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Re: Creatine transporter deficiency

Posted: Sun Sep 03, 2017 4:05 pm
by Creatineman

α-Ketoglutarate is also a natural compound synthesized in a mammal as part of the Krebs cycle. It has high chemical affinity for nitrogen to reduce nitrogen overload and also for trans-amination, and plays a role in the prevention of ammonia toxicity. As an important intermediate in the Krebs cycle, α-ketoglutarate easily permeates muscle cell membrane and α-ketoglutarate has been a desirable tool to boost muscle energy. Furthermore, α-ketoglutarate is a co-catalyst by undergoing oxygenation alongside oxygenases, to permit oxygenation of various cellular targets. It is often a compound recommended to athletes. In contrast, in the present invention, α-ketoglutarate is utilized because of its remarkably high chemical affinity for nitrogen in general, but, particularly, for the guanidine-functional group from creatine. As described below, we were able to exploit this property of α-ketoglutarate in bioengineering an ionic-bonded creatine α-ketoglutarate vehicle for creatine to deliver the latter to the muscle against a pre-existing high concentration gradient barrier for dietary creatine.

Our interest in α-ketoglutarate was mostly because of its remarkably high chemical affinity to the nitrogen of the guanidinoacetate group of creatine. We were able to exploit this property of α-ketoglutarate to bioengineer an ionic-bonded creatine α-ketoglutarate delivering vehicle for creatine and be able to deliver above creatine at a level above that the level normally encountered by the body. Chemical analysis of clinical samples support the fact that increased creatine was available within a short time period after sublingual ingestion, after about ten minutes. Essentially twice of the normal level secreted is observed.

Most notably was the time required for the supplement to become effective. The product of the invention produced peak performance within as little as ten minutes after delivery. The other supplements required from 2-8 hrs before full benefits were seen
There was a relatively high distribution of (14)C-AKG in the tissues (e.g. liver, brain, bones, skin, muscles), 3 h after gavage, up to 70% of the administered dose.

In conclusion, the high rate of retention of the carbon from AKG allows the postulation that there is a non-energetic mode of metabolism of intragastrically administered AKG. After conversion to final metabolites, AKG penetrates into all tissues and organs of rats, including the bone tissue. Intestinal absorption of AKG does not depend on the type of AKG salt administered.

Creatine-Alpha-Ketoglutarate is alpha-ketoglutartae (AKG) added to a molecule of creatine to aid in absorption and uptake. Creatine-AKG is creatine bonded to a molecule of AKG, a precursor of glutamine, an essential amino acid required for muscle growth. AKG is absorbed by the intestines, which eliminates the possibility of gastrointestinal problems associated with other forms of creatine, such as creatine monohydrate. It also does not need the help of a creatine transporter to enter cells, but it taken directly into muscle cells. After the creatine is taken in, the remaining AKG is used as energy for the muscles by being converted into creatine phosphate.

Muscle and Fitness Magazine September 2006

I am stopping creatine phosphate which has not done anything after 3.5 weeks, and starting creatine AKG today.

Re: Creatine transporter deficiency

Posted: Wed Sep 20, 2017 5:33 pm
by auract
@Creatineman how did it go with Creatine-Alpha-Ketoglutarate? I'm looking forward to hearing about your experience!

Re: Creatine transporter deficiency

Posted: Wed Sep 20, 2017 10:41 pm
by Creatineman
auract wrote:@Creatineman how did it go with Creatine-Alpha-Ketoglutarate? I'm looking forward to hearing about your experience!

Hi Auract. I am still on it 2.5 weeks later. I am going to give it a good try of 4-6 weeks because the information in the patent makes it sound like it could actually work. Studies on arginine, and ornithine AKG say that when administered they have an effect that is not seen when arginine, and AKG or ornithine, and AKG are administered as a mixture meaning the A-AKG, and O-AKGs are making it to the cell intact. So that is more evidence creatine-AKG could work. AKG is used to detoxify ammonia so if it works, then it also has that beneficial effect if a child has a problem with ammonia or a urea cycle disorder.

I have sent the saliva away, so will know in a few more weeks if I have slc6a8. There is over 120 different mutations in the slc6a8 gene per Dr Joseph Clarke, Professor or Neurology at University of Cincinnati, and the one who patented cyclocreatine ( so there could be a lot of variability in severeness of phenotype. Though there is only one creatine transporter supposedly which means those 120 mutations are just effecting the transporters effectiveness by different amounts ie 50% loss of function, 99% loss of function, 25% loss of function, 100% loss of function etc. In some studies children with the disease have zero brain creatine but normal muscle creatine levels, and muscles are thought not to contain AGAT, and GAMT, so they can't make creatine so that finding does not make sense if there is truly only one creatine transporter. Maybe there is another one that works in conjunction with slc6a8 which hasn't been discovered yet... I don't know.

