Restriction diets are useful when trying to manage symptoms related to the gut, and the low oxalate diet is no exception. We see this in people:
- With SIBO on a low FODMAP diet
- With IBS on an SCD diet
- And the Keto diet seems to help out people with a variety of issues.
But just because a diet manages symptoms in the short-term doesn’t make it a great long term solution.
An excellent example of this is the use of PPIs in people with gastritis. Sure, decreasing acid exposure to a damaged stomach wall will decrease symptoms. But it doesn’t typically address the underlying issue. So, people take them for months on end to manage symptoms and end up paying later down the road.
The low oxalate diet: Makes sense on paper but what does the data say?
You see the same thing happening with oxalates. On paper, a low oxalate diet makes sense if you buy in to a lot of the info put out on the topic. Oxalates are a toxin that plants such as spinach, beets, nuts, potatoes and sweet potatoes use to defend against us. We absorb them, they circulate throughout the body poisoning cells, and destroying mitochondria.
The problem is, the data on this is shaky at best. First of all, most of it is in petri dishes. Secondly, when we take a look at how oxalates behave in the body, it’s unlikely that consuming oxalates is either:
- B)The primary cause of any problem
But to be clear, they are an issue for a significant number of people. At the onset of gut healing, decreasing oxalate intake is an intelligent way to start the process. But it’s only the first step and something you should move beyond to address the underlying cause.
Another significant issue is that we produce oxalate, and production is equal to or greater than intake in the diet.
Note: I recently published a bit of a rundown on how we process oxalate on youtube. Click here to check it out if you haven’t already.
Are oxalates toxins?
This one is pretty easy to quash right away. If oxalates were a human toxin, you’d expect to see mortality increase in a population as people consume more. With regard to oxalate, nuts are loaded with them. But as nut intake increases, mortality actually decreases. This is the opposite effect you’d see with a toxin.
Similarly, legumes are also high in oxalate, but higher consumption is associated with lower mortality risk. It’s not a large effect, but if they were a toxin mortality would increase. Soy, another high oxalate food, shows no increase or decrease in mortality with increased intake. So it’s hard to really take oxalate as a toxin seriously. Mercury, lead, arsenic, and even alcohol are toxins.
This isn’t to say that people can’t have problems with oxalate. People with primary hyperoxaluria have a defect in glyoxylate metabolism that increases oxalate production. As a result, they have an elevated amount of oxalate in the urine. These people are more likely to form kidney stones and can have problems elsewhere when calcium oxalate stones form.
Secondary/enteric hyperoxaluria occurs via excess absorption from the gut. But addressing the cause should be the focus , not dropping oxalate intake to zero. Potential causes include leaky gut, inflammation, a high fat diet, and low calcium intake.
We have very efficient means of eliminating oxalate in both the stool and urine. But this capacity is limited and depends on:
- The amount we make
- How much we absorb
- How much inflammation we have in the gut or kidneys
Clearly this isn;t simply a function of how much oxalate we eat in our diet.
Removal of oxalate from tissues
As I mentioned, we have a pretty great system for getting rid of oxalate. Oxalate is pumped out of cells via a transporter known as Solute Carrier Family 26 Member 6(SLC26A6). This transporter exchanges chloride outside of the cell for oxalate, sulfate, or bicarbonate inside the cell. In other words, when oxalate enters, SLC26A6 kicks it to the out if there is adequate extracellular chloride.
- The brain
- Bone marrow
- Immune system
- Reproductive tissues
In the intestine it plays a pivotal role in reducing oxalate absorption. This is coupled with another transporter that pulls oxalate out of the blood. Thus, we have efficient means of removing the oxalate that we eat, as well as produce.
When oxalate from the diet or blood enters enterocytes and colonocytes, SLC26A6 sends the oxalate right back in to the gut in a process called secretion. This prevents absorption in to the blood and removes excess oxalate from the body.
Oxalate absorption from the diet
Oxalate absorption throughout the gut varies depending on the presence of transporters. There is low absorption in the small intestine and proximal colon and high absorption in the distal colon.
But this isn’t because oxalate doesn’t enter the cells in the small intestine, it does. The small intestine and proximal colon have a high expression of SLC26A6 that pumps oxalate back in to the gut. Thus, these portions of the gut cause net oxalate secretion, or removal. The distal colon has net absorption…sort of. Back to that in a minute
So increased oxalate absorption, as seen in secondary/enteric hyperoxaluria probably has something to do with SLC26A6, right? Absolutely. In a nice little study in mice, obese mice excreted 3.3x more oxalate in their urine than healthy controls. This was not due to changes in diet because the mice were pair-fed, meaning their diets were identical.
