This article [Cave et al., 2007: (http://www.ncbi.nlm.nih.gov/pubmed/17296492)] provides a general overview of nonalcoholic fatty liver disease (NAFLD), and the authors discuss the fact that 20-30 percent of Americans have NAFLD. The percentages are higher when one considers the numbers of people with alcohol-induced fatty liver disease. Cave et al. (2007) discuss some of the therapeutic approaches that have been used in human studies, but most of the approaches the authors discuss are not likely to be very effective, in my opinion. There's a great deal of validity to the role of aberrant one-carbon metabolism in NAFLD, as the authors discuss. In my opinion, however, the use of betaine in NAFLD should be abandoned. Uridine, reduced folates, such as levoleucovorin or L-methylfolate, with methylcobalamin, purine nucleotides, magnesium, and arginine would, in my opinion, be more rational as therapeutic strategies. Ethyl pyruvate could conceivably have some usefulness in NAFLD, and I know sodium pyruvate has been researched in alcohol-associated FLD. There's one on the use of ethyl pyruvate in alcoholic FLD [Yang et al., 2003: (http://www.ncbi.nlm.nih.gov/pubmed/14647036)]. Ethyl pyruvate would have advantages over pyruvate, as someone noted, in a recent comment to the posting on pyruvate in the context of neuroprotection (http://hardcorephysiologyfun.blogspot.com/2009/02/pyruvate-and-ethyl-pyruvate-in.html), and pyruvate itself could, in my opinion, conceivably increase urinary phosphate excretion, by its conversion into alpha-ketoglutarate in the distal tubule cells of the kidneys [(http://hardcorephysiologyfun.blogspot.com/2009/02/potential-for-hypophosphatemia-or.html); (http://hardcorephysiologyfun.blogspot.com/2009/02/urea-cycle-renal-glutaminase-activity.html)], etc. Ethyl pyruvate could be used in low dosages and could conceivably be used in a manner that would more specifically target the liver (or at least not be subject to renal clearance en masse, due to poor transport across cell membranes, as the pyruvate anion would, as noted by the person who commented). If one were going to research one or more of those things, it would be necessary to choose the dosages rationally and not be afraid to increase them to dosages in the adequate or therapeutic ranges. I'm forgetting to mention some other things, and a person would obviously want to talk to his or her doctor before taking anything in the context of NAFLD or any other liver disease. I could go into all the mechanisms and research, but I've discussed most of those things in past postings.
It's worth reading about NAFLD, in my opinion, because, as Cave et al. (2007) discuss, the condition generally goes along with insulin resistance and prediabetes and with obesity. The numbers of articles, both in the context of animal models and in relation to humans, are very large, and the research on animal models of NAFLD provide a framework for learning about mitochondrial disorders and energy metabolism. Abnormalities in cellular energy metabolism play an important role in lots of different disease states, in my opinion, and the research on mitochondrial functioning in NAFLD is relevant to the study of disease states outside the liver. NAFLD is generally viewed as being both a cause and a consequence of obesity, but some of these articles don't quite give the reader a sense of the way in which, for example, drug-associated or drug induced fatty liver disease can cause large amounts of weight gain or even obesity in short periods of time, in association with liver damage. I came across one case report, a few months ago, of drug-associated NAFLD in which a person gained 10 kg (22 lbs) over several months (Shuster, J. Hospital Pharmacy 2008; 43(3): 172-176). There are many similar and more extreme examples. NAFLD is not simply an excess of free fatty acids in the liver or something vague. It's a set of relatively specific pathological abnormalities, such as enlarged mitochondria, triglyceride accumulation in cytoplasmic micelles, and paracrystalline inclusions, which are abnormal patterns in the cristae (structures formed by the infoldings of the inner mitochondrial membrane) of the mitochondria ("prismatic" cristae, hexagonal cristae, and other "atypical cristae"). It's also worthwhile to note that NAFLD is often difficult to diagnose with liver function tests (with blood tests). Mofrad et al. (2003) [Mofrad et al., 2003: (http://www.ncbi.nlm.nih.gov/pubmed/12774006)] found that significant percentages of people with NAFLD had severe liver damage and no elevation in serum liver enzymes, in a commonly-used blood test. I talked about that article in a previous posting (http://hardcorephysiologyfun.blogspot.com/2008/12/sensitivity-issues-with-blood-tests-for.html). It's often necessary to use a transabdominal ultrasound to diagnose NAFLD. I think CT or MRI scans are also used, but I'm not sure which diagnostic approaches are used most frequently.
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