HoldsUp

Amon · Nutrients 2022 · uncontrolled observational cohort study · n=319

Safety Data in Patients with Autoimmune Diseases during Treatment with High Doses of Vitamin D3 According to the "Coimbra Protocol".

Cited 26 times in the scientific literature.

Level 4 - case-series / case-control

Uncontrolled observational cohort / case series without a comparator group

PubMed 35458137 · doi:10.3390/nu14081575 · record verified 2026-08-29

What was done

Safety data were analyzed for 319 patients with various autoimmune diseases (mean age 43.3 ± 14.6 years; 65.5% female) receiving high-dose oral vitamin D3 according to the Coimbra Protocol for up to 3.5 years. The protocol included a strict low-calcium diet and daily fluid intake of at least 2.5 L. More than 6,100 laboratory measurements were evaluated across the study period.

What was found

The mean daily vitamin D3 dose was 35,291 ± 21,791 IU. Mean laboratory values remained within normal limits: total serum calcium was 2.4 ± 0.1 mmol/L, serum creatinine was 0.8 ± 0.2 mg/dL, estimated GFR was 92.5 ± 17.3 mL/min, serum cystatin C was 0.88 ± 0.19 mg/L, serum TSH was 1.8 ± 1 mIU/L, and 24-hour urinary calcium excretion was 6.9 ± 3.3 mmol/24 h. The authors reported a very weak relationship between vitamin D3 dose and subsequent serum or 24-hour urinary calcium levels.

Why it matters

It provides long-term observational safety and laboratory monitoring data on high-dose vitamin D3 supplementation paired with dietary calcium restriction and hydration in autoimmune disease patients.

Limits

The study was uncontrolled and observational. The abstract reports only aggregate mean laboratory values rather than the incidence, frequency, or severity of individual hypercalcemia or acute kidney injury events. Specific autoimmune diagnoses, clinical efficacy outcomes, and dietary adherence metrics are not provided in the abstract.

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