Joseph Clarke has an interview here:

There is a study on orphan drugs that mentions there is 42,000 males in the USA with the CTD in case someone is wondering because a lot of websites say the prevalence of it is unknown.

Taking the creatine AKG it does not feel as strong as whatever is in Muscletechs Creactor.... there's really not many forms of creatine that the "free acid creatine" in that could be. One of the few things it could be is cyclocreatine. There is a carbon nitrogen double bond in cyclocreatine that is not in normal creatine. There is a lab test that may even be able to be done at home to test for its presence but I am too sick to do it. Maybe if someone has a scientist friend they could ask if they would test it for carbon nitrogen double bond for 100$ or something. I got quoted 1000$ from a lab to do a test to find out definitively what it is but I don't really want to pay that because if it came back with cyclocreatine I would not be surprised anyway. On some websites on creactor they have an infograph saying the free acid creatine is 100% creatine by weight, comparing it to monohydrate which is 87% creatine by weight, 13% water. And on the bottle they say it is 'free of acids, and salts'. Assuming those statements are true then it can't be creatine-amino acid or creatine-fatty acid or creatine bonded to anything else. And Creactor does not dissolve well in water at all which is argument for it being a lipid/not water soluble. All those things point to it potentially being cyclocreatine. The reason I don't just take creactor is because I don't like taking something I don't know what it is, and if it is cyclocreatine it gives up a phosphate group to recycle ATP 160 fold slower than actual creatine so it is better to find a form of real creatine to treat it imo rather than cyclocreatine even though it would work. As they say here
"To conclude, an ideal Cr analog unfortunately does not exist"

And Muscletech sold something in the past that killed people which means they have no problem putting not just dangerous but lethal things in their products so I really want to know what it is in case it is dangerous... though if it is cyclocreatine it looks safe

"cCr has recently been evaluated in a phase I/II clinical study in terminal cancer patients. Safety and pharmacokinetic profiles were established (O'Keefe et al. and Schimmel et al., unpublished data). In a dose escalation study over a period of 10 wk, cCr was administered continuously by intravenous infusion at dose levels ranging from 10 to 150 mg/kg. Hypoglycemia and fluid retention were noted as dose-dependent and reversible side effects. The maximum tolerated dose was determined to be 80 mg/kg. No significant hematological, liver, or renal changes were observed. The good tolerance of high levels of cCr also in animal models and its unique mechanism of action make it a potentially attractive addition to cancer chemotherapy."

"Although guanidino compounds may have adverse effects on the nervous system in uremia, oral Cr (or cCr) supplementation is very unlikely to induce neurological complications in normal individuals, since only slight alterations in cerebrospinal fluid and brain concentrations of guanidino compounds may be expected. Cr and its analogs have been given to animals in high amounts and over several weeks and months with no neurological side effects. Likewise, oral Cr supplementation in humans with up to 30 g/day for several days as well as cCr administration in a phase I/II clinical study in gram amounts per day over an extended period of time also had no adverse neurological effects"

If all else fails there is always creactor to take...

The patent you linked on creatine-leucine looks good actually. I might buy that, and try it next if creatine-akg does not work. Dipeptides are well absorbed by the intestines, like up to over 90% in some studies, so if it made it through the stomach, and all our amide/peptide breaking bonds enzymes in the intestines in tact then it might work. Technically speaking creatine is not an amino acid, and it is an amide bond between creatine-leucine, but that same di peptide data can probably be applied to it. Same for creatine-amide bond to fatty acids.

So yes I thing the C-AKG so I will be staying on it. I will post back here when I get test results or when I get more better on the C-AKG. I bought it from my in case wondering.

Re: Creatine transporter deficiency

Posted: Thu Sep 21, 2017 4:11 pm
by auract
There is actually as second creatine transporter but it seems to be synthesized only in the retina.

There are also paralog genes where things get more complicated: ... 191301367X

Regarding the functioning of the transporter, the type of mutation does not easily correlate with the phenotype. For example, even a large deletion does not mean a severe phenotype and small mutations can be lethal to the entire transporter. For example, one base pair mutation may end up encoding an end of gene signal if in the right location. I suspect you're on to something though. It is possible that in some cases that go undetected, a partial transporter may lead to learning impairments that are not severe and definitely no seizures.

Have you seen this paper on fenugreek's effects on how the creatine is assimilated? I've been meaning to try it with monohydrate or glutamate but we're still having difficulties with administering the base formula for supplements ... 015-1145-1

Re: Creatine transporter deficiency

Posted: Thu Sep 21, 2017 9:11 pm
by Creatineman
Interesting thanks for those links. There is another creatine transporter in testis also ... 4396902542

There is a mild case of the transport defect here ... 480.x/full

We identified a 3-year-old male with CRTR deficiency referred for study owing to mild psychomotor retardation with independent walking acquired at 18 months and expressive language impairment. He never experienced epileptic seizures. Clinical examination revealed clumsiness in his gait and subtly abnormal hand movements.

