This article [Zimmermann et al., 1996: (http://www.ncbi.nlm.nih.gov/pubmed/8676818)] is really interesting, and the authors discuss and cite research showing that alpha-ketoglutarate and other keto acids (and even free-form amino acids, under some circumstances) can significantly decrease serum phosphate and parathyroid hormone (PTH) levels. I was really surprised by this, but there are dozens of articles showing the same thing. The authors of some of the older articles attributed the effect of the keto acids or amino acids, which were used with the intention of reducing either serum PTH or serum phosphate levels or both, in people with kidney disease, to the phosphate-binding effect of the calcium in calcium salts of keto acids (a.k.a. ketoacids). But it's pretty clear that it's not the calcium, primarily, because several articles show the effect can occur in response to the intake of ornithine alpha-ketoglutarate or other amino acids or keto acids (without any increase in calcium intake) [here's one of them: Combe and Aparicio, 1994: (http://www.ncbi.nlm.nih.gov/pubmed/7853797)]. I don't have time to put the rest up now, but I will shortly. In most of the articles, the authors have attributed it to the capacity of the amino acids to drive extracellular phosphate into cells, such as in association with increases in nucleotide biosynthesis and DNA replication, etc. It's similar to the hypophosphatemia that can occur in the "refeeding syndrome" (a disturbance in the homeostasis of phosphate or sodium or potassium, etc., in response to an acute increase in nutriture, basically, although that definition is imprecise: http://scholar.google.com/scholar?num=100&hl=en&lr=&q=refeeding+hypophosphatemia), and I found some other articles discussing hypophosphatemia in response to increases in the amino acid intakes of people on total parenteral nutrition (such as in some disease state that necessitates the intake of food by some other route than enterally, or orally) [Lamiell et al., 1990: (http://www.ncbi.nlm.nih.gov/pubmed/2108005)]. In that case, the authors more or less definitively established that the amino acids per se were causing hypophosphatemic encephalopathy (abnormal state of consciousness, such as confusion or extreme fatigue or drowsiness or dementia) in a man.
The message that comes out of a lot of the articles, taken together, is, in my opinion, that disease states or physical trauma or muscle wasting, etc., increases the likelihood that a person could develop hypophosphatemia or another electrolyte abnormality (or a milder depletion of serum phosphate). What's interesting and unfortunate is that these are the very disease states in which L-glutamine and arginine have been used therapeutically. The authors of this article
[Maier-Dobersburger et al., 1994: (http://www.ncbi.nlm.nih.gov/pubmed/8201756)] refer to the fact that physical trauma or muscle wasting and undernutrition can increase the requirements of cells for "growth-promoting" substrates [(http://scholar.google.com/scholar?num=100&hl=en&lr=&q=catabolic+glutamine+OR+ketoglutarate); (http://scholar.google.com/scholar?num=100&hl=en&lr=&q=wasting+glutamine+OR+ketoglutarate)], which glutamine would be an example of, and cause the normal phosphate intake to become inadequate. This increase in the requirement for glutamine or arginine or exogenous nucleotides makes the use of those compounds rational, but the message that comes from the articles on the hypophosphatemic effects that can occur, as in response to supplementation with alpha-ketoglutarate and other amino acids or keto acids, is that the amino acids could then, in my opinion, exacerbate the hypophosphatemia in some people.
In my opinion, high doses of glutamine or conceivably arginine or other amino acids could decrease the serum phosphate in people who are not suffering from obvious disease states, particularly under certain conditions. For example, Maier-Dobersburger et al. (1994) noted that low vitamin D status has been associated with hypophosphatemia, and I think low magnesium intake is associated with low serum phosphate, also. But I think the potential hypophosphatemic effects of some of these amino acids or keto acids might have something to do with an increase in the excretion of phosphate by the kidneys, such as in response to changes in the acid-base balance. There are at least two articles showing that the ingestion of only 2 grams of L-glutamine can increase serum bicarbonate [Welbourne, 1995: (http://www.ncbi.nlm.nih.gov/pubmed/7733028); Welbourne et al., 1998: (http://www.ncbi.nlm.nih.gov/pubmed/9537612) (http://www.ajcn.org/cgi/reprint/67/4/660.pdf)], and the authors suggested that the effect might have occurred in response to the growth-hormone release that glutamine had induced. Glutamine is used as a growth hormone releaser and was shown to release growth hormone in one of those articles (Welbourne, 1995), but I don't think that's the main mechanism for the increase in serum bicarbonate in response to glutamine. Welbourne et al. (1998) discuss the fact that the breakdown of glutamine, into glutamine and ultimately alpha-ketoglutarate or glucose (by glutaminase and either glutamate dehydrogenase or aspartate aminotransferase, respectively) in the kidneys, is an important mechanism whereby ammonia, derived from glutamine, can be excreted as the ammonium cation (NH4+) and thereby acidify the urine (in response to metabolic acidosis). Bichara et al. (1990) found that an increase in the urinary loss of phosphate occurred in concert with an increase in the urinary acidification, produced by ammonia excretion (as the ammonium cation), and part of this increase in the acidification of the urine was the result of an increase in serum parathyroid hormone (PTH). The PTH had increased in response to metabolic acidosis, and the extra PTH contributed to the phosphaturia (loss of phosphate and ammonia in the urine). It's long been known that, all other things being equal, elevations in PTH increase phosphate excretion, but the interesting thing is the association with ammonia excretion and with acidosis per se. In "milk alkali syndrome," the high amounts of phosphate and calcium in cow's milk can lead to metabolic alkalosis (when a person drinks excessive amounts of milk, and the syndrome usually occurs in very young children, as far as I know).
