June 29, 2017

Oxalates, Kidney Stones and Autism: Oh My!

Oxalates & Kidney Stones

by Aaron Mello, CNTP, MNT

Low oxalate diets are a popular discussion in the holistic health world right now. New science over the last few years is beginning to illuminate connections between oxalate consumption and many health conditions. Perhaps the best known health issue correlated with high oxalate levels at this point is kidney stones. But research is beginning to show that other conditions, including asthma, autism, depression, cystic fibrosis, and more, may be related as well.

Although much more remains to be learned, functional medicine practitioners have begun using low oxalate diets in certain situations with impressive results. In this article I will review what the science supports at this point. Interestingly, there is more to understanding the clinical application of low oxalate diets beyond just learning which foods are high in oxalates and avoiding them. It seems that issues with gut health such as intestinal permeability, also known as leaky gut, contribute to oxalate overload as well. Keep reading to learn more!

What are oxalates?

Oxalate is a broad term that refers to a substance comprised of two carbon atoms and four oxygen atoms, written as C2O4.  Oxalates are negatively charged anion molecules which readily bond with many positively charged cations including hydrogen, calcium and magnesium to form oxalic acid. Oxalates are found primarily in plant foods where they result from the incomplete oxidation of carbohydrates. Oxalates are also present in some animal foods, but typically in much lower levels.

Oxalates in plants, often in the form of calcium oxalate, dissuade insects from eating the plant. The crystals formed by calcium oxalate are present in more than 200 plant families and deter insect consumption through two mechanisms: The prismatic crystals are physically abrasive to the mouth parts of insects and they also interfere with the conversion of plant material to insect biomass during digestion (1).

Which foods are high in oxalates?

A large source of frustration and confusion when it comes to oxalates is that many foods we conventionally think of as being “health foods” are high in oxalates. To further complicate things, high oxalate foods do not fit neatly into a single category or group of foods. Rather, many different and seemingly unrelated foods are high in oxalates and learning which foods fall in this category is largely a task of rather tedious memorization. There is no real pattern to follow to remember how much oxalate foods contain, and individual foods vary in oxalate content depending on soil conditions and other factors. Click here for a good resource list of foods that are high in oxalates. In the next section I will explain how gut health impacts oxalate absorption, and then expand on the role a high oxalate burden plays in various health conditions.

The gut-oxalate connection

First, it’s important to understand that the amount of oxalates eaten does not necessarily correlate with a high oxalate burden in the body. In other words, oxalate absorption in the intestine may be more important than oxalate consumption. Although many foods are high in oxalates, some people are able to tolerate them better than others. A primary reason for this phenomenon appears to be differences in how much oxalate people absorb from the diet in the intestine. Interestingly, oxalates seem to be absorbed not just in the small intestine, but in the colon as well (2). Of course, eating a lower oxalate diet can be helpful in the short term, but addressing issues with over absorption of oxalates is another important way to reduce oxalate body burden.

Two primary factors have been identified that increase the absorption of oxalates from the diet, also known as “enteric hyperoxaluria”: intestinal permeability and low levels of certain probiotic bacteria in the gut that degrade oxalates.

Intestinal permeability

I’ve written about intestinal permeability, also known as leaky gut previously. See here and here for more information. It’s not difficult to see how a leaky gut could contribute to increased absorption of oxalates in the small intestine, similar to how it allows partially digested proteins to be absorbed and enter the bloodstream prematurely, and some research supports this model (3). Another compounding factor which contributes to leaky gut and oxalate absorption is steatorrhea, or poor fat digestion (4). In addition to intestinal permeability, the absence of certain probiotic bacteria are implicated in enteric hyperoxaluria.

Reduced levels of probiotic bacteria

Several species of probiotic bacteria have been demonstrated to “eat” and degrade oxalates, preventing them from being absorbed and instead metabolizing them into byproducts that are excreted with the feces. The most prominent species is oxalobacter formigenes, the absence of which has been demonstrated in multiple studies to be correlated with elevated urinary oxalate levels, or hyperoxaluria (5) (6) (7), which is a reflection of oxalate load in the body. The catch about o. formigenes is that it is not currently available as a supplement or a drug, although a drug form is being developed.

