# The Effects of Vitamin D Replacement with a High-Dose Treat-to-Goal Strategy

## TL;DR

A high-dose vitamin D treatment strategy effectively restores and maintains vitamin D levels over five years without increasing adverse events.

## Contribution

A treat-to-goal protocol for vitamin D supplementation is shown to be effective and safe over a long-term period.

## Key findings

- The intervention group achieved 91.6% vitamin D adequacy compared to 16.9% in controls.
- Vitamin D levels remained stable at 40 ng/mL in the intervention group for up to five years.
- No significant increase in adverse events was observed in the intervention group.

## Abstract

Introduction: Vitamin D deficiency [25(OH)D < 30 ng/mL] is widely prevalent globally and the efforts to tackle it have been rather unsuccessful to date. Despite different cutoffs used to define it, many clinicians adhere to the 2011 Endocrine Society definition. We present a special treat-to-target protocol aiming to restore and maintain vitamin D sufficiency. Methods: We reviewed the efficacy and safety of our vitamin D supplementation protocol over 5 years, and compared it to a group of patients who self-reported never taking vitamin D supplements. We recorded the baseline, 2-month, and annual 25(OH)D (D) measurements, along with subjects’ age, sex, BMI, history of osteoporosis, nephrolithiasis, nephrocalcinosis, and renal colics. According to our supplementation protocol, replenishment of vitamin D involves cholecalciferol dosing in two steps: a loading dose (LD) for 2 months and a maintenance dose (MD) thereafter. Please refer to the main text for loading and maintenance dose titration. Results: Of 8329 cases with vitamin D measurements, 2248 had adequate follow up data of 3524.5 patient-years and were included in the study: a total of 1575 intervention subjects and 673 controls, with an average follow-up of 18.8 months. Baseline vitamin D concentrations of 22.6 ng/mL (controls) did not change significantly (2 months: 22.2; 1 year: 21.7; 2 years: 22.0; 3 years: 23.8; 4 years: 21.8; and 5 years: 22.1 ng/mL), while concentrations of 21.9 ng/mL (intervention group) reached and remained 40 ng/mL (2 months: 41.0; 1 year: 39.4; 2 years: 39.0; 3 years: 39.3; 4 years: 40.4; and 5 years: 39.4 ng/mL). Vitamin D adequacy was achieved in 91.6% of patients in the intervention arm compared to only 16.9% in controls (p < 0.0001). Mean D and rates of adequacy were significantly higher over time in the intervention arm (p < 0.0001). The incidence of renal adverse events or hypervitaminosis did not differ between groups (p > 0.05). Conclusions: Our intervention protocol appears highly efficient in achieving and maintaining vitamin D adequacy over 5 years, with no increase in adverse events compared with controls, presenting it as an effective long-term strategy.