In this article [Laroche et al., 2009: (http://www.ncbi.nlm.nih.gov/pubmed/19148564)], Laroche et al. (2009) discussed so-called "phosphate diabetes." Phosphate diabetes is an old term that now encompasses genetic forms of vitamin D-resistant rickets and, from what I can tell, idiopathic forms of cellular phosphate depletion. The condition is distinct from severe hypophosphatemia, I guess, because the serum phosphate levels tend to be (but do not have to be) lower than 0.85 mM. The 24-hour urinary phosphate excretion also tends to be more than 20 mmol in phosphate diabetes, but the phosphaturia threshold, or renal threshold phosphate concentration, is used in the actual diagnosis and should be less than 0.83. The renal threshold phosphate concentration is a "normalized concentration" (TmPO4/GFR). The explanations for these terms are using terms that are very confusing. TmPO4 is the (estimated) concentration of tubular phosphate (because you can't easily measure the tubular fluid phosphate concentrations) at which the renal tubular reabsorption rate is maximal, and all of the superfluous PO4 will be excreted in the urine at a tubular phosphate concentration higher than that threshold value. The GFR is easily obtained, and the TmPO4/GFR is the TmPO4 normalized to the GFR by the use of a normogram (it's not an equation, and one has to draw a line through a chart). I can't get the original full text of the article showing the normogram, and most of the articles that cite it don't show the thing. Here's the chart in a book that's unprintable (http://books.google.com/books?id=9gvBlktAT6YC&pg=PA618&lpg=PA618&dq=%22renal+threshold+phosphate%22+TmPO4+GFR&source=bl&ots=L17iWRr9PQ&sig=c7eHPGGeQSWGaiMg3tztkmd7SrA&hl=en&ei=4rhwSvL8LpnmlQecsun_Dw&sa=X&oi=book_result&ct=result&resnum=17) One has to calculate the TRP (expressed as a percentage), first, and, to calculate the TRP, one has to know the fasting urinary creatinine and phosphate concentrations and the fasting serum phosphate and creatinine concentrations. It would be nice to have an equation, even a complex one, instead of a "gram." It seems that a high TmPO4/GFR means that the urinary phosphate loss is high, in relation to the total amounts of water being filtered per unit time, and that the person is almost overtly hypophosphatemic. Of course, one has to assume that the normogram is valid, but at least one might use that to attempt to make some kind of quantitative evaluation of subtleties in phosphate homeostasis. At least there's something.
I'm not going to go into a lot of detail in this posting, but there are some old articles that discuss fibromyalgia-like symptoms in "phosphate diabetes" [Amor et al., 1995a: (http://www.ncbi.nlm.nih.gov/pubmed/7788334); Amor et al., 1995b: (http://www.ncbi.nlm.nih.gov/pubmed/7788335)]. I can't get the full texts of those, and they look, at first glance, to be odd articles. But they're actually very much consistent with other research on the effects of phosphate depletion. The condition also has been found in people with chronic fatigue syndrome, and De Lorenzo et al. (1998) [De Lorenzo et al., 1998: (http://pmj.bmj.com/cgi/reprint/74/870/229.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/9683977)] discuss research [one or both of the articles by Amor et al. (1995)] showing that the pain and other symptoms of phosphate depletion may not resolve after the serum phosphate has increased or normalized and may require more time to be relieved. I've discussed the risks of phosphate supplementation in past postings, and phosphate can bind magnesium and calcium and prevent their absorption, etc. If one used any extra phosphate, at low doses under a doctor's supervision, for some abnormality or set of symptoms that a doctor had confirmed or suspected, one might consider using supplemental magnesium. The dosages of magnesium required to overcome the binding to phosphate could be significant, and I don't know what they might be. The same thing could conceivably be true in the case of supplementation with oral ATP disodium, although the dosages of that would probably be low enough to not provide a big amount of phosphate.
To say that someone has phosphate diabetes is, as far as I can tell, basically like saying phosphate depletion, and it can cause pain and osteomalacia, etc. The authors of a lot of the articles cite research claiming that phosphate diabetes occurs more in men, but that doesn't make sense to me. Maybe the equation/gram is only valid in men because they used men in 1975 to derive it. I don't know, but fibromyalgia is more common in women, I think, than in men. So maybe they're not looking for phosphate depletion in women with those symptoms. Researchers have also compared the musculoskeletal pain in vitamin D deficiency to the pain in fibromyalgia [see Holick, 2004, and others: (http://scholar.google.com/scholar?hl=en&q=%22vitamin+D%22+pain+fibromyalgia)]. The association of chronic fatigue syndrome with phosphate depletion is also consistent with the hypothesized association of chronic fatigue syndrome with impairments in the adrenergic regulation of energy metabolism [Bains, 2008: (http://www.cfids-cab.org/MESA/Bains.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/18684570)]. That's a great article. This is a bad search, but there's some research showing that sympathomimetics can increase phosphate reabsorption [such as LeClaire et al., 1992: (http://scholar.google.com/scholar?q=adrenoreceptor+phosphate+transport+OR+uptake&hl=en)], and adrenergic agonist drugs tend, from what I've read so far, to increase cellular phosphate uptake. But chronic stress and the adrenergic activation associated with it, as discussed by Bains (2008), can produce hypophosphatemia in the long term. One could make the argument that phosphate depletion might be one factor sustaining ATP depletion in the brain in chronic fatigue syndrome, for example, because phosphate depletion can produce ATP depletion and hypoxic and ischemic injuries to the brain, in extreme cases. In more mild cases, the result could be the "pseudodepression" discussed by Amor et al. (1995a) in the context of phosphate diabetes, etc.
But De Lorenzo et al. (1998) give the impression that phosphate supplementation tends to not necessarily be all that effective or to have predictable effects, and that's the impression I've gotten from other articles. I tend to think ATP disodium might be more useful, given that adenosine nucleotides can serve a kind of phosphate buffering effect (as researchers have discussed), along with magnesium (via the retention of adenosine nucleotides as MgATP2-, etc.), and that magnesium deficiency is thought to impair parathyroid hormone (PTH) secretion by reducing adenylate cyclase activity (which is magnesium-dependent) in the parathyroid tissue [Bush et al., 2001: (http://www.ncbi.nlm.nih.gov/pubmed/11767924)]. There are other reasons, but, to the extent that phosphate depletion can lead to adenosine nucleotide depletion, the cAMP levels in parathyroid tissue might, as in magnesium deficiency-associated hypocalcemia, be lower in the context of phosphate depletion and might mean that the "safeguarding" effect of PTH secretion, in response to the potential decrease in serum calcium that could occur in vulnerable individuals taking exogenous phosphate, could be compromised in the context of phosphate depletion. The use of ATPNa2 instead of sodium phosphate could conceivably compensate for that, but, above some dosage, supplementation with a source of exogenous phosphate, in any form, would probably start to cause some problems.
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