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Creatine as a way of reducing demand for SAMe

mgk

Senior Member
Messages
155
The examine.com page for creatine says:
Creatine is involved indirectly in whole body methylation processes. This is due to creatine synthesis having a relatively large methyl cost, as the creatine precursor known as guanidinoacetate (GAA) requires a methyl donation from S-Adenosyl Methionine (SAMe) in order to produce creatine. This may require up to half of the methyl groups available in the human body.[33][120]

Creatine supplementation will downregulate the body's own production of creatine by suppressing the enzyme which mediates the above conversion (Guanidinoacetate methyltransferase or GAMT)[121], and because of this it is thought that SAMe gets backlogged and is more available for other processes that require it.

Has anyone tested this? It's especially appealing since creatine prices are much lower than a lot of the other supplements we're taking, probably owing to the fact that it's so popular with body builders.
 

drob31

Senior Member
Messages
1,487
I've been taking creatine non-stop for a while, and honestly it feels like I'm partially over methylated. MB12 makes me feel tired, but methylfolate seems to give me energy. I'm not sure what to make of it.
 

mgk

Senior Member
Messages
155
I've been taking creatine non-stop for a while, and honestly it feels like I'm partially over methylated. MB12 makes me feel tired, but methylfolate seems to give me energy. I'm not sure what to make of it.
If this creatine theory is correct, I think you would have a greater neurological response per unit dose of the methylation supplements compared to someone who isn't supplementing with creatine since more of the methylation byproducts would be used for purposes other than replenishing creatine.

What doses of mb12 and mfolate are you taking? Also have you started adb12 and LCF yet?
 

Gondwanaland

Senior Member
Messages
5,092
Would this - higher creatin endogenous synthesis - be the reason why some people (myself, @Sidereal ) get high uric acid from methylation? Of course there is a glitch down that path causing uric acid accumulation (lead?).
 
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Sherpa

Ex-workaholic adrenaline junkie
Messages
699
Location
USA
I have tried supplementing with low doses (500mg) of Creatine MagnaPower occasionally... and it seems to support muscle recovery during exertion.
 

mgk

Senior Member
Messages
155
Would this - higher creatin endogenous synthesis - be the reason why some people (myself, @Sidereal ) get high uric acid from methylation? Of course there is a glitch down that path causing uric acid accumulation (lead?).
I think it's one of the reasons. Take a look at this study (emphasis mine):

Relation between creatinine and uric acid excretion.
The relation between creatinine and uric acid metabolism was analysed in 77 male patients with primary gout and 62 healthy male subjects. Significant positive correlations between 24 hour urinary creatinine and uric acid excretion were shown in both groups. The mean urinary creatinine and uric acid excretions in the patients with gout were significantly increased as compared with those of normal male controls. These results suggest that there is a close correlation between creatinine and uric acid synthesis. In addition, it seems that accelerated uric acid synthesis seen in some patients with gout is due to increased creatinine synthesis.

One possible mechanism for this association is the increased supply of creatine from the diet. This exogenous creatine is subsequently metabolised to creatine phosphate, then creatinine. The phosphate donor is ATP. Increased degradation of ATP has been shown to cause accelerated urate synthesis.

Another possible mechanism for the association between creatinine and uric acid synthesis is endogenous creatine synthesis, by methylation of guanidinoacetic acid. In this reaction S-adenosylmethionine is converted to S-adenosylhomocysteine, which is then catalysed to adenosine. Accelerated creatine synthesis may cause increased synthesis of adenosine, which is degraded subsequently to inosine, hypoxanthine, xanthine, and uric acid.

If I understood this correctly, even if creatine supplementation would reduce endogenous creatine synthesis, it may not reduce uric acid levels because dietary creatine intake also ends up creating uric acid. I don't know if one reaction creates significantly less uric acid than the other though. That's an interesting question.
 
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mgk

Senior Member
Messages
155
I think I might skip this supplement since I already have enough genes against my kidneys and don't want to wake them up :eek:
Thanks for bringing this up. There seem to be conflicting reports about it on different sites. Even the wiki page seems to be all over the place:
There are reports of kidney damage with creatine use, such as interstitial nephritis; patients with kidney disease should avoid use of this supplement. In similar manner, liver function may be altered, and caution is advised in those with underlying liver disease, although studies have shown little or no adverse impact on kidney or liver function from oral creatine supplementation. In 2004 the European Food Safety Authority (EFSA) published a record which stated that oral long-term intake of 3g pure creatine per day is risk-free. The reports of damage to the kidneys by creatine supplementation have been scientifically refuted.

Regardless, I think we can all agree that if you have kidney issues, it would be prudent to consult a doctor before trying it.

I also want to mention that a lot of these reports are addressing creatine use for athletic performance enhancement, which calls for doses much higher than what you would find in a typical diet. The recommended dose is usually 5g/day, which is the amount you would get from eating about 2 pounds of beef (~1kg).