Some other species of bacteria are able to degrade oxalates, even though it is not their preferred food. The probiotic medical food VSL#3® has been used in several studies to reduce hyperoxaluria, and contains the following eight species of bacteria:

  • Streptococcus thermophilus
  • Bifidobacterium breve
  • Bifidobacterium longum
  • Bifidobacterium infantis
  • Lactobacillus acidophilus
  • Lactobacillus plantarum
  • Lactobacillus paracasei
  • Lactobacillus helveticus

These bacteria are often absent as a result of antibiotic use, which has been demonstrated to wipe out o. formigenes (8), as well as other commensal oxalate-degrading bacteria. Therefore, a history of antibiotic use may be an indication of oxalate issues in patients.

Endogenous oxalate production

In addition to dietary oxalate, oxalates are synthesized in the body. Excess intake of ascorbic acid, a primary component of the Vitamin C complex, has been shown to increase oxalate levels. Two studies evaluated the effects of 2g of supplemental ascorbic acid found significant increases in urinary oxalate excretion in both kidney stone-forming and healthy participants (9) (10). Another analysis of of the diets of 1473 men found that ingestion of more than 1g of ascorbate per day was a risk factor for kidney stone disease (11).

Another common source of oxalate exposure comes from some types of mold, particularly the black mold aspergillus niger. Aspergillus is not to be confused with what is perhaps the most common form of black mold discussed in terms of health, stachybotrys. Like stachybotrys, aspergillus is also found in damp areas like around the shower and has been shown to contribute to the deposition of oxalate crystals in body tissues (12).

In addition, Candida albicans may contribute to oxalate levels in the body as well (13). High levels of arabinose on an Organic Acid Test are correlated with high oxalate levels, which makes sense as arabinose is a primary fuel for fungal oxalate production (14).

Health conditions related to high oxalate levels

Many different diseases and health conditions are associated with a high oxalate burden in the body. In the next section I’ll review the conditions that are most strongly supported by science as being related, starting with kidney stones.

Kidney stones

As I’ve mentioned, the best known implication of high oxalate levels is the formation kidney stones, or nephrolithiasis. 80% of kidney stones are comprised of calcium oxalate, making up a clear majority of cases (15). Kidney stones are a primary cause of kidney disease and infections that are estimated to effect 3-20% of people worldwide. And as anyone who has ever had a kidney stone knows, they are extremely painful. If you’ve never had a kidney stone, ask someone who has. Their description of the amount of pain involved should be enough motivation to continue reading to learn how you can best prevent one from occurring. But kidney stones are certainly not the only health condition associated with high oxalate status. Keep reading to learn more about other issues that appear to be related!

Although most stones are made of calcium oxalate, dietary calcium has been demonstrated in multiple studies to decrease urinary oxalate excretion, which is a reflection of total body burden. High calcium intake appears to bind oxalate in the gut and limit its absorption. Two prospective studies showed that doses of dietary calcium showed an inverse relationship with stone formation (16) and that calcium calcium intake played a role in limiting stone formation in a cohort of stone-forming participants (17). Paradoxically, although calcium supplementation is often discussed as a risk factor for kidney stones, in some cases it may reduce risk by binding oxalate in the gut and preventing it from being absorbed.

COPD and Asthma

Respiratory problems like COPD and asthma appear to be correlated with hyperoxaluria.

One Russian study on patients with Chronic Obstructive Pulmonary Disease (COPD) and hyperoxaluria evaluated the role that oxalates play in respiratory obstruction in a cohort of 104 patients. They found that insoluble oxalates contribute to the pathogenesis of respiratory inflammation and propose that disturbances in oxalate metabolism contributes to this inflammation. The study concludes that reducing oxalate levels may be an effective treatment option for COPD (18).

One pediatric study found a strong correlation between asthma and kidney stones. Of a pool of 865 pediatric patients with nephrolithiasis, 142 had been diagnosed with asthma, and researchers drew these conclusions: The children with asthma were four times more likely to also have kidney stones, compared to the general pediatric population, and children with kidney stones were four times more likely to have asthma. The researchers concede that this merely establishes a correlation, but recommend that more research be done to establish or rule out a causative relationship between the two conditions (19).

Thyroid health

The thyroid is the only gland in the body that is known to collect oxalates. However, not much research is available to support a causative link between oxalate deposition in the thyroid and thyroid disease. One study which evaluated the presence of oxalates routine thyroid gland autopsies found oxalates 79 out of 100 seemingly healthy thyroid tissue samples (20). The presence of oxalates increases with age, suggesting that the body lacks a mechanism to degrade and remove them from thyroid tissue.

