Hyperoxaluria and Functional Deficiencies
For the first 12+ months of my illness, the bulk of any diet changes, supplements, or specific treatments were a crapshoot, at best. I tried the paleo-keto version of the Wahls Protocol, embarked on the extremely restrictive auto-immune protocol, and (as per a recommendation from Mount Sinai) began taking 2,000mg of Quercetin daily, without really understanding why these changes or supplements might or might not help. Even recommendations from my CFS specialist, such as trying an alkaline diet, seemed to be based on an educated guess. I found that I felt better on a low histamine diet by trying it, not due to test results or an understanding of the underlying mechanisms. I found that I felt better avoiding lectins simply by trial and error.
This changed in May of 2021 when I received some test results from Genova. After 12+ months of mostly normal blood tests, two Genova tests (Metabolomix and GI Effects) provided evidence of some very specific things that were not going well with respect to my microbiome, digestion, and nutrient assimilation. They showed significant dysbiosis and nutrient deficiencies, despite the fact that I had been eating a whole foods diet rich with high quality protein, healthy fats, and fruits and vegetables, in addition to supplementing with vitamins, minerals and probiotics for over a year. They showed low pancreatic elastase, fat malabsorption, impaired detoxification, metabolic imbalance, and severe oxidative stress. They showed imbalances which I could now work on correcting in a more targeted way.
It was around this time, as I was trying to get to the root of the dysbiosis, that I learned about oxalates.
Oxalates: An Introduction
Despite there being medical literature on oxalate-induced issues which goes back for more than 100 years, oxalates are rarely recognized as a potential root cause for the problems they can cause, with the exception of in the case of kidney stones. The Cleveland Clinic does have an introductory page on hyperoxaluria which outlines some basics:
Primary hyperoxaluria occurs when the body produces oxalates endogenously, in some cases due to a functional B6 deficiency
Secondary hyperoxaluria occurs when oxalates get absorbed in the intestinal tract (rather than being processed and excreted), either due to a high oxalate diet or conditions in which oxalates are unable to be appropriately degraded
In a healthy gut, oxalates are degraded by gut microbes. For many years, oxalate degradation within the gut was attributed to a single species, oxalobacter formigenes, but a recent paper published by Fujian Medical University found that there are more than 1,700 species of bacteria that degrade oxalates. When I mention oxalates as a potential issue to those who haven’t heard of the problems they can cause, some point out that there are ancestral populations who have consumed high-oxalate diets for generations without issue. This may be due to minimal exposure to antibiotics. What research has found is that individuals with a history of antibiotic use are at a greater risk from dietary oxalates.
What does this have to do with chronic illness?
Oxalates and COVID-19
A recent study examining the faecal microbiome of individuals who had COVID-19 found elevated oxalate levels relative to healthy controls (8). The study examined samples from when patients were admitted until hospital discharge, and found that oxalate levels did not return to that of healthy controls at the time of discharge. From the study:
According to our results, oxalate was enriched in the faeces of COVID-19 patients… As our results showed that the elevation in the level of faecal oxalate was not significantly improved when the patients were discharged, the effect of oxalate on the development and recovery of COVID-19 needs further attention.
Oxalates and Inflammation
Oxalates are now known to play a role in activation of the NLRP3 inflammasome, which promotes subsequent release of proinflammatory cytokines (10).
Oxalates and Dysbiosis
Recent research has found that high oxalate concentrations in the gut can lead to dysbiosis. One study (6) found that a high concentration of oxalate was found to be inhibitory to many beneficial gut microbes.
Candida, a common topic in the alternative medicine community, grows in two different forms: an egg-shaped yeast cell or as a filamentous hyphal form (9). Research has found that a certain amount of Candida in its yeast form is normal and not perceived as a threat by the immune system. When in its hyphal form, yeast cells excrete a toxin called Candidalysin, which can be harmful to human cells. A high concentration of oxalates can lead to Candida transitioning to its hyphal form (7).
Oxalates and Malabsorbtion
There are some papers discussing the role that secondary hyperoxaluria can play in fat processing issues, which can then lead to more oxalate absorption (11).
Oxalates and Impaired Sulfur Chemistry
One of the early indicators of hyperoxaluria I had was a large amount of sulfur excretion on my Metabolomix test. Oxalates use the same transporters as sulfate because they are shaped alike biochemically. Because of this, we excrete additional sulfur in the urine when oxalate levels rise. This can cause additional problems due to the importance of sulfur in the body and the many ways in which it is used.
This blog post provides an in-depth discussion of how oxalates can impair sulfur chemistry, leading to sulfur wasting (which would result in high urine levels) and the additional issues that can lead to.
Oxalates and Neuropathy
While there are many potential causes for neuropathy, oxalates can be implicated as well. Case studies have found deposition of calcium oxalate crystals in damaged nerves (1), (2), and (3), and improvement with organ transplants (3).
One case study in particular (4) outlines an instance of facial numbness and pain which ensued following facial exposure to a high-oxalate plant.
