title: Vitamin D3 effects on lipids differ in statin and non-statin-treated humans: superiority of free 25-OH D levels in detecting relationships.
abstract: BACKGROUND
  Inverse associations between 25-OH vitamin D levels and cardiovascular morbidity and mortality have been reported.
  
  
  OBJECTIVE
  Our goals were to 1) investigate effects of correcting inadequate D status on lipids, 2) determine whether free 25-OH D is better correlated with lipids than total 25-OH D.
  
  
  METHODS
  A randomized, double-blind placebo-controlled trial was performed.
  
  
  METHODS
  Participants resided in the general community.
  
  
  METHODS
  Adults with inadequate D status were randomized to D3: 14 men, 12 women, age 60 ± 8 years (mean ± SD) or placebo: 12 men, 11 women: 59 ±12 years.
  
  
  METHODS
  Responses to 12-week oral vitamin D3 titrated (1000-3000 IU/d) to achieve 25-OH D levels ≥25 ng/mL were compared to placebo.
  
  
  METHODS
  Measurements were 25-OH D (tandem mass spectometry), free 25-OH D (direct immunoassay), lipids (directly measured triglyceride, cholesterol, and subfractions; plant sterols and cholesterol synthesis precursors), and safety labs before and after 6 and 12 weeks D3 or placebo. Data were analyzed by repeated measures ANOVA and linear regression.
  
  
  RESULTS
  Vitamin D3 was titrated to 1000 IU/d in 15/26 (58%), to 2000 IU/d in 10, and 3000 IU/d in one patient. D3 had no effect on cholesterol or cholesterol subfractions except for trends for decreases in atorvastatin-treated patients (cholesterol, P = .08; low-density lipoprotein [LDL] cholesterol, P = .05). Decreased campesterol concentrations (P = .05) were seen with D3 but not placebo in statin-treated patients. Relationships between total 25-OH D and lipids were not detected, but inverse linear relationships were detected between free 25-OH D and triglycerides (P = .03 for all participants [n = 49], P = .03 in all statin-treated [n = 19], and P = .0009 in atorvastatin-treated [n = 11]), and between free 25-OH D and LDL cholesterol (P = .08 overall, P = .02 in all statin-treated, and P = .03 for atorvastatin-treated), and total cholesterol (P = .09 overall; P = .04 for all statin-treated, and P = .05 for atorvastatin-treated).
  
  
  CONCLUSIONS
  Vitamin D lipid-lowering effects appear limited to statin-treated patients and are likely due to decreased cholesterol absorption. Relationships between lipids and D metabolites were only detected when free 25-OH D was measured, suggesting the superiority of determining free 25-OH D levels compared to total 25-OH vitamin D levels when analyzing biologic responses.
authors.affiliation: MD, 302 Silver Avenue, San Francisco, CA 94112. Janice.schwartz@ucsf.edu.
authors.forename: Lynn
authors.initials: L
authors.lastname: Kane
authors.forename: Kelly
authors.initials: K
authors.lastname: Moore
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.forename: Daniel
authors.initials: D
authors.lastname: Bikle
authors.forename: Janice B
authors.initials: JB
authors.lastname: Schwartz
mesh_terms: D000284:Administration, Oral; D000368:Aged; D002762:Cholecalciferol / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D016014:Linear Models; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014815:Vitamins / Q000008:administration & dosage
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D014815:Vitamins; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D
references.citation: J Endocrinol Invest. 2003 Aug;26(8):748-53
references.pmid: 14669830
references.citation: Neurochem Res. 2001 Nov;26(11):1237-44
references.pmid: 11874206
references.citation: Am J Epidemiol. 1990 Jan;131(1):20-31
references.pmid: 2293749
references.citation: Circulation. 2012 Jul 17;126(3):252-4
references.pmid: 22718801
references.citation: Ann Intern Med. 2011 Dec 20;155(12):820-6
references.pmid: 22184689
references.citation: Arch Intern Med. 2007 Sep 10;167(16):1730-7
references.pmid: 17846391
references.citation: Kidney Int. 1998 May;53(5):1353-7
references.pmid: 9573552
references.citation: J Clin Endocrinol Metab. 2009 Jan;94(1):26-34
references.pmid: 18854395
references.citation: Atherosclerosis. 1970 Sep-Oct;12(2):313-7
references.pmid: 5493100
references.citation: N Engl J Med. 2007 Jul 19;357(3):266-81
references.pmid: 17634462
references.citation: J Clin Endocrinol Metab. 2010 Feb;95(2):471-8
references.pmid: 20133466
references.citation: Circulation. 2007 Feb 20;115(7):827-8
references.pmid: 17309931
references.citation: Metabolism. 2008 Jun;57(6):741-8
references.pmid: 18502255
references.citation: Clin Biochem. 2009 Jul;42(10-11):1174-7
references.pmid: 19302999
references.citation: J Clin Endocrinol Metab. 1986 Oct;63(4):954-9
references.pmid: 3745408
references.citation: J Lipid Res. 2009 Apr;50(4):730-9
references.pmid: 19043140
references.citation: Epidemiology. 1990 Jan;1(1):58-64
references.pmid: 2081241
references.citation: Kidney Int. 2012 Jul;82(1):84-9
references.pmid: 22398410
references.citation: J Lipid Res. 2002 Jul;43(7):1078-85
references.pmid: 12091492
references.citation: Am J Clin Nutr. 2008 Aug;88(2):554S-557S
references.pmid: 18689401
references.citation: J Nutr Biochem. 1990 May;1(5):272-6
references.pmid: 15539215
references.citation: Arterioscler Thromb Vasc Biol. 2012 Oct;32(10):2510-5
references.pmid: 22947589
references.citation: J Biol Chem. 2004 Dec 10;279(50):52772-80
references.pmid: 15452130
references.citation: J Clin Endocrinol Metab. 2008 Mar;93(3):677-81
references.pmid: 18089691
references.citation: Lipids Health Dis. 2012 Mar 20;11:42
references.pmid: 22433171
references.citation: Cancer Causes Control. 2000 May;11(5):459-66
references.pmid: 10877339
references.citation: Am J Clin Nutr. 2007 Jan;85(1):54-9
references.pmid: 17209177
references.citation: Steroids. 2011 Mar;76(4):331-9
references.pmid: 21236284
references.citation: J Lipid Res. 1989 Mar;30(3):379-86
references.pmid: 2542424
references.citation: Arch Intern Med. 2007 Jun 11;167(11):1159-65
references.pmid: 17563024
references.citation: Eur J Endocrinol. 1997 Nov;137(5):495-502
references.pmid: 9405029
references.citation: Nat Rev Immunol. 2011 Aug 19;11(9):584-96
references.pmid: 21852793
references.citation: J Lab Clin Med. 2003 Feb;141(2):131-7
references.pmid: 12577049
references.citation: Trends Endocrinol Metab. 2010 Jun;21(6):375-84
references.pmid: 20149679
references.citation: Clin Pharmacol Ther. 2009 Feb;85(2):198-203
references.pmid: 18754003
references.citation: Clin Lab Med. 2006 Dec;26(4):787-802
references.pmid: 17110240
references.citation: J Lipid Res. 2001 Feb;42(2):181-7
references.pmid: 11181746
references.citation: Ann N Y Acad Sci. 2013 May;1287:45-58
references.pmid: 23682710
references.citation: Circulation. 2012 Jul 17;126(3):270-7
references.pmid: 22718799