Another study found the highest incidence of oxalate thyroid crystals in nodular goiters (88%), 60% of follicular adenomas, 33% of follicular carcinomas, and only 5.4% of papillary carcinomas. Overall, crystals were found in 69% of benign nodules and only 7.6% of malignant nodules. Graves’ disease, focal thyroiditis, and subacute thyroiditis showed a low prevalence of oxalate crystals (21). More research needs to be done to illuminate the role oxalates play in thyroid disease.

Autism

Hyperoxaluria is positively correlated with autism diagnoses. One study found that autistic children had serum oxalate levels three times that of healthy children and urine oxalate levels that were 2.5 times that of normal children. Interestingly, this study did not find an increased prevalence of kidney stones in the autistic children (22).  High levels of arabinose, a fuel for fungal oxalate production, are also common in autism.

Treatment options for hyperoxaluria

If you suspect that high oxalate burden is playing a role in a health problem, a great first line defense is to limit your exposure to high oxalate foods. It’s important to do this gradually, as suddenly eliminating high oxalate foods can lead to “oxalate dumping,” a phenomenon which is often different depending on the individual. Eliminating oxalates “cold turkey” can initially result in a reduction of symptoms like headaches, muscle twitches, digestive issues, or rashes, but after a few days these symptoms can return with a vengeance. So it’s generally best to gradually decrease oxalate intake and watch closely for symptoms, which can be delayed by several days.

A good first step is to check out the list of food oxalate content on the lowoxalate.info website here. Begin by studying the list and learning which foods are high in oxalates, and gradually begin decreasing these foods and substitute lower oxalate foods in their place. The list is long and can be somewhat overwhelming, as there is no real pattern to high oxalate foods. Be patient with yourself and focus first on just learning the list, as your best bet is to reduce high oxalate foods gradually anyway.

Other treatment options

Of course, we don’t just want to stay on a strict low oxalate diet for the rest of our lives. As I have suggested earlier in this article, many people can tolerate relatively high oxalate intake and underlying health conditions like intestinal permeability, lack of probiotic bacteria that degrade oxalate, calcium deficiency, and exposure to black mold can all contribute to a high oxalate burden. Work with a qualified functional medicine practitioner to investigate and resolve these issues.

Here are some options to try:

  • Increase water intake: This will help the kidneys excrete oxalates more effectively.
  • Increase calcium-rich foods: Calcium binds oxalate in the gut and prevents it from being absorbed. We typically don’t recommend calcium supplements unless there is a very specific need, but increasing consumption of calcium-rich foods can be helpful.
    • Best food sources of calcium include:
      • Dairy foods from organic, grass-fed cows (if dairy is well tolerated).
      • Soft bones from wild-caught cold-water fish like salmon and sardines.
        • Note that some sardines are boneless; opt for bone-in sardines and eat the soft bones.
      • Cruciferous vegetables like kale, broccoli, Brussels sprouts, bok choy and cauliflower.
        • These foods are a double edged sword – they contain a lot of calcium, but some of them are high in oxalates, especially if steamed. The chart on lowoxalate.info lists boiled broccoli and Brussels sprouts as being low in oxalates, whereas raw versions are medium and steamed are high!
        • The catch is that boiling leaches not just oxalates but also other nutrients, including calcium, out into the cooking water.
        • Cauliflower seems like an especially good choice for calcium, as it is low in oxalates regardless of how it is prepared. Bok choy is also low, although they don’t distinguish between raw and cooked.
      • Sesame seeds can be a good source of calcium as well, but only if the seeds are soaked for 8-12 hours to eliminate phytates that otherwise bind the calcium and prevent it from being utilized by the body.
  • Magnesium glycinate: Magnesium can also bind oxalates and alleviates muscle cramps as well, which can be a symptom of oxalate dumping. Magnesium weakens stomach acid and should either be taken apart from meals, or with some fresh squeezed lemon juice or organic apple cider vinegar in water if taken with food.
  • Vitamin B6: This is a cofactor for an enzyme that degrades oxalates in the body and has been shown to reduce oxalate production (23).
  • Lipase enyzmes and/or Ox bile: Steattorhea, or fat mildegestion can contribute to oxalate absorption in the gut. Reducing dietary fat and/or supplementing with these digestive aides can help.
  • Probiotics containing Lactobacillus acidophilus and Bifidobacterium lactis: These strains both help to degrade oxalates.
  • Increase intake of omega-3 fats from cold-water fish like wild-caught salmon and limit omega-6 fats from grain-fed meat: Omega-3 fats help reduce oxalate problems, whereas omega-6 fats contribute to them (24).
  • Evaluate candida and aspergillus mold exposure: through lab testing.

