The Vitamin D Trap: What Blood Tests Don’t Tell You

Have you ever wondered why your child reacts so strongly to certain foods, environmental triggers, or even absolutely nothing at all? Did you know that mast cells, the immune cells responsible for allergic reactions, can spontaneously release histamine without an allergen, infection, or any clear trigger? And what if that was happening because their vitamin D system was not working properly?

Dr Sam Yanuck’s latest deep dive into the vitamin D system and mast cells could reshape how we think about allergic reactions. When vitamin D levels are low, mast cells become unstable and can degranulate—like a bag of marbles bursting through a torn net—spilling histamine and inflammatory compounds into the body. This has serious implications for children with complex health conditions like PANDAS, PANS, autism, ADHD, and severe allergies

The Vitamin D System: More Than Just a Number

We all know vitamin D is important, but the real question is can your body actually use it? Vitamin D has to be absorbed, converted, activated and put to work. If any part of this process goes wrong, mast cells can become overactive, flooding the body with inflammation, triggering allergic responses and even affecting brain function.

So how does this system work, and where can it go wrong?

 

Absorption and Conversion in the Liver

Vitamin D from sunlight, food or supplements first needs to be converted in the liver into 25OHD3, the form measured in blood tests.

But this step does not always go smoothly. If your child has poor gut absorption or liver dysfunction, their body may struggle to process vitamin D properly. Many chronically ill children face this challenge due to gut issues, leaky gut or toxin overload.

Activation in the Kidneys

Once in the bloodstream, 25OHD3 needs to be converted into its active form, 1,25(OH)2D3, also known as calcitriol.

This step relies on interferon gamma, a key part of the Th1 immune response. If your child has a weak Th1 response, which is common in conditions like PANDAS, PANS and other immune dysregulation cases, they may not be making enough active vitamin D.

Vitamin D Receptor (VDR) Activation

Even once activated, vitamin D still needs to bind to the vitamin D receptor, or VDR, to do its job.

This is where things can go wrong. Oxidative stress and chronic infections like EBV, CMV and candida can suppress VDR function, which we see all too often in children with chronic health issues. Another common issue is VDR mutations, small genetic variations that affect how well the receptor works, making it harder for vitamin D to carry out its role in immune regulation.

The good news is that testing for VDR mutations is simple. A quick cheek swab can provide insight into whether your child’s vitamin D pathway is functioning optimally or if they may need extra support.

This means that even if a blood test shows good vitamin D levels, their body may not actually be using it properly. Understanding both environmental factors like infections and genetic factors like VDR mutations can help tailor the right approach for each child.

Vitamin D Breakdown

Vitamin D does not just stay in the body indefinitely. Both 25OHD3 and its active form, 1,25(OH)2D3, are constantly being broken down by an enzyme called CYP24A1.

Here is where things get tricky. IL-4, a cytokine that tends to be elevated in allergic children, speeds up this breakdown. Many children with eczema, asthma or environmental allergies have high IL-4 levels, so their vitamin D is being cleared out before it can be used effectively.

 

Why This Matters for Mast Cells and Your Child

Mast cells should only release histamine when needed, but when the vitamin D system is out of balance, they can fire off at random. This can lead to sudden histamine surges that mimic food allergies but with no obvious cause. It can also bring on brain fog, gut inflammation, skin rashes and worsening PANDAS and PANS symptoms seemingly out of nowhere.

Many of the children we see at Brainstorm Health follow this exact pattern. They struggle with chronic infections, poor gut health, weak Th1 immunity and high allergic inflammation, all of which interfere with the vitamin D system and leave their immune defences on edge.

 

What Can You Do?

If your child struggles with allergies, food sensitivities, inflammation or PANDAS PANS, supporting their vitamin D system could be a missing piece of the puzzle. Here is how you can help.

Test, do not guess

A simple vitamin D blood test, whihc can also be done as a bloodspot, measuring 25OHD3 is a good place to start, but it does not tell the full story. If your child’s levels look normal but they are still experiencing symptoms, further testing may be needed.

Looking at additional markers like 1,25(OH)2D3 and inflammatory cytokines such as IL-4 and interferon gamma can give a clearer picture of how well the vitamin D system is actually functioning.

Support absorption and liver function

If your child has gut issues, improving digestion and absorption is essential.

The liver plays a key role in converting vitamin D into its active form, so supporting liver function is just as important as increasing vitamin D intake. Animal-based foods rich in choline, taurine and glycine can help this process.

Strengthen Th1 immunity

A weak Th1 response is common in children with immune dysregulation, including those with PANDAS and PANS. Strengthening immune balance with nutrients like zinc, selenium and vitamin A can help shift the immune system towards a healthier balance.

