Serum 25-hydroxyvitamin D in the VITamin D and OmegA-3 TriaL (VITAL): Clinical and demographic characteristics associated with baseline and change with randomized vitamin D treatment

Heike Luttmann-Gibson; Samia Mora; Carlos A Camargo; Nancy R Cook; Olga V Demler; Amit Ghoshal; Jay Wohlgemuth; Kris Kulkarni; Julia Larsen; James Prentice; Michael Cobble; Vadim Bubes; Chunying Li; Georgina Friedenberg; I-Min Lee; Julie E Buring; JoAnn E Manson

doi:10.1016/j.cct.2019.105854

Serum 25-hydroxyvitamin D in the VITamin D and OmegA-3 TriaL (VITAL): Clinical and demographic characteristics associated with baseline and change with randomized vitamin D treatment

Contemp Clin Trials. 2019 Dec:87:105854. doi: 10.1016/j.cct.2019.105854. Epub 2019 Oct 24.

Authors

Heike Luttmann-Gibson¹, Samia Mora², Carlos A Camargo³, Nancy R Cook⁴, Olga V Demler⁵, Amit Ghoshal⁶, Jay Wohlgemuth⁶, Kris Kulkarni⁷, Julia Larsen⁶, James Prentice⁶, Michael Cobble⁸, Vadim Bubes⁵, Chunying Li⁵, Georgina Friedenberg⁵, I-Min Lee⁴, Julie E Buring⁴, JoAnn E Manson⁴

Affiliations

¹ Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02215, USA; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Landmark Center West, 401 Park Drive, Boston, MA 02215, USA.
² Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02215, USA; Division of Cardiovascular Medicine and Center for Lipid Metabolomics, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02215, USA. Electronic address: smora@bwh.harvard.edu.
³ Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA; Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
⁴ Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02215, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
⁵ Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Avenue, Boston, MA 02215, USA.
⁶ Quest Diagnostics, 27027 Tourney Road, Valencia, CA 91355, USA.
⁷ Atherotech Diagnostics, 201 London Pkwy #400, Birmingham, AL 35211, USA; VAP Diagnostics R&D Laboratory, 201 London Pkwy, Birmingham, AL 3521, USA.
⁸ Atherotech Diagnostics, 201 London Pkwy #400, Birmingham, AL 35211, USA.

Abstract

Background: The VITamin D and OmegA-3 TriaL (VITAL) is a completed randomized, placebo-controlled trial of vitamin D₃ (2000 IU/day) and marine omega-3 (1 g/day) supplements in the primary prevention of cancer and cardiovascular disease. Here we examine baseline and change in 25-hydroxyvitamin D (25(OH)D) and related biomarkers with randomized treatment and by clinical factors.

Methods: Baseline 25(OH)D was measured in 15,804 participants (mean age 68 years.; 50.8% women; 15.7% African Americans) and in 1660 1-year follow-up samples using liquid chromatography-tandem mass spectrometry and chemiluminescence. Calcium and parathyroid hormone (iPTH) were measured by chemiluminescence and spectrophotometry respectively.

Results: Mean baseline total 25(OH)D (ng/mL ± SD) was 30.8 ± 10.0 ng/mL, and correlated inversely with iPTH (r = -0.28), p < .001. After adjusting for clinical factors, 25(OH)D (ng/mL ± SE) was lower in men vs women (29.7 ± 0.30 vs 31.4 ± 0.30, p < .0001) and in African Americans vs whites (27.9 ± 0.29 vs 32.5 ± 0.22, p < .0001). It was also lower with increasing BMI, smoking, and latitude, and varied by season. Mean 1-year 25(OH)D increased by 11.9 ng/mL in the active group and decreased by 0.7 ng/mL in placebo. The largest increases were noted among individuals with low baseline and African Americans. Results were similar for chemiluminescent immunoassay. Mean calcium was unchanged, and iPTH decreased with treatment.

Conclusion: In VITAL, baseline 25(OH)D varied by clinical subgroups, was lower in men and African Americans. Concentrations increased with vitamin D supplementation, with the greatest increases in those with lower baseline 25(OH)D. The seasonal trends in 25(OH)D, iPTH, and calcium may be relevant when interpreting 25(OH)D levels for clinical treatment decisions.

Clinical trial registration: VITAL ClinicalTrials.gov number NCT01169259.

Keywords: 25-hydroxyvitamin D; Parathyroid hormone; Seasonal effects; VITAL trial; Vitamin D.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Biomarkers
Black or African American
Body Mass Index
Calcium / blood
Cardiovascular Diseases / ethnology
Cardiovascular Diseases / prevention & control
Cholecalciferol* / administration & dosage
Comorbidity
Dietary Supplements*
Double-Blind Method
Fatty Acids, Omega-3* / administration & dosage
Female
Humans
Male
Middle Aged
Neoplasms / ethnology
Neoplasms / prevention & control
Residence Characteristics
Seasons
Sex Factors
Smoking / epidemiology
Socioeconomic Factors
Vitamin D* / analogs & derivatives
Vitamin D* / blood
White People

Substances

25-hydroxyvitamin D
Biomarkers
Calcium
Cholecalciferol
Fatty Acids, Omega-3
Vitamin D

Associated data

ClinicalTrials.gov/NCT01169259

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding