Does Magnesium Supplementation Reduce Oxalate Absorption? Soluble vs Insoluble (and Partially Soluble) Oxalate Salts, and Why It Matters
Should I take Magnesium supplements to block absorption of oxalates in food?
What constitutes a low-oxalate diet? How long does it take to solve oxalate issues? Can we restore them once remediation is complete? How best to block their absorption? Once oxalate issues are confirmed, there are plenty of questions we are likely to have, but the one that seems to lead to most confusion is whether we should use magnesium supplements to block absorption of dietary oxalates.
A 2019 review puts forward a case for the use of magnesium supplementation to avoid calcium oxalate stones, and has been referenced by many and conclusive proof that this practice should be widely adopted. However, there’s some important nuance in this area that has important implications for what we may want to do on the frontline. But, before we get into this, let’s remind ourselves of some important principles and then take a look at what the paper says. Key principles here:
- Oxalates cause inflammation when they a) aggregate into their calcium oxalate form, and b) do so in high enough concentration
- Magnesium oxalate salts are soluble, meaning that they dissolve in liquid and can therefore move across barriers of the body (such as those found in the intestinal tract but also the kidney) with ease. Calcium oxalate salts, and the crystals that they subsequently form, are insoluble and tend to get ‘stuck’ wherever they form
- Some papers report magnesium oxalate as soluble, other report it as insoluble. This is highly confusing when reading papers. Classification of solubility helps us to understand this contradiction: magnesium oxalate is best defined as ‘sparingly soluble’, which means that it does not form a solute as easily as ‘soluble’ salts like sodium oxalate but does so much more easily than ‘insoluble’ salts like calcium oxalate. However, ‘sparingly soluble’ agents will indeed become soluble providing there is enough provided (and this is when we are talking about supplements). I will refer to magnesium as partially-soluble from this point on
Let’s look at the evidence provided, both in this 2019 study and from the body of evidence we have available, and consider how it stacks up against both ideas.
What this paper tells us
The thrust of the paper is this:
- Oxalate-stone formers are more likely to show low magnesium status
- Epidemiologic studies show that the higher the magnesium intake, the lower the rate of stone formation
- Magnesium decreases intestinal absorption of oxalate
- Magnesium can bind up oxalate in the urinary tract and, in doing so, form magnesium oxalate salts (which are much more soluble – and thus, moveable – and leave the body without problems)
- Magnesium maintains citrate concentrations at the kidney, which provides a further benefit (as citric acid inhibits oxalate crystal formation)
This is a conclusion that is based on observation. And indeed, they point to two papers (Lindberg et al, 1990, and Vagelli, 1998) that show that taking magnesium with meals is associated with reduced stone formation. So does this mean that we can conclude that we should, after all, be taking magnesium with meals? Not so fast.
At first glance, the above findings appear to provide a conclusive case for taking magnesium supplements with higher-oxalate foods. However, there are many who argue that magnesium should be taken away from meals, specifically because it makes oxalate stones more soluble (more moveable) and therefore leaves the individual vulnerable on the basis that a) oxalates in the intestines are more easily absorbed and b) although this arrives in a soluble form, complexed as magnesium oxalate, the usage of magnesium in the body (for metabolic purposes) makes it inevitable that a proportion of the oxalic acid will be liberated (due to the removal of magnesium ions from the magnesium oxalate salt) and therefore could become free to bind with calcium (with the end result being an increase calcium oxalate crystal formation).
The main rationale for taking magnesium supplementation away from the meal is firmly based on mechanistic understanding. It centres on the how, once magnesium and oxalic acid react, they form magnesium oxalate and how magnesium salts are more soluble than those formed from calcium. Soluble salts cross various barriers in the body with increased ease, explaining both why magnesium can be of help – it permits the safe removal of oxalic acid from the body – but could also allow for increased absorption from the intestines. Indeed, this 2019 does recognize research that shows magnesium oxalate to be 100 times more soluble than calcium oxalate.
This is a fairly intuitive explanation and supports the idea that we should take magnesium to ensure that there is sufficient competition with calcium (more magnesium oxalate formed, less calcium oxalate) plus in improved retention of citrate in the urinary tract (which reduces stone formation further) but to take it away from meals to minimize overall uptake of oxalic acid into the body. However, this goes against the conclusions of the 2019 study discussed above.
