Skip to main content
    • Aa
    • Aa

Identification and assessment of markers of biotin status in healthy adults

  • Wei Kay Eng (a1), David Giraud (a1), Vicki L. Schlegel (a2), Dong Wang (a3), Bo Hyun Lee (a2) and Janos Zempleni (a1)...

Human biotin requirements are unknown and the identification of reliable markers of biotin status is necessary to fill this knowledge gap. Here, we used an outpatient feeding protocol to create states of biotin deficiency, sufficiency and supplementation in sixteen healthy men and women. A total of twenty possible markers of biotin status were assessed, including the abundance of biotinylated carboxylases in lymphocytes, the expression of genes from biotin metabolism and the urinary excretion of biotin and organic acids. Only the abundance of biotinylated 3-methylcrotonyl-CoA carboxylase (holo-MCC) and propionyl-CoA carboxylase (holo-PCC) allowed for distinguishing biotin-deficient and biotin-sufficient individuals. The urinary excretion of biotin reliably identified biotin-supplemented subjects, but did not distinguish between biotin-depleted and biotin-sufficient individuals. The urinary excretion of 3-hydroxyisovaleric acid detected some biotin-deficient subjects, but produced a meaningful number of false-negative results and did not distinguish between biotin-sufficient and biotin-supplemented individuals. None of the other organic acids that were tested were useful markers of biotin status. Likewise, the abundance of mRNA coding for biotin transporters, holocarboxylase synthetase and biotin-dependent carboxylases in lymphocytes were not different among the treatment groups. Generally, datasets were characterised by variations that exceeded those seen in studies in cell cultures. We conclude that holo-MCC and holo-PCC are the most reliable, single markers of biotin status tested in the present study.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Identification and assessment of markers of biotin status in healthy adults
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Identification and assessment of markers of biotin status in healthy adults
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Identification and assessment of markers of biotin status in healthy adults
      Available formats
Corresponding author
*Corresponding author: J. Zempleni, fax +1 402 472 1587, email
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

1 J Zempleni , SS Wijeratne & YI Hassan (2009) Biotin. Biofactors 35, 3646.

2 G Camporeale , EE Shubert , G Sarath , et al. (2004) K8 and K12 are biotinylated in human histone H4. Eur J Biochem 271, 22572263.

3 K Kobza , G Camporeale , B Rueckert , et al. (2005) K4, K9, and K18 in human histone H3 are targets for biotinylation by biotinidase. FEBS J 272, 42494259.

4 V Pestinger , SSK Wijeratne , R Rodriguez-Melendez , et al. (2011) Novel histone biotinylation marks are enriched in repeat regions and participate in repression of transcriptionally competent genes. J Nutr Biochem 22, 328333.

5 L Rios-Avila , V Pestinger & J Zempleni (2012) K16-biotinylated histone H4 is overrepresented in repeat regions and participates in the repression of transcriptionally competent genes in human Jurkat lymphoid cells. J Nutr Biochem 23, 15591564.

6 JS Stanley , JB Griffin & J Zempleni (2001) Biotinylation of histones in human cells: effects of cell proliferation. Eur J Biochem 268, 54245429.

7 LM Bailey , RA Ivanov , JC Wallace , et al. (2008) Artifactual detection of biotin on histones by streptavidin. Anal Biochem 373, 7177.

8 T Kuroishi , L Rios-Avila , V Pestinger , et al. (2011) Biotinylation is a natural, albeit rare, modification of human histones. Mol Genet Metab 104, 537545.

9 G Camporeale , AM Oommen , JB Griffin , et al. (2007) K12-biotinylated histone H4 marks heterochromatin in human lymphoblastoma cells. J Nutr Biochem 18, 760768.

10 NA Filenko , C Kolar , JT West , et al. (2011) The role of histone H4 biotinylation in the structure and dynamics of nucleosomes. PLoS One 6, e16299.

11 B Bao , V Pestinger , I HY , et al. (2011) Holocarboxylase synthetase is a chromatin protein and interacts directly with histone H3 to mediate biotinylation of K9 and K18. J Nutr Biochem 22, 470475.

14 NM Green (1975) Avidin. Adv Protein Chem 29, 85133.

17 DL Weiner , RE Grier & B Wolf (1985) A bioassay for determining biotinidase activity and for discriminating biocytin from biotin using holocarboxylase synthetase-deficient cultured fibroblasts. J Inherit Metab Dis 8, 101102.

18 B Wolf , GS Heard , KA Weissbecker , et al. (1985) Biotinidase deficiency: initial clinical features and rapid diagnosis. Ann Neurol 18, 614617.

19 DM Mock & ME Dyken (1997) Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants. Neurology 49, 14441447.

21 DM Mock & DD Stadler (1997) Conflicting indicators of biotin status from a cross-sectional study of normal pregnancy. J Am Coll Nutr 16, 252257.

25 SL Stratton , CL Henrich , NI Matthews , et al. (2012) Marginal biotin deficiency can be induced experimentally in humans using a cost-effective outpatient design. J Nutr 142, 2226.

30 G Kaur Mall , YC Chew & J Zempleni (2010) Biotin requirements are lower in human Jurkat lymphoid cells but homeostatic mechanisms are similar to those of HepG2 liver cells. J Nutr 140, 10861092.

31 NM Green (1965) A spectrophotometric assay for avidin and biotin based on binding of dyes by avidin. Biochem J 94, 23c24c.

32 TD Durance (1991) Residual avidin activity in cooked egg white assayed with improved sensitivity. J Food Sci 56, 707709.

34 KJ Livak & TD Schmittgen (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2( − Delta Delta C(T)) method. Methods 25, 402408.

38 CG Staggs , WM Sealey , BJ McCabe , et al. (2004) Determination of the biotin content of select foods using accurate and sensitive HPLC/avidin binding. J Food Compost Anal 17, 767776.

41 DM Mock , CL Henrich , N Carnell , et al. (2002) Lymphocyte propionyl-CoA carboxylase and accumulation of odd-chain fatty acid in plasma and erythrocytes are useful indicators of marginal biotin deficiency. J Nutr Biochem 13, 462470.

45 SL Stratton , TD Horvath , A Bogusiewicz , et al. (2011) Urinary excretion of 3-hydroxyisovaleryl carnitine is an early and sensitive indicator of marginal biotin deficiency in humans. J Nutr 141, 353358.

46 TD Horvath , SL Stratton , A Bogusiewicz , et al. (2010) Quantitative measurement of urinary excretion of 3-hydroxyisovaleryl carnitine by LC–MS/MS as an indicator of biotin status in humans. Anal Chem 82, 95439548.

47 DM Mock , SL Stratton , TD Horvath , et al. (2011) Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans. J Nutr 141, 19251930.

50 DM Mock & NI Mock (1997) Serum concentrations of bisnorbiotin and biotin sulfoxide increase during both acute and chronic biotin supplementation. J Lab Clin Med 129, 384388.

52 RS Solorzano-Vargas , D Pacheco-Alvarez & A Leon-Del-Rio (2002) Holocarboxylase synthetase is an obligate participant in biotin-mediated regulation of its own expression and of biotin-dependent carboxylases mRNA levels in human cells. Proc Natl Acad Sci U S A 99, 53255330.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 4
Total number of PDF views: 73 *
Loading metrics...

Abstract views

Total abstract views: 185 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 29th May 2017. This data will be updated every 24 hours.