Biotin Reduces Ammonia Levels In Brain And Blood

[haidut]

Rat study, but should be applicable to humans as well. Human equivalent dosage is about 20mg of biotin per day, which may seem very high to some. However, it has been shown to be safe in humans for up to a year administration and incidentally this is the dose used in humans to lower cholesterol and liver fat.

http://www.ncbi.nlm.nih.gov/pubmed/7647902

"...Blood ammonia levels after ammonia loading were lower, although not significantly, in the arginine glutamate-treated rats than in the biotin-treated animals. In mice also, increases in blood and brain ammonia levels after ammonia loading were prevented by the administration of biotin. The decrease in brain glutamate and aspartate after ammonia loading was lower and the brain glutamine level was higher in biotin-treated mice than in the controls. These findings indicate the protective effect of biotin against ammonia intoxication."

 

[tara]

Am I reading this right - does it say that more biotin -> higher (less decreased) glutamate and aspartate in brain than controls after ammonia loading?
I thought higher brain glutamate and aspartate were were associated with increased risk of exitotoxic damage? Why would we want them to be decreased less?

 

[Stryker]

The role of glutamine synthetase in the brain is to protect against excitotoxicity by converting excess ammonia and glutamate to glutamine.

However..

"Hyperammonemia could induce the formation of inducible NOS in astroglial cells, with the consequent NO formation, deactivation of GS and dawn-regulation of glutamate uptake. "

so to my understanding if biotin is protective against and lowers blood and brain levels of ammonia, NOS and therefore NO is reduced and GS isn't deactivated. GS Will convert more glutamate to glutamine.

Therefore high levels of ammonia will cause less of a decrease in brain glutamate through reduction of GS.

Biotin Treatment > Reduced ammonia > Reduced NOS > Reduced NO > More active GS > Less glutamate > Higher Glutamine

 

[kineticz]

I found I get really anxious and nightmares with biotin. Thoughts?

 

[haidut]

The role of glutamine synthetase in the brain is to protect against excitotoxicity by converting excess ammonia and glutamate to glutamine.

However..

"Hyperammonemia could induce the formation of inducible NOS in astroglial cells, with the consequent NO formation, deactivation of GS and dawn-regulation of glutamate uptake. "

so to my understanding if biotin is protective against and lowers blood and brain levels of ammonia, NOS and therefore NO is reduced and GS isn't deactivated. GS Will convert more glutamate to glutamine.

Therefore high levels of ammonia will cause less of a decrease in brain glutamate through reduction of GS.

Biotin Treatment > Reduced ammonia > Reduced NOS > Reduced NO > More active GS > Less glutamate > Higher Glutamine

Thanks for the info. If biotin can reduce NO, then it is becoming more and more interesting for a number of conditions. Btw, on one of my threads on biotin I posted a study showing that uniquely among all the vitamins known in clinical practice, biotin leads to elevated levels of ATP and CO2 as a result of dramatically improved glucose metabolism. Here is the thread.
viewtopic.php?f=10&t=5862

The study used 100 microMol biotin and was done in vitro. I can't seem to find any reliable data on humans that shows how much biotin needs to be ingested to get this concentration. However, the same group that published the study on biotin causing elevation in ATP and CO2 published several other studies in rats showing prevention of diabetes and reversal of glucose metabolism issues with human equivalent doses of 10mg-20mg per day for 4-8 weeks.
Even more interestingly, Peat once wrote that both Hans Selye and Albert Szent-Györgyi thought that cancer is essentially caused by persistent biotin deficiency. I can't find the direct quote but here is another article by Peat hinting at biotin being helpful:
viewtopic.php?t=1268
"...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."

I have no idea why Peat did not include cancer in the above list of condtions treatable by "poisoning" glycolysis, especially given that he mentions using DCA?!?! But we can make the connection.