Perilla is particularly effective in steering the immune response away from a Th2-dominant allergic state and towards Th1, helping to regulate inflammation and immune function. Microimmunotherapy can also play a role by using highly diluted immune mediators to gently guide the immune system without overstimulation.

Reduce oxidative stress and infections

The vitamin D receptor, or VDR, acts like a lock, with vitamin D as the key. When the key fits, the immune system can regulate inflammation, fight infections and keep things running smoothly. But if that lock is jammed, vitamin D cannot do its job properly.

As mentioned earlier, chronic infections such as EBV, CMV, and candida can interfere with VDR function, making it harder for the body to use vitamin D effectively. Even if blood levels appear normal, vitamin D may not be working as it should.

Clearing these infections can help restore balance. Antivirals, immune modulators and Microimmunotherapy can be valuable tools in gently nudging the immune system back to a healthier state, allowing it to respond appropriately to threats rather than remaining stuck in overdrive.

Balance allergic inflammation

If your child has high IL-4, their body may be breaking down vitamin D too quickly, getting rid of it before it can do its job. This is common in children with allergies, asthma and eczema, where the immune system leans too far towards a Th2-dominant response.

To slow this process and bring the immune system back into balance, mast cell stabilisers and anti-inflammatory strategies can help calm the overactive response. This reduces inflammation and gives vitamin D a chance to work as it should, supporting immune function rather than being rapidly depleted.

 

The Bigger Picture

This research on vitamin D and mast cells helps make sense of so much of what we see in complex kids. The unpredictable reactions, the worsening symptoms despite a so-called clean diet, the immune dysregulation that does not follow a simple pattern.

By understanding these deeper mechanisms, we can take a more targeted approach, helping children stabilise and improve in ways that once seemed out of reach.

If your child is struggling with inflammation, histamine reactions or PANDAS PANS, looking beyond basic vitamin D levels to the entire vitamin D system, how it is absorbed, activated, used and broken down, could be the missing link.

 

IMPORTANT

The information provided in this article is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. It is crucial to consult with medical doctors or qualified functional medicine practitioners to address specific health concerns and obtain personalised guidance tailored to individual needs. Never add any supplements to your plan until it has been assessed and approved by your medical doctor or a suitable qualified practitioner who is familiar with your health history. 

Concerned about your child’s health? We’d love to have a chat with you. 

Click the link here to book your Free Discovery Call.

 

References

Mekinian, A., Chavala, C., Deharo, P., et al., 2022. ‘Mast cells and vitamin D status: a clinical and biological link in osteoporosis and allergic diseases’, International Journal of Molecular Sciences, 23(17), p. 9405764. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405764/ (Accessed: 13 March 2025).

Tang, L., Wang, D., Sun, B., et al., 2024. ‘Vitamin D influences the activity of mast cells in allergic reactions’, International Journal of Molecular Sciences, 25(2), p. 10528041. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10528041/ (Accessed: 13 March 2025).

Loser, K., Beissert, S., 2010. ‘Evidence that vitamin D3 promotes mast cell–dependent reduction of chronic UVB-induced skin pathology’, Journal of Clinical Investigation, 120(11), pp. 3860-3872. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2839149/ (Accessed: 13 March 2025).

Ong, P.Y., Leung, D.Y.M., 2014. ‘Vitamin D3 represses IgE-dependent mast cell activation via mast cell vitamin D receptor’, Journal of Allergy and Clinical Immunology, 134(2), pp. 345-353. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154631/ (Accessed: 13 March 2025).

Wintergerst, E.S., Maggini, S. and Hornig, D.H., 2007. ‘Role of vitamins D, E, and C in immunity and inflammation’, Journal of Clinical Nutrition, 85(2), pp. 488S-494S. Available at: https://pubmed.ncbi.nlm.nih.gov/23830380/ (Accessed: 13 March 2025).

Baeke, F., Takiishi, T., Korf, H., et al., 2010. ‘Vitamin D and molecular actions on the immune system: modulation of innate and autoimmune responses’, Frontiers in Immunology, 11(1), p. 2861286. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861286/ (Accessed: 13 March 2025).

Wong, C.K., Ho, C.Y., Ko, F.W., et al., 2021. ‘The complex interplay between immunonutrition, mast cells, and inflammation’, Nutrients, 13(5), p. 8537261. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537261/(Accessed: 13 March 2025).

Carnevale, V., Modica, S., Piemontese, M., et al., 2023. ‘Immunomodulatory actions of vitamin D in various immune-related diseases: a narrative review’, Journal of Endocrinology and Metabolism, 226(4), p. 10379649. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10379649/ (Accessed: 13 March 2025).