Phosphate in Meats, etc.

The author of this article [Massey, 2003: (http://jn.nutrition.org/cgi/content/full/133/3/862S)(http://www.ncbi.nlm.nih.gov/pubmed/12612170?dopt=Abstract)] discussed the fact that the phosphorus in meat exists mainly in phosphates but that the phosphorus in vegetable proteins exists mainly in phytate compounds. Some of the phosphate in meat is apparently bound to proteins (Massey, 2003), and I'm assuming the author is referring to phosphate bound covalently to proteins (phosphorylated proteins). Massey (2003) provides a figure of 20 mg phosphorus per gram of meat protein (~ 61 mg PO4 per g meat protein) (assuming phosphate is about 32.6 percent phosphorus). Not all of that PO4 is going to be derived from phosphorylated proteins, though, because polyphosphates (mixtures of diphosphates and triphosphates, evidently) are apparently added to many meats, to enhance the capacities of the meats to hold water and to increase the pH of the meats [Dusek et al., 2003: (http://cat.inist.fr/?aModele=afficheN&cpsidt=14847707)]. Dusek et al. (2003) found that the average concentration of free, water-soluble phosphate (provided as pyrophosphate, or P2O5) in meats (the authors also provided a large table showing the amounts in specific meats) was 16 mg/g protein. So 50 grams of meat protein could provide 800 mg of phosphate. Dusek (2003) provided a figure of 10.6 mg P per gram of protein, as a figure that should be used to calculate the amount of protein-bound phosphate in meat (p. 765). I'm reasonably certain that Dusek (2003) are not referring to phosphorus pentoxide (a "corrosive" powder that doesn't look like it could be hydrolyzed enzymatically by mammals or any other life forms, but I could be wrong about that: (http://www.wuzhouchem.com/cataloged/inor/phosphorus_pentoxide.htm)]. The description of the phosphate as P2O5 is a way of describing the stoichiometry and does not refer to some nonexistent, free compound with P2O5 as its structural formula [see here: (http://books.google.com/books?id=71g3AAAAMAAJ&pg=PA55&lpg=PA55&dq=P2O5+meat&source=bl&ots=m4FtWBiE-y&sig=XIszbFeyN-lLs7yb04bh_ytRNBs&hl=en&ei=ymZoSveMJIH4NIjS-PUM&sa=X&oi=book_result&ct=result&resnum=18)]. Regardless of the precise amounts of phosphate, the point is that a diet high in meat protein could conceivably provide a gram or more of phosphates. And one can't really estimate his or her phosphate intake by looking at the dietary "phosphorus" intake. It's astonishing to me that one so seldom sees descriptions of the actual phosphate contents or phytate contents of foods. The provision of the "phosphorus content" really doesn't tell one much.

That type of information may be important, given that marginal hypophosphatemia can produce really serious problems. I was reading about that, but I'm not up for citing a lot of articles. There's research showing that phosphate depletion basically produces effects that mimic those of a mitochondrial disorder. PO4 depletion tends to cause ATP depletion and can cause cardiomyopathy, encephalopathy, liver disease, myopathy, deficient immune function, and the more commonly-seen manifestation of hemolysis. But the cardiomyopathy, myopathy, and encephalopathy are the problems, in postmitotic cell types, one sees in mitochondrial disorders. It's also the case that an increase in glycolytic activity tends to increase phosphate uptake into cells and that phosphate activates glycolysis, etc. Another interesting thing is the fact that both, for example, glutamine depletion and phosphate depletion can occur following intense exercise or surgical trauma, etc. But glutamine and some other free amino acids can produce a hypophosphatemic effect, both by increasing phosphate uptake into cells (i.e. utilization for growth, etc., as in the "refeeding syndrome") and, probably, by increasing the urinary excretion of PO4. An excessive PO4 intake can also cause metabolic alkalosis, and PO4 depletion can cause metabolic acidosis. But glutamine, for example, has been shown to cause alkalosis or, rather, an acute increase in serum bicarbonate and also a hypophosphatemic effect and hypocalcemic effect (this effect is more pronounced with alpha-ketoglutarate and other ketoacids). Ketoacids, for example, have been used to reduce parathyroid hormone levels, but they also can reduce serum phosphate (an effect that is not produced by the reduction in parathyroid hormone (PTH) levels, given that an acute increase in PTH increases urinary phosphate excretion) and calcium levels. So it's kind of a catch 22, given that glutamine supplementation may, in my opinion, in vulnerable individuals, tend to drive PO4 into cells and decrease serum PO4, in theory, exacerbate the alkalosis that can result from PO4 supplementation. But PO4 supplementation may (or may not) increase serum PO4 and may, like glutamine (more so with some of those ketoacids), potentially, decrease serum calcium and produce metabolic alkalosis.

