Biotin: High doses of vitamin B7 could mask heart problems

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Taking supplements that contain high levels of biotin (vitamin B7) can lead to falsely low results on a blood test used to detect heart attacks, according to an FDA warning issued late last year.

For adults, the recommended dietary allowance (RDA) for biotin is 0.03 milligrams (mg), which is easily obtained through a healthy, varied diet.

Many multivitamins and prenatal vitamins contain far more biotin than the RDA.

And some supplements — particularly those marketed to improve hair, nails, and skin — contain 20 mg, or nearly 650 times the RDA.

But biotin levels higher than the RDA may interfere with lab test results, including blood tests for troponin, which doctors use to diagnose heart attacks.

These inaccurate results can lead to missed diagnoses with potentially serious consequences. In at least one case, a person who was taking high doses of biotin died following a falsely low troponin test result.

Biotin, or vitamin B7, is an essential nutrient.

And there is no issue with the lower doses found in multivitamins, said study author Danni Li, an associate professor of laboratory medicine and pathology at the University of Minnesota.

But high doses of biotin can cause falsely low results in a blood test that measures the protein troponin – which is used to help diagnose heart attacks.

In 2017, the U.S. Food and Drug Administration issued a safety alert on the issue.

It hasn’t been clear, though, how popular high-dose biotin use is. So Li and her colleagues looked into the question, using data from a long-running U.S. health survey.

The researchers found that high-dose biotin supplements have risen from obscurity to become notably more popular in recent years.

By 2016, about 3% of U.S. adults were using them. That was up from 0.1% in 1999 to 2000, the researchers reported in the Aug. 11 issue of the Journal of the American Medical Association.

High-dose biotin was defined as 1 milligram (mg) per day or more, which is many times greater than the recommended dietary intake of 30 micrograms a day.

Overall, Li said, women were much more likely to use the supplements. Among women aged 60 and older, over 7% took at least 1 mg per day, while another 2% used doses of 5 mg or more.

That’s concerning because older adults are at increased risk of a heart attack, particularly if they have conditions like high blood pressure or diabetes.

“If you’re taking high-dose biotin and you have a heart attack, there’s a good chance you might not be diagnosed correctly,” said Dr. Anne Thorndike, chair of the American Heart Association’s nutrition committee.

For people with risk factors for heart attack, it’s best to avoid large doses of biotin, according to Thorndike.

She also said ER doctors should be aware of the potential for biotin interference, and ask patients with possible heart attack symptoms about any supplement use.

The findings are based on responses to the U.S. National Health and Nutrition Examination Survey. It periodically surveys a nationally representative sample of Americans about their health and lifestyle habits.

During the 1999 to 2000 wave, very few people were taking high-dose biotin.

By 2015 to 2016 – the most recent information available – just under 5% of all women were using the supplements, as were 0.7% of men.

Biotin deficiency can cause brittle nails, hair loss and skin rash. But the condition is also rare, according to the U.S. National Institutes of Health (NIH), and there is little evidence biotin supplements promote healthier skin, hair and nails.

Thorndike said a balanced diet is always a better source of nutrients than pills are.

“People often spend a lot of money on supplements,” she said. “I’d rather see them spend that money on nutritious foods. There’s plenty of evidence supporting the benefits of a healthy diet.”

Food is more complex than a pill, providing the body with combinations of not only vitamins and minerals, but protein, fiber, fats and plant compounds, Thorndike noted.

Food sources of biotin include liver, eggs, pork, sweet potatoes, sunflower seeds and almonds, according to the NIH.

If people choose to take large doses of biotin, Li said, they should tell their doctor ahead of any planned lab tests. And, in general, she said, it’s best to consult a doctor before starting high-dose supplements, especially when someone is on medications for any health conditions.

Supplements can potentially interact with medications.


In mammals, biotin serves as a covalently bound coenzyme for four carboxylases: acetyl-CoA carboxylase (isoforms α and β; EC 6.4.1.2); pyruvate carboxylase (EC 6.4.1.1); propionyl-CoA carboxylase (EC 6.4.1.3); and 3-methylcrotonyl-CoA carboxylase (EC 6.4.1.4) (1).

