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I have the following facts:

  • It is possible to convert ATP <-> creatine vice-versa. (ref - non scientific)
  • CP supplementation protects against metabolic syndrome. ref1 ref2
  • Fructose digestion depletes NADH via TG synthesis. ref

I assume that CP supplementation regenerates not just ATP, but NADH, if it is depleted, and so it restores the redox balance in the liver. Both ATP and NADH are similar energy storing molecules, so I guess there is a biochemical pathway which converts ATP to NADH, or there is a pathway, which regenerates NADH using CP. Am I right, if so, which pathway is it?

note:

I might be wrong. From one of the references:

Taken together, this study provides direct evidence that creatine reduces lipid accumulation in hepatocytes by the stimulation of fatty acid oxidation and TG secretion.

So maybe ATP is enough to prevent TG accumulation in the liver.

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Creatine itself is never converted into ATP. Creatine-phosphate on the other hand can donate its phosphate group to ADP, phosphorylating to form ATP and creatine. This is a buffer system for high-energy phosphates, and is very important in organs with rapid ATP turnover, notably muscle.

The mechanism of the findings described in the papers is not fully understood yet I think. But it is not via ATP, because the supplementation is not creatine-phosphate, but creatine itself, which does not yield ATP.

Regarding NADH: ATP is very different from NAD/NADH in terms of molecular structure, and the two are not interconverted by any pathway that I know of. (Probably this is not what you meant, but just to be clear.) But it is certainly true that reducing power in the form of NADH can be used to phosphorylate ADP into ATP; this is the task of the mitochondrial respiratory chain, where NADH is oxidized to NAD by complex I. On the other hand, I am not aware of a physiologically relevant process that uses ATP to reduce NAD into NADH.

The liver is a main site of synthesis of creatine itself, and this syntesis consumes methyl groups donated by the S-adenosylmethionine system. The authors of your ref1 seem to suggest that reduced synthesis of creatine following supplementation is a possible mechanism. Similar effects have been observed with choline supplementation, but again this effect is not well understood and a current research topic. A recent review is found here.

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  • $\begingroup$ Creatine supplementation maybe increases the high energy phosphate reservoir. By "stimulation of fatty acid oxidation" I think they mean that the hepatocytes degrade fatty acids to produce energy for the conversion of creatine into creatine-phosphate. It would be interesting to check the regulation of CP synthesis, but I have no time for it currently. $\endgroup$
    – inf3rno
    May 10, 2015 at 15:36
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    $\begingroup$ I agree with @inf3rno that the creatine supplementation might increase the high-energy phosphate reservoir – this is the physiological basis for creatine supplementation in athletes. However, I know of no study whatsoever that has ever shown that we have been able to increase the reservoir of creatine phosphate by supplementing with creatine in the diet – this is the reason athletes take the supplement but there's no data (That I am aware of) actually suggest that it works the way we think it does $\endgroup$
    – Vance L Albaugh
    Dec 8, 2015 at 3:58

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