Home >> ALL ISSUES >> 2018 Issues >> Biotin interference: answering questions, reducing the risk

Biotin interference: answering questions, reducing the risk

image_pdfCreate PDF

David Wild

November 2018—Biotin use is not rare, and don’t count on it being listed in the patient’s electronic medical record. Those are some of the findings of a Mayo Clinic study published recently in Clinical Biochemistry (Katzman BM, et al. 2018;60:​11–16).

Mayo Clinic’s laboratory isn’t alone in having fielded questions from clinicians about biotin interference in immunoassays. Nikola Baumann, PhD, DABCC, co-director of Mayo Clinic’s central clinical laboratory and central processing, who spoke at this year’s AACC annual meeting on what Mayo is doing to limit the interference risk, said her laboratory’s research and experience, and that of others, has provided sufficient data to help in answering some of the most common questions, though the answers “aren’t black and white.”

Two such questions: How prevalent is biotin use, and who is taking it? In one week in July 2017, she and colleagues surveyed 4,000 Mayo Clinic outpatients who presented for scheduled blood collections. Of those surveyed, 1,944 returned completed paper questionnaires (972 female, 963 male, nine unspecified).

“I found it quite surprising that eight percent said, yes, they were taking biotin,” Dr. Baumann said in her presentation. “And what was also interesting is that five percent didn’t know if they were taking biotin. So people are taking over-the-counter supplements and may not even be aware what they’re taking.” Of those who said they consumed biotin, 79 percent were female, 21 percent male. Median age was 62.

In the same study, biotin was quantified in 1,442 residual waste plasma samples collected for physician-ordered electrolyte panels from patients presenting to the emergency department in March 2017. Nearly 50 percent had detectable biotin concentrations. Dr. Baumann and coauthors wrote, “There was an alarmingly high percentage of samples (7.4%) with biotin concentrations that fell at or above the lowest thresholds for assay interference (10 ng/mL) reported by Roche Diagnostics.” Nearly two percent of samples had biotin concentrations greater than or equal to 20 ng/mL.

Dr. Baumann

In the 107 samples in which biotin measured greater than or equal to 10 ng/mL, the EMR was reviewed to determine if biotin or multivitamin use had been noted. For only two was biotin use noted in the EMR. Thirty-three patients had multivitamin use listed. “One of the interventions that has been proposed is to use clinical decision support tools to query medication lists, but in our experience we have found that would not be robust,” Dr. Baumann said, because biotin use is often not listed in the EMR.

During the two-week period in which samples were obtained, only one patient in the study cohort had a physician-ordered test that would have been affected by his plasma biotin concentration. The authors say this may be a limitation of the study as residual samples were obtained from patients with a physician-ordered electrolyte panel rather than their targeting patients on whom immunoassays were ordered. “However, even with this conservative estimate,” they write, “we could extrapolate that 26 patients in the ED per year would be expected to have an erroneous laboratory result due to biotin interference.”

Another common question for laboratories: What serum biotin concentrations can laboratories and providers expect to see in patients taking biotin supplements in the range of 1,000 to 10,000 mcg/day?

In 2015, when Mayo Clinic’s laboratory began to investigate the interference problem, “we really didn’t have much information to go off of,” Dr. Baumann said, other than manufacturer package inserts.

One manufacturer suggests blood not be drawn from patients taking high biotin doses until at least eight hours after the last biotin dose. The biotin threshold provided is less than 25 ng/mL. Another manufacturer indicates that laboratories should expect to see a 7.3 percent decrease in T3 results at 10 ng/mL. “So manufacturer package inserts take different approaches,” Dr. Baumann noted.

Then, in 2017, a study conducted by Roche Diagnostics and published in the International Journal of Pharmacokinetics examined serum concentrations in healthy subjects taking 5-, 10-, or 20-mg biotin daily (Grimsey P, et al. 2017;2[4]:​247–256).

In the study, serum concentrations when blood samples were drawn one hour post-dose were 40.5 ng/mL among those administered 5 mg/day, 90.6 ng/mL among those administered 10 mg/day, and 183.8 ng/mL among those taking 20 mg/day. Three hours after a biotin dose, serum concentrations dropped to 16.2 ng/mL in the 5-mg group, 32.7 ng/mL in the 10-mg group, and 63.7 ng/mL in the 20-mg group. Twelve hours after a dose, biotin levels were 4.9 ng/mL in the 5-mg group, 10.3 ng/mL in the 10-mg group, and 20.9 ng/mL in the 20-mg group.

After five days of biotin supplementation, peak serum concentrations were comparable to those of day one, with levels decreasing by 12 hours but not returning to baseline, a pattern that points to “a bit of a cumulative effect that needs to be investigated further,” Dr. Baumann said.

“What’s interesting here is that biotin is rapidly absorbed and there is a broad distribution of concentrations following a single dose of biotin,” she said.

Dr. Baumann uses a total hCG assay in use at Mayo to put the results in context. It has a biotin threshold in the package insert of 80 ng/mL. “In the case of this assay, most of the patients would be below this threshold by about three hours post-dose.”

With a free T4 assay used in her laboratory, which has a manufacturer threshold of 20 ng/mL, the serum concentrations of patients on 20-mg biotin consistently over several days could be above the threshold even 12 hours post-dose. “So, when I’m asked the question, ‘how long should a patient refrain from biotin?’ the answer is, ‘it depends,’” Dr. Baumann said.

At Mayo Clinic, patients are instructed to refrain from biotin supplements for at least 12 hours to make it consistent with fasting instructions. “However, the endocrinologists themselves ask patients whether they take biotin, and if the patients have been taking biotin for a long time, the endocrinologists ask them to refrain from biotin use for a week.”

While the Roche pharmacokinetic study provides important insights, it does not capture some of the “complexities” of biotin use, Dr. Baumann said. For example, while study subjects were healthy, patients with impaired renal function excrete biotin more slowly, and Mayo has had a few cases in which interference was still being observed more than 72 hours after a biotin supplement was taken. “So these are hard questions to answer, but I think these data give us an idea that if you’re taking a regular low-dose biotin, refraining from biotin use for 12 hours before a sample is drawn is probably enough.” If patients are taking higher-dose biotin for long periods, they need to refrain for a longer period. “And it also depends on the threshold of the assay.”

How biotin is used in immunoassays is another common question, she said. The vitamin can be part of the soluble components of the reagent—free biotinylated analogs and antibodies and streptavidin-coated particles—or part of pre-complexed reagents, where the biotin streptavidin complexes are preformed in the reagent. “Or biotin can be not used at all in the assay design, in which case the manufacturer is usually using anti-animal antibodies instead.”

CAP TODAY
X