These carboxylases catalyze essential steps in the metabolism of glucose, amino acids and fatty acids. Furthermore, eukaryotic cells can covalently attach biotin to histones (DNA-binding proteins) in an enzyme-mediated reaction (2,3).

Biotinylation of histones might play a role in processes such as cell proliferation and DNA repair (3,4).

Evidence is accumulating that biotin plays a role in the regulation of gene expression in addition to its role as a covalently bound group in carboxylases and histones.

For example, the expression of genes encoding glucokinase, phosphoenolpyruvate carboxykinase and ornithine transcarbamylase decreases in response to biotin deficiency (5).

Recently, evidence has been provided that the expression of genes encoding the cytokine interleukin-2 (IL-2) and IL-2 receptor γ correlate with biotin status in human lymphoid cells (6).

Cytokines are messenger proteins of the immune system that are secreted by immune cells in response to stimulation by antigens (7).

After secretion, cytokines bind to receptors on the surface of target cells such as T cells and natural killer cells. Some cells that are not immune cells may also secrete or bind cytokines (7).

Binding of cytokines to receptors triggers intracellular signaling cascades (7,8), which play important roles in processes such as cellular growth, proliferation, differentiation and apoptosis (7–9).

Effects of biotin on cytokine metabolism may account for the essential role of biotin in immune function that has been observed in previous studies (10–12).

Regulation of the immune response by cytokines is a complex network, involving >60 cytokines and cytokine receptors (7). Cytokines exhibit a substantial amount of cross-talk, e.g., IL-2 receptor γ serves as receptor for IL-2, IL-4, IL-7, IL-9, and IL-15 (7,8).

DNA microarrays permit simultaneous screening for the expression of a large number of genes; thus, microarrays are a powerful tool with which to investigate the effects of nutrients on complex networks of gene expression such as in cytokine metabolism.

In the present study, DNA microarrays were used to determine whether supplementation of healthy adults with biotin affects

1) the expression of genes that play a role in immune function (cytokine metabolism, signal transduction, cell proliferation, stress response and apoptosis), and

2) the expression of genes that play a role in biotin utilization.

LITERATURE CITED

1.Zempleni, J. & Mock, D. M. (1999) Biotin biochemistry and human requirements. J. Nutr. Biochem.10:128–138.Google ScholarCrossrefPubMed 

2.Hymes, J., Fleischhauer, K. & Wolf, B. (1995) Biotinylation of histones by human serum biotinidase: assessment of biotinyl-transferase activity in sera from normal individuals and children with biotinidase deficiency. Biochem. Mol. Med.56:76–83.Google ScholarCrossrefPubMed 

3.Stanley, J. S., Griffin, J. B. & Zempleni, J. (2001) Biotinylation of histones in human cells: effects of cell proliferation. Eur. J. Biochem.268:5424–5429.Google ScholarCrossrefPubMed 

4.Peters, D. M., Griffin, J. B., Stanley, J. S., Beck, M. M. & Zempleni, J. (2002) Exposure to UV light causes increased biotinylation of histones in Jurkat cells. Am. J. Physiol.283:C878–C884.Google ScholarCrossref 

5.Dakshinamurti, K. (2003) Regulation of gene expression by biotin, vitamin B6 and vitamin C. Daniel, H. Zempleni, J. eds. Molecular Nutrition CABI Publishing Oxfordshire, UK.Google Scholar 

6.Rodriguez-Melendez, R., Camporeale, G., Griffin, J. B. & Zempleni, J. (2003) Interleukin-2 receptor γ-dependent endocytosis depends on biotin in Jurkat cells. Am. J. Physiol. (in press).

7.Klein, J. & Horejsi, V. (1997) Interleukin-2 receptor γ-dependent endocytosis depends on biotin in Jurkat cells. Immunology Blackwell Science Oxford, UK.Google Scholar 

8.Sugamura, K., Asao, H., Kondo, M., Tanaka, N., Ishii, N., Ohbo, K., Nakamura, M. & Takeshita, T. (1996) The interleukin-2 receptor γ chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Annu. Rev. Immunol.14:179–205.Google ScholarCrossrefPubMed


More information: The U.S. National Institutes of Health has more on biotin.

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