After reviewing the clinical description of seven cases under the age of 4 years diagnosed previously,7,10,11,14,15 we conclude that our patient has a mild presentation of this condition with late-onset walking and no seizures or autistic behaviour

Lipoic acid increases creatine uptake also

I took both ALA, and fenugreek with no effects. Maybe AlA, and fenugreek only work in a normal person with functioning creatine transporters.

Re: Creatine transporter deficiency

Posted: Wed Sep 27, 2017 6:34 am
by Creatineman
Still have not got test results yet.
It is possible to make home made liposomal creatine. The instructions to make liposomal vitamin c are here just replace vitamin c with creatine monohydrate.

Re: Creatine transporter deficiency

Posted: Mon Oct 02, 2017 4:15 pm
by auract
Creatineman, what are your thoughts and have you tried any PCr-Mg-complex? Some papers speculate that this might bypass the CRT1 transporter.

Re: Creatine transporter deficiency

Posted: Thu Oct 05, 2017 4:26 am
by Creatineman
I don't know where to get that though, and yes I saw that paper. There is creatine magnesium chelate available which might be similar... but I thought that would only go through creatine, not magnesium transporters... I have been on the cre-akg for 4 weeks, and I don't think it has done much unfortunately. I will make the home made liposomal stuff soon, and see how that goes.

There is creatine nitrate also which seems interesting... it looks like the FDA didn't approve it at first because there was debate about wether or not it splits apart in water or the digestive tract, and if it doesn't split apart, then it is a "new dietary ingredient", and the patent holder thermolife was having problems getting that approval. ...

Here is ready made liposomal creatine: ... -creatine/

Re: Creatine transporter deficiency

Posted: Sat Oct 07, 2017 5:08 am
by Creatineman
Taking creatine nitrate for a bit not pyruvate anymore.

Re: Creatine transporter deficiency

Posted: Sun Oct 15, 2017 10:11 pm
by Creatineman

Magnesium Creatine Chelate

I think the main benefit of MCC doesn't have to do with buffering in the GI tract at all. Since its chelated it enters the cell through a different channel other than the sodium dependent tranporter which monohydrate uses. MCC utilizes a ligand-grated cation channel. ... elate.html

Creatine Mono uses sodium dependent transporters to enter the cell
MCC uses ligand-gated cation channel to enter the cell, ... onohydrate

The idea behind MCC is that by using a different transporter to get the creatine to the muscle cells, less is lost in transport and broken down into the waste product creatinine. ... e-chelate/

Creatine: Magnesium Creatine Chelate, often abbreviated MCC, is a newer form of creatine that is chemically bonded to magnesium rather than a water molecule as in creatine monohydrate. This special form of creatine is absorbed through a different pathway than creatine monohydrate. Creatine monohydrate is absorbed through a sodium-dependent transporter, while magnesium creatine chelate is absorbed through a lignand-gated cation channel. Because the magnesium that is bound to the creatine is a cation, the entire molecule now becomes a cation, making it absorbable through this pathway while creatine monohydrate is not. (1)

I am going to try this soon.

And about the home made lipsomal. Regular creatine might only be stable in water for a very short time- Jeff Golini says its half life conversion to creatinine is only 10 minutes which means making a liposomal several day batch of it wont work, and might even be dangerous because the liposome would carry the creatinine inside it into the cells. Creatine phosphate might be stable for longer in water, and if creatine magnesium chelate powder just taken normally orally doesn't work, that is probably stable in water for a while too, and so could be put in a liposome.

Re: Creatine transporter deficiency

Posted: Sun Oct 22, 2017 3:55 am
by Creatineman
Although creatine is not an amino acid the same absorption mechanisms for amino acid chelates can probably be applied to magnesium creatine chelate- which means it can make it into cells in tact through more than one mechanism. ... 69A6698B6A

Such amino acid chelates are absorbed intact into the mucosal cells and move, also intact, into the portal bloodstream where they are, because of their ligand makeup, transported to certain tissue sites. Upon reaching a selected site, they are either utilized intact or disassociated into mineral cations and free amino acids or dipeptides for utilization

Once absorbed, it is transported intact via a dipeptide transport mechanism to a specific site within the system where the metal ion and amino acid ligand portions are then utilized as needed.

I have been taking five grams three times a day... unfortunately any more than this causes diarrhoea. If that dosage is not high enough to fully treat the transport defect- though there will definitely be improvement on it- then it can be turned into the home made liposomal form.