Effect of vitamin D on mast cells

Vitamin D is an essential fat soluble vitamin that functions as a hormone. Its primary function is to promote intestinal absorption of calcium, magnesium, phosphate, iron and zinc. It also has a variety of anti-inflammatory and immunoregulatory effects. Deficiency of vitamin D3 has been linked previously to a number of inflammatory conditions, like asthma, diabetes mellitus, eczema and other atopic disorders.

A significant portion of vitamin D is produced in the skin when exposed to sunlight. The precursor 7-dehydrocholesterol in the skin is changed to form cholecalciferol, vitamin D3, when irradiated with UVB light. In the liver, cholecalciferol (vitamin D3) is metabolized to form 25-dihydroxyvitamin D3. In the kidney, it is further metabolized to 1,25-dihydroxyvitamin D3. Vitamin D2 and D3 supplements may also be taken orally.  They will be processed by the liver in a similar fashion. Vitamin D3 is much more active than vitamin D2.

Vitamin D3 can exert a number of effects on mast cells. Though the mechanism is unclear, vitamin D3 seems to regulate the action of COX, the enzyme that produces prostaglandins.  Accordingly, vitamin D3 can disrupt prostaglandin production.

It interferes with the production of cytokines, and chemokines, including Il-1, IL-6, IL-33, and TNF. It inhibits release of IL-6 and CRP.  It is thought that vitamin D affects the stability of the mRNA for these molecules.  This means that the genes for these molecules are not being used appropriately and so they cannot be made.

Vitamin D3 can also induce production of anti-inflammatory mediators. IL-4 and IL-10 are mast cell mediators that regulate inflammation.  Vitamin D3 is required for their production and release.  IL-10 can mitigate inflammation resulting from IgE activation.  A single application of vitamin D3 to the skin decreased the immediate skin response to an IgE allergen.  It decreased production of leukotrienes and histamine.  Mast cells have vitamin D receptors (VDRs) inside their cells and close to where the genes are stored.  Mast cell VDRs must be present to see these effects.

Long term use of vitamin D3 (30-40 days) was found to cause mast cell apoptosis (programmed cell death) in a cell model. Vitamin D3 also directly impeded the differentiation and maturation of mast cell precursors.

There is a lot we do not know about how vitamin D3 interacts with mast cells but it is generally considered to have an anti-inflammatory and anti-allergic effect.


Yip KH, et al. Mechanisms of vitamin D3 metabolite repression of IgE-dependent mast cell activation. Journal of Allergy and Clinical Immunology 2014: 13395), 1356-1364.e14

Conti P, Kempuraj D. Impact of vitamin D on mast cell activity, immunity and inflammation. Journal of Food and Nutrition Research 2016: 4(1), 33-39.

22 Responses

  1. lori June 26, 2016 / 1:18 pm

    awesome information, and validation too. i had a feeling keeping my vitamin D up was helping with the degranulation process. you rock Lisa for all the vital information we get from you. thanks again!

    • Mark June 27, 2016 / 1:50 pm

      ditto Lori

  2. Scott June 26, 2016 / 1:48 pm

    According to Afrin in the “Presentation, Diagnosis, and Management of Mast Cell Activation Syndrome,” vitamin D deficiency by clinical criteria is often present in MCAS patients (p177) .

    • Lisa Klimas June 26, 2016 / 1:56 pm

      Most mast cell patients are deficient. Last year, I got my vitamin D deficiency under control and I couldn’t believe how much it helped. Brain fog, poor energy, and muscle pain all improved.

      • Scott June 26, 2016 / 1:58 pm

        I forgot to mention that i love this blog, thank you so much!!

        • Lisa Klimas June 26, 2016 / 2:01 pm

          Haha, thanks!

      • Mark June 28, 2016 / 1:00 pm

        Has Dr. Afrin, anyone else, posed a theory why? FWIW, add my own experience plus familiarity w/ many anecdotal accounts.

        Vitamin D in ongoing high doses can be toxic, bears monitoring, as my endocrinologist has provided since initially detecting alarming deficiency, associated(?) osteopenia after my SMCD had been diagnosed.

        Despite no other risk factors for osteopenia, my brilliant diagnostician recognized SMCD warranted endocrinology evaluation. Indeed.

        Yet explanations remain elusive, I gather. As with much else, how much can we reliably extrapolate from lab results when the NIH has investigated so little of the vast diversity of mast cell biology, Reports indicate “vitamin D supplementation may be effective for the prevention of asthma exacerbations, [chronic urticaria. etc.] but the findings need to be confirmed by clinical trials”


        So far as I know, since the NIH reported “Elevated tryptase levels are associated with GREATER bone density” in the SM patients they investigated, they have done nothing to follow up, to find some explanation. As with other surprising, unwelcome data, including many SM subjects whose serum serotonin was higher amongst many more symptomatic SM subjects, notwithstanding lower serum tryptase/BM MC proliferation.

        Drs. Akin, Metcalfe describe the subjects with worse bone loss as suffering “less severe disease” despite more Anaphylaxis, GERD. True so long as they see themselves treating test results rather than people.


