The authors of this article [Hathcock et al., 2007: (http://www.ajcn.org/cgi/content/full/85/1/6)(http://www.ncbi.nlm.nih.gov/pubmed/17209171?dopt=Abstract)] reviewed a number of clinical trials in which researchers had used dosages of vitamin D ranging from 2,000-100,000 IU/day of vitamin D3, and the research generally shows that hypercalciuria hardly ever occurs at dosages of vitamin D3 of 2,000-4,000 IU/day. Hypercalcemia hardly occurred at any of the reasonable dosages and didn't even occur at 100,000 IU/day. There probably isn't a dose of vitamin D3 that has zero potential to elevate urinary calcium, and the slight elevations in serum calcium that oral vitamin D3, in particular, tends to cause (in my opinion) have the potential to exacerbate thrombogenic conditions, as discussed in past postings (http://hardcorephysiologyfun.blogspot.com/2009/01/calcium-magnesium-serum-calcium-vitamin.html).
Sayer et al. (2004) [Sayer, 2004: (http://cs.portlandpress.com/cs/106/0549/1060549.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/15027893)] analyzed a lot of research on the mechanisms underlying nephrocalcinosis, which technically refers to an increase in the calcium contents of the kidneys but is generally taken to mean calcification, meaning the deposition of calcium phosphate (usually in the form of apatite), in parts of the kidneys, and Sayer et al. (2004) basically argued that hypercalciuria is the factor that seems to be associated with nephrocalcinosis. Even relatively small increases in the intake of phosphate have generally decreased the rate of urinary calcium excretion, and phosphate (from sodium or potassium phosphate) at something like 1,000 mg/day has been used to prevent kidney stones in recent decades. Then I guess everyone decided that phosphate is a "vice" or something and had to be removed from the diets of everyone. The research that I've discussed in recent postings indicates that taking very high dosages of phosphate (generally supplemental phosphate at greater than 70-100 mg/kg/day), along with hormonal vitamin D at dosages that cause intermittent hypercalcemia and hypercalciuria, creates the conditions that can cause nephrocalcinosis. But vitamin D itself generally does not cause either hypercalciuria or hypercalcemia, and there's some moderate dosage (i.e. 2,000-4,000 IU/day, as a conservative dosage) that could help keep the parathyroid hormone levels low but could do so without elevating urinary calcium unnecessarily. There's likely to be some middle ground, in my opinion.
One approach would be to use adequate dosages of magnesium (the research is really disorganized in magnesium, and that's the reason I keep avoiding citing all the articles I have on it), given that magnesium has the potential to help prevent nephrocalcinosis (http://scholar.google.com/scholar?hl=en&q=magnesium+nephrocalcinosis), in my opinion, and avoid calcium supplements and get calcium from milk or something like that. (There's some research claiming to show that magnesium decreases apatite formation but increases amorphous calcium phosphate formation, which is not really dangerous, but the research in actual animals generally shows that urinary magnesium wasting, from any number of causes, and decreases in magnesium status/intakes can increase the risk of calcification, in the kidneys and other sites.) I don't take supplemental calcium anymore and get enough calcium from milk that I use to "eat cereal." But anyway, the dosage range of magnesium is large, and I don't really feel like getting into a discussion of it and then have to "wade" through the research. The research on magnesium is not reader-friendly, really, and is surprisingly complex. Magnesium oxide (MgO) is absorbed relatively slowly, throughout much of the small intestine, and chelated magnesium aspartate (MgAsp) or MgAsp HCl (they're not the same) are absorbed more rapidly and are probably absorbed through either the amino acid or dipeptide transporters or by passive diffusion. Magnesium from magnesium oxide is likely to be absorbed by divalent metal transporters or by passive diffusion and the solvent drag mechanisms that enhance the absorption of some cations by passive diffusion. Some people report in the literature that the bioavailability of chelated MgAsp is basically too high for some people to be able to tolerate, and there might be something to that. If it enters the brain too rapidly, it can cause sort of drowsiness or mental sluggishness. The last time I tried chelated MgAsp, I experienced that sort of problem with it and went back to MgO. Some people can't tolerate MgO, however, at higher dosages, given the nausea and GI effects that it can cause. In that case, MgAsp might be preferable. Magnesium orotate would potentially be problematic, in my opinion, because of the orotate, as I discussed, indirectly, in one of my old papers (http://hardcorephysiologyfun.blogspot.com/2009/08/some-more-old-papers-of-mine.html).
