In this article [Kelleher et al., 1996: (http://www.ncbi.nlm.nih.gov/pubmed/8836557)], Kelleher et al. (1996) found that either citrate or fructose-1,6-bisphosphate protected cultured astrocytes and also neurons co-cultured with astrocytes against death due to hypoxia. The idea was that citrate would act as a phosphofructokinase inhibitor and inhibit the excessive glycolytic flux ("hyperglycolysis") that can occur after a traumatic brain injury or in cells under extreme hypoxic stress. That inhibition of phosphofructokinase could actually help explain the alkalinizing effect that citrate supplementation produces [McNaughton et al., 1990: (http://www.ncbi.nlm.nih.gov/pubmed/2079058)], given that glycolytic activity can lead to metabolic acidosis, especially after or during hypoxia. Those authors (McNaughton et al., 1990) found that citrate increased serum bicarbonate in a dose-dependent manner, and that's not necessarily good, past a certain point. That can be harmful in the context of phosphate depletion, etc., in the sense that an increase in serum bicarbonate can reduce oxygen unloading from hemoglobin. Increases in serum bicarbonate also fairly reliably decrease serum ionized calcium by increasing the binding of calcium to albumin (by deprotonating the sites on albumin that normally bind calcium or magnesium, etc.). Kelleher et al. (1996) noted that either fructose-1,6-BP or citrate had been found, by other researchers, to decrease the ionized calcium concentrations in the media of cultured astrocytes or neurons. There's some research showing that phosphocitrate is one "mediator" that can reduce calcium influx into mitochondria, I think, and potassium or sodium or magnesium citrate(s) have been used to prevent kidney stones. Citrate normally helps to prevent calcification in the tubular fluid, and there's a lot of research on the use of magnesium in combination with citrate (to prevent kidney stones, etc.) (http://scholar.google.com/scholar?hl=en&q=magnesium+citrate+nephrolithiasis+OR+urolithiasis&as_ylo=&as_vis=0). It's interesting that Kelleher et al. (1996) found that fluorocitrate, an aconitase inhibitor, also was protective, and the authors suggested that fluorocitrate had increased citrate availability by decreasing its conversion to isocitrate by aconitase. That could lend credence to the calcium-modulating effect or another mechanism. It doesn't necessarily rule out an effect on the TCA cycle, though, even in those experiments, and there's reason to think that citrate could have some usefulness as an energy substrate (or citric acid, which is sold also but that might be too acidic or something and evidently, but maybe not surprisingly, doesn't have the alkalinizing effect that citrate has) [Sakhaee et al., 1992: (http://www.ncbi.nlm.nih.gov/pubmed/1552616)]. There's research showing that 10-15 percent of the ATP production by cells in the proximal tubules comes from citrate oxidation [cited in Mandel, 1985: (http://www.ncbi.nlm.nih.gov/pubmed/3888090)]. I'm thinking that the use of magnesium citrate could be less likely than the use of alpha-ketoglutarate salts to cause GI-related problems, given that at least two, presumably, of citrate's ionizable carboxylate groups would be chelating the magnesium, somewhat. Apparently magnesium citrate's a salt and not a coordination compound but behaves more like a coordination compound [Lindberg et al., 1990: (http://www.ncbi.nlm.nih.gov/pubmed/2407766)]. Those authors found that Mg2+ citrate forms a soluble complex and that the bioavailability of Mg2+ from it is higher than the Mg2+ bioavailability from Mg2+ oxide. I should mention that the amount of citrate in that is large. Mg2+ citrate is about 11.3 percent magnesium. So 400 mg of elemental Mg2+, from Mg2+ citrate, would also provide 3,636 mg (3.636 grams) of citrate. So it's like a citrate supplement without the sodium or lousy calcium or potassium, etc. I haven't done any reading to see what the characteristics of the pharmacology of citrate are going to be. I'd watch for that bicarbonate effect, though, because it's not necessarily going to be rosy for a person in a disease state. But there's also the fact that, as Kelleher et al. (1996) allude to, citrate is not especially abundant. I think that the flux through citrate synthase is normally relatively low, and the reason is that oxaloacetate is in great demand. Citrate is also a major precursor of or substrate used in the formation of cytosolic acetyl-CoA and could be "lipogenic" to some extent, but one could say the same thing about glucose or glutamine or any number of "citrate precursors." It could be more true for citrate, though. There's actually research showing that citrate can help prevent ketoacidosis in people taking C5 ketones [Mochel et al., 2005: (http://www.ncbi.nlm.nih.gov/pubmed/15781190)]. Mochel et al. (2005) found that citrate restored ketogenesis, basically, in people who had been taking triheptanoin, a seven-carbon precursor that's oxidized to form C5 ketones (5-carbons) and acetyl-CoA (2-carbons). It's like an "adjunctive anaplerotic agent" in that context. But those types of lipid-based energy substrates have the potential to be problematic, given that acyl-CoA thioesters tend to accumulate and inhibit all sorts of mitochondrial enzymes, etc., in my opinion.
I see that "lemonade-based" therapies (and cranberry-juice-but-not-cranberry-juice-concentrate-based therapies), as sources of citrate, have been used, instead of the citrate salts, to prevent calcium oxalate kidney stones (http://scholar.google.com/scholar?hl=en&q=nephrolithiasis+cranberry+OR+lemonade&as_ylo=&as_vis=0). Someone should change the name of citrate to something that will be taken seriously in neuroscience research. Seriously. "Well, did you take the @#$%*&ng lemonade for your stroke, like I told you, or did you sip it in a straw and get little piddly, lazy-afternoon, "lazy-lemonade" doses. Did you get that great big keg of sleepy-time lemonade like I @#$---Ah, you know, what I usually tell people is to take a half gallon or don't even take a sip."
(I was going to mention that the side effects associated with alpha-ketoglutarate salts are thought to be a consequence, at least in part, of the net charge of -2 of alpha-ketoglutarate, in the physiological pH range. Mg2+ citrate could conceivably have a net charge of -1, as opposed to the -3 charge of free citrate, much as MgATP(2-) vs. ATP(4-) have different effective net charges. Mg2+ citrate could be absorbed as a "monoanion," to some extent, and then yield the trianionic citrate in the extracellular fluid or whatever, etc.)
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