        • Lisa Klimas June 28, 2016 / 1:42 pm

          I have not seen a theory on low vitamin D in mast cell disease (any mast cell disease). Afrin and a few others have mentioned it in passing but I haven’t seen any substantive. I’m now wondering if this has been investigated for autoimmune disease, I’ll take a look around. It seems intuitive that vitamin D could be consumed faster in an inflammatory environment. It also seems intuitive to me that it could be consumed faster in any environment where mast cells are differentiating and maturing, like in a mast cell patient. But I haven’t seen any data on that, it’s just me speculating. I saw the vitamin D/asthma article.

          You are very right that vitamin D can be toxic if it’s high. It’s actually one of the most toxic vitamins. It is important to get a blood level to monitor vitamin D while supplementing.

          There have been studies going both ways on bone density, excessive and deficient. I have written about this in a lot of detail; unfortunately, as you know, these data sets are from SM patients. I can’t wait for unified criteria for MCAS so there is one less hoop to jump through in setting up studies and trials.

          Thanks for your two cents, always appreciated.

          • Shira July 7, 2016 / 5:21 pm

            Yes, Vit. D has been investigated quite extensively as a treatment for AI issues, mainly MS. See the Coimbra Protocol that treats AI conditions with very high doses of Vitamin D.

  3. Nancie June 26, 2016 / 3:38 pm

    Since we are all so sensitive to additives, preservatives, etc. , does anyone have a recommended brand of vitamin D3 that works for you? Lisa – great post!

    • Shelley June 29, 2016 / 9:04 am

      I use carlsons liquid drops 4000 IU per drop….I need to take 16,000 IU day put 4 drops on a spoon with some juice and drink it down. Easiest D3 to take not many Icky fillers also since liquid. I only take that much because my vit. D is 12-29 they want to see it in the 60’s. Hope this helps:):)

  4. Christina Zacny June 26, 2016 / 4:23 pm

    Thank you for this Lisa and all the great info in your blog. I am really severely deficient in iron, zinc, magnesium, and now they believe D, because my bones break very easily (literally just by walking). I have been using supplements for these and am going to try iron again since my numbers have fallen low enough that they are talking about another transfusion. I’ve been spending as much time in the sun as I can every day and have noticed a significant decrease in anaphylactic events. It’s been 2 months since the last time I went into anaphylactic shock and experienced periodic paralysis. I had only made it 2 weeks between episodes before this. I also see an improvement in my Beau’s lines on my nails. I felt like I was absorbing vitamins better and your entry today gives me hope for a continued improvement of my symptoms. Thank you so much Lisa!

  5. Diana June 26, 2016 / 4:36 pm

    I had no idea Vitamin D supplementation was prescribed because it enhances Mast Cell Apoptosis. I have been taking VDS since March. My symptoms are more controlled – However the somnolence caused by Levocetirizine is difficult to overcome.
    Thank you Lisa for sharing your knowledge and experience with us.

    • Lisa Klimas June 27, 2016 / 12:35 am

      I don’t think it’s prescribed for that reason specifically but vitamin D is an important thing to keep track of in mast cell patients.

  6. Kim June 26, 2016 / 4:40 pm

    Thank you so much for all your great information Lisa. It is so appreciated by all.

  7. Shauna June 26, 2016 / 11:03 pm

    Thank you so much for this. Love this blog, but this post gives me hope! My daughter with MCAD has been having an increasingly difficult time this last year, with pain and inflammation growing worse every month.

    We just found out a couple weeks ago that she has become very, very low in vitamin D, and are starting supplements. Knowing that there could potentially be a connection between her vitamin D and her increased difficulties gives me some hope that the vitamin supplementation may really help with this. 🙂

    • Lisa Klimas June 27, 2016 / 12:34 am

      It helped me a shocking amount. A lot of my symptoms I chalked up to masto were really from low vitamin D. It took about four weeks to get the full benefits but it helped a lot with brain fog, muscle pain and fatigue.

  8. Sander June 27, 2016 / 4:42 am

    Does any body know what is the minimum, the maximum and the optimum vitamin D level for mastocytosis patients ?

  9. DIANE June 27, 2016 / 12:49 pm

    So grateful for all you do. Thank you!!

  10. Maria June 28, 2016 / 9:08 am

    Now I know why my skin has improved so much. My Vit D level was 27. Since I started taking Micellized Vit D drops I raised it to 46. I take 4800 units a day now because my hematologist wants it a little higher.
    Thanks for the info

  11. Sander June 29, 2016 / 4:32 am

    Hi Maria, I take a combined supplement of vitamin D3 and vitamin K2.
    I was told that there are discussions about the minimum and maximum values.
    The latest values I have heard is minimum 50 and maximum 70 for vitamin D3. Also my vitamin D3 was too low !
    In summer time you need to take a different dose (lower) when compared to winter times.
    I was told that a good minimum level of vitamin D is really important! For the bone structure the tandem vitamin K2 and vitamin D3 is important. Besides that I was told by my doctor that a minimum vitamin D level also a positive influence on gen regulation (Lisa writes the same in her blog). And I get the impression that we feel better with higher values of vitamin D.
    So any data/ experiences we can share together on the minimum or maximum values is I think beneficial for all of us !

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