So what do we need to consider here? The first step is to consider the limitations in the literature, specifically that:
- The two studies reported that taking magnesium with meals was associated with reduced stone formation. This comes down to “correlation is not causation”, and it is important to note that the researchers could only speculate on how this effect was achieved
- The researchers arrived at these findings using magnesium oxide. Magnesium oxide is poorly absorbed, especially when taken on an empty stomach, although taking it with a meal has a substantial effect on improving absorption. In other words, taking this form with a meal would allow for improved magnesium status, something that has a clear benefit in avoiding the formation of calcium oxalate crystals in the urinary tract, and therefore we may see such results despite increased intestinal absorption. It’s worth pointing out that Lindberg et al did also measure the responses to magnesium citrate
- The papers in question used few participants. The Lindburg paper used only 11 volunteers, while the Vagelli paper used nine.
- Those taking magnesium supplements showed increased calcium oxalate formation. This was reported in the Lindburg paper (no data available from the Vagelli paper on this) and is quite an important finding. Unfortunately, it was not reported in the abstract or the conclusions, yet it has a crucial impact on our discussion. Although the total oxalate content of the urine decreased in those taking magnesium supplements, the amount of calcium oxalate found in the urine increased when volunteers took magnesium oxide, showing a moderate rise when taken on an empty stomach (increasing from 5.60 10-8M in controls to 6.55) and a particularly strong rise when taken with a meal (now coming in at 7.11). Even more interesting here is how magnesium citrate showed almost no impact when taken on empty stomach (5.98) but calcium oxalate formation was heavily increased when taken with a meal (now reaching 7.37).
The last point is the most nuanced but also the most important to get our heads round. Although there are a lot of dynamics at play here, including downstream impacts on both overall calcium status and calcium behaviour, especially in the urinary tract, there is one powerful point that we cannot ignore: taking magnesium supplements with a meal increased calcium oxalate formation. Let’s be clear what this means: there was more calcium oxalate in the urine but less of this was in the crystal form. This is a positive sign, but throws up a question: if magnesium supplementation with food allows more calcium oxalate to make it into the urine (but then offsets this by inhibiting its crystallization), could this go wrong in individuals who use up magnesium at a higher rate (eg. those who consume magnesium at a higher rate but then have less available at the point the oxalic acid reaches the urinary tract).
Total urine concentration of oxalate, aka oxalic acid, was reduced in both groups taking magnesium supplements (both oxide and citrate), and this was especially noticeable when taken with a meal, but it is important to note that we are less worried about oxalic acid and more about calcium oxalate, and mostly about oxalate crystals (although oxalic acid can indeed bind with minerals, which can have negative impacts on mineral status, it is the latter that is responsible for the inflammatory symptoms endemic to oxalate problems). The reality is that it is difficult to form any conclusions on what this paper means for our understanding on oxalates, particularly in regards to magnesium absorption, as it tracked only 11 volunteers for only two weeks. We cannot know how much of the urinary content reflected ‘oxalate dumping’ and what we would have seen over a longer time period.
The reliance on magnesium oxide supplements in the literature is also a major problem, not just for the two studies highlighted above but for the entire body of evidence we have. As mentioned above, magnesium oxide provides poor absorption. As a result, some take the reflexive position that we should see little effects from its use; however, the literature shows reliable changes in multiple markers. How can this be? Here, it’s important to note that magnesium oxide still delivers a large dose of magnesium into the intestinal tract, where it can sit. Magnesium oxide supplementation increases intestinal pH and crystallization of calcium oxalate is reduced at higher pH. Its important to point out that calcium oxalate crystals are not soluble, and therefore poorly absorbed. This means that, even though we typically do not want to see oxalate crystals formed, crystallization in the intestines can actually reduce the amount of absorbed oxalate.
