One possible theory for why some react harshly to vitamin D
I’ve had horrible reactions to vitamin d supplementation, and I’ve found the cofactors explanation to be inadequate.
Symptoms that I’ve had feel much more like a delayed immune response it will usually show up later in the first day once I start the vitamin d but it will build and worsen so long as I keep taking it.
Usually presents with : horrible muscle weakness, cold sweats, sore throat sometimes visually red, feel like my face gets puffier as well, irritability, just very flu like symptoms
Something that has come up a lot in recent research especially in autoimmune papers for (pSS, SLE, MS, RA) is the role of certain Viruses usually Epstein Barr Virus or CytoMegalo Virus.
Both have shown wide effects on upregulating, binding, blocking, down regulating certain human receptor and transport proteins
CMV does show some interesting interactions with Vitamin D Receptors
But EBV has hyper specific peptide sequences [EBNA-3, EBNA-2] that bind onto VDR and perform unique functions
https://pmc.ncbi.nlm.nih.gov/articles/PMC11115686/
They found that EBNA-3 occupied the coactivators that are present in VDR but left the actual binding pocket of vitamin d open so it was still capable of binding vitamin d still.
So if you have a foreign protein occupying coactivators. They are bound to both VDR and Vitamin D and your immune system possibly can begin to develop antibodies.
This is how anti-ebna antibodies are developed and since your immune system can mistakenly build antibodies against things they are bound to you can see anti vitamin d antibodies ( once again commonly in autoimmune populations )
https://www.sciencedirect.com/science/article/abs/pii/S156899722400209X
So if you form antibodies against vitamin D from this mishap now once they circulate and target free vitamin d and launch white blood cells
I do think that the EBV reactivation / delayed antibody response combination map on surprisingly well to this specific symptom presentation that people have. Although I’m unsure how you would make vitamin d more tolerable if this was the cause.