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    Registered User HalleluYAH's Avatar
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    Question Study Article: Effects of chronic creatine ingestion

    Do you feel that this study, or any others out there of which I am unaware, confirms the creatine transporter is negatively effected by long term creatine use? In other words; is the creatine transporter down regulated with continued exposure to supplemental creatine? And, in your opinion, does the following study provide sufficient proof to support cycling creatine?

    Creatine supplementation in health and disease. Effects of chronic creatine ingestion in vivo: down-regulation of the expression of creatine transporter isoforms in skeletal muscle.

    Guerrero-Ontiveros ML, Wallimann T.

    Institute for Cell Biology, Swiss Federal Institute of Technology, ETH-Honggerberg, Zurich.

    Interest in creatine (Cr) as a nutritional supplement and ergogenic aid for athletes has surged over recent years. After cellular uptake, Cr is phosphorylated to phosphocreatine (PCr) by the creatine kinase (CK) reaction using ATP. At subcellular sites with high energy requirements, e.g. at the myofibrillar apparatus during muscle contraction, CK catalyzes the transphosphorylation of PCr to ADP to regenerate ATP, thus preventing a depletion of ATP levels. PCr is thus available as an immediate energy source, serving not only as an energy buffer but also as an energy transport vehicle. Ingestion of creatine increases intramuscular Cr, as well as PCr concentrations, and leads to exercise enhancement, especially in sprint performance. Additional benefits of Cr supplementation have also been noticed for high-intensity long-endurance tasks, e.g. shortening of recovery periods after physical exercise. The present article summarizes recent findings on the influence of Cr supplementation on energy metabolism, and introduces the Cr transporter protein (CreaT), responsible for uptake of Cr into cells, as one of the key-players for the multi-faceted regulation of cellular Cr homeostasis. Furthermore, it is suggested that patients with disturbances in Cr metabolism or with different neuro-muscular diseases may benefit from Cr supplementation as an adjuvant therapy to relieve or delay the onset of symptoms. Although it is still unclear how Cr biosynthesis and transport are regulated in health and disease, so far there are no reports of harmful side effects of Cr loading in humans. However, in this study, we report that chronic Cr supplementation in rats down-regulates in vivo the expression of the CreaT. In addition, we describe the presence of CreaT isoforms most likely generated by alternative splicing.
    Last edited by HalleluYAH; 03-16-2006 at 10:35 AM.
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  2. #2
    Registered User xxghostxx's Avatar
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    This seems to be the case but maybe only at supra-physiological dosing schematics. I haven't looked into it enough, but this study was interesting in respect to this topic.

    Acute and moderate-term creatine monohydrate supplementation does not affect creatine transporter mRNA or protein content in either young or elderly humans.

    Tarnopolsky M, Parise G, Fu MH, Brose A, Parshad A, Speer O, Wallimann T.

    Department of Medicine (Neurology and Rehabilitation), McMaster University, Hamilton, ON, Canada. tarnopol@mcmaster.ca

    Animal studies have shown that supra-physiological creatine monohydrate (Cr-mH) supplementation for 3 months reduced skeletal muscle creatine transporter (CRT) content. The doses of Cr-mH (1-2 g/kg/day) used in these studies were between 5 and 10 times those usually used in human studies, and it is unclear whether a down-regulation of CRT would occur in humans at the recommended doses of 0.1-0.2 g/kg/day. We measured CRT, and citrate synthase (CS) protein content using Western blotting before and after 2 months of Cr-mH supplementation and weight training in young men (N = 11 Cr-mH (0.125 g/kg/ day); N = 8 placebo). CRT and CS were also measured before and after 4 months of Cr-mH supplementation and weight training in elderly (> 65 years) men and women (N = 14 Cr-mH (0.075 g/kg/day); N = 14 placebo). Finally, CRT mRNA was measured using competitive RT-PCR before and after 8-9 days of Cr-mH loading in young men and women (N = 14, CR-mH (mean = 0.18 g/kg/day); N = 13, PL). Total creatine content was significantly elevated after the Cr-mH supplementation period as compared to placebo in each of the studies. Neither Cr-mH supplementation, nor exercise training resulted in measurable alterations in CRT protein content and acute Cr-mH loading did not alter CRT mRNA. There were no gender differences in CRT mRNA or total creatine content in the young subjects and no gender differences in total creatine content or CRT protein content in the elderly subjects. Weight training in young men did not increase CS protein content, however, in the elderly there was a significant increase in CS protein content after exercise training (p < 0.05). These results demonstrated that Cr-mH supplementation during weight training resulted in increases in skeletal muscle total creatine without reductions in CRT protein and acute Cr-mH loading did not decrease CRT mRNA content.
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    Registered User HalleluYAH's Avatar
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    Thanks for the reply xxghostxx. Excellent feedback indeed.

