Creatine transporter deficiency

Discuss autism diets and biomedical treatments of autism.

Moderator: ModeratorBill

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Sat Jul 08, 2017 6:05 am

/
Last edited by Creatineman on Wed Jul 19, 2017 5:56 am, edited 1 time in total.

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Mon Jul 10, 2017 2:04 am

I left a comment on the association for creatine deficiencies facebook page saying the transport defect is may be treatable with creatinol o phosphate, creatine glycerol phosphate, and creatine phosphate. Hours later the comment has been deleted, and I'm blocked from commenting on the page...
Last edited by Creatineman on Wed Jul 19, 2017 5:57 am, edited 1 time in total.

auract
Posts: 12
Joined: Thu Jun 15, 2017 3:46 pm

Re: Creatine transporter deficiency

Postby auract » Tue Jul 11, 2017 11:44 am

Creatineman, COP does not end up as creatine.

"Even after COP loses the phosphorus group, it metabolizes into creatinol and not creatine"

https://examine.com/supplements/creatinol-o-phosphate/

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Tue Jul 11, 2017 10:18 pm

/
Last edited by Creatineman on Wed Jul 19, 2017 5:57 am, edited 1 time in total.

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Wed Jul 12, 2017 5:01 am

/
Last edited by Creatineman on Wed Jul 19, 2017 5:58 am, edited 1 time in total.

auract
Posts: 12
Joined: Thu Jun 15, 2017 3:46 pm

Re: Creatine transporter deficiency

Postby auract » Wed Jul 12, 2017 4:19 pm

Creatineman, since you are self diagnosed have you looked into getting a measurement of your urine creatine to creatinine ratio. That seems to be a common panel for diagnosing creatine transporter deficiency and it doesn't have the same wait time as genetic testing or even MRS.

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Wed Jul 12, 2017 10:02 pm

I am sending a sample overseas for slc6a8 testing. It will take 5 weeks or so for the results.
Last edited by Creatineman on Wed Jul 19, 2017 5:58 am, edited 1 time in total.

atillathedan
Posts: 4
Joined: Fri Jun 02, 2017 2:13 am

Re: Creatine transporter deficiency

Postby atillathedan » Sun Jul 16, 2017 5:17 pm

Hi Creatineman-

from your post do I understand correctly that you are taking the creatine phosphates that you mentioned?

I would Loe to find something that will help my son but am obviously weary of giving him anything without a doctors sign off.

Also if you don't mind me asking, you mentioned that you are self diagnosed CTD - have you considered getting a metabolic screening to confirm? That is how our son was diagnosed.

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Wed Jul 19, 2017 6:08 am

I took COP for 2 weeks. I am always hopeful when I start a new form of creatine however now at the 2 week mark I don't think COP did anything. The reason I am only taking them for short term is this- months ago I took a product called creactor by company muscletech. There is 2 types of creatine in it- creatine HCL, and what they call on the label "free acid creatine the purest form of creatine free of acids, and salts". I took it for 4 days, and noticed a very positive difference in my health. After looking at the label, and seeing those 2 ingredients I thought it must be one of them that is working so I will buy, and take one of them so that I am not taking a 50/50 mix of them. I stopped the creactor, started taking creatine HCL, and deteriorated rapidly, which means it was not the creatine HCL that worked. I have been trying over the past 6 months to figure out what the "free acid creatine" in creactor is because I messaged the company on facebook to ask what it is, and they dodge the question everytime. So I have experimented with a number of different creatines over the past 6 months. I know I only have to try them for 2 weeks to know if they work because I noticed a difference within 4 days on creactor. The types of creatine I tried were- HCL, ethyl ester, anhydrous, HMB, malate, orotate, gluconate. All did nothing.

I sent an email to the FDA telling them muscletech has not labelled their product creactor properly. Hopefully the FDA investigates, and muscletech has to issue a statement saying what the chemical is. Muscletech sold a product called hydroxycut in the past that KILLED multiple people so they are known for being dodgy. Based on how strong the creactor product is I would not be surprised if it is cyclo creatine in there. I wanted to find a form of creatine to treat the disease that is not under patent though, and so is easier to get.

I am going to start on the creatine glycerol phosphate today. Based on metabolic nutritions email it will work. I will be sending a buccal swap away for slc6a8 testing soon.

Metabolic nutrition did not explain in the email how creatine glycerol phosphate crosses cell membranes without the transporter but this might be it

https://socratic.org/questions/why-does ... an-glucose

glycerol is lipid soluble so it diffuses by simple diffusion directly through the cell membrane while glucose is a polar molecule so it diffuses via facilitated diffusion which means it needs a channel protein to work and this means the surface area for the glucose to get in is less than the one for the glycerol. he glycerol has the whole cell membrane to pass through, while glucose has only the channel proteins which do no cover the whole membrane.

