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Deep dive into oxalates

Oxalates are natural compounds found in some vegetables, fruits, nuts, and grains and they are also made in small amounts in the human body. High oxalate levels are the most common cause of kidney stones and they also may be implicated in a variety of other conditions and symptoms. For most people, oxalate levels are dictated by dietary oxalate intake, gut health, and the microbiome. While the most common strategy to reduce oxalate levels is a low oxalate diet, addressing gut health and the microbiome may reduce oxalate levels without a restrictive diet.

Where do oxalates come from?

Oxalates come from the diet and are also made by the liver.

 

Foods high in oxalates:

  • Fruits: raspberries, oranges, grapefruit, dates, kiwi1
  • Vegetables: spinach, carrots, rhubarb, beets, eggplant, Swiss chard, spinach, potatoes, sweet potatoes, yams1
  • Nuts and seeds: almonds, cashews, peanuts, pecans, sesame seeds1
  • Grains: soy, wheat, buckwheat, barley1

Oxalate absorption into the bloodstream is dependent on the state of the oxalates in food and the contents in the intestines since only soluble oxalates will be absorbed2. pH and the concentrations of calcium, magnesium, and phosphate will dictate the solubility of oxalates2. Oxalates are likely to be absorbed in the stomach, the small intestine, and the colon2. In the colon, the amount of oxalates available to be absorbed will be dependent on bacterial degradation of oxalates2.

Depending on these factors, 5-15% of dietary oxalates are absorbed4, contributing to 20-40% of serum oxalates3. Some individuals may be hyper-absorbers of oxalates due to surgeries removing parts of the intestine (particularly various weight loss surgeries) and diseases causing malabsorption, which may include celiac disease, inflammatory bowel disease, small intestine bacterial overgrowth and more4. When fat is not absorbed in the small intestine, it will essentially bind up calcium, so then calcium cannot bind to oxalates and prevent absorption4. So conditions affecting the gallbladder may also result in increased absorption of oxalates. Oxalate absorption in the colon may increase to over 30% when there are digestive issues5

The liver can also produce oxalates from ascorbic acid (Vitamin C)4. Primary hyperoxaluria is a genetic condition resulting in the liver producing too much oxalates, though this