Potentially Harmful Supplements: Turmeric and High-Dose Vitamin C
Early on in my illness, I took high doses of supplements recommended by Mount Sinai (turmeric) and published chronic fatigue specialist Sarah Myhill (vitamin C). Thankfully, I eventually discontinued these after not too long, upon realizing that they weren’t helping. I now know that both of these supplements have the potential to make a significant contribution to total oxalate load. A single turmeric capsule has been shown to contain nearly 8mg of oxlate (7). While synthesis, absorption, and urinary excretion of dietary oxalates is complex, studies have found that turmeric supplementation provides a significant contribution to urinary oxalate excretion (7).
As early as 2007 (14), case studies have shown the potential risks of high-dose vitamin C supplementation with respect to oxalates. A history of COVID-19 adds further complication to this picture. More recent studies (12, 13) have shown high-dose vitamin C supplementation in COVID-19 patients leading to hyperoxaluria and (in some cases) renal failure.
Recommendations vary as to how much Vitamin C is safe. Some suggest that the level should be kept to 250mg per day, including sources from food. My primary care physician has suggested that 400-500mg may be safe. Chris Masterjohn, in a thorough write-up of the primary mechanisms, suggests that 200-400mg should be safe, and gives some recommendations for managing glutathione status if one plans to go beyond that.
Related Research on Chronic Fatigue Syndrome
A study on the metabolic features of Chronic Fatigue Syndrome (18) found an increase in hydroxyproline, a precursor to glyoxylate. This may be related to collagen breakdown. As per the paper cited, glyoxylate “can be transaminated in mitochondria to produce glycine and metabolized in peroxisomes to oxalate and peroxide.”
Oxalates and Vitamin B Deficiencies: Primary Hyperoxaluria
In August of 2021, I invested in further testing via an Organic Acids Test (OAT) and Amino Acids test from Great Plains Laboratory. I then reached out to Susan Owens for a consultation. Due to her work with the autism project, she has analyzed hundreds of OATs over the years, and has a specific methodology for normalizing the data and comparing it with a normal (healthy) population.
While I knew I had been unintentionally consuming large quantities of oxalates for several months and had not been processing them appropriately (secondary hyperoxaluria), I was not prepared to learn that I was an endogenous producer as well (primary hyperoxaluria). My test results showed multiple markers of a functional B6 deficiency, resulting in endogenous production. Elevated levels of glycolic acid, pyroglutamic acid, and beta-alanine (amongst other markers) indicated that I had a severe functional B6 deficiency. Test results also showed potential thiamine and B12 deficiencies despite supplementation, indicating that I should increase my thiamine further and switch to B12 shots, as my body wasn’t processing the form in capsules appropriately.
Oxalate “Dumping,” and Probiotics to the Rescue
Upon beginning to reduce oxalate consumption, it’s recommended to do so slowly, at a pace of no more than 10% per week, to reduce the risks of “dumping.” The idea is that when you drastically lower your intake, your body will go from storage to excretion mode, and begin to release stored oxalate from your tissues. The amount released during a “dump” can be much more than one might consume in a day (even with a high oxalate diet), and can result in symptoms that include everything from joint pain to feeling like you have the flu. There is limited published research on this phenomenon; most of the information available is based on personal anecdotes from individuals with hyperoxaluria who have gone through a process of reducing their oxalate intake.
I initially drastically reduced my oxalate intake unintentionally at the beginning of the summer (due to going low FODMAP and cutting out sweet potatoes). I eventually began tracking them more carefully. Once I had reduced my intake to 50–70mg per day, I found that I would experience oxalate dumping fairly regularly, often simply triggered by some mild physical activity. While not completely debilitating, the symptoms are unpleasant, at best.
There is published research (15, 16, 17) showing that Visbiome (previously known as VSL#3) probiotics can increase oxalate degradation in the gut. From what I’ve heard, it is the only probiotic on the market that has been shown to have this effect in published studies. Following an anecdote from a member on one of the forums who indicated these probiotics reduced her dumping symptoms, I started taking 2 visbiome capsules per day when I felt that I might be on the verge of experiencing dumping symptoms. I eventually increased to 2 capsules everyday and found (anecdotally) that the dumping episodes decreased in both frequency and severity.
Where I am Now
I’m currently supplementing with high-dose B1 and the associated cofactors and receiving cyanocobalmin (B12) shots every other day as per NHS guidelines. I’ve been lowering my oxalate intake since June, and am now at around 50–70mg of oxalates per day.
Prior to introducing B1 and reducing my oxalate consumption, I felt as though my recovery had plateaued. I was experiencing mild bloating on occasion, was unable to tolerate magnesium, was becoming increasingly reactive to different foods and chemicals, and just generally felt as though I had a great deal of inflammation.
Following the reduction in oxalate and the supplement adjustments, the mild bloating I had experienced on occasion went away. After increasing vitamin B1, I became able to tolerate magnesium, potentially indicating that I had previously been thiamine deficient. My reactivity to simple things like chlorinated water has greatly decreased, and I’ve been able to start incorporating higher-histamine foods back into my diet without issue.
While I am in no way back to 100%, my energy has greatly improved and I can now do a lot more than I could before without fearing a relapse. Taking the steps that I’ve outlined here has resulted in significant improvements.