What is known now is that biotin deficiency does result in highly upregulated aerobic glycolysis and inhibition of oxidative phosphorylation, manifested in high lactate and low CO2. So, essentially the Warburg Effect.
In summary, biotin supplementation leads to:

• 
  increased ATP
  increased CO2
  decreased lactate in serum, brain, liver and muscle
  restored insulin sensitivity and glucose tolerance
  direct prevention of developing diabetes (I don't know of another vitamin that has this effect)
  decreased NO
  decreased ammonia
  decreased glutamate
  decreased fatty acid synthase (an effect proposed by Peat to be a major factor behind aspirin preventing cancer)

The list probably goes on and on but even in its current form it is quite impressive. Maybe thiamine + biotin would be ultimately Peat supplement, assuming all problems stem from low CO2 and increased fatty acid oxidation...

 

[Peata]

Awesome. We need to compile a list of all the substances you and others have researched and list what effects they have like you did above = In summary, biotin supplementation leads to:

increased ATP
increased CO2
decreased lactate in serum, brain, liver and muscle
restored insulin sensitivity and glucose tolerance
direct prevention of developing diabetes (I don't know of another vitamin that has this effect)
decreased NO
decreased ammonia
decreased glutamate
decreased fatty acid synthase (an effect proposed by Peat to be a major factor behind aspirin preventing cancer)

A quick reference guide for all those things talked about on the forum.

 

[tara]

Thanks for the explanation Stryker and haidut.
I added biotin into my vit-B mix a few weeks ago. I'll keep it in for a while.

 

[Stryker]

personally breathing through my nose is very clear and deep after continuous large doses of biotin and a clear flowing feeling in the head like the opposite of a headache. Lactic acid buildup in the legs on an intense bike ride is also delayed.

i guess that correlates well with all the above mentioned mechanisms of action.

 

[Bluebell]

The list probably goes on and on but even in its current form it is quite impressive. Maybe thiamine + biotin would be ultimately Peat supplement, assuming all problems stem from low CO2 and increased fatty acid oxidation...

What kind of dosages of B1 and biotin might be good for long term use?

re. lactic acid production, I used to have a really big problem with this. I fixed this issue for the most part before starting biotin, but still I am glad to be taking biotin at 10mg, knowing that it's tweaking my body chemistry in the right direction. I think I am still prone to overproduce lactic acid.

I have also heard that biotin has an anti-fungal effect, for example in people with internal yeast problems that manifest as toenail fungus and other fungal infections.

 

[haidut]

The list probably goes on and on but even in its current form it is quite impressive. Maybe thiamine + biotin would be ultimately Peat supplement, assuming all problems stem from low CO2 and increased fatty acid oxidation...

What kind of dosages of B1 and biotin might be good for long term use?

re. lactic acid production, I used to have a really big problem with this. I fixed this issue for the most part before starting biotin, but still I am glad to be taking biotin at 10mg, knowing that it's tweaking my body chemistry in the right direction. I think I am still prone to overproduce lactic acid.

I have also heard that biotin has an anti-fungal effect, for example in people with internal yeast problems that manifest as toenail fungus and other fungal infections.

Most human studies used 2mg-10mg dosages. It's hard to say without getting some tests before and after taking some biotin to gauge its effects. Some people may need as high as 20mg+ and others would probably do well on <1mg daily.

 

[narouz]

I have also heard that biotin has an anti-fungal effect, for example in people with internal yeast problems that manifest as toenail fungus and other fungal infections.

That's very interesting, Bluebell.
I'd never heard that before.

 

[Peata]

I took 15 mg. Biotin a few hours ago and still enjoying those effects of sinus and head clearing, easier breathing and more energy. It is the same feeling I got when I took a lot of Ceylon Cinnamon.

 

[haidut]

I took 15 mg. Biotin a few hours ago and still enjoying those effects of sinus and head clearing, easier breathing and more energy. It is the same feeling I got when I took a lot of Ceylon Cinnamon.

Given the clearing of sinuses it could be the increase in CO2, which biotin also causes.

 

[Agent207]

Should we have to be coutious with biotin supplementation because the statement that isolated b vitamins can cause an imbalance between them? ist this true? and, in that case, happens with biotin too?

