Urinary excretion of 3-hydroxyisovaleryl carnitine is an early and sensitive indicator of marginal biotin deficiency in humans.
Mounting evidence indicates that marginal biotin deficiency is not rare, contrary to previous assumptions. Accordingly, robust indicators of biotin status would be useful. In a study of 10 healthy adults, we recently provided evidence that abnormally increased plasma concentration of 3-hydroxyisovaleryl carnitine (3HIA-carnitine) is a sensitive indicator of marginal biotin deficiency. We sought to determine whether urinary excretion of 3HIA-carnitine (expressed as the ratio to urinary creatinine) significantly increases in marginal biotin deficiency. Marginal, asymptomatic biotin deficiency was induced experimentally in the same 10 healthy adults (8 women) by feeding undenatured egg white with meals for 28 d. Biotin status was repleted by a mixed general diet plus biotin supplementation. Urinary excretion of 3HIA-carnitine was determined by liquid chromatography-tandem MS on d 0, 14, and 28 (depletion) and on d 35 and 50 (repletion). Mean urinary 3HIA-carnitine concentration increased with depletion (P < 0.0001; d 0 vs. 28) and decreased with repletion (P = 0.0002; d 28 vs. 50). Urinary 3HIA-carnitine excretion was greater than the upper limit of normal in 9 of 10 participants by d 14 and decreased to within normal limits by d 50 in all participants. This study provides evidence that urinary excretion of 3HIA-carnitine is an early and sensitive indicator of marginal biotin deficiency. The ease of collection of untimed urine samples and application of a new analytical method with simplified sample preparation suggest that urinary 3HIA-carnitine is likely to be a useful indicator for large population studies.
Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Shawna L
SL
Stratton
Thomas D
TD
Horvath
Anna
A
Bogusiewicz
Nell I
NI
Matthews
Cindy L
CL
Henrich
Horace J
HJ
Spencer
Jeffery H
JH
Moran
Donald M
DM
Mock
D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001710:Biotin / Q000172:deficiency* / Q000627:therapeutic use; D002331:Carnitine / Q000031:analogs & derivatives* / Q000652:urine; D004529:Egg White; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D043586:Methylmalonyl-CoA Decarboxylase / Q000097:blood; D009752:Nutritional Status; D012016:Reference Values; D013997:Time Factors; D014804:Vitamin B Deficiency / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000652:urine*
C098116:3-hydroxyisovalerylcarnitine; D015415:Biomarkers; D001710:Biotin; D043586:Methylmalonyl-CoA Decarboxylase; D002331:Carnitine
Am J Clin Nutr. 1997 Apr;65(4):951-8
9094878
J Nutr. 2009 Jan;139(1):154-7
19056637
Anal Chem. 2010 Nov 15;82(22):9543-8
21028833
Am J Clin Nutr. 2004 Oct;80(4):932-5
15447901
Am J Clin Nutr. 1992 Feb;55(2):326-30
1734668
Am J Clin Nutr. 2006 Aug;84(2):384-8
16895887
Int J Vitam Nutr Res. 1982;52(4):375-85
7160963
Biomed Environ Mass Spectrom. 1989 Sep;18(9):652-6
2790256
J Pediatr Gastroenterol Nutr. 1998 Mar;26(3):245-50
9523856
J Nutr Biochem. 2002 Aug;13(8):462
12165358
Am J Clin Nutr. 2002 Feb;75(2):295-9
11815321
Eur J Clin Nutr. 1989 Mar;43(3):169-73
2499449
Clin Chim Acta. 1995 Aug 31;240(1):35-51
8582058
Anal Chem. 2010 May 15;82(10):4140-4
20397702
Proc Soc Exp Biol Med. 2000 Jan;223(1):14-21
10632957
J Nutr. 2005 May;135(5):973-7
15867267
Neurology. 1997 Nov;49(5):1444-7
9371938
Am J Clin Nutr. 1995 Feb;61(2):385-91
7840079
J Am Coll Nutr. 1997 Jun;16(3):252-7
9176832
Am J Med Genet C Semin Med Genet. 2006 May 15;142C(2):64-76
16602099
Mol Genet Metab. 2008 Dec;95(4):201-5
18974016
Am J Clin Nutr. 1999 Mar;69(3):352-3
10075316
J Nutr. 1997 May;127(5):710-6
9164991
Ann Neurol. 1982 Nov;12(5):485-6
7181453
J Nutr. 2002 Jul;132(7):1945-50
12097674
Clin Chem. 2007 Apr;53(4):717-22
17272485
Int J Vitam Nutr Res. 1984;54(2-3):217-22
6500847
Adv Drug Deliv Rev. 2009 Nov 30;61(14):1353-62
19716391
Proc Natl Acad Sci U S A. 1975 Mar;72(3):883-7
1055387
Am J Clin Nutr. 2002 Nov;76(5):1061-8
12399279
Am J Clin Nutr. 2010 Dec;92(6):1399-405
20943794
J Inherit Metab Dis. 1994;17(6):678-90
7707691