For our purposes, reducing the demand on SAMe, we're talking about much lower doses. According to this article, estimates put creatine intake from food at about 1g for men and 0.6g for women. That covers about half of the body's daily creatine needs. The other half needs to be synthesized. So supplementing with even 500mg (1/10 the recommended dose) could reduce SAMe demand significantly.
 
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melamine

Senior Member
Messages
341
Location
Upstate NY
I felt overly-cautious when trying creatine because of previous chronic kidney disease (CKD). I was reading on another thread here that mild CKD is considered yet another possible associated condition of ME. Like others, mine has varied. The year it was first tested it was mild to moderately reduced. It came into normal range a year or two later and has pretty much stayed there, though probably in the borderline area of normal.

To the extent that I had experimented with creatine I never noticed any effect.
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
Here is what the tried-and-true creatine monohydrate experience is like out in the normal world:
Normal daily dose is 5g, but you can start with a divided loading dose of 20g/day or so. You take it on an empty stomach with something to provoke an insulin response, like sugar (grape juice was traditionally recommended).

It needs to be thoroughly dissolved in hot water, else creatine crystals get unabsorbed by you - but they can get utilized by colon bacteria which create gas. The longer it then sits, the more turns to creatinine, which is why there shouldn't be premade drinks (but such drinks are sold if people will wrongly buy them).

Drink with lots of water to avoid headaches. For 2 days or so, you notice nothing much. The next day you might gain a pound of water. The day after that, maybe two pounds. All in all, a ~200 pound person might gain 7-10 pounds of water in a week, which is intracellular so BP should not rise. You also get noticeably stronger, maybe by 5-10%.

People who don't gain the weight are non-responders or else they hadn't taken it correctly, or have not taken enough.

More expensive forms have consistently proven to have no extra benefit, except for generating money for the sellers.
 

mgk

Senior Member
Messages
155
I found a study on this which suggests that it actually works, though the dose they used is higher than I guessed.

Oral creatine supplements lower plasma homocysteine concentrations in humans.
OBJECTIVE:
To determine if oral creatine supplements will lower the concentration of total plasma homocysteine (tHcy).

SETTING/PARTICIPANTS:
Apparently healthy volunteers, at least 19 years old, were recruited from the University of South Alabama and surrounding community. DESIGN/INTERVENTION/MAIN OUTCOME: Participants took multi-vitamins daily for four weeks, then were randomly divided into two groups. The control group (C) continued to take multi-vitamins daily for an additional four weeks. The experimental group (EX) took multivitamins plus an amount of creatine each day equal to twice their daily creatinine excretion, for the additional four weeks. Total plasma homocysteine concentrations were measured in all participants at the beginning and at the end of the second four week interval.

RESULTS:
There were no statistically significant differences between the two groups in age, initial tHcy, serum folate, erythrocyte folate, serum vitamin B12, or creatinine excretion. After four weeks of creatine supplements, tHcy in EX changed by an average of -0.9 micromol/L (range: -1.8 to 0.0), compared to an average change of +0.2 micromol/L in C (range: -0.6 to 0.9) during the same four weeks. The difference in the changes in tHcy between the two groups was statistically significant (p < 0.01).

CONCLUSION:
Creatine supplements may be an effective adjunct to vitamin supplements for lowering tHcy.

I couldn't find the actual amount of creatine they took in grams, but based on this page, the normal range of creatinine excretion is about 1000mg-2000mg for men and 700mg-1300mg for women. So in the study they probably supplemented about 2000mg-4000mg for men and 1400mg-2600mg for women.
 
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Critterina

Senior Member
Messages
1,238
Location
Arizona, USA
I have not tested this, but my own response to 5 g creatine once or twice a day (following lab results showing lower than usual creatinine) was an 18% increase in physical performance after 5 days of supplementation. I was used to doing a loop course in Southern California, up one canyon, across a ridge, and down another canyon, 5.1 miles. And since I was participating in a fitness/wellness program at work, I knew it was reliably 100 minutes, with almost no variation. After 2 days, I did it in 88 minutes. After 5 days, in 82 minutes.
I have the MTRR +/+ in my signature, and the BHMT 08 +/+, so in terms of methylation, I have a double-whammy affecting my production of Me/SAMe. I'm not saying that my lack of SAMe led to a lack of creatine, and therefore a lack of methylation products (and obviously muscle power), but you could probably weave a plausible story out of it. Also, I didn't notice the water gain, but there was a drastic improvement in my performance.
 
Messages
516
I was hoping it would do something for brain fog etc. at the time, but it only helped with exercise tolerance. This was a few rounds of micronized creatine (only bought because pharmaceutical grade). I'm interested in the idea it could relieve methylation but looks subtle. Was interesting in it again because bodybuilders suggest it synergizes with d-ribose for ATP. Seems like a perfect substance for CFS on paper but then there's reality.