This article [Reusz et al., 1990: (http://fetalneonatal.com/cgi/reprint/65/10/1125.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/2248503)], along with other articles that describe the adverse effects or absence of adverse effects of different dosages of supplemental phosphate in people who have X-linked hypophosphatemic rickets (XLHR) (or autosomal dominant hypophosphatemic rickets), are likely to be relevant to an understanding of the risks (or lack thereof) of phosphate supplementation in humans who don't have genetic disorders. Sitara et al. (2004) [Sitara et al., 2004: (http://www.geocities.com/razzaquems/MatrixBiology.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/15579309)] noted that the mechanisms underlying the hypophosphatemia in those two sets of genetic disorders are not perfectly understood, but the actions or serum levels of FGF-23 (fibroblast growth factor-23) are augmented in both sets of genetic disorders. The PHEX gene product is an endopeptidase, a protease enzyme, and mutations in that gene evidently are the root cause of XLHR and, among other phenotypic changes, serve to augment the actions of FGF-23 (http://scholar.google.com/scholar?q=phex+hypophosphatemia&hl=en). One could make the argument that the hyperphosphaturia in people who have those genetic disorders would cause those people to be at a lesser risk of developing ectopic calcification, as in response to any given dosage of supplemental phosphate. But I don't think that's true. Researchers have reported many cases of nephrocalcinosis, which is calcification of parts of the kidneys and would be the main risk of (particularly excessive) phosphate supplementation (in my opinion), in people with XLHR who have taken the combination of phosphate and hormonal vitamin D (HVD), which is calcitriol (1alpha,25-dihydroxyvitamin D3), that has been the standard therapeutic approach to treating the hypophosphatemia in those disorders. FGF-23, a protein that is "hyperfunctional" in these genetic forms of hypophosphatemia, decreases renal HVD formation and decreases phosphate reabsorption by proximal tubule epithelial cells. With regard to HVD formation, one could make the argument that the decreases in serum HVD, in many people who have these genetic disorders, would make the supplemental HVD less toxic than it would be in normal people, thereby confounding an attempt to sort through the risks of HVD vs. supplemental phosphate and to get a sense of the risks of different dosages of phosphate in normal people. But I don't think that's likely to be a valid reason for ignoring the data in some of these articles, either, because HVD seems to have been causing the same hypercalciuria and hypercalcemia in people with genetic hypophosphatemia as it tends to in normal humans.
The dosages of phosphate that have been associated with nephrocalcinosis in humans, as described by Reusz et al. (1990), are really high (a mean of 136.4 mg/kg bw/day, or 9548 mg/day, for a 70-kg human), and the "lower" range of dosages of phosphate (50-100 mg/kg bw/day, which is about 3500-7000 mg/day, or a mean of 69.9 mg/kg bw/day, which is 4893 mg/day) were not associated with nephrocalcinosis but were still quite high. Those dosages (more than 4000-5000 mg of phosphate/day, from any supplemental phosphate and food-derived phosphate, combined) are similar to the dosages that, for example, Heaney (2004) [Heaney, 2004: (http://www.mayoclinicproceedings.com/content/79/1/91.full.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/14708952)] was saying would potentially cause problems in humans. But almost no one ingests anywhere near those amounts of phosphate (which were, as discussed, not associated with nephrocalcinosis) per day, and a maximum of only 2300 mg/day of supplemental phosphate was required to treat people (who did not have genetic disorders) who displayed idiopathic (cause-unknown) phosphate depletion ("phosphate diabetes"). My point is that it's not a choice between the use of massive amounts of phosphate and the appalling consequences of the phosphate depletion that could occur, in the 21st century, here, in people who ingest only sources of "phytates," in whole grains and other vegetable- and plant-derived foods, that may provide little utilizable phosphate. There's a middle ground between the use of high doses of phosphate (and the state of blind terror, at the prospect of phosphate-induced nephrocalcinosis, that could go along with that) and the sense of "comfort in the majority viewpoint" that seems to potentially go along with phosphate deprivation and with the development of hypoxic brain injuries and osteomalacia and arthropathy (potentially, neuropathic, degenerative arthropathy/osteopathy) (http://scholar.google.com/scholar?hl=en&q=hypophosphatemia+osteopathy+OR+arthropathy) (it seems to me that the lower back pain and lumbar vertebral collapse/degeneration that characterize phosphate depletion are somewhat reminiscent of the neuropathic arthropathy seen in Charcot foot disease, for example, meaning that the symptoms and manifestations could be partially neuropathic in origin) that can result from intracellular phosphate depletion.
