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Biotin supplements taken at common over-the-counter doses can can interfere with the results of certain hormone assays, giving falsely high or low results that could lead to a misdiagnosis, researchers reported.

In six healthy adults taking 10 mg/day of biotin for 1 week, biotin-associated interference was found in nine of 23 biotinylated assays (39%), compared with zero of 14 non-biotinylated assays (P=0.007 for comparison), according to Danni Li, PhD, of the University of Minnesota in Minneapolis, and colleagues.

The results of five of eight biotinylated competitive immunoassays (63%) tested falsely high, and the results of four of 15 biotinylated sandwich immunoassays (27%), tested falsely low, the authors wrote in the

"Clinicians may want to ask about biotin ingestion even if assay results are not suspect because biotin interferences can cause either falsely normal or abnormal results," they stated. "It may be advisable for patients to stop taking biotin, preferably for a week as studied herein, before undergoing laboratory testing. Alternatively, in the presence of biotin ingestion, non-biotinylated assays would be preferred."

Biotin supplements, especially very large doses of 10-15 mg/d, or 333-fold greater than the dietary recommendation of 30 μg/d, have become popular for presumptive health benefits such as stimulating hair growth and treating conditions including biotinidase deficiency, diabetes, lipid disorders, and diabetic peripheral neuropathy, Li's group noted.

High doses of biotin may interfere with laboratory tests because biotin is a common component of immunoassays, in the form of biotinylated antibodies or analogues. These assays use the strong, stable, and specific binding between biotin and streptavidin to amplify sensitivity for detecting low analyte levels. Excessive biotin in a blood sample can compete with biotinylated components in the assay, potentially falsely decreasing results in sandwich immunoassays or falsely increasing them in competitive immunoassays, they explained.

Although some assay manufacturers' package inserts acknowledge the possibility of biotin interference, little is known about whether or how specific tests are affected by biotin supplements. "To our knowledge, the current study is the first to systematically assess the association of biotin ingestion (10 mg/d for 7 days) in healthy adults with performance of 37 assays that measure 11 analytes over four major diagnostic systems," Li's group wrote.

The mean age of participants in the nonrandomized, crossover study was 38. Four were men and two were women. They were asked to stop taking vitamin supplements 2 weeks before the study started. Then they took 10 mg/d of biotin for 1 week. Blood tests for analysis were taken at baseline (day 0), on day 7 of biotin treatment, and 1 week after treatment had stopped (day 14).

The blood samples were sent to four different clinical laboratories using different diagnostic systems. Assays were performed to assess levels of nine hormones: thyroid-stimulating hormone, total thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine, parathyroid hormone, prolactin, N-terminal pro-brain natriuretic peptide, and 25-hydroxyvitamin D. Assays were also performed for two non-hormones: prostate-specific antigen and ferritin.

The study was not randomized or blinded to the investigators or participants, but it was blinded to the clinical laboratories.

The authors reported that the mean baseline serum biotin concentration was 774 pg/mL (95% CI 554-1,004 pg/mL) compared with a mean day-7 concentration of more than 3,600 pg/mL (95% CI 3,601-3,601 pg/mL, P<0.001).

Biotin ingestion was associated with falsely decreased Roche cobas e602 thyroid-stimulating hormone levels by a mean of 0.72 mIU/L (95% CI −1.13 to −0.32 mIU/L, P=0.006), a 37% reduction from baseline, although all results remained within the normal reference range.

The interference was much greater when measured by the Vitros 5600 thyroid-stimulating hormone assay, for which levels significantly decreased by a mean of 1.67 mIU/L (95% CI −2.08 to −1.26 mIU/L, P<0.001), a 94% reduction from baseline, with all results falsely decreased to below the reference range.

Biotin ingestion was associated with falsely reduced OCD Vitros 5600 N-terminal pro-brain natriuretic peptide results by an average of more than 13.9 pg/mL (95% CI −24.7 to −3.12 pg/mL, P=0.03), to less than 11.1 pg/mL in all participants.

Finally, biotin supplements were associated with statistically significant false increases in four assays: the Roche cobase602 assays measuring total triiodothyronine, free triiodothyronine, and free thyroxine; and the SiemensVista Dimension 1500 measuring free triiodothyronine.

"Biotin interference was of greatest clinical significance in the OCD Vitros thyroid-stimulating hormone assay, where falsely decreased concentrations (to <0.15mU/L) could have resulted in misdiagnosis of thyrotoxicosis in otherwise euthyroid individuals," Li's group wrote. "Likewise, falsely decreased OCD Vitros N-terminal pro-brain natriuretic peptide, to lower than assay detection limits, could possibly result in failure to identify congestive heart failure."

In addition to the small sample size and lack of blinding, another important study limitation was that no formal dose-response pharmacokinetic assessments of biotin at various doses was performed, so that the minimal dose and duration required to alter test results remains undetermined, they stated.

"Despite these limitations, this study reinforces cautionary advice regarding potential limitations of assays that use biotin streptavidin binding for clinical evaluation of individuals who ingest large doses of biotin," the researchers said. "Based on these findings, manufacturers may need to consider modifying biotinylated assays to minimize the effects of biotin ingestion. Laboratories could identify assays that contain biotinylated components.

"Future studies, including patients with normal and abnormal analyte concentrations, are recommended to further clarify the extent and pharmacokinetics of ingested biotin interference on various assay platforms," they concluded.

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