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Are We Missing A Deeper Mechanism in Tissue Energetics?
Pediatric gastroenterologist Donald Mock, MD, PhD, of the University of Arkansas, believes that this research points to a fundamental mechanism by which biotin might help tissue energetics. Mock has a doctorate in biochemistry and a longstanding interest in water-soluble vitamins and health. He has written peer-reviewed papers about biotin and was an author on a 2015 paper with Sedel that discussed high-dose biotin, hypoxia, and MS.31
"It looks as if there may be neurologic conditions where there is impairment in energy transduction, in ATP production, in myelin synthesis, all of which may respond to biotin," says Mock. "There is something profound that these findings are trying to tell us," he continues. "I think if we pay enough attention, we may discover that nerve specific energetics are impacted by biotin."32 Mock says, for instance, that he is fascinated by a different study on biotin-responsive genetic basal ganglia disease.
The basal ganglia area of the brain is affected in diseases such as Parkinson's and Huntington's. In hereditary basal ganglia disease, symptoms can be severe and disabling, including marked confusion, difficulty swallowing, paralysis, and coma. Early treatment can halt the disorder. Ten patients in Saudi Arabia responded well to a combination of high-dose biotin along with thiamine. The researchers suggest renaming the disease biotin-thiamine responsive basal ganglia disease associated with SLC19A3 gene mutations.33 Overall, says Mock, "both this and the MS study suggest we take a closer look at these B vitamins and their effect on tissue hypoxia and energy metabolism."
Mock and other researchers note that although the supplement is well tolerated, further safety studies need to be carried out. In addition, 5 patients in the biotin group had apparent hypothyroidism, but it was due to high plasma biotin levels interfering with testing assays, producing misleading results. This could apply to other tests that involve similar assays which utilize (strept)avidin-biotin technology. It is suspected that a washout period of between 5 and 15 days would be necessary before utilizing tests based on this technology.24
Sedel emphasizes that biotin seems to help only in progressive MS patients, not in those who are in a relapsing-remitting phase: "Biotin doesn't help accelerate recovery after relapse, it only helps when you are progressive."21 He believes the vitamin works on the consequences of demyelination, and that it may also help genetic diseases of the myelin, such as adrenoleukodystrophy (a disease that became famous in the movie Lorenzo's Oil) and Charcot-Marie-Tooth disease.
Reframing multiple sclerosis – and perhaps other neurological conditions – as diseases that in part are due to hypoxia, impaired mitochondrial function, and faulty tissue energetics, opens a new way forward to novel treatments. In a 2009 paper, researchers at Oregon Health and Science University in Portland suggested that "evidence is evolving that mitochondria are key players in axonal degeneration in all stages of MS, playing crucial roles in energy metabolism and cell homeostasis. Anti-inflammatory agents do not completely prevent axonal injury and are largely ineffective in treating progressive MS … therapies that target mitochondria and enhance their functioning warrant investigation."3
Notes .pdf
Recommendations for Tests Using (Strept)Avidin-Biotin Technology
Various laboratory tests, including tests for thyroid function as well as cardiac, fertility, hormonal, bone metabolism, and more, may rely on (strept)avidin-biotin technology, and raised levels of biotin in the blood may possibly interfere with results. Here are important points to know.1,2
- In five reported cases, high doses of biotin likely affected results of thyroid function laboratory tests that used (strept)avidin-biotin technology.
- The amount of biotin that may interfere is variable across tests.
Some have an interference threshold at about 100 ng/mL of plasma biotin (meaning that below 100 ng/mL the results are not biased, and above 100 ng/mL results are biased), while the threshold can be as low as 5 ng/mL for other tests.
- Instruction manuals for some of the interfered tests indicated that, "In patients receiving therapy with high biotin doses (>5 mg/day), no sample should be taken until at least 8 hours after the last biotin administration."
- In the studies for progressive MS, biotin is given at 100 mg three times daily. Preliminary research indicates that after a washout period of between 5 and 15 days, a biotin plasma level <5 ng/mL is achieved, and the test can be safely taken. Research is ongoing.
References
1. Peyro Saint Paul L, Debruyne D, Bernard D, Mock DM, Defer GL. Pharmacokinetics and pharmacodynamics of MD1003 (high-dose biotin) in the treatment of progressive multiple sclerosis. Expert Opin Drug Metab Toxicol. 2016 Mar;12(3):327- 44. PMID: 26699811,
2. Personal communication with Delphine Bernard, PhD, Project Leader, R&D, Medday Pharmaceuticals, Paris, France, on June 9, 2016
Letter to the Editor of New England Journal of Medicine
Note: A letter in the New England Journal of Medicine on August 18, 2016, reflects the growing interest in biotin therapies. Three physicians – Sebastian Kummer, MD; Derik Hermsen, MD; and Felix Distelmaier, MD, of Heinrich Heine University Hospital in Düsseldorf, Germany – write the commentary. The authors note: "Apart from its administration in nutritional deficiency or nonmedical applications, biotin plays an important role in the therapy of several inherited metabolic diseases (e.g., biotin– thiamine–responsive basal ganglia disease and biotinidase deficiency). Moreover, biotin is frequently used as a supportive treatment in patients with disorders of mitochondrial energy metabolism." They then report on 6 children receiving high-dose biotin treatment in the context of inherited metabolic diseases, in which biotin interfered with thyroid function tests. This is a well known-phenomenon whose pharmacokinetics were discussed in detail in a paper in 2016 by Sedel and colleagues as well (see "Recommendations for Tests Using [Strept]Avidin-Biotin Technology," above).
The authors of the letter note, "After discontinuation of biotin treatment, interference with laboratory tests has been reported to disappear within 8 hours. In our patients, thyrotropin and thyroid hormone levels were normalized 24 to 48 hours after the discontinuation of biotin, whereas levels of anti–thyrotropin receptor antibodies took up to 7 days to normalize." Because biotin is such an important treatment modality for some conditions, the authors conclude, "It is crucial to increase the awareness of this problem in the medical community."
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