This article is interesting [Sethi et al., 2004: (http://www.ncbi.nlm.nih.gov/pubmed/15201623)], and the authors found that propionyl-L-carnitine (PLC) can enhance the beta1-adrenoreceptor density in the hearts of rats, in which experimental heart failure had been induced, and increase the beta-adrenoreceptor activation-induced increases in adenylate cyclase activity in the hearts of the rats. The authors discussed the fact that ketones, such as acetoacetate, had been shown to produce similar effects. PLC has been researched a lot in the treatment of intermittent claudication (IC) due to peripheral arterial disease (PAD) (IC is symptomatic PAD that produces pain, usually in the legs or ankles, when a person walks or exercises). There's actually a considerable amount of research on the effects of ketones (i.e. acetoacetate and beta-hydroxybutyrate) on cognitive functioning and in neuroprotection, but some of the methods used to elevate ketone levels (or the conditions associated with elevated ketone levels) are potentially harmful. The way PLC works is sort of not entirely clear, but it's anaplerotic (http://hardcorephysiologyfun.blogspot.com/2009/01/coenzyme-sequestration.html) and can maintain the activities of the tricarboxylic acid cycle (TCA cycle) enzymes (and thereby maintain ATP levels) under conditions of metabolic stress, in particular. Biotin is required for propionyl-CoA carboxylase activity, and methylcobalamin/vitamin B12 (via their conversion into 5'-deoxyadenosylcobalamin) is required for methylmalonyl-CoA mutase activity. Those enzymes' activities are required for propionyl-L-carnitine to work properly. Puchowicz et al. (2008) [Puchowicz et al., 2008: (http://www.nature.com/jcbfm/journal/v28/n12/abs/jcbfm200879a.html)] found that administering the ketone beta-hydroxybutyrate reduced the postischemic infarct volume (damaged part of the brain) in an experimental model of stroke in rats. The authors suggested that the mechanism of neuroprotection by beta-hydroxybutyrate might be due to an anaplerotic effect (maintaining mitochondrial ATP production, essentially, as discussed above) and be similar to the cardioprotective effects of PLC. Acetyl-L-carnitine (ALCAR) was tested as a neuroprotective in Alzheimer's disease, but the trials were discontinued in phase II or III (phase III, as far as I know). My opinion, in view of the research showing the acetyl- group donation by ALCAR, is that ALCAR is more cholinergic than PLC [which, in view of articles such as this one, by Puchowicz et al. (2008), may be more "adrenergic"], and that might have implications for conditions associated with a disturbed balance of cholinergic and adrenergic neurotransmission (in major depression, for example, there tends, very generally, to be a deficit in noradrenergic/adrenergic neurotransmission and overactivity of cholinergic neurotransmission in the brain). There's still not as much research on the effects of PLC on the brain, but I think there could be some potential in that area. BDNF production in some parts of the brain, in response to physical exercise, for example, is dependent on beta1-adrenoreceptor activation [Ivy et al., 2003: (http://www.ncbi.nlm.nih.gov/pubmed/12759116)]. That's pretty well-known to be true, but the extent to which that BDNF exerts any consistent effects is less clear. ALCAR, PLC, and unesterified, free L-carnitine are definitely not equivalent. Research has shown that they can have very different effects. I think there's a tendency for the research to get stuck on the concept that something is good for one condition and for nothing else. PLC, in my opinion, has tended to be viewed as in some way "selective" for heart-related conditions, but, in my opinion, there's no real basis for thinking PLC would act selectively in the heart. Vermeulen et al. (2004) [Vermeulen et al., 2004: (http://www.psychosomaticmedicine.org/cgi/content/full/66/2/276) (http://www.ncbi.nlm.nih.gov/pubmed/15039515?dopt=Abstract)] cited research showing that carnitine and PLC (and carnitine esters, in general) can cross the blood-brain barrier and enter the brain. The authors seemed to assume that PLC was acting outside the brain, but I have no idea why they would assume that. Something that decreases "physical" fatigue could just as easily be expected to act mainly in the brain, in my opinion, given that exhaustion during voluntary, physical exercise may be partially produced, first, by "fatigue" in the brain (maybe because of something like astrocyte glycogen depletion or an increase in the lactate to pyruvate ratio in the brain). Astrocyte glycogen depletion is one explanation for the "need to sleep," meaning that scientists are not sure why people need sleep at all and think that depletion of "brain glycogen," which is largely in astrocytes, may be one explanation for "sleep" [Kong et al., 2002: (http://www.jneurosci.org/cgi/content/full/22/13/5581) (http://www.ncbi.nlm.nih.gov/pubmed/12097509?dopt=Abstract)].
I tried to find the original article on that, and the title of it is "Exercise begins and ends in the brain." It's in a European journal that evidently isn't indexed in Pubmed. Pubmed is a really strange search engine and has some...problems. It sounds like some people in exercise physiology journals are trying to scoff at that idea now, in the articles that have been published subsequently. They're falling back on the 1940's concept of the VO2max. Here are some articles discussing the problems with that concept, a concept that reminds me, in relation to protein intake, of the idea of "nitrogen balance" [Robergs, 2001: (http://faculty.css.edu/tboone2/asep/Robergs1Col.PDF); Carlson, 1995: (http://www.chestjournal.org/content/108/3/602.full.pdf+html) (http://www.ncbi.nlm.nih.gov/pubmed/7656603?dopt=Abstract)]. I shouldn't be so critical, but research in some areas of exercise physiology is bizarre. There isn't effective integration, into research on exercise physiology, of new information on neurobiology, and researchers keep testing things in elite athletes. In people with mitochondrial disorders, an understanding of ways to even measure the factors that utterly crippled people's capacities to exercise came extremely slowly. There's some necessity not to test things in people who are seriously ill, but many, many people, people who do not have isolated mtDNA mutations or inherited metabolic disorders, cannot exercise at all. I think the people outside the exercise physiology research field have probably done a lot of the research showing that things like PLC improve exercise tolerance in people with PAD and heart disease (http://scholar.google.com/scholar?num=100&hl=en&lr=&q=propionyl-L-carnitine+exercise), and I would be willing to bet that there are some crazy articles testing it in elite athletes and finding no results. I'm not sure why one would expect meaningful performance enhancements in finely-tuned athletes. I'd sort of worry about the whole concept of using something to enhance performance, but that's not really the idea. The idea is to build up a person's muscle mass to the point that his or her body can regulate basic functions, such as buffering plasma electrolyte levels and maintaining the blood sugar, by gluconeogenesis in the skeletal muscles, in the fasted state. Once the muscles of a person with PAD, for example, could do that, with guidance from his or her doctor, one might expect to see less of a need for something like PLC. Has there ever been a positive result in elite athletes? They're already in fantastic shape. I don't claim to know the way in which the research should be done, but, in my opinion, there are some issues with research in that area. I guess that's unrelated to the original topic.
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