Biotin As A Treatment For Multiple Sclerosis (MS)

[haidut]

I posted a study some time ago showing that biotin dramatically increases CO2 production from glucose and as a result increases ATP levels several fold. It was an in vitro study and when I calculated the dosage I freaked out b/c my numbers were showing a human would need at least 200mg biotin to get that effect.
It seems that my calculations were not far off. This human study used 300mg daily dose of biotin in patients with MS and the results were so promising that 2 clinical trials are already underway.

http://www.ncbi.nlm.nih.gov/pubmed/25787192

"...CONCLUSIONS: These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going."

 

[jjhotcakes]

100-300 mg of biotin seems like a lot. In the abstract there's no mention of unwanted effects from high dose biotin (for an average of 9+ months), though given how common headache is reported on the web from biotin supplementation at 5 mg a day or even less, I sort of expect there should have been some reported unwanted effects. Haidut, do you have access to the full paper? Is there any mention of headaches or hypoglycemia or anything?

I'm particularly curious about this study because based on what they authors are speculating in the abstract, it seems that high dose biotin might be useful in some non-MS cases that may involve a similar etiology (if we knew what the etiology was, of course).

 

[haidut]

100-300 mg of biotin seems like a lot. In the abstract there's no mention of unwanted effects from high dose biotin (for an average of 9+ months), though given how common headache is reported on the web from biotin supplementation at 5 mg a day or even less, I sort of expect there should have been some reported unwanted effects. Haidut, do you have access to the full paper? Is there any mention of headaches or hypoglycemia or anything?

I'm particularly curious about this study because based on what they authors are speculating in the abstract, it seems that high dose biotin might be useful in some non-MS cases that may involve a similar etiology (if we knew what the etiology was, of course).

The paper is free, so you can read the whole thing here:
http://www.sciencedirect.com/science/ar ... 4815000061

There were no serious side effects. Biotin is considered extremely safe, very similar to riboflavin in terms of safety.
"... From these observations, the dose of 300 mg/day was thought to be associated with the best clinical response. In addition, the treatment appeared to be safe: transient diarrhea, the only minor adverse effect, was noted in 2 patients."

 

[jjhotcakes]

Interesting. I wonder why headache would be so commonly reported at 5 mg and no mention in the paper at 100+ mg. Surprisingly, they even went to 600 mg, though noted there was no noticeable benefit at 600 versus 300, but in some cases 100 mg was not as good as 300 mg.

Among the "other symptom improvements" 5 people had improvements in fatigue, which is of note. I would be interested in how they quantified that.

A couple of things things stood out that seem worth highlighting for anyone else reading this thread.
1. The results were apparently cumulative and not seen immediately. In fact, there's a note that in two people there was no observable benefit, but the authors suggest that it may have been due to the "short" term supplementation of *only* 8 months.
2. The authors mention that oral biotin supplementation appears to be 100 percent absorbed. That's interesting.

 

[haidut]

Interesting. I wonder why headache would be so commonly reported at 5 mg and no mention in the paper at 100+ mg. Surprisingly, they even went to 600 mg, though noted there was no noticeable benefit at 600 versus 300, but in some cases 100 mg was not as good as 300 mg.

Among the "other symptom improvements" 5 people had improvements in fatigue, which is of note. I would be interested in how they quantified that.

A couple of things things stood out that seem worth highlighting for anyone else reading this thread.
1. The results were apparently cumulative and not seen immediately. In fact, there's a note that in two people there was no observable benefit, but the authors suggest that it may have been due to the "short" term supplementation of *only* 8 months.
2. The authors mention that oral biotin supplementation appears to be 100 percent absorbed. That's interesting.

Well, we'll have to wait for the results of the clinical trial to find out how biotin helped. In the meantime, I still maintain that it is the big increase in CO2 and ATP that I posted about in the biotin thread for controlling blood glucose. But I may be wrong...

 

[paymanz]

and high dose biotin can effect vitamin b5 status in body,it blocks b5 actions.i read something about that a while ago.should be careful about that if use heavy doses of biotin i guess.

 

[haidut]

and high dose biotin can effect vitamin b5 status in body,it blocks b5 actions.i read something about that a while ago.should be careful about that if use heavy doses of biotin i guess.

