Researchers at the Cleveland Clinic and the University of Catania in Italy examined real-world scenarios to compare the effects of 25-hydroxyvitamin D3 (a metabolite of vitamin D) with two different dosing schedules of vitamin D3 to identify the most effect therapeutic strategies for vitamin D deficiency, as well as the key indicators that predict response to treatment.
“Our study confirms the necessity of personalizing vitamin D supplementation for each patient, rather than using a standardized dosage for all individuals, especially for specific groups such as the elderly, obese and others,” the researchers wrote. “Personalization should be based on measuring the patient’s serum 25(OH)D levels before treatment.”
High-risk groups
Naturally found in the skin, vitamin D is a hormone created from the cholesterol precursor 7-dehydrocholesterol. Although its synthesis is dependent on sun exposure, vitamin D can be acquired through diet, including foods such as mushrooms and oil-rich fish.
“Once activated, the vitamin D receptor can bind to thousands of genomic loci, thereby modulating the expression of numerous target genes,” the researchers explained. “Today, it is recognized that vitamin D not only regulates calcium homeostasis, but also plays crucial roles in immune system function, cell growth and differentiation and energy metabolism.”
Despite its importance, vitamin D remains a global concern and as deficiency in the vitamin severely affects more than 40% of the population. However, understanding how much vitamin D is necessary for an individual is still up for debate.
It is clear that certain groups need vitamin D, including children and adolescents to prevent nutritional rickets and respiratory infections; pregnant women to reduce risk for preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth and neonatal mortality; and high-risk prediabetes patients who may slow the progression to diabetes mellitus if they consume vitamin D.
Getting the right amount of vitamin D may depend on whether an individual is receiving daily or weekly dosing as compared to monthly intake.
“We investigated the difference in the delta increase in serum 25(OH)D levels between patients who received calcifediol supplementation and those who received biweekly or monthly cholecalciferol administration,” the researchers noted.
Study details
This retrospective, cross-sectional study included 105 adult patients, both male and female, who presented with symptoms of vitamin D deficiency and were experiencing symptoms such as asthenia, fatigue and muscle pain, or sought treatment for bone demineralization conditions. Patients were split into three groups based on the kind of supplementation prescribed: cholecalciferol 25,000 IU every two weeks, cholecalciferol 50,000 IU once a month and calcifediol (25(OH)D3) 0.266 mg once a month.
Statistical analysis determined differences between the three groups for serum 25(OH)D level increases, comparing pre-treatment values with those after six months of treatment. However, the frequency of administration did not impact the degree of serum 25(OH)D compensation.
“Calcifediol is absorbed more efficiently in the intestine, its hydrophilic nature reduced sequestration by adipose tissue, and the shorter half-life allows for a quicker response to dose adjustments,” the researchers wrote. “Consequently, our results suggest that calcifediol may be superior to cholecalciferol in terms of supplement potency. However, it is noteworthy that, unlike cholecalciferol, both calcifediol and calcitriol are not classified as food supplements. As a result, cholecalciferol remains the more practical option for routine supplementation.”
The study found that for patients with pre-treatment 25(OH)D levels above 19.5 ng/dL, “achieving optimal skeletal and extraskeletal vitamin D targets may require higher doses of supplementation.”
It also concluded that pre-treatment 25(OH)D levels were the only indicator of how well patients responded to treatment. This is significant because the elderly and the obese have more challenges reaching optimal vitamin D levels. The researchers suggest that this supports the argument that personalized treatment plans “should take into account pre-treatment vitamin D deficiency to ensure the most effective outcomes.”
“This approach will likely enhance the efficacy of supplementation while minimizing the risk of under- or over-supplementation in diverse patient groups,” the added.
Source: Clinical Nutrition. doi: doi.org/10.1016/j.clnu.2025.03.004. “Retrospective real world study on vitamin D supplementation: Looking for the most effective molecule and its frequency of use”. Authors: Andrea Crafa et al.
