Miao Tian, MD, Pathology Resident
Nam Tran, PhD, Director of Clinical Chemistry
Introduction: Biotin interference for immunoassay-based laboratory tests has been recognized for decades (1-3). In recent years, the emergence of high dose biotin supplementation and unproven regimens for treating multiple sclerosis has brought biotin interference back into the spotlight. In November 2017, The United States Food and Drug Administration (FDA) issued a safety warning stating that biotin can interfere with laboratory tests (4). This warning was made based on a case in which a patient taking high dose biotin died after a potentially falsely low troponin lab result. However, it must be noted that biotin interference was not confirmed and troponin measurements following the event were made post-mortem. Nonetheless, this FDA warning prompted significant concern by patients and healthcare providers alike. Now two years later, is biotin interference still a problem?
In a previous blog article, we discussed biotin is an essential co-factor for several carboxylases responsible for gluconeogenesis and metabolism of fatty acids and certain amino acids (5). High concentrations of biotin in patient samples can compete the biotinylated reagents for binding to streptavidin thus interfere the reaction of the immunoassays. Reference intervals for serum biotin concentrations are 0.05-0.83 ng/mL (6). The biotin interference threshold, where the assay exhibits >10% change in results, for some assays have been reported to be 20 ng/ml (7)
Katzman BM et al at studied the prevalence of biotin supplement usage and plasma biotin concentrations among 1944 outpatients presenting to the emergency department (2). They found that serum concentration of biotin was 10 ng/mL (the lowest known interference threshold) or higher in 7.4% of outpatients presenting to the ED, indicating that the biotin supplement use is not rare among the patient population at the Mayo Clinic in Rochester, MN. However, there could be a sampling bias where patients taking biotin may more tend to attend the survey than those who were not taking biotin, so the prevalence measured here could be higher than actual. It is worth noting that the prevalence of biotin interference may also be geographic dependent, as another study in Australia showing less than 1% of patients presenting to ED had over 10 ng/ml serum concentration (8).
Laboratory Best Practice: For laboratory best practice, the most effective strategy to mitigate the biotin interference would be an early intervention. First and foremost, public education and patient awareness is the primary line of defense. Patients who need laboratory testing should be notified to refrain from taking supplements and allow several hours or days to “wash out” any residual biotin. One of the pharmacokinetic studies of biotin shows that for patients taking biotin doses of up to 5 mg twice a day. or 10 mg once a day, serum biotin levels could reach <30 ng/ml at 8-hour post-ingestion; while for those taking biotin at >10 mg daily or patient has kidney insufficiency, longer period of delaying sample collection is needed (9). Patients also need disclose their biotin intake to the clinicians and the detailed medication history should be documented to the electronic medical record.
Another strategy to avoid the biotin interference is to utilize assays that are not susceptible to biotin interference. However, this may not be feasible for many institutions, and assays that are not affected by biotin may be impacted by other immunoassay interferences such as heterophilic antibodies and fibrin. With that said, upcoming assays are incorporating various countermeasures against free biotin without significantly altering assay performance.
It is worth noting that biotin deficiency is very rare, there is no official recommended daily intake for biotin in the US. Standard multivitamin in the market contains 30 – 60 µg which is a suggested biotin intake for adults. Doses under 2,500 µg/day make up the majority of biotin sales, and such dosages have no risk for immunoassay interference. Biotin sales with more than 2,500 µg doses actually have declined over the past three years which may be attributed to public education about biotin interference (10). At very rare situations where the patients have certain conditions like multiple sclerosis, higher doses (e.g. more than 5,000 µg) may be prescribed by physician. Such a high dose has a potential to lead to test interference. However, these high doses are under physician's direct care and should be recorded in patient's electronic medical records. Taken together, biotin interference for immunoassay-based laboratory tests is very rare. With public education and more and more patients' awareness, the biotin interference eventually will not be a problem in the future.
- Samarasinghe S, Meah F, Singh V, Basit A, Emanuele N, Emanuele MA, Mazhari A, Holmes EW. Biotin interference with routine clinical immunoassays: understand the causes and mitigate the risks. Endocr Pract. 2017 23(8):989-998
- Katzman BM, Lueke AJ, Donato LJ, Jaffe AS, Baumann NA. Prevalence of biotin supplement usage in outpatients and plasma biotin concentrations in patients presenting to the emergency department. Clin Biochem. 2018 60:11-16
- Bowen R, Benavides R, Colón-Franco JM, Katzman BM, Muthukumar A, Sadrzadeh H, Straseski J, Klause U, Tran N. Best practices in mitigating the risk of biotin interference with laboratory testing. Clin Biochem. 2019 Aug 29. In press
- FDA Safety Communication. The FDA Warns that Biotin May Interfere with Lab Tests. 2017 Nov 28. Available from: https://www.fda.gov/medical-devices/safety-communications/fda-warns-biotin-may-interfere-lab-tests-fda-safety-communication
- Mcmahon RJ. Biotin in Metabolism and Molecular Biology. Annu Rev Nutr 2002 22:221–239.
- LabCorp, LabCorp Vitamin B7 (Biotin) test catalog entry [Internet], Available from: https://www.labcorp.com/test-menu/36691/vitamin-bsub7-sub.
- Roche Diagnostics. Elecsys T3 package insert, 2017-10, V 2.0 English.
- Trambas CM, Liu KC, Luu H, Louey W, Lynch C, Yen T, Sikaris KA. Further assessment of the prevalence of biotin supplementation and its impact on risk. Clin Biochem. 2019 65:64-65.
- Grimsey P, Frey N, Bendig G, Zitzler J, Lorenz O. Population pharmacokinetics of exogenous biotin and the relationship between biotin serum levels and in vitro immunoassay interference. Int J Pharmacokinet 2017 2:247–256
- Roche Diagnostics 2018. Available from: https://biotinfacts.roche.com/understan