I concur, this high dose was for treating a serious condition. Most people should do fine on the supplements available that are often in the range 1mg-5mg per pill.

 

[docall18]

I find Biotin causes acne for me. Maybe its due to reducing B5 which is often used to control acne.

 

[Such_Saturation]

Interesting. I wonder why headache would be so commonly reported at 5 mg and no mention in the paper at 100+ mg. Surprisingly, they even went to 600 mg, though noted there was no noticeable benefit at 600 versus 300, but in some cases 100 mg was not as good as 300 mg.

Among the "other symptom improvements" 5 people had improvements in fatigue, which is of note. I would be interested in how they quantified that.

A couple of things things stood out that seem worth highlighting for anyone else reading this thread.
1. The results were apparently cumulative and not seen immediately. In fact, there's a note that in two people there was no observable benefit, but the authors suggest that it may have been due to the "short" term supplementation of *only* 8 months.
2. The authors mention that oral biotin supplementation appears to be 100 percent absorbed. That's interesting.

Probably because 5mg needs a ***t ton of silicon dioxide.

 

[lexis]

http://www.gizmag.com/ccsvi-multiple-sc ... oni/13447/

 

[NathanK]

Has Ray ever spoken about Biotin?

 

[haidut]

post 102316 Has Ray ever spoken about Biotin?

Yes, he said that Warburg and Selye thought that biotin deficiency is a direct cause of cancer. He also said, that biotin, like thiamine can inhibit excessive glycolysis and act just like the anti-cancer chemical DCA.
http://members.westnet.com.au/pkolb/peat4.htm
"...Therapeutically, even powerful toxins that block the glycolytic enzymes can improve functions in a variety of organic disturbances "associated with" (caused by) excessive production of lactic acid. Unfortunately, the toxin that has become standard treatment for lactic acidosis--dichloroacetic acid--is a carcinogen, and eventually produces liver damage and acidosis. But several nontoxic therapies can do the same things: Palmitate (formed from sugar under the influence of thyroid hormone, and found in coconut oil), vitamin B1, biotin, lipoic acid, carbon dioxide, thyroid, naloxone, acetazolamide, for example. Progesterone, by blocking estrogen's disruptive effects on the mitochondria, ranks along with thyroid and a diet free of polyunsaturate fats, for importance in mitochondrial maintenance."

"...Heart failure, shock, and other problems involving excess lactic acid can be treated "successfully" by poisoning glycolysis with dichloroacetic acid, reducing the production of lactic acid, increasing the oxidation of glucose, and increasing cellular ATP concentration. Thyroid, vitamin B1, biotin, etc., do the same."

 

[miles]

If an ms sufferer were to try 300mg of biotin, does anyone know what the best source would be? Thanks. Miles

 

[haidut]

OK, as I suspected, my original guess that biotin helped MS through improvement in ATP levels and oxidative metabolism has turned out to be correct. This follow up study, confirmed the results of the first one and explained that the primary mechanism of action of biotin in MS is through improvement of cellular energy status.


http://www.sciencedirect.com/science/ar ... 0815300733

"...However, evidence suggests that, in MS patients, axonal ATP production is simultaneously compromised due to defects in their neuronal mitochondria (Dutta et al., 2006, Mahad et al., 2009 and Su et al., 2009). The resulting imbalance between energy supply and energy demand causes a state of ‘virtual hypoxia’ which may be the trigger for neuron degeneration (Luessi et al., 2012 and Trapp and Stys, 2009). If insufficient ATP is available for Na+/K+ ATPase to restore the membrane potential, the neuron will enter a state of depolarization characterized by a further influx of Na+. This state can activate the Na+/Ca2+ exchanger in reverse mode, leading to an increase in intra-axonal Ca2+ as Na+ ions are removed from the neuron (Trapp and Stys, 2009). Excessive levels of Ca2+ in the neuron can activate a number of Ca2+-mediated degenerative pathways (Trapp and Stys, 2009). In chronic MS lesions, axonal levels of Na+/K+ ATPase are decreased, which may exacerbate the state of membrane depolarization (Young et al., 2008)."