Also, Goodyer et al. (1987) [Goodyer et al., 1987: (http://www.ncbi.nlm.nih.gov/pubmed/2822887)] discussed the dosage range of HVD (40 ng/kg/day, or 2800 ng/day, for a 70-kg human) that had been associated with the development of nephrocalcinosis in people with XLHR or autosomal dominant hypophosphatemic rickets (ADHR), and researchers have generally used very high dosages of either vitamin D2, vitamin D3, and/or HVD in people who have had those disorders. Goodyer et al. (1987) supposedly found adverse effects associated with an intake of 4000 IU/day of vitamin D2 in people with XLHR or ADHR, but one wonders if, given all of the problems, reported in old articles, with vitamin D supplements containing ten times the labeled content of vitamin D, the dosage was actually higher. That dosage range (4000 IU/day) of vitamin D has not been reported to cause hypercalcemia in studies in normal humans. Another possibility is that the people were taking vitamin D and HVD and that the hypercalcemia was attributed to the vitamin D (as opposed to the HVD, which is the more likely culprit, in my opinion). I say that because I've never seen any case report in which a person with XLHR or ADHR was given, as a standalone treatment, only a low dosage of 4000 IU/day of vitamin D3 or vitamin D2. In most cases, the dosages have been massive, and hypercalciuria seems more likely to be a cause of the nephrocalcinosis than phosphate supplementation per se, in most of these people. Gross et al. (1998) [Gross et al., 1998: (http://www.ncbi.nlm.nih.gov/pubmed/9598513)] found that 2.5 ug HVD/day (2500 ng/day), in normal humans who had prostate cancer, caused hypercalciuria in everyone, at dosages ranging from 1500-2500 ng/day. Reisz et al. (1990) argued, despite the past research that had associated hypercalciuria with nephrocalcinosis and that they cited, that hypercalciuria had been associated more with the development of kidney stones than with the development of nephrocalcinosis, but, in most trials in people who have not had XLHR or ADHR, the participants have not taken both HVD and phosphate supplements, in massive dosages. The dosages of vitamin D (198-1370 IU/kg/day, or 13860-95900 IU/day) and HVD (5-35 ng/kg/day , or 350-2450 ng/day) are large and, perhaps not surprisingly, the people who displayed nephrocalcinosis had been the ones who had experienced multiple episodes of hypercalciuria or hypercalcemia. Nephrocalcinosis requires pathologically-increased concentrations of both calcium and phosphate, usually, to occur. Additionally, Seikaly et al. (1996) [Seikaly et al., 1996: (http://www.ncbi.nlm.nih.gov/pubmed/8545232)] found that nephrocalcinosis was more common in people who were taking HVD and phosphate and who had renal tubular acidosis. Metabolic acidosis, in the proximal tubule epithelial cells that reabsorb most of the phosphate from the tubular fluid, can cause urinary phosphate loss, but intracellular phosphate depletion can also be an important cause of metabolic acidosis. Thus, metabolic acidosis can be both a cause and a consequence of intracellular phosphate depletion, and it's important to remember these types of complexities. The insulin resistance and mitochondrial toxicity that can result from chronic phosphate depletion have the potential to actually increase the risk of calcification, because inorganic phosphate is constantly going to be "dumped" from its "storage" in intracellular phosphocreatine and adenosine nucleotide pools, etc. That's been suggested to be one mechanism for tissue-specific calcification in any number of disorders, in people who do not have XLHR. When there are these constant metabolic crises, such as can occur in response to intracellular phosphate depletion, there will tend to be these frequent, intermittent "episodes" in which phosphate is lost from cells or from its intracellular binding to organic compounds (such as creatine) and elevated, pathologically, in the extracellular or intracellular (cytosolic or mitochondrial) fluid. More specifically, for example, rhabdomyolysis is a fairly common result of intracellular phosphate depletion, and rhabdomyolysis can cause both wild elevations in serum phosphate (and, hence, phosphate concentrations in the kidneys, potentially contributing to nephrocalcinosis) and elevations in myoglobin and other proteins, released from necrotic muscle cells. Chronic rhabdomyolysis, such as in response to exercise in a person who is phosphate-depleted, has the potential to cause more kidney damage than phosphate supplementation ever would, and there are reports of people dying from rhabdomyolysis that was associated with (and likely to have been a consequence of, in my opinion) intracellular phosphate depletion in muscle cells and other cells (http://scholar.google.com/scholar?hl=en&q=hypophosphatemia+rhabdomyolysis+renal+failure).