Removing oxalate from the diet in the obese mice corrected their hyperoxaluria. This indicates that excess oxalate came from dietary absorption, and not production.
Chronic inflammation as a driver of oxalate accumulation
The obese mice had an 80% reduction in SLC26A6 activity in their jejunum when compared to the healthy mice. This led to net oxalate absorption in obese mice; the healthy mice had net oxalate secretion back in to the gut. Must be the genes, right? Not so much.
Treating healthy jejunal tissue with the same inflammatory soup that one would experience with obesity leading to excess lipopolysaccharide(LPS) in the gut dramatically decreased expression of SLC26A6. This decreased jejunal secretion by 46%, converting the jejunum in to a net oxalate absorber. AND I MUST EMPHASIZE THIS: INFLAMMATION CAUSED THE OXALATE PROBLEM, THE OXALATE PROBLEM DIDN’T CAUSE THE INFLAMMATION!!!
Now, it’s important to point out that this transporter works in basically the same way everywhere. So systemic inflammation induced by LPS likely decreases SLC26A6 in all tissues where it’s expressed; it’s the same inflammatory soup. So, in systemic inflammation, you’d expect to see oxalate accumulate more rapidly in tissues where SLC26A6 is highly expressed.
Insights from kidney stone formers
People who form kidney stones aren’t the only people who have issues with oxalate. But, you can argue they have the most severe issues outside of PH, which is more about production than absorption. When we look at kidney stone formers, men and older women who consume the most oxalate have a 22% and 21% increased risk of forming stones when compared to the lowest. There was no increase in risk from oxalate or spinach intake in young women.
To put this in to perspective, men who weigh more than 220lbs have a 44% higher risk when compared to men who weigh 150lbs. Women who fit the same bill have a 90% increased risk. Having a HgA1c indicative of pre-diabetes increases risk by 68% and HgA1c indicative of diabetes increases risk by 182%.
When we look at the physiology behind stone formation it makes perfect sense. Obese people and those with Type 2 diabetes are more at risk for leaky gut, chronic inflammation, and activated immune cells. Both accumulate more LPS in their gut. Each condition has leaky gut leading to increases absorption of LPS. Increased absorption of LPS increases systemic inflammation and immune activation. This chain of events locks oxalate into tissues and forms calcium oxalate stones.
LPS, inflammation, and oxalate production
LPS also promotes an environment where more oxalate can be formed in the body. Type 2 diabetics and people on their way to Type 2 diabetes create more glyoxylate, a precursor to oxalate. Exposing the liver to LPS impairs autophagy, leading to an accumulation of enzymes that break down glucose, including lactate dehydrogenase(LDH).
You wouldn’t necessarily see this in obesity as in the mouse model above. It’s more of a byproduct of the Type 2 diabetes-induced glyoxylate formation and conversion to oxalate. But how?
A recent study in mice showed that LDH was the primary route of oxalate production in the liver. Knocking down LDH in the liver of mice with PH 1 & 2 caused a dramatic drop in urinary oxalate. It also decreased oxalate stone formation.
Based on all this data, tackling obesity and/or type 2 diabetes would yield far better results than decreasing oxalate intake. In fact, it would produce 2-9x the results, and all the mechanisms match up.
Reducing inflammation will yield better results than a low oxalate diet
Leaky gut induced inflammation is likely the biggest culprit in oxalate accumulation. It affects absorption from the gut as well as our ability to remove it. Addressing inflammation addresses the primary cause of the problem, but temporarily lowering oxalate intake is useful.
This helps explain why a low oxalate diet works for autism. Data has shown that children with autism have much higher plasma and urinary oxalate levels than healthy children.
But, children with autism also have leaky gut, which impairs oxalate removal. They have a more than 5-fold elevation in lipopolysaccharide-binding protein, a marker of LPS absorption, than healthy controls. This explains the chronic inflammatory state and may ultimately be the reason oxalates are a problem.
The most pragmatic approach is to address leaky gut at some point, not maintain a low oxalate diet ad infinitum. Our intestine is exquisitely designed to handle oxalate with transporters that pump it back in to the gut. Most of our other organs do as well, and it’s unlikely that oxalate is triggering leaky gut.
But we’re not finished. We have a little friend in our colon who can provide us with a little assistance from time to time. If you’ve dabbled with a low oxalate diet for any significant amount of time I’m sure you’ve heard of her: Oxalobacter formigenes.