    Interestingly the authors of the study you posted entitled it "Acute and moderate-term creatine...". This seems to support that creatine use for up to three (or more) consecutive months does not harm CRT. I wonder how this might change with prolonged "chronic" use of, say, more than six consecutive months?

    Again, excellent feedback.
    Last edited by HalleluYAH; 03-16-2006 at 10:57 AM.
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    Registered User xxghostxx's Avatar
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    Originally Posted by HalleluYAH
    Again, excellent feedback.
    Thanks. Here is a full paper which also seems to be of interest in this discussion:

    Creatine supplementation in health and disease:
    What is the evidence for long-term efficacy?
    Wim Derave, Bert O. Eijnde and Peter Hespel
    Exercise Physiology and Biomechanics Laboratory, Department of Kinesiology, Faculty of Physical Education and
    Physiotherapy, Catholic University of Leuven, Leuven, Belgium
    Abstract
    Creatine supplementation is an established ergogenic aid in sports and is now claimed to have therapeutical applications in a
    variety of diseases. The available literature mainly covers the short-term (one to several weeks) effects of creatine supplementation
    on skeletal muscle function in health and disease, which is of little help to evaluate the long-term (two or more months)
    potential of creatine as a drug in chronic disorders, such as neurodegenerative diseases or muscular dystrophies. Recent findings
    in healthy humans indicate that the beneficial effect on muscle function and muscle total creatine content may disappear
    when creatine is continuously ingested for more than two or three months. The mechanism for this habituation to chronic creatine
    exposure is poorly understood. The primary purpose of the present review article is to critically evaluate the available
    evidence for long-term efficacy of creatine administration and to hypothesize about ways to optimize creatine administration
    regimens. (Mol Cell Biochem 244: 49–55, 2003)
    Key words: creatine supplementation, skeletal muscle, energy metabolism
    http://<br /> http://www.springerli...jpv1611r6h.pdf
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    Registered User HalleluYAH's Avatar
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    hey ghost, the link was broken, so I fixed it. I just read the conclusion, and it appears the study article confirms what you have already said. it also confirms that there is no prrog that prolonged CrM supplementation down regulates CRT in humans. What is your stance?

    Here is the corrected link to the study article you posted...
    http://www.springerlink.com/media/98...jpv1611r6h.pdf
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    Anger and other side effects

    But men please look at the reply regarding anger and be honest with yourself. Anger is a terrible thing if it goes unchecked. Please if there are others who have issues with anger please share them openly here so other won't feel like they are the only one that experiences anger. If there are many of you that come forward then maybe finally someone will take NOTICE that there are anger issues that some how relate to taking supplements and working out. Now listen to me carefully guys I am not pointing a finger at anyone ok?? I am just asking for those who have anger issues to come forward and share your stories. You might find out you are not alone. Sometimes we end up hurting the ones we love the most. And hey guys, there are ways to deal with this anger. But denial isn't one of them. I look forward to your responses and thank you once again for forgiving me.

    Are any of you having any emotionsl side effects from ingestion. Let's hear from you.
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    Actual Pharmacist Bane's Avatar
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    Cycle everything. If God meant us to consume 5 grams creatine per day, he would have made our food contain that much. Homeostasis is such a bitch.
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    Last edited by Bane; 03-20-2006 at 05:02 AM.
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    C6H13NO2 pu12en12g's Avatar
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    Originally Posted by Speakthetruth
    But men please look at the reply regarding anger and be honest with yourself. Anger is a terrible thing if it goes unchecked. Please if there are others who have issues with anger please share them openly here so other won't feel like they are the only one that experiences anger. If there are many of you that come forward then maybe finally someone will take NOTICE that there are anger issues that some how relate to taking supplements and working out. Now listen to me carefully guys I am not pointing a finger at anyone ok?? I am just asking for those who have anger issues to come forward and share your stories. You might find out you are not alone. Sometimes we end up hurting the ones we love the most. And hey guys, there are ways to deal with this anger. But denial isn't one of them. I look forward to your responses and thank you once again for forgiving me.

    Are any of you having any emotionsl side effects from ingestion. Let's hear from you.
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    Here we go again....
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