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Tue Jul 25, 2017 3:51 am

Here is some data on the % of things that CGP is by weight. The weight of each thing was just googled by "molecular weight of x" in case you want to do your own maths to confirm.

creatine 131 g/mol.

glycerol 92 g/mol

phosphate 95 g/mol

131+92+95=318 g/mol for CGP total.

131 / 318 times 100= 41% creatine by weight

92/318 times 100 =29% glycerol by weight

95/318 times 100 = 30% phosphate by weight


I will assume the following dose. Maybe less is needed maybe more. Assuming this works for me, which I won't know until I have been on it for weeks more, because I have only been on it 6 days, this is what I plan to take long run unless I think it can be lowered:

15g twice per day/ 30g a day total.
.41 times 30= 12.3g creatine
.29 times 30= 8.7g glycerol
.30 times 30= 9g phosphate

The following is just an assumption to work with. Maybe the bio availablity is lower, maybe it is higher:

Assume 50% of oral dose makes it across guts, into portal vein to liver, from liver, into blood = 15g, and then 50% of that makes it into cells =7.5g into cells. .41 times 7.5g= 3g of creatine into cells if the assumption is true. We only make 1-2g of creatine a day so that should be enough.

I have emailed them to find out how much lipoic acid, and other ingredients are in it which they have listed on the side but they don't have the quantity listed. I saw on a website that I can't find now it had it listed, and it was only 100mg lipoic acid per 10g serving, and small amount of the other minerals as well.

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Wed Jul 26, 2017 12:45 am

CGP would go through the glycerol transporter, and maybe a phosphate transporter also.


https://www.jstage.jst.go.jp/article/bp ... 4_785/_pdf

The aim of the present study was to kinetically characterize
carrier-mediated glycerol transport in the perfused rat small intestine to help in identifying the carrier involved
and to explore the possibility that the carrier might be used as a pathway for oral drug delivery and a target for
drug development.


https://www.jstage.jst.go.jp/article/bp ... 3_553/_pdf

Thus, the present study has provided in situ evidence for the
presence of an Na-dependent carrier-mediated transport system for glycerol in the rat small intestine. It would
be interesting to examine the possibility that the carrier-mediated glycerol transport system could be involved in
drug absorption and also that it could be used for oral drug delivery.


https://pubchem.ncbi.nlm.nih.gov/compou ... n=ATC-Code
Data from studies in humans and animals indicate glycerol is rapidly absorbed in the intestine and the stomach, distributed over the extracellular space and excreted.

Following absorbption from GI tract, glycerin is distributed throughout the blood.

Following oral administration, glycerin is rapidly absorbed from the GI tract, and peak serum concn occur with 60-90 min.

/HUMAN EXPOSURE STUDIES/ Ten men and four women were given glycerol orally at a dose calculated to result in an average daily intake of 24 000 mg/kg bw per day, for 50 days. No toxic effects were reported. The only effect was a slight tendency towards an increase in body weight.

so it is safe.



If this didn't work for me in 4-6 weeks, or even if I get better on it, I will try creatine decanoate also. Decanoic acid is extremely lipid soluble


The permeability of the blood-brain barrier to ... (14)C-labelled /decanoic acid/ was studied by injecting ... /decanoic acid/ into common carotid artery of rats, and decapitating the rat 15 sec later ... the uptake of decanoic acid was 88%.

Metabolism of capric acid is rapid; in humans given [1-14C]decanoic acid orally, about 52% of the radioactivity was recovered within 2.5 to 4 hr.

... Decanoic acid is very lipid sol; a log octanol/water partition coefficient of 4.09 is reported.

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Fri Jul 28, 2017 2:50 am

I found an even better form of creatine glycerol- tri creatine glycerol which is 81% creatine by weight

https://www.google.com/patents/US20110172306

I'm in the process of getting some from manufacturers in China.

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Fri Jul 28, 2017 1:53 pm

Some % of the creatine to glycerol ester bond will be hydrolysed by esterase enzymes in guts/liver/blood


https://sci-hub.cc/10.2165/00003088-198510050-00002


Phopshate absorption. Maybe the phosphate transporter can take in CGP or CP also though some of that will be destroyed in intestines-

http://www.ijkd.org/index.php/ijkd/article/view/345/176

http://derangedphysiology.com/files/Phy ... tments.pdf

I'm trying to figure out the optimal dosage for CGP or tri creatine glycerol or creatine phosphate...