This creates questions as to how best to employ magnesium supplements in oxalate issues, with such questions further complicated when we consider a 2011 paper that went into further depth on oxalate absorption in the intestines, measuring not just to the total absorption from a dose of oxalate (and how this varied when magnesium was added) but the mechanisms behind this. They noted that, in healthy volunteers, oxalate absorption was mainly passive and based on the amount of total soluble oxalate in the intestines. They also found that the total amount of oxalate absorbed was unchanged by the addition of magnesium. In light of all other evidence we have showing the number of ways that magnesium can impact on intestinal absorption, this points more to the net effect of magnesium being neutral (eg. the positives it offers are neutralized by the negatives) rather than it having no effect. This has big implications for individual therapy on the frontline, where we may see important differences in the intestinal conditions between two individuals and can expect these conditions to be largely different to those observed in otherwise-healthy controls. We should also note that we have an active oxalate transporter (SLC26A6) that appeared to offer no effects in this study, although human oxalate transporters are well-established to behave differently to those in mice).
It also speaks to the problem that we consistently come up against in nutritional research, which is the differential effect of any one nutrient in multiple compartments of the body (and, as a consequence, how individuals may see different responses to the same intervention, depending on what is going on in their gut and metabolic factors that affect what is happening at the kidneys).
There is one larger study that is worth examining. A retrospective analysis of 7,000 stone formers found very little effect of magnesium status on stone formation, which again might be easily interpreted as evidence that magnesium isn’t that important in oxalate issues. However, knowing that we have ample evidence of pronounced effects from clinical studies, this better speaks to the way that magnesium has multiple effects on oxalate metabolism and thus, that effects from magnesium may relate less to whether it is used or not and more to how/when it is used, and in who. This interpretation is supported by the fact the study acknowledged that that urinary citrate levels were higher in those that benefitted. As such, this study clearly can be used to support the idea that a) magnesium supplementation provides an overall help, with the most measurable benefit being the reduced formation of calcium oxalate crystals in the urinary tract and b) this benefit can potentially be offset by other effects of magnesium supplementation (in other words, there may be downsides to magnesium supplementation that transpire in locations other than urinary tract). So this is not proof, but certainly supports the idea of taking magnesium of an empty stomach, rather than with food.
Details and reaching an understanding
Further studies underline the importance of not confusing the average response from a large group with what we can expect in any one individual with any one dietary intervention. For example, another study from 2004 found that magnesium absorption was reduced by 35% when paired with a dose of highly-soluble oxalic acid (from spinach), indicating that more magnesium (and, presumably, magnesium oxalate) was retained in the gut. This makes sense when we consider that the oxalates in spinach are highly soluble, so that an agent that makes some of these oxalates partially-soluble (ie. magnesium) would provide a strong positive effect in these circumstances.
A 2003 study compared the absorption of 10mg of oxalate, either as a free acid (highly soluble) or bound to sodium or calcium. They found that absorption of free oxalate was 17%, while that in the sodium form saw 13% absorbed while the calcium form was only 2% absorbed. The most obvious difference between the two forms is that sodium oxalate is soluble (like the magnesium form, albeit at higher concentrations of magnesium), while calcium oxalate is not. Crucially, they did not test magnesium oxalate absorption. Two other papers (Holmes, 2004, and Chai & Liebman, 2004) also conclude that the biggest factor influencing the rate of dietary oxalate absorption is the amount of soluble oxalates in the gut. However, once again, neither researcher measured magnesium oxalate absorption, although magnesium’s partially soluble nature means it is well-characterized in increasing the solubility of insoluble oxalates but reducing the solubility of soluble oxalates.
Both a 2000 paper and a 2005 paper (by the same research group) investigated absorption of oxalate in the presence of both calcium and magnesium and came to broadly similar conclusions; magnesium reduced absorption, but calcium reduced this further. The later paper went further in that they provided different doses of magnesium, comparing effects of placebo, low-dose magnesium (243mg) or high-dose magnesium (486mg, both in the form of magnesium aspartate). The oxalate was radio-labelled so that the researchers could easily measure where it ended up. What they found was very interesting: there was a reduction in oxalate absorption when they provided magnesium alongside it, but that these benefits were less pronounced at the higher dose. In other words, magnesium alongside oxalate was beneficial but, at a higher dosage, these benefits started to fade. Clearly, it cannot be a case that “more magnesium = less oxalate absorption”. There needs to be more than one interaction going on here, with certain outcomes achieved by low doses (eg. soluble oxalates become only partially soluble) and other outcomes enhanced (eg. same effect on soluble oxalates, but increased effects on making insoluble oxalates partially soluble) when there is increased availability of magnesium. Further data for such considerations come from two papers (Leibman & Chai, 1997, and Brogen & Savage, 2003) that tracked the impact of calcium on oxalate absorption at different doses; they found that, unlike magnesium, calcium showed dose-dependant inhibition of oxalate absorption.