"...We hypothesize that treatment with high-dose biotin reverses this state of virtual hypoxia through its role as a cofactor for PC, MCC, and PCC. These three enzymes are central to aerobic energy production and generate intermediates for the tricarboxylic acid (TCA) cycle (Fig. 3) (Tong, 2013). All three of these enzymes are known to be expressed in astrocytes and neurons (Ballhausen et al., 2009 and Hassel, 2000)...By increasing the available intraneuronal pool of ATP, high-dose biotin may reduce demyelinated neural dysfunction and the adverse effects of hypoxia (Lazzarino et al., 2010 and Trapp and Stys, 2009)."

This is pretty exciting, since it suggests that biotin can be used to reverse tissue hypoxia. The brain is the most sensitive organ to hypoxia and if biotin can reverse hypoxia there it should be able to reverse it anywhere else. Hypoxia is one of the primary triggers of cancer and one of the main drivers of cancer growth. I posted a study earlier this year showing that reversing tumor hypoxia is a possible cancer treatment.
viewtopic.php?f=123&t=6067

The reversal of hypoxia in tumors was done by opposing adenosine, so it suggests using caffeine. The MS study suggests that biotin can do the same, so combining caffeine and biotin can be synergistic for hypoxic conditions. High doses of thiamine, niacinamide, riboflavin and aspirin also have been shown to reverse hypoxia.

Now the bad news. The companies that ran the MS studies have applied to the FDA for designating high-dose biotin as a drug called MD1003.
http://www.bioworld.com/content/meddays ... -iii-trial
"...MD1003, a concentrated, patented, formulation of biotin (vitamin H), administered orally at 300 mg per day, was well tolerated. One patient in the treatment arm committed suicide but that was not considered to be related to the drug. It also emerged that MD1003 confounded immunoassay tests that use biotinylated antibodies or substrates."

"...MD1003 is thought to have a twofold effect, activating acetyl-CoA carboxylases that are the rate-limiting enzymes in the production of fatty acids required for myelin synthesis, and also activating the Krebs cycle in axons that have been demyelinated, increasing their energy supply."

"...Assuming positive results, there will be sufficient data to file for approval in Europe. "For the FDA we would have to discuss whether there needs to be a U.S. study or [if it will be sufficient] to show the data we have are applicable to a U.S. population," said Sedel."

As far as I can see the application is likely to be successful, which will lead to the FDA forcing biotin vendors to further lower the dose per capsule available in supplements. The current legal maximum is 10mg per capsule, which is already low enough to be inconvenient for use in MS. When MD1003 officially becomes a new drug, the biotin capsules will likely be limited to no more than 1mg per capsule in order to make self-medication with biotin impractical and very costly. I don't know if this will affect the powder vendors, but given the recent FDA action against caffeine powder vendors I would not be surprised if biotin powder vendors suffer the same fate.

 

[Such_Saturation]

It seems like mitochondria need to be working well to be able to position themselves correctly inside neurons. This is also seen in Parkinson's disease models.

 

[haidut]

post 103104 It seems like mitochondria need to be working well to be able to position themselves correctly inside neurons. This is also seen in Parkinson's disease models.

Do you think biotin may be dopaminergic in addition to restoring TCA function?

 

[Such_Saturation]

post 103107

post 103104 It seems like mitochondria need to be working well to be able to position themselves correctly inside neurons. This is also seen in Parkinson's disease models.

Do you think biotin may be dopaminergic in addition to restoring TCA function?

I don't know about that, but there is something called "biotin-responsive basal ganglia disease" mentioned at http://www.mdsabstracts.com/abstract.as ... 7&id=99308 Basal ganglia diseases include Parkinsonism.