In any case, vitamin D supplementation seems, in my opinion, to be a safer way to deal with resistance exercise-induced phosphate depletion than phosphate supplementation is. ATP disodium, more than nucleotide monophosphates, could start to provide significant amounts of phosphate at high doses (ATP disodium is 48.4 percent "phosphate" by mass, or something close to that). It would mainly become something to consider at doses higher than those that anyone would use, but, at lower doses, that (the contribution of ATP-derived phosphate) might have some useful effects in the context of resistance exercise, etc. I think sodium phosphate supplementation sounds very problematic, in general, and I've discussed that in past postings.

I actually think that researchers or whomever might consider administering oral nucleotide triphosphates instead of monophosphates or considering the issues that relate to phosphate depletion or sequestration (such as by uridine, derived from triacetyluridine (TAU), or the ribose-induced activation of glycolysis), even temporarily or intermittently, given that the phosphorylation of nucleosides can increase phosphate utilization or sequester phosphate. The turnover of nucleotides is very dynamic, and the issue is not likely to be phosphate sequestration as much as the potential for the gradual depletion of phosphate or increase in phosphate utilization or turnover. Ribose is known to enhance the activities of glycolytic enzymes, by its entry into the nonoxidative pentose cycle and conversion into glycolytic intermediates, and phosphate availability has been shown to be limiting for PRPP formation under some circumstances. The ribose-induced increases in uric acid are not nearly as great as those produced by the fructose-induced phosphate sequestration and ATP depletion, and ribose does not appear to deplete ATP or purine nucleotide pools, in general, very much. But, over time, there could be a ribose-induced increase in phosphate turnover or utilization. I came across research showing that uridine can decrease inorganic phosphate levels, acutely, in ex vivo tissue preparations, I think, by its incorporation into uridine nucleotides (monophosphates, diphosphates, and triphosphate). Those effects occurred at high concentrations, but it's conceivable to me that the usefulness of TAU in mitochondrial disorders could, over time, be compromised by the gradual depletion of phosphate, either from the uridine-induced increases in glycolytic activity or the incorporation of uridine and uridine-derived pyrimidines into nucleotide pools. I think it would mainly occur in vulnerable individuals, in disease states, and the same would be true for any supposed effects of ribose. Adenosine has also been shown to increase glycolytic activity, such as by the AMP-induced activation of phosphofructokinase, I think, if I remember correctly, or by a "physiological" activation of AMPK and the AMPK-activation-induced transcription or phosphorylation of glycolytic enzymes. It could become really important, because glycolytic activity is already going to be accelerated in many of the disease states in which nucleotides would be expected to be therapeutic. In the case of glutamine, glutamine has been shown to preserve the purine nucleotide pools in the heart during ischemia and to reduce glycolytic glucose utilization, by serving as an alternate energy substrate. And phosphate availability can determine glutaminase activity (the activity of glutaminase, which is "phosphate-activated glutaminase" in many cell types, can become dependent on phosphate availability) and hence the capacity of glutamine to actually be deaminated and serve as an energy substrate, upon its entry into the TCA cycle as alpha-ketoglutarate or as other intermediates that its carbons are incorporated into. So glutamine could, under some circumstances, reduce phosphate turnover, but the potential for a hypophosphatemic effect, in some individuals, could produce unpredictable and tissue-specific decreases or changes in phosphate availability. I think some of these factors could become really important in some situations, as in disease states, given that phosphate depletion can mimic the effects of mitochondrial disorders. Resistance exercise, in the long term, can increase red blood cell 2,3-bisphosphoglycerate and serum phosphate levels but can decrease those levels in the short term, for example. These are just my opinions, however, and people with kidney disease or other conditions would want to be especially careful to regulate their phosphate intakes. Even the small amounts of phosphate from nucleotides could affect serum phosphate and calcium balance, under those circumstances. Another thing to remember is that any phosphates can inhibit iron and magnesium and calcium absorption, and one could consider taking those types of supplements a few hours apart. The main thing with any phosphate sources is not to provide a large amount at any one time, in any one dosage. The acute phosphate nephropathy has mainly been reported in the context of the 23-gram dosages of sodium phosphate, given twice daily, in preparation for some medical procedures. But there's no downside to being extra cautious with sources of phosphate. The amounts of phosphate provided in commonly-used dosages of nucleotide triphosphates, such as ATP disodium, are similar to or less than those found in small servings of meats or milk, but, again, it wouldn't hurt, in my opinion, to spread the total dosage out across the day, etc.