Furthermore, "high" intakes of phosphate are well known to actually decrease urinary calcium excretion [Hegsted et al., 1981: (http://jn.nutrition.org/cgi/reprint/111/3/553.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/7205408); LaFlamme and Jowsey, 1972: (http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=292432&blobtype=pdf)(http://www.ncbi.nlm.nih.gov/pubmed/5080411)], and the high urinary calcium excretion that accompanies phosphate depletion is thought to be due, in large part, to the ongoing breakdown of hydroxyapatite in the bone tissue [Laroche et al., 1993: (http://www.ncbi.nlm.nih.gov/pubmed/8358977)]. Incidentally, I scaled those dosages of phosphate that were given to dogs and that were associated with calcification, in the study by LaFlamme and Jowsey (1972), and the equivalent human dosages would be massive (I did the calculations awhile ago, and it works out to 8000-some mg/day or more of phosphate). I honestly don't understand what the problem is with those types of dosage considerations in research in animals. The disregard for the physiological norms, in the context of dosages of so many nutrients or compounds that are given to animals, is significant, in my opinion, and is an ongoing issue in animal research.
Incidentally, Laroche et al. (1993) discussed the neuropsychiatric and pain-related manifestations of intracellular phosphate depletion and also found that people who had phosphate diabetes (intracellular phosphate depletion) displayed symptoms consistent with reflex sympathetic dystrophy. That's a condition that's mysterious and that causes bizarre, extreme pain and other symptoms. I don't have time to go into all of that, but it's basically more evidence that neuropathy and neurological damage can sometimes be one manifestation of phosphate depletion, in my opinion (and is evidence that the "back pain" or "bone pain" of phosphate depletion may be neuropathic in origin and may not have to do with bone problems per se, independent of the central nervous system).
It's also important to remember that increases in the phosphate intake could bind magnesium in the GI tract and produce adverse effects by that mechanism. Supplemental magnesium could conceivably reduce some of the supposed risk of increases in the dietary phosphate/(Ca+Mg) intake ratio, in my opinion, although I can't make any guarantees, at all, about safety in individuals or even in general. All I can offer is my sense of things. Even though supplemental magnesium increases phosphate reabsorption in animals and can decrease parathyroid hormone release (magnesium only increases PTH levels, up to a point, when a person has been grossly deficient in magnesium) [Thumfart et al., 2008: (http://www.ncbi.nlm.nih.gov/pubmed/18701629)], magnesium has been shown to reduce the incidence or extent of calcification in animals taking massive amounts of phosphate. I'll collect some of those articles, but the point is that the use of supplemental magnesium is worthwhile, in my opinion, and is likely to be especially worthwhile in the context of an increase in the phosphate intake, from food or another source, in relation to the intakes of magnesium and calcium, etc. That said, one would want to monitor one's electrolytes and discuss these issues with one's doctor. Magnesium can elevate serum potassium and cause natriuresis (an increase in urinary sodium excretion) at high dosages, even though a high-magnesium diet (Thumfart et al., 2008) decreased urinary sodium loss in animals in that article.
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