These are some more articles discussing the use of creatine in combination with prescription antidepressants or medications to treat Parkinson's disease [Roitman et al., 2007: (http://www.ncbi.nlm.nih.gov/pubmed/17988366); Amital et al., 2006: (http://ajp.psychiatryonline.org/cgi/reprint/163/10/1840-b.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/17012702); Bender et al., 2006: (http://www.ncbi.nlm.nih.gov/pubmed/17030762)]. Amital et al. (2006) researched the effects of creatine at 3 grams per day, for one week, and then 5 grams per day, for four weeks (and then also for eight weeks after the end of the trial), in a person who was being treated with prescription medications for post-traumatic stress disorder and depression with fibromyalgia. The authors found that, during the course of the trial, the person's scores on the Hamilton Depression Rating Scale had decreased, indicating that the creatine had evidently produced an antidepressant effect in the person, and that the person's symptoms of fibromyalgia had improved. Roitman et al. (2007) found that the full antidepressant effect in the patients had required four weeks to emerge, but the greatest reductions in the Hamilton Depression Rating Scale had occurred within the first two weeks in most of the people. Roitman et al. (2007) also found that some people experienced a greater improvement in mood from 3 grams/day of creatine than from 5 grams/day.
Bender et al. (2006) used 4 grams a day of creatine for two years (after an initial phase of 20 grams per day for 6 days and then 2 grams per day for six months), in a randomized, placebo-controlled trial and found that the people who had taken creatine had not had to increase the dosages of their dopaminergic medications for Parkinson's disease to the extent that the people taking the placebo had had to increase their dosages, and that effect was statistically-significant. The other main result of the trial was the finding that creatine had produced a statistically-significant reduction in symptoms of depression, as measured by the "score" on Item 3 of Part I of the Unified Parkinson's Disease Rating Scale (UPDRS). Incidentally, I don't think the "loading dose" concept of creatine makes much sense, especially given the potential for high-dose creatine to produce plasma and extracellular fluid volume expansion in some people [Powers et al., 2003: (http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=155510&blobtype=pdf)(http://www.ncbi.nlm.nih.gov/pubmed/12937471)]. To the extent that that effect would occur more with high-dose than with low-dose creatine, one would expect the body to be less able to adapt or compensate to that effect in the context of a "loading dose." But that's just my opinion. Obviously, one would want to discuss this with one's doctor before using creatine or any supplement, particularly given that Roitman et al. (2007) found that, in one of the ten patients, creatine produced transient improvement in the person's mood and then worsened it. Roitman (2007) also found that creatine produced mania or hypomania in the people in the trial who had been diagnosed with bipolar disorder.
In my opinion, creatine would be more effective in this context in combination with adenosine monophosphate/triphosphate or guanosine monophosphate or both, for complex reasons. I think it's a really important point, but it's just my opinion. I could explain my reasoning in more detail, but I'd have to cite a lot more articles and can't do that right now. I discussed some of the rationale for the combination in a past posting (http://hardcorephysiologyfun.blogspot.com/2009/03/creatine-cr-phosphocreatine-pcr-and.html), and I discussed some of the research and details on orally-administered guanosine monophosphate and adenosine monophosphate or adenosine triphosphate in this posting (http://hardcorephysiologyfun.blogspot.com/2009/03/adenosine-and-guanosine-in-animal.html). Other approaches that might potentiate the effects of creatine, in my opinion, would be the use of methylcobalamin at ~5 mg/day or something (with the intent of disinhibiting creatine kinase enzymes and tricarboxylic acid cycle enzymes by reducing methylmalonic acid levels), the use of L-methylfolate or levoleucovorin in combination with methylcobalamin (with the intent of reducing the accumulation of sarcosine, which may be produced from high-dose creatine, given that folate depletion can compromise the metabolism of sarcosine and dimethylglycine and betaine, as I've discussed in the context of research cited in past postings), and the use of adenosine and guanosine to elevate serum uric acid to high-normal levels, under a doctor's supervision (with various "purposes" in mind, including the disinhibition of creatine kinase, which is inhibited by peroxynitrite, through the scavenging of peroxynitrite by uric acid) [discussed and cited here: (http://hardcorephysiologyfun.blogspot.com/2009/03/creatine-cr-phosphocreatine-pcr-and.html)]. Poortmans et al. (2005) [Poortmans et al., 2005: (http://www.ncbi.nlm.nih.gov/pubmed/16260971)] discussed the fact that the elevation of urinary methylamine and formaldehyde, in response to high-dose creatine administration, could have resulted from the metabolism of some of the creatine to sarcosine, evidently by the creatinase enzymatic activity in microorganisms in the G.I. tract, if memory serves (humans don't express a creatinase enzyme, as far as is known). Sarcosine can be metabolized to methylamine by sarcosine reductase or to formaldehyde and glycine, by sarcosine oxidase, and methylamine can be metabolized to formaldehyde and ammonia by semicarbazide-sensitive amine oxidase (SSAO) (Poortmans et al., 2005). Formaldehyde can then be converted into formate, and the activities of the folate cycle enzymes, which are dependent upon adequate pools of reduced folates, such as L-methylfolate or levoleucovorin, and vitamin B12 (i.e. methylcobalamin), are important for the normal metabolism of formate.
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