Here is a few more treatments also


https://encrypted.google.com/patents/WO ... 09A2?cl=en

phosphocreatine-Mg disodium salt complex

Again I think it just the phosphate group that makes that compound able to enter cells without the transporter. They just made a fancy version of creatine phosphate so they can patent it.

https://sci-hub.cc/https://doi.org/10.1 ... 006.06.058

THE CREATINE TRANSPORTER MEDIATES THE UPTAKE OF
CREATINE BY BRAIN TISSUE, BUT NOT THE UPTAKE OF TWO
CREATINE-DERIVED COMPOUNDS

CrOBzl and PCr-Mg-CPLX

creatine benzyl ester breaks down into benzyl alcohol which may be a problem if taken every single day long term. but I will read more on it.

https://sci-hub.cc/https://doi.org/10.1 ... 009.06.009

In vivo neuroprotection by a creatine-derived compound:
Phosphocreatine–Mg-complex acetate



https://sci-hub.cc/10.2217/nnm.13.205

Dodecyl creatine ester and lipid
nanocapsule: a double strategy for
the treatment of creatine transporter
deficiency

https://sci-hub.cc/10.1021/jm400545n

Synthesis and Biological Evaluation of New Creatine Fatty Esters
Revealed Dodecyl Creatine Ester as a Promising Drug Candidate for
the Treatment of the Creatine Transporter Deficiency

This revealed a
structure-activity relationship: the longer the carbon chain is
the greater the entry in both brain endothelial and astroglial
cells. The compound showing the most interesting properties
was the dodecyl creatine ester, whereas the shortest carbon
chains (ethyl to octyl) displayed limited diffusion through cell
membranes. The octadecyl creatine ester was detected in brain
endothelial cells but not in astroglial cells, indicating that it was
probably stuck into the endothelial phospholipid bilayer


These experiments show that the incorporation of creatine
fatty esters in endothelial, astroglial, and neuronal cells depends
on the length of the carbonyl chain. We sought a new
therapeutic strategy for creatine transporter deficiency, using
experiments with the pathological model. Human fibroblasts
from patients with cerebral creatine deficiency caused by a
transporter deficiency were used to investigate whether the
dodecyl creatine ester could enter the cells even if it could not
be taken up by the SLC6A8 transporter. Creatine content in
the fibroblasts was increased, especially in the pathological
fibroblasts when treated by dodecyl creatine ester. This
demonstrated that the dodecyl can be acted up by cellular
esterases, which we demonstrated are active in these cells, and
replenishes the creatine content in these cells. Interestingly, the
ethyl creatine ester was not able to penetrate the cells and so
did not increase creatine content. This suggests that on the
basis of published observations,16,17 ethyl creatine ester is not
an effective drugable compound because of its poor cell
membrane permeability. In contrast, dodecyl creatine ester is a
good candidate for development as a treatment option in
patients with creatine deficiency transporter

However, further investigations are needed for the protection
of dodecyl creatine ester chemical structure from the
degradation by plasma esterases. A vehicle approach such as
the use of Lipid NanoCapsules (LNC) would be a suitable way
to cross the BBB and deliver dodecyl creatine ester into the
parenchyma target cells. Besides a nanovector approach, further
strategy such as the improvement of the chemical template, e.g.,
exploiting the chemical properties of the cationic guanidine to
induce the self-assembly of dodecyl creatine ester could be also
considered. To treat the creatine transporter deficiency, the
challenge will be to protect the dodecyl creatine ester from the
degradation in biological fluids, deliver it through the BBB, and
improve neuronal creatine and phosphocreatine to restore the
neuronal functionality


So octadecyl (8 carbon fatty acid) bonded to creatine via ester bond was not fat soluble enough to pull the creatine into the cell with it, but 12 carbon fatty acid was (they call it dodecyl but the common name is lauric acid). Creatine fatty acids can be bought from the manufactuers so this is another potential treatment.

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Sun Jul 30, 2017 8:44 am

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278747/

Naturally occurring phosphate in food is organically bound, and only 40% to 60% of it is absorbed in the gastrointestinal tract

So that would include creatine phosphate which is kind of proof it goes through the phosphate transporter instead of the creatine transporter because patents say creatine mono is 14% absorbed from the intestines, and one study says mono is 1/5 of 1% to 3% absorbed lol.

https://sci-hub.cc/10.1111/j.1525-139X.2007.00309.x

Phosphate is absorbed in the small intestine both by
passive paracellular diffusion along an electrochemical
gradient and actively across the cells by the luminal
sodium phosphate cotransporter type 2b (1). This transporter
is very similar to the sodium phosphate cotransporters
found in the renal tubules and is also stimulated
by 1,25(OH)2 vitamin D. Nicotinamide is a well-known
inhibitor of these transporters (2) and the oral administration
of nicotinamide to hemodialysis patients has
been shown to produce a significant reduction in serum
phosphorus levels (3). The same effect reducing serum
phosphorus concentration has been recently shown with
oral nicotinic acid, which gets converted to nicotinamide
inside the body (4).

