Lemke · Frontiers in immunology 2021 · narrative review and hypothesis paper · n=?

Vitamin D Resistance as a Possible Cause of Autoimmune Diseases: A Hypothesis Confirmed by a Therapeutic High-Dose Vitamin D Protocol.

Cited 64 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review and hypothesis paper presenting mechanistic reasoning and anecdotal clinical experience without controlled trial data.

PubMed 33897704 · doi:10.3389/fimmu.2021.655739 · record verified 2026-08-29

What was done

This paper presents a hypothesis and narrative review regarding acquired vitamin D resistance in autoimmune diseases. The authors review mechanistic concepts, genetic polymorphisms affecting vitamin D pathways, and pathogen-induced vitamin D receptor signaling blockades, alongside clinical observations from applying the high-dose Coimbra protocol (up to 1000 I.U./kg body weight daily titrated against serum parathyroid hormone levels) in patients with multiple sclerosis.

What was found

The abstract reports no quantitative clinical trial data, statistical analyses, or formal cohort outcome metrics. It asserts narratively that acquired vitamin D resistance is biologically plausible and that doses up to 1000 I.U. vitamin D3 per kg body weight can be administered safely when monitored via serum parathyroid hormone.

Why it matters

It outlines the theoretical rationale behind high-dose vitamin D protocols for autoimmune conditions, arguing that clinical unresponsiveness may stem from receptor-level resistance rather than simple deficiency.

Limits

The abstract provides no empirical data, sample sizes, control groups, or standardized safety and efficacy endpoints. The claims rely on mechanistic reasoning, literature review, and informal clinical experience rather than prospective controlled clinical trials.

Cited by