Oxalobacter formigenes: our oxalate degrading friend
Anyone who has thought about doing a low oxalate diet has heard of Oxalobacter formigenes. Many believed that the primary way it helps with oxalate is by degrading the oxalate we eat. It’s not.
Oxalate secretion also happens in the colon, and guess which critter we find nestled up next to the SLC26A6 transporter. You got it, Oxalobacter formigenes.
But O. formigenes isn’t just chilling there to passively grab a snack. She’s also secreting proteins that upregulate the transporter that pulls oxalate out of the blood and in to the gut. To the tune of 2.4x. Cool!
But let’s not forget that inflammation decreases this by 80%. Eliminating inflammation will increase SLC26A6 4x as much, almost double what colonization with O. formigenes will.
A low oxalate diet reduces O. formigenes in the gut
So now you’re probably asking yourself, what if I don’t have O. formigenes? Well, good question. I don’t think it’s all that big of a deal unless you’re pumping out oxalates. And it appears that exposing oneself to a diet with oxalate is the best way to ensure you have O. formigenes.
Based on the study just mentioned, a low oxalate diet will pretty much wipe them out. Maintaining oxalate consumption maintains O. formigenes colonization. And who knows the effect when inflammation reduces SLC26A6 based oxalate secretion it to the gut by 80%?
But, is it hard to colonize with O. formigenes if you weren’t born with it? Good news, you weren’t born with it so you can probably get it.
Prevalence of O. formigenes in US and hunter gatherer Mothers
A glaring problem with the hypothesis that oxalates are universally toxic is the high consumption of oxalates in hunter gatherer populations. Despite high intake, they don’t appear to have a problem handling oxalates.
It must be the presence of O. formigenes, right? Well, there’s a problem with that theory.
Despite those populations having a higher prevalence of O. formigenes colonization, it’s still only 60-80% of them. So why aren’t the other 20-40% of them doubled over in pain from their high oxalate consumption? Could it be because they aren’t overweight and diabetic?
But what about mothers and children here in the US? While O. formigenes colonization is much lower here, it’s not something we take from Mother to child from birth, nor do hunter gatherers.
Children in the US AND in hunter gatherer populations don’t have O. formigenes at birth. In the US children, colonization didn’t begin until 1 year of age. In the hunter gatherer populations the earliest was 3 months and 9 months in Amer-indians and Hadza, respectively. However, the general trend in all groups was no colonization until 1 year of age.
So how do these children get colonized with O. formigenes if they aren’t born with it? If oxalate consumption drives O. formigenes colonization, they must get exposed to oxalate from some external source.
Given that hunter gatherers don’t shop at CVS for formula, the mothers must have passed oxalate to the child via breast milk. Kind of odd for a mother to pass a human toxin along to their child in breast milk. Particularly one so heavily consumed for the vast majority of primate evolution.
Additionally, in the US cohort, children had O. formigenes even when their mother didn’t. Children born from mothers who were negative for O. formigenes could still be colonized with O. formigenes up to 2 years of age, when the study stopped.
Taking all of the data in to consideration, oxalate is most definitely not a human toxin. Indeed, if oxalate were toxic to us, mothers wouldn’t pass it to their non-colonized babies. There also wouldn’t be a beneficial response in doing so.
It’s also abundantly clear that the modern human lifestyle which drives obesity, Type 2 diabetes, hyperglycemia, leaky gut, and chronic inflammation is the primary driver of oxalate problems. While lowering oxalate in the diet may provide symptomatic relief, there’s little doubt that doing so chronically will decrease colonization with O. formigenes and make things worse in the long run.
Regardless, O. formigenes colonization probably only provides modest benefit anyways since 20-40% of hunter gatherers, who have a high oxalate diet, aren’t colonized with O. formigenes.
The real problem with addressing these issues with a low oxalate diet is that you are ignoring the actual cause of the problem. And by ignoring the problem you are likely making it much worse and more difficult to correct.
We know several drivers of leaky gut and most of them are correctable by modifying your behavior. We’ve covered 3 in our short course 3 Common Causes of Leaky Gut.
Other factors are involved, too. Persistent viral and bacterial infections, microbial dysbiosis, heavy metal toxicity, and even some things outside of our control such as our genetic predisposition to inflammatory bowel disease and other genetic factors, including primary hyperoxaluria. But, ignoring the lifestyle component only makes these things worse, and you have no control over genetic predispositions.
Thus, while a low oxalate diet may be useful in the short term to manage the symptoms associated with secondary/enteric hyperoxaluria, anything short of identifying and addressing the actual cause will likely cause problems further down the road.