This is the label of a creatine phosphate supplement by biotech

http://www.pps-shop.fi/images/kuvat/phospSF.jpg

Niacin =nicotinamide. O_O

Edit: A bottle of biotech creatine phosphate arrived to me today in the mail, and it says on it creatine monohydrate 60%, potassium phosphate 38.5%. I emailed biotech to ask if it is creatine phosphate or just a mix of the two, and they said it is a mix...but I'm not sure.... I have ordered some creatine phosphate from a manufacturer in China. I have been on CGP for almost 2 weeks, and it appears to be working. I want to find out if it is the creatine phosphate part, or if it is the creatine glycerol part that is working so I will try CP on its own.

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Fri Aug 11, 2017 8:41 am

So I have been on CGP for a bit over 3 weeks. Based on the assumption it was creatine phosphate, as it exists in the body,, and with an additional ester bonded glycerol to the creatine, I expected to have felt more by now, because I expected creatine phosphate to be able to go through phosphate transporters. I had been contemplating that it was not actually creatine phosphate but couldn't find the structural diagram of it; until just now:

http://www.chemicalbook.com/ChemicalPro ... 25291.aspx

It is NOT creatine phosphate as it exists in the body. Creatine phosphate as it exists in the body has a phosphate nitrogen acid anhydride bond, which has a high bond energy, and best I can tell can only be broken by creatine kinase enzyme which exists mainly in the cell, a little in the blood too. Maybe some will get broken down by stomach acid also. Creatine glycerol phosphate is creatine ester bonded to glycerol ester bonded to phosphate, and we have esterase enzymes all through out our guts ... I messaged the company to ask them this but they never responded. So it is just another gimmicky form of creatine. I ordered some creatine phosphate from China but it has not arrived yet. If someone (or their kid) wants to take creatine phosphate; the predominate type of creatine in the body, and that can hopefully go through phosphate transporters, then they may have to buy it from the manufacturers on Ali Baba. Bio tech said their creatine phosphate supplement is just a mix of creatine monohydrate, and potassium phosphate though I have a feeling they are lying about it, and it is actually creatine phosphate.

There is someone on ebay USA selling 5kg of it but they wouldnt ship to Aus which is why I didn't get it but if someone else wants some that would be easier than getting it from Ali Baba. Or I would sell 1kg of the stuff I ordered once it arrives.

auract
Posts: 12
Joined: Thu Jun 15, 2017 3:46 pm

Re: Creatine transporter deficiency

Postby auract » Thu Aug 24, 2017 2:02 am

Thanks for posting the updates! It's very useful to see your experimentation.

There was a new parent that tried to tackle the solubility of all these creatine compounds


https://www.google.com/patents/US9642825

Did you end up doing the blood test or genetic test?

auract
Posts: 12
Joined: Thu Jun 15, 2017 3:46 pm

Re: Creatine transporter deficiency

Postby auract » Thu Aug 24, 2017 2:04 am

@atillathedan I tried sending a direct message on this board. It seems we are in similar boats w our kiddos so it would be great to compare notes.

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Sat Aug 26, 2017 3:31 am

Creatine phosphate didn't work.
Last edited by Creatineman on Sun Sep 03, 2017 8:49 pm, edited 2 times in total.

auract
Posts: 12
Joined: Thu Jun 15, 2017 3:46 pm

Re: Creatine transporter deficiency

Postby auract » Mon Aug 28, 2017 5:40 pm

Sharing the studies on cyclocreatine would indeed be super helpful. Thanks!

Creatineman
Posts: 40
Joined: Tue Jun 13, 2017 7:13 am

Re: Creatine transporter deficiency

Postby Creatineman » Thu Aug 31, 2017 8:39 am

creatine analogs

https://www.dropbox.com/sh/e62ezt4eqe8g ... TLaZa?dl=0

and some other studies

https://www.dropbox.com/sh/a33scukzzfze ... Cw7_a?dl=0

And I have a folder with stacks on GAMT, AGAT, and the CTD but it is on my hard drive which I don't have with me atm. I can upload them when I get it.


Return to “Diet and Biomedical Treatments for Autism”