 

[Philomath]

OK, as I suspected, my original guess that biotin helped MS through improvement in ATP levels and oxidative metabolism has turned out to be correct. This follow up study, confirmed the results of the first one and explained that the primary mechanism of action of biotin in MS is through improvement of cellular energy status.


http://www.sciencedirect.com/science/ar ... 0815300733

"...However, evidence suggests that, in MS patients, axonal ATP production is simultaneously compromised due to defects in their neuronal mitochondria (Dutta et al., 2006, Mahad et al., 2009 and Su et al., 2009). The resulting imbalance between energy supply and energy demand causes a state of ‘virtual hypoxia’ which may be the trigger for neuron degeneration (Luessi et al., 2012 and Trapp and Stys, 2009). If insufficient ATP is available for Na+/K+ ATPase to restore the membrane potential, the neuron will enter a state of depolarization characterized by a further influx of Na+. This state can activate the Na+/Ca2+ exchanger in reverse mode, leading to an increase in intra-axonal Ca2+ as Na+ ions are removed from the neuron (Trapp and Stys, 2009). Excessive levels of Ca2+ in the neuron can activate a number of Ca2+-mediated degenerative pathways (Trapp and Stys, 2009). In chronic MS lesions, axonal levels of Na+/K+ ATPase are decreased, which may exacerbate the state of membrane depolarization (Young et al., 2008)."

"...We hypothesize that treatment with high-dose biotin reverses this state of virtual hypoxia through its role as a cofactor for PC, MCC, and PCC. These three enzymes are central to aerobic energy production and generate intermediates for the tricarboxylic acid (TCA) cycle (Fig. 3) (Tong, 2013). All three of these enzymes are known to be expressed in astrocytes and neurons (Ballhausen et al., 2009 and Hassel, 2000)...By increasing the available intraneuronal pool of ATP, high-dose biotin may reduce demyelinated neural dysfunction and the adverse effects of hypoxia (Lazzarino et al., 2010 and Trapp and Stys, 2009)."

This is pretty exciting, since it suggests that biotin can be used to reverse tissue hypoxia. The brain is the most sensitive organ to hypoxia and if biotin can reverse hypoxia there it should be able to reverse it anywhere else. Hypoxia is one of the primary triggers of cancer and one of the main drivers of cancer growth. I posted a study earlier this year showing that reversing tumor hypoxia is a possible cancer treatment.
viewtopic.php?f=123&t=6067

The reversal of hypoxia in tumors was done by opposing adenosine, so it suggests using caffeine. The MS study suggests that biotin can do the same, so combining caffeine and biotin can be synergistic for hypoxic conditions. High doses of thiamine, niacinamide, riboflavin and aspirin also have been shown to reverse hypoxia.

Now the bad news. The companies that ran the MS studies have applied to the FDA for designating high-dose biotin as a drug called MD1003.
http://www.bioworld.com/content/meddays ... -iii-trial
"...MD1003, a concentrated, patented, formulation of biotin (vitamin H), administered orally at 300 mg per day, was well tolerated. One patient in the treatment arm committed suicide but that was not considered to be related to the drug. It also emerged that MD1003 confounded immunoassay tests that use biotinylated antibodies or substrates."

"...MD1003 is thought to have a twofold effect, activating acetyl-CoA carboxylases that are the rate-limiting enzymes in the production of fatty acids required for myelin synthesis, and also activating the Krebs cycle in axons that have been demyelinated, increasing their energy supply."

"...Assuming positive results, there will be sufficient data to file for approval in Europe. "For the FDA we would have to discuss whether there needs to be a U.S. study or [if it will be sufficient] to show the data we have are applicable to a U.S. population," said Sedel."

As far as I can see the application is likely to be successful, which will lead to the FDA forcing biotin vendors to further lower the dose per capsule available in supplements. The current legal maximum is 10mg per capsule, which is already low enough to be inconvenient for use in MS. When MD1003 officially becomes a new drug, the biotin capsules will likely be limited to no more than 1mg per capsule in order to make self-medication with biotin impractical and very costly. I don't know if this will affect the powder vendors, but given the recent FDA action against caffeine powder vendors I would not be surprised if biotin powder vendors suffer the same fate.

I just bought a 250 gram bag of biotin just in case! I can't buy bulk powdered caffeine on Amazon anymore

 

[ken]

I just wanted to add that a friend has had that operation. She speaks highly of it. I believe she had it twice, but I don't remember why. I only see her occasionally,got married and moved away.

 

[haidut]

I just wanted to add that a friend has had that operation. She speaks highly of it. I believe she had it twice, but I don't remember why. I only see her occasionally,got married and moved away.

What operation? This thread is about biotin and MS.