typically be fixed. By taking optimal doses and obtaining optimal blood levels this does two things. First it optimizes the health of most and may be enough to overcome what is affecting those with VDR or intracellular metabolic machinery issues. 

See even if you have “normal” blood levels of vitamin D3, levels like our governments recommend, it will not have the desired effects for those either in those with or without VDR or metabolic machinery genetic issues. 

Thus, 30% of the population who suffer only from VDR genetic issues and more if you include metabolic vitamin D machinery issues are ignored. That is a great deal of the population. Imagine how much pain and suffering could be relieved just in that group with VDR issues? 

Again, vitaminDwiki has an exhaustive list of all the different diseases caused by VDR issues and more than I can list in this short article.

  1. Bienertova-Vasku J, Zilamal F, Pohofala A, et al. (Aug 22. 2017). Allelic variants in vitamin D receptor gene associated with adiposity measure in the central-European population. BMC Med Genet. 18(1):90.
  3. He Y, Wu Z, Lan T,Wang Y, et al. (Dec. 2019). The 25(oh)d/VDR signaling may play a role in major depression. Biochem Biophys Res Commun.
  4. Ibid. (1).
  5. Fang Y, Jing L, Ming-Xiu F, et al. (July 13, 2017). Association between the vitamin D receptor gene polymorphisms and diabetic neuropathy risk: a meta-analysis. Neuropathy online
  6. Hahna JM, Suppa MS. (August 1, 2017). Abnormal expressin of vitamin D receptors in keloid scars. Burns. 43(7):1506-1515.
  7. Kong YY, Zheng JM, Zhang WJ, et al. (Jul 2007). The relationship between vitamin D receptor gene polymorphism and deciduous tooth decay in Chinese children. BMC Oral Health. 17(1):111
  8. Ysalcin S, Covic A,Kanbay M. (July 2, 2014). What do we know and do not know about vitamin D? A casual association between vitamin D receptor genetic polymorphisms and hypertension. J Clin Hypertension. 16(9):628.
  9. Zhang JZ, Wang M, Ding Y, et al. (July 2018). Vitamin D receptor gene poilymorphism, serum 25-hydroxyvitamin D levels, and risk of vitiligo: a meta-analysis. Medicine (Baltamore). 97(29):e11506.


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