This is a review of the recent research from 2015 and 2016 which shows that the vitamin biotin, at high doses, may have a role to play in progressive MS. You may listen to this as a podcast here.
Personally, I do not have any direct clinical experience of the use of biotin but I have already recommended it to my patients who have MS of the progressive kind. When I or any colleagues of mine have any positive outcomes to report, we can share this via another podcast.
Thanks to the work of neuroscientist Dr. Frédéric Sedel and his team it has been discovered that a higher than normal dose of biotin can help myelin synthesis in progressive MS.
Frédéric Sedel, MD, PhD, is co-founder and Chief Executive Officer (CEO) of MedDay Pharmaceuticals. He is a trained neurologist and neuroscientist who studied Inborn Errors of Metabolism (IEM) with the legendary Jean-Marie Saudubray at the Necker Children’s Hospital in Paris. He has published 80 peer-reviewed articles, mostly dedicated to IEMs in adult neurology, and has spoken at more than 30 leading international conferences over the last 5 years.
Frédéric Sedel maintains that it is entirely rational to consider supporting biochemical pathways in those with IEMs. He describes how errors of metabolism might include fatty-acid β-oxidation defects, or involve key cofactors such as biotin as well as thiamine, riboflavin, vitamin E and coenzyme Q10; while errors of intoxication might include porphyrias, urea-cycle defects, homocystinurias, and more.
Carboxylase & Carboxyl Groups
A Carboxyl Group is the univalent radical -COOH; present in and characteristic of organic acids.
Biotin is involved in carboxylase reactions, which is to say that it acts as a catalyst to add carboxyl groups or catalyzes the release of carbon dioxide from the carboxyl group of certain organic acids.
In other words, biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis.
In Sedel’s clinical study in 2015[i], 23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (average of 9.2 months).
In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two patients exhibited progressive reappearance of P100 waves, with normalisation of latencies in one case. Proton magnetic resonance spectroscopy (H-MRS) in one case showed a progressive normalisation of the Choline/Creatine ratio. One patient with left homonymous hemianopia (is the loss of half of the field of view on the same side in both eyes) kept on improving from 2 to 16 months following treatment onset. These are all markers of improvement.
Sixteen patients out of 18 (89%) with prominent spinal cord involvement were considered as improved as confirmed by blinded review of videotaped clinical examination in 9 cases. In all cases improvement was delayed from 2 to 8 months following treatment onset.
These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. As a result of this study’s success, two double-blind placebo-controlled trials are on-going, and one of which is reported on below.
A second published paper, led by Dr. Frédéric Sedel arrived at these conclusions[ii].
- High-dose biotin is a promising novel treatment for progressive multiple sclerosis.
- 300 mg biotin daily improved MS-related disability in an open-label study.
- Biotin is essential for fatty acid synthesis and energy production.
- High-dose biotin may promote axonal remyelination by enhancing myelin production.
- High-dose biotin may also reduce axonal hypoxia through enhanced energy production.
Another group of researchers have also identified biotin as one of a number of nutrients of potential benefit in progressive forms of MS[iii].
The nutrients include antioxidants (idebenone) & lipoic acid, sunphenon epigallocatechin-3-gallate (green tea extract) as well as biotin.
In 2016 a paper was published on one of the two double-blind placebo-controlled trials mentioned above. [iv] High dose biotin was used in 154 progressive MS patients and benefits were confirmed in terms of reversing or stabilising disability progression, and it had a good safety profile.
It is proposed that biotin in progressive MS
1) increases energy production in demyelinated axons and/or
2) enhances myelin synthesis in oligodendrocytes. Biotin is highly bioavailable; absorption and excretion are rapid.
A good question to ask is “why don’t normal doses of biotin work? And how was it that 300 mg was found to be the ideal dose?” Dr. Frédéric Sedel has the answer.
He describes that one way to activate a defective pathway is to use very high dose of co-enzymes. 300 mg a day turned out to be the dose which had the best efficacy. When Sedel and his co-workers decreased the dose to 100 mg daily the effect was decreased, or completely vanished.
When the dose was increased to 600 mg a day it was not well tolerated by patients. They experienced anxiety and tremor, so the dose was clearly too high. That’s very empirical, but 300 mg a day works nicely. In addition, Sedel’s studies indicate that 300 mg is already near the plateau of maximum absorption. It is probably both the highest dose that can be absorbed and also well tolerated.
Biotin has no effect on inflammation, but it probably has a very profound effect on axonal metabolism, and that must be the major route through which biotin works in progressive MS,[v] says Sedel.
Typically supplements contain microgramme doses of biotin. It would be nigh on impossible to obtain the daily 300 mg from existing products on the market. However, Allergy Research Group have followed this research closely and have now made available a product which provides 100 mg per capsule, to be taken three times a day, called “Hi Biotin”.
Pioneers need to be recognised for their dedication & commitment in discovering new, and safe, means by which to help support challenging conditions for which there is no cure. Dr. Frédéric Sedel & his team are just that.
I believe that we are going to be hearing more about high dose biotin, … and you first heard about it here.
Thanks for listening. Until the next podcast.
[i] Sedel F, Papeix C, Bellanger A, Touitou V, Lebrun-Frenay C, Galanaud D, Gout O, Lyon-Caen O, Tourbah A. High doses of biotin in chronic progressive multiple sclerosis: a pilot study. Mult Scler Relat Disord. 2015 Mar;4(2):159-69. doi: 10.1016/j.msard.2015.01.005. Epub 2015 Jan 24. View Abstract
[ii] Sedel F, Bernard D, Mock DM, Tourbah A. Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis. Neuropharmacology. 2015 Sep 5. pii: S0028-3908(15)30073-3. doi: 10.1016/j.neuropharm.2015.08.028. [Epub ahead of print] View Full Article
[iii] Shirani A, Okuda DT, Stüve O. Therapeutic Advances and Future Prospects in Progressive Forms of Multiple Sclerosis. Neurotherapeutics. 2016 Jan;13(1):58-69. doi: 10.1007/s13311-015-0409-z. View Abstract
[iv] 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. doi: 10.1517/17425255.2016.1136288. Epub 2016 Feb 17. View Abstract
[v] Sedel F, Bernard D, Mock DM, Tourbah A. Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis. Neuropharmacology. 2015 Sep 5. pii: S0028-3908(15)30073-3. doi: 10.1016/j.neuropharm.2015.08.028. [Epub ahead of print] View Full Article