In conclusion

Science is still illuminating the role oxalates play in many health conditions, but there is evidence to support potential benefits from reducing oxalates for several health conditions. By working with a qualified functional medicine practitioner you can get to the root cause of your health issues. If they are caused by high oxalate burden, it’s important to determine what is causing that, as a high oxalate load is almost certainly a downstream consequence of another issue and not a root cause itself.

References

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  2. Liebman, M., and I. A. Al-Wahsh. “Probiotics and Other Key Determinants of Dietary Oxalate Absorption.” Advances in Nutrition: An International Review Journal 2.3 (2011): 254-60. Web. doi:10.3945/an.111.000414.
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  5. Sidhu, Harmeet, Bernd Hoppe, Albrecht Hesse, Klaus Tenbrock, Sabine Bromme, Ernst Rietschel, and Ammon B. Peck. “Absence of Oxalobacter Formigenes in Cystic Fibrosis Patients: A Risk Factor for Hyperoxaluria.” The Lancet 352.9133 (1998): 1026-029. Web. doi:10.1016/S0140-6736(98)03038-4.
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  11. Taylor, E. N. “Dietary Factors and the Risk of Incident Kidney Stones in Men: New Insights after 14 Years of Follow-up.” Journal of the American Society of Nephrology 15.12 (2004): 3225-232. Web. doi:10.1097/01.ASN.0000146012.44570.20.
  12. Ghio, Andrew J., David S. Peterseim, Victor L. Roggli, and Claude A. Piantadosi. “Pulmonary Oxalate Deposition Associated WithAspergillus NigerInfection: An Oxidant Hypothesis of Toxicity.” American Review of Respiratory Disease 145.6 (1992): 1499-502. Web. doi:10.1164/ajrccm/145.6.1499.
  13. Takeuchi, Hideo, Taira Konishi, and Tadao Tomoyoshi. “Detection by Light Microscopy of Candida in Thin Sections of Bladder Stone.” Urology 34.6 (1989): 385-87. Web.
  14. Loewus, F.a., K. Saito, R.k. Suto, and E. Maring. “Conversion of D-Arabinose to D-Erythroascorbic Acid and Oxalic Acid in Sclerotinia Sclerotiorum.” Biochemical and Biophysical Research Communications 212.1 (1995): 196-203. Web. doi:10.1006/bbrc.1995.1956.
  15. Bangash, K., F. Shigri, A. Jamal, and K. Anwar. “Spectrum of Renal Stones Composition; Chemical Analysis of Renal Stones.” International Journal of Pathology 9.2 (2011): 63-66. Web.
  16. Curhan, Gary C., Walter C. Willett, Eric B. Rimm, and Meir J. Stampfer. “A Prospective Study of Dietary Calcium and Other Nutrients and the Risk of Symptomatic Kidney Stones.” New England Journal of Medicine 328.12 (1993): 833-38. Web.
  17. Borghi, Loris, Tania Schianchi, Tiziana Meschi, Angela Guerra, Franca Allegri, Umberto Maggiore, and Almerico Novarini. “Comparison of Two Diets for the Prevention of Recurrent Stones in Idiopathic Hypercalciuria.” New England Journal of Medicine 346.2 (2002): 77-84. Web.
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  20. Reid, John D., Chang-Hyun Choi, and Norman O. Oldroyd. “Calcium Oxalate Crystals in the Thyroid: Their Identification, Prevalence, Origin, and Possible Significance.” American Journal of Clinical Pathology 87.4 (1987): 443-54. Web.
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  22. Konstantynowicz, Jerzy, Tadeusz Porowski, Walentyna Zoch-Zwierz, Jolanta Wasilewska, Halina Kadziela-Olech, Wojciech Kulak, Susan Costen Owens, Janina Piotrowska-Jastrzebska, and Maciej Kaczmarski. “A Potential Pathogenic Role of Oxalate in Autism.” European Journal of Paediatric Neurology 16.5 (2012): 485-91. Web. doi:10.1016/j.ejpn.2011.08.004.
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