 

[Orion]

I took 15 mg. Biotin a few hours ago and still enjoying those effects of sinus and head clearing, easier breathing and more energy. It is the same feeling I got when I took a lot of Ceylon Cinnamon.

Found some 2500mcg biotin tonight, are you taking 15 x 1000mcg for example? How was today?

I realize that I took very small doses in the past that exacerbated acne quickly, I wonder if the mega doses will be different...

 

[Peata]

Found some 2500mcg biotin tonight, are you taking 15 x 1000mcg for example? How was today?

I realize that I took very small doses in the past that exacerbated acne quickly, I wonder if the mega doses will be different...

I took 15 MG at two different times yesterday.

Today I took 15 MG and had the same effect but I also started feeling a little bit nauseous, kind of a strange feeling not that different to when I first went on Metformin until I adjusted to it. So this afternoon I just took 5 MG (so that's a total of 30 MG yesterday and 20 today).

 

[Orion]

I took 15 MG at two different times yesterday.

Today I took 15 MG and had the same effect but I also started feeling a little bit nauseous, kind of a strange feeling not that different to when I first went on Metformin until I adjusted to it. So this afternoon I just took 5 MG (so that's a total of 30 MG yesterday and 20 today).

I will try 15mg per day over the weekend and report back. Skin has been doing very well in last few weeks, so hoping to have a additional positive effect and not backfire on me.

 

[Philomath]

I have no idea why Peat did not include cancer in the above list of condtions treatable by "poisoning" glycolysis

Ask Kevin Trudeau

 

[haidut]

Ask Kevin Trudeau

Well, I get the risk factor. But he does mention heart failure, shock, etc and they are actual conditions defined by FDA as diseases. So, if you risk to mention them why not mention the prime conditions associated with overproduction of lactate - i.e. diabetes, stroke, cancer, etc??
And unlike Trudeau, Peat is not selling a book containing a secret, proprietary mix of herbs on which no studies can be found.

 

[paymanz]

A biotin-coupled bifunctional enzyme exhibiting both glutamine synthetase activity and glutamate decarboxylase activity. - PubMed - NCBI

Abstract
PURPOSE:
To purify and study native form and enzymatic activity of the 42 kDa biotin-coupled protein (p42), which is related to glutamate action in chick retina.

METHODS:
p42 was purified using molecular filtration in the presence of 0.7 M sodium chloride. Purity and identification of p42 were studied by SDS-PAGE, 2D-PAGE, LC-MS/MS, and MALDI-TOF MS. The native form of p42 was investigated using native-PAGE and Ferguson plot. Biotin-coupled property was examined by Western blot analysis. Enzymatic actions of p42 were studied using glutamate as substrate in the presence or absence of glutamine.

RESULTS:
p42 was successfully purified from chick retinal protein solution using the molecular filtration. Western blot analysis with avidin showed that p42 was a biotin-coupled protein. Using SDS-PAGE, 2D-PAGE, LC-MS/MS, and MALDI-TOF MS, purified p42 was identified as a glutamine synthetase with four isoforms. Native-PAGE, followed by Ferguson plot analysis, showed two molecular forms of p42 corresponding to homotetramers and homooctamers. Enzymatic reaction followed by paper chromatography showed that p42 catalyzed the synthesis of glutamine from glutamate in the presence of ammonium ion, ATP, and magnesium ion. At prolonged reaction time, gamma-aminobutyric acid (GABA) was also formed. With glutamate and glutamine present at equal concentrations in the reaction mixture, GABA could be rapidly detected, but GABA could not be detected when glutamate concentration was more than four-fold that of glutamine. The results indicated that p42 also had glutamate decarboxylase activity. Both enzymatic activities were inhibited by avidin. High concentrations of Mn(2+) inhibited synthetase activity of p42 but not decarboxylase activity.

CONCLUSION:
p42 was purified from chick retinal protein solution using molecular filtration in the presence of sodium chloride. The protein was a biotin-coupled bifunctional enzyme that contained glutamine synthetase activity and glutamate decarboxylase activity. Biotin was possibly involved in these activities. Mn(2+) showed different effects on the two activities.