Despite this CYP24A1 gene defect on one of the two copies occurs about 1/100 live births having issue with both copies (copies of two both sides is 1:40,000 which is rare. It is wise to be careful.1 So, if you start taking higher doses of vitamin D3 and start having symptoms of hypercalcemia you need to check. 

Check if you have a defect in one or both copies defective of this gene. As About 1/300 will have some a single gene defect and issue with calcium at higher doses of vitamin D3. Also, in some populations it may be more or less common.

That you might have a defect in this or similar but not yet discovered genes is the reason it is best to work with a health professional. Especially if family issues with blood calcium. It is important to check your vitamin D blood levels, blood calcium level and even your parathyroid levels initially. 

Checking these blood levels initially as a baseline. Also, for completeness check for genetic defects in these genes. Though if you have a partial but severe defect in your CYP24A1 genes you will typically have a history of issues with blood calcium levels like kidney stones. 

Not all people with kidney stones have an issue with the CYP24A1. In my experience most people with kidney stones in fact did better with optimal blood levels. Just trying to cover all bases as many of you have lost faith in the medical profession and last thing, I want to happen is you end up harming yourself. No matter how unlikely that is. 

I can think of possible scenarios where issues with higher dose vitamin D3 consumption is especially likely. In cases where many family members have issues with calcium. Again, like kidney stones. If it is related to a CYP24A1 gene defect, then that is great news as now you know the cause and can do something about it. 

It does not mean you do not need vitamin D3. You just need to be careful in how much you take. So  if you are taking optimal doses of vitamin D3 it is best after initially checking your blood levels to check your calcium and vitamin D3 levels monthly, then less often as it becomes clear how you respond to this dosing and where your blood levels of vitamin D3 fall. 

For those of you who want to check if they have a CYP24A1 or other gene defects then over on vitamindwiki I believe they give a link to labs that do this testing for low prices. You can also find resources to check for genetic defects in the vitamin D receptor or the machinery that activates vitamin D3 inside cells to initiate all its hormonal effects.

Typically, when this defect-the mild form-is found in adults is only after they have taken higher doses of vitamin D3 without checking their blood levels of vitamin D or calcium for several months. It takes that long before these people to become so ill they seek medical attention. 

Curious that someone who has a severe defect would not be diagnosed until later in life. As those who are born with the severe form of CYP24A1 defect typically have issues with hypercalcemia early in life alerting them to this issue. 2 Second signs and symptoms of hypercalcemia are hard to miss. 

Nausea, bone pain and fatigue for starters. So even if you are not aware that you have this defect, it seems questionable. Why after starting a new supplement (in this case vitamin D3) and then shortly thereafter start having symptoms. Symptoms that you are ill. 

That you would not connect these symptoms to the new supplement and stop it. Going to have your levels checked if available. So, what exactly happens to cause this genetic defect resulting in high calciferol (the active form of vitamin D3) blood levels and hypercalcemia? 

Well with this gene you receive one copy from each parent. In some people they are born with only one working copy of this gene. This occurs about once every 800 births. Typically, as I explained above they are the ones who started high doses and develop high blood calcium levels    

Then in some, like those babies who develop vitamin D induced hypercalcemia at birth and possible the case above. They are born with two defective copies of the CYP24A1 gene which occurs in approximately one in 100,000 births. Resulting in idiopathic infantile hypercalcemia. 3

It is a bit more complicated though as it appears that even if you have two functional genes, they may be not fully functional. Never easy is it. Those with one fully functioning CYP24A1 gene may to do as well as those with two functional copies. As often the body uses only one copy of the two copies we have. One from each parent, typically.

It is when both copies are defective or severely impaired that people have issues. Even then it takes a dose 100 times greater than the current recommended daily allowance (RDA) of 600 IU/day. That dose or even greater for prolonged periods of time. 

Typically, years.  For those with these defects for them to have a problem with hypercalcemia. It seems from what I have researched it is a sliding scale. The worse the gene defect the lower the dose needed to cause hypercalcemia. 

Obviously more research is needed as this defect of the CYP24A1 gene and its association with vitamin D3 induced hypercalcemia was only discovered in 2011. The How much calcium you ingest also matters? If you are using a calcium antacid like a candy you are going to have an issue. 

Even people with two normally functioning CYP24A1 genes should not be doing that. Especially how with inflamed our bodies are from what we eat, our poor gut health and that it takes time even with optimal blood levels for the body to heal. 

That is it will heal if with the vitamin D3 you start eating healthier food. What we eat, how it affects us and how to fix it is basically what I am striving to accomplish in my next book. So, a lot of information without a simple answer. Now optimal dosing to reach optimal blood levels. 

However, many more (30+%) have genetic defects in either or both their vitamin D receptor or the machinery that activates vitamin D3. Thus, they may have the increased calcium absorption but not the intracellular benefits that intracellular gives most.  That is chronic inflammation of arteries results in cholesterol plaques and eventually atherosclerosis. 


  1. Jones G. CYP24A1 mutations and human disease (1% are carriers). Endocrine Abstracts. 2016. 41 S14.3 DOI: 10.1530/endoabs. 41.514.3.
  2. Cappellani, D., Brancatella, A., Kaufmann, M., Minucci, A., Vignali, E., Canale, D., De Paolis, E., Capoluongo, E., Cetani, F., Jones, G., & Mhc m5arcocci, C. (2019). Hereditary Hypercalcemia Caused by a Homozygous Pathogenic Variant in the CYP24A1 Gene: A Case Report and Review of the Literature. Case reports in endocrinology, 2019, 4982621.
  3. Ibid (2)

*The information posted above is for educational purposes only. Always check with your doctor before initiating any changes in your medical treatment. If you do not, then The Two-Minute Health Fact, Dr. Judson Somerville, nor The Optimal Dose is responsible!


Jasmit Daid · July 22, 2020 at 2:20 am

I’ve read your book and began the optimal dose myself however I’m not quite sure how much my calcium intake should be (both dairy and non-dairy sources).

I noticed you said neither of your patients got hypercalcemia; can you share how much calcium (rough estimate would be fine) they were consuming or how much you would advise to stay under.

I’m also taking 600mg of magnesium and 600mcg of mk-7 vitamin k2. Any insight on the calcium intake would be greatly helpful. Thank you!

Jason Fella · September 29, 2020 at 4:36 am

Hey Doc! I read your book recently, and it was eye-opening to say the least, and I’ve studied nutrition and natural health for a LONG time. The winter syndrome particularly interests me because I’ve been searching for answers to my unexplained hunger issues for the last few years, to no avail…until I read your book. I am SURE this is related, as my D levels are indeed extremely low. When you were experiencing winter syndrome, did you sometimes feel even hungrier after you ate? Or you could feel full and starving at the same time? It’s maddening. I hope this helps.

Reshma Joshi · October 22, 2020 at 3:04 pm

what time of day should you take vitamin D3? Since you said you will sleep well, should I take couple of hours before bed?

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