It is worth noting that all the available evidence supports our understanding that magnesium has three main effects on oxalates:
- altering the pH in favour of more alkaline conditions in various bodily compartments which discourage formation/absorption of calcium oxalate crystals (POSITIVE across the body, NEGATIVE in the gut when taken with meals)
- at moderate doses, a calcium-sparing effect, where magnesium binds with agents in place of calcium, freeing up more calcium and therefore making it able to form insoluble calcium oxalate crystals in the gut (POSITIVE)
- at higher doses, an increased amount of partially-soluble oxalates which presumably permits increased absorption (NEGATIVE when consuming insoluble oxalates in the diet)
- competition with calcium for binding with oxalate in the urinary tract, and therefore lower formation of calcium oxalate here (POSITIVE)
- increased retention of citrate at the kidneys, which further inhibits for the formation of oxalates (POSITIVE)
What we know, and what we do not
What we know…
- Individuals with low magnesium status are more likely to form oxalate crystals
- The benefits of magnesium supplementation are most obvious when correcting a magnesium deficiency, rather than taking those who are already well-supplied and adding more
- There are no studies that adequately measure differential effects of oxide, citrate, glycinate, malate, etc, nor any studies that measure intestinal uptake following the use of such supplements
- These benefits have been well-linked to the effects of increased magnesium and improved retention of citrate in the urinary tract, but are complicated due the effects of magnesium elsewhere
- It’s complex
Questions that remain…
Oxide vs commonly used forms. Other than Lindberg’s 1990 study, which compared the commonly-used citrate form to the poorly-absorbed oxide version, there have been no studies that undertake a head-to-head comparison of different types of Magnesium. In fact, almost all research in this area was conducted in the eighties and nineties and was done so using magnesium oxide, a form that is rarely used in clinic due to its poor absorption. As such, it is difficult to extrapolate conclusions that may directly relate to clinical choices in the current day, where practitioners tend to use the better-absorbed forms (such as citrate, ascorbate, glycinate, aspartate, etc). The Lindburg study showed no significant differences between the two forms, although we must bear in mind that this data came from only 11 participants.
Impact of magnesium ‘burn rate’. One concern is that emotional and physical stress can deplete magnesium availability (due to increased usage). If, as is implied above, taking magnesium with a meal increases oxalic acid absorption but does so in the ‘harmless’ magnesium oxalate form (and, thus, has a net positive effect), will this same effect be seen in individuals who burn through the magnesium they absorb at a quicker rate? Obviously, the less magnesium there is available, the less ability this magnesium pool has of continually binding to oxalic acid and the more chance of ‘free’ oxalic acid being spilled into circulation (where calcium can take over and bind it, forming calcium oxalate crystals in the process).
Why I don’t recommend it with meals
As I hope I’ve made clear above, the use of magnesium supplements with oxalate-rich meals is subject to many considerations. And this means that, depending on the individual in question, their current dietary intake and the doses involved, it can provide both benefits and harm.
Thus, while I wouldn’t consider it ‘wrong’ to use magnesium supplements with meals for all of the complexities discussed above, there are two very simple conclusions that we can make:
- magnesium is hugely important for the metabolism in general and supplementation provides multiple benefits
- in those with oxalate issues, magnesium provides a mixed benefit/harm profile when used with meals but provides only benefits when taken away from meals
- there are no such concerns for using calcium with meals
- in both the head-to-head comparisons we have for calcium and magnesium (when taken with meals), calcium outperformed magnesium
Summary: if you want to block oxalate absorption, your choice is between a combination of effects from magnesium, which will hopefully result in a positive outcome, or getting a more simple/reliable benefit from calcium.
There was some fresh look at oxalate detox from Chris Masterjohn lately at https://chrismasterjohnphd.substack.com/p/can-biotin-help-detoxify-oxalate
That’s a great article, thanks for sharing it!