I've never seen a report of true toxicity from magnesium at anything resembling a reasonable dosage (even 1500-2000 mg/day have been used in some research), and the occasional reports of hypermagnesemia have generally occurred in people taking 2500-3000 mg/day or more. The intravenous magnesium dosages used in various therapeutic contexts produce really high serum magnesium levels, but any excess is likely to mainly end up being excreted in the urine almost immediately. There could be some problems with fasting blood glucose levels decreasing in diabetics, in response to Mg supplementation, and it can transiently lower blood pressure and elevate serum potassium (and decrease urinary sodium reabsorption). The changes in sodium and potassium excretion might produce the acute decreases in blood pressure, but, supposedly, the low-level calcium channel blocking effect can reduce blood pressure a little bit. But the blood pressure changes seem to not really persist to as great a degree as one might think. In people who are hypertensive, there might be more of a lasting effect, but I don't know that I'd expect much in that area. The research is sort of mixed on that, but there can be a transient decrease in blood pressure that does not last longer than a day or two, after any increase in the dosage. Obviously, one would want to talk about these things with one's doctor. Magnesium, like many things, could cause side effects (such as electrolyte abnormalities, etc.) that could be detrimental, in conjunction with the effects of medications, for example, but that would not really constitute toxicity, in my opinion, at reasonable dosages. Even in the cases of supposed death by magnesium dosages of 15,000-30,000 mg per day, the person had been drinking the whole bottle of the OTC magnesium supplement for a long time, in one case. And it wasn't clear to me that the existing kidney failure, not the bizarrely high dosages of magnesium, hadn't actually been the cause of death. Magnesium could conceivably increase phosphate turnover or the dietary phosphate requirement, either by binding to phosphate in the GI tract, thereby potentially increasing the requirement, or by increasing the activities of glycolytic enzymes. Reporting on the research on magnesium is like pulling teeth, though, because of the variable qualities of the bioavailabilities and even percent absorption of different magnesium salts or chelated forms. The only other thing I can think of to say is that magnesium aspartate may not mean chelated magnesium aspartate, depending on the manufacturer's labeling practices. Chelated MgAsp is not the same thing as MgAsp as a salt. In MgAsp, the Asp(2-) and Mg2+ are ionized. In chelated MgAsp, the Mg is bound to the aspartate by coordinate covalent bonds. A chelate tends to be absorbed (a significant percentage of a dosage) intact and transported by dipeptide or amino acid transporters or by passive diffusion, but a salt (an ionic pair in crystalline form that dissociates upon entry into solution) dissociates in water.
I should mention that I don't take a multivitamin, because of all of the potentially problematic "ingredients" in it. The only "minerals" or metals I take in supplemental form are selenium, from sodium selenite, at about 150 ug/day, 150 ug of iodine (from potassium iodide), magnesium, and a low dose of molybdenum. Iodine can basically shut down thyroid function at dosages slightly higher than the RDA of 150 ug/day, especially some people, and selenium can also decrease thyroid hormone levels (and cause obesity or something and decrease serum IGF-1 levels, etc.) at dosages of even 200-300 ug/day, according to some research [(http://scholar.google.com/scholar?q=selenium+thyroid+adverse&hl=en); Hawkes et al., 2008: (http://www.ncbi.nlm.nih.gov/pubmed/18565425)]. I can't get the articles showing IGF-1 decreases to show up, but one has to ask oneself what the mechanism would be for that. It doesn't sound like a good effect to me and doesn't sound like a great way of supposedly preventing cancer, but the decreases in IGF-1 may (or may not) only occur at the higher dosage range. But overt selenium deficiency (it's probably uncommon) can also decrease thyroid hormone formation. The function of selenium, in my opinion, is to serve as a cofactor of thioredoxin reductase enzyme complexes, glutaredoxin reductase enzyme(s), glutathione peroxidase enzymes, etc. (and ribonucleotide reductase). It seems like it can have relatively significant effects on antioxidant enzymes, but I'd suggest watching out for those adverse effects. The dosage that causes those effects in one person might be lower than the dosage that causes them in another person. One approach would be to stick to the low end of the range or evaluate how much selenium one gets from his or her diet Manganese is abundant in foods and has been shown to cause psychiatric and neurological derangements, when given in excess, in supplemental form. So I definitely don't supplement with that. Copper and zinc are very problematic in supplemental form, in my view, and are abundant in foods, and I don't take those. And then there's all the potentially neurotoxic or "choroid-plexus-epithelial-cell-toxic" vitamin A and beta-carotene in some multivitamins. I take a small amount of iron protein succinylate, because I work out like a @#$%&%$ madman. That's an exaggeration, but it's a bare-bones approach. In any case, I can't advise anyone on these more boring topics, even, or on any other topics. One would want to talk with one's doctor about these things.
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