The relevance of this is that, in my opinion, the metabolism of glutamine, as opposed to alpha-ketoglutarate, in the kidneys, with relevance to the potential for phosphate excretion to be "coupled" to urinary acidification by glutamine-derived ammonium, seems like it would be subject to more regulatory mechanisms than the metabolism of alpha-ketoglutarate (and could, in my opinion, be somewhat less likely to produce hypophosphatemia than alpha-ketoglutarate would be. Phosphate depletion can occur during endurance events, in athletes, and this type of thing could happen in a person starting an exercise program, etc. It would be wise for a person to monitor his or her serum phosphate levels, under a doctor's supervision, when starting any of these supplements. And one should discuss, with his or her doctor, any risk factors that he or she might have for the development of electrolyte disturbances. I don't have time to go into the other relevant points, but glutamine metabolism in the kidneys is very different from glutamine metabolism in the liver and in other organs [Baverel and Lund, 1979: (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1161843)]. Also, some articles discuss the fact that exogenous alpha-ketoglutarate would, as expected, enter the cytosol in the cells of the kidneys, and cytosolic alpha-ketoglutarate produces different regulatory effects, in comparison to glutamine itself, on glutamine metabolism and, for example, dicarboxylic acid uptake from the blood into cells in the kidneys. Some articles discuss the fact that not much alpha-ketoglutarate is likely to be converted into glutamine, even though alpha-ketoglutarate can sometimes "spare" glutamine breakdown. This fact is relevant in the context of the kidneys, in particular.
Taking phosphate supplements without a doctor's supervision, especially at anything resembling a high dose, is, in my opinion, unwise and potentially dangerous. I don't know if they're even available, because (in response to the black-box warning, by the FDA, of the risk for acute renal failure due to high-dose phosphate ingestion, to prepare for some medical procedures, in some people) some companies withdrew their over-the-counter phosphate-containing products sometime last year. The doses of phosphate associated with acute renal failure, due to acute phosphate nephropathy (http://scholar.google.com/scholar?q=acute+phosphate+nephropathy&hl=en&lr=), tended to be very large (18 grams or more, in some cases, but I only looked at a couple of articles today). In my opinion, the use of something like vitamin D supplementation or "milk intake" (apparently milk has a high level of phosphate in some unusual form, complexed with casein and calcium in colloidal form), to alter one's phosphate absorption or excretion, would be a safer approach. I mentioned some of the issues with vitamin D supplementation in past postings. Magnesium has really complex interactions with PTH and phosphate metabolism, and I can't go into those now.
But the problem with the approach of increasing one's phosphate intake would, in my opinion, be that an acute increase in phosphate intake will tend to increase PTH release, thereby exacerbating any PTH-mediated urinary phosphate loss (Combe and Aparicio, 1994, cited above, discuss that). An increase in the serum 25-hydroxyvitamin D level will decrease PTH levels [this effect, which is linear up to like 200 nM of 25(OH)D, simply cannot be due to more and more renal 1alpha,25-dihydroxyvitamin D (hormonal vitamin D) production, because the production of hormonal vitamin D plateaus above a certain 25(OH)D level] and reduce urinary phosphate loss by that mechanism, as far as I know. The metabolic effects of abnormally-high hormonal vitamin D are very different, in the absence of a granulomatous disease, than the effects of elevated 25(OH)D levels (within the range of "safe" levels). Some articles have shown serum 25(OH)D levels to be roughly-inversely associated with serum hormonal vitamin D levels, over a certain range of 25(OH)D levels (probably reflecting a reduction in the output of macrophage-derived hormonal vitamin D or something, etc.). I think low magnesium intake can decrease serum phosphate, but increasing magnesium can increase PTH responsiveness and increase PTH output, in some cases. The situation is really complicated with magnesium.
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