Written by Pharmacy Solutions
Summary
- High-dose biotin treatment can cause insidiously misleading laboratory results by fully mimicking the typical laboratory pattern of Graves’ disease and sometimes persisting for several days after biotin application [13]
- A Somewhat Bizarre Case of Graves Disease Due to Vitamin Treatment [14]
- A Single 10 mg Oral Dose of Biotin Interferes with Thyroid Function Tests[15]
- High-dose biotin in infants mimics biochemical hyperthyroidism with some commercial assays [16]
- The FDA has received a report that one patient taking high levels of biotin died following falsely low troponin test results when a troponin test known to have biotin interference was used [17]
Brief Overview
Biotin, also known as vitamin B7, is a water-soluble vitamin often found in multi-vitamins, prenatal vitamins, and dietary supplements marketed for hair, skin, and nail growth. Most people get enough biotin from the foods they eat. However, certain groups are more prone to deficiency, such as patients with a rare genetic disorder called “biotinidase deficiency”, alcohol dependence, and pregnant and breastfeeding women.
Biotin deficiency is very rare in the United States and can cause thinning hair and loss of body hair; brittle nails; a rash around the eyes, nose, mouth, and anal area; skin infection; pinkeye; high levels of acid in the blood and urine; nervous system disorders; and seizures. Symptoms of biotin deficiency in infants include weak muscle tone, sluggishness, and delayed development.
Intake recommendations
The Food and Nutrition Board (FNB) based its determination of Adequate Intake (AI) for all populations on the amount of biotin in human milk consumed by infants and then used body weight to extrapolate AIs for other groups. Table 1lists the current AIs for biotin [1].
High Dose Biotin
Several studies have found no adverse effects of 10–50 mg/day of biotin, even up to 200 mg/day oral or 20 mg/day intravenously when administered to patients with inherited biotin metabolic diseases and acquired biotin deficiency[1] The recommendations for adequate intake in adults has been estimated to be 30 µg/day [1],[2]. This usual dietary intake is not expected to be high enough to affect immunoassays based on the streptavidin-biotin binding. However, patients with inherited metabolic diseases like propionic acidemia, biotinidase deficiency,and patients with parenteral nutrition receive a higher dosage of biotin, with daily oral doses in case of inherited metabolic diseases ranging from 10 to 40 mg per day [3], [4].
Supraphysiological biotin administration is also used in certain auto-immune conditions aimed at reducing hair loss or fortifying hair and nails(up to 20 mg per day). It is sometimes listed as an unnamed supplement to improve hair, nails, and skin, and is not considered a medication by the patient, therefore not worth mentioning [5]. More recently, very high doses of biotin (300 mg per day) have been used in clinical trials in multiple sclerosis and demyelinating pathologies [6]. Although the therapeutic mechanism for high-dose biotin in biotin-thiamin responsive basal ganglia disease (BTBGD)remains unknown, high doses of biotin alone (5-10 mg/kg-d) had been used in the successful treatment of this disease [7]. Excess biotin has not been shown to have any toxic effects in humans. However, high plasma biotin (>30 µg/L) can lead to clinically misleading interferences with streptavidin-biotin immunoassays. [8]
Dangerous Lab Interference causing false-positive/negative
Biotin in blood or other samples taken from patients who are ingesting high levels of biotin in dietary supplements can cause clinically significant incorrect lab test results. High dose biotin may interfere with diagnostic assays that:
- Use biotin-streptavidin technology
- Are commonly used to measure levels of hormones (such as thyroid hormone)
- Measure other analytes such as 25-hydroxyvitamin D, producing falsely normal/abnormal results
The results of many hormonal immunoassays (troponin, natriuretic peptides, therapeutic drug assays, serology tests) may be misleading because of biotin interference. Many non-hormonal immunoassays may also be inaccurate in biotin-treated patients, showing falsely low tumor markers and ferritin levels, falsely high vitamin B12 and folate levels, and falsely negative serologies. [9] Many immunoassays provide highly inaccurate results if tested less than two days after the ingestion of biotin (seven days for thyroid receptor antibodies). As a result, biotin administration must be discontinued at least two days prior to sampling[10].
Recent case reports have described lab results falsely indicating Graves disease and severe hyperthyroidism in patients taking 10–300 mg biotin per day, including six children receiving high doses of biotin (2–15 mg/kg per day) to treat inherited metabolic disease[13]. According to the Food and Drug Administration (FDA), a patient with a high intake of supplemental biotin died following a troponin testthat gave a falsely low result, because the test was subject to biotin interference[17].
The FDA advises healthcare providers to ask their patients about any supplements they may be taking that contain biotin and to consider biotin interference as a possible source of error if laboratory test results do not match the clinical presentation of the patient.
Tables 2 and 3 lists current assays that may be impacted by high-dose biotin.
Table 2: Potential some potential errors in hormone testing, due to biotin interference [9]
Table 3: Assays prone to biotin interference [10]
What can be done to suspect and overcome these interferences?
The possibility of an analytical artifact may be inferred from various signs [11]:
- Lack of coherence with the clinical presentation; e.g. a thyrotoxic biochemical profile in a patient who is clinically euthyroid. The anomaly may extend to several other endocrine investigations to heighten suspicion of assay interference.
- Comparison of physiologically dependent variables: lack of the usual balance between the hormone and its regulating factor, evoking, for example, the very rare syndrome of inappropriate secretion of TSH.
- Extremely unusual analyte concentration.
- Markedly different results given by different analytical methods: as mentioned above, these analytical errors are method-dependent, because they impact specifically streptavidin-biotin based immunoassays.
One method of biotin neutralization is highly efficient and may be easily performed in any clinical laboratory, either to investigate unexpected hormonal profile, or to prevent artifact for known biotin supplementation. [8]
Another method enables laboratories to confirm biotin interference in the appropriate clinical setting. Moreover, it enables laboratories to remove the interference and report accurate and reliable results, without the need for patients to withhold beneficial therapy prior to blood tests. [12]
The original blog post can be found here.
