Vitamin D3 Loading Is Superior to Conventional Supplementation After Weight Loss Surgery in Vitamin D-Deficient Morbidly Obese Patients: a Double-Blind Randomized Placebo-Controlled Trial

Abstract

Background: Bariatric patients often suffer from vitamin D deficiency (VDD), and both, morbid obesity and VDD, are related to non-alcoholic fatty liver disease. However, limited data are available regarding best strategies for treating VDD, particularly, in bariatric patients undergoing omega-loop gastric bypass (OLGB). Therefore, we examined the efficacy and safety of a forced vitamin D dosing regimen and intervention effects in liver fibrotic patients.

Methods: In this double-blind, randomized, placebo-controlled trial, 50 vitamin D-deficient patients undergoing OLGB were randomly assigned to receive, in the first month postoperatively, oral vitamin D3 (≤3 doses of 100,000 IU; intervention group) or placebo as loading dose (control group) with subsequent maintenance dose (3420 IU/day) in both groups until 6-month visit.

Results: Compared with control group, higher increase of 25(OH)D (67.9 (21.1) vs. 55.7 nmol/L (21.1); p = 0.049) with lower prevalence of secondary hyperparathyroidism (10 vs. 24 %; p = 0.045) was observed in intervention group. No (serious) adverse events related to study medication were found. The loading dose regimen was more effective in increasing 25(OH)D in patients with significant liver fibrosis while this was not the case for conventional supplementation (placebo with maintenance dose) (71.5 (20.5) vs. 22.5 nmol/L (13.8); p = 0.022; n = 14).

Conclusions: Our findings indicate that a high vitamin D3 loading dose, in the first month postoperatively, with subsequent maintenance dose is effective and safe in achieving higher vitamin D concentrations in OLGB patients. Unexpectedly, it is more effective in patients with significant liver fibrosis which is of potentially high clinical relevance and requires further investigation.

Trial registration: ClinicalTrials.gov NCT02092376.

Keywords: Gastric bypass; Liver fibrosis; Obesity; Omega-loop gastric bypass; Secondary hyperparathyroidism; Vitamin D; Vitamin D supplementation; Weight loss.

Conflict of interest statement

Conflict of Interest

All authors have no commercial associations that might be a conflict of interest in relation to this article.

Authors’ Contributions

The authors’ responsibilities were as follows: The project idea came from ML, RK, and RM. ML, BL, RK, CK, EK, MT, FL, GP, and RM designed the research. ML, RK, CK, ST, FL, and GP conducted the research. ML analyzed the data and performed statistical analyses. ML drafted the manuscript with appreciable input from RK, CK, ST, FL, GP, KS, EK, FH, MT, MK, RM, and BL. ML, RK, and BL had prime responsibility for the final manuscript content. All authors read and approved the final manuscript.

Grant Information

The work of this paper was partly supported by the Austrian Biobanking and BioMolecular resources Research Infrastructure (BBMRI.at) funded by the Austrian Federal Ministry of Science, Research and Economy (BMWFW GZ 10.470/0016-II/3/2013) and by the non-profit organization “Special Institute for Preventive Cardiology and Nutrition-SIPCAN Save Your Life” (Salzburg) for personnel costs, and Fresenius Kabi supplied, cost-free, the Oleovit and placebo oil, but all had no role in the design and conduct of the study, the collection, analysis, and interpretation of data, in the preparation of the manuscript, or in the review or approval of the manuscript.

Figures

Fig. 1

CONSORT flow chart of participant recruitment in the randomized controlled trial

Fig. 2

Change in serum 25-hydroxy vitamin D concentration (nmol/L) over the time between intervention and control groups. Note: 25(OH)D 25-hydroxy vitamin D. Repeated measure analysis of variance and post hoc analysis with Bonferroni correction, adjusted for baseline value, season, age, and sex with intention-to-treat analysis: intervention (n = 25) and control (n = 25). Error bars: standard deviation; *p < 0.05 (intervention vs. control)

Fig. 3

Change in serum 25-hydroxy vitamin D concentration (nmol/L) over the time between intervention and control groups in patients without (a) and with significant fibrosis (b). Note: 25(OH)D 25-hydroxy vitamin D. Repeated measure analysis of variance and post hoc analysis with Bonferroni correction, adjusted for baseline value, vitamin D dose, season, age, and sex and intention-to-treat analysis: intervention (n = 25) and control (n = 25). Significant fibrosis = F ≥ 2, n = 14. No significant fibrosis = F ≤ 1, n = 29. Error bars: standard deviation; *p < 0.05 (intervention vs. control)

Fig. 4

Estimates of the prevalence of secondary hyperparathyroidism over the time between intervention and control groups. Note: SHPT secondary hyperparathyroidism. Generalized estimating equations (GEE) with a logit link function for binary outcomes, adjusted for baseline value and sex; bars represent standard error; at 6 months, n = 21 in intervention and n = 22 in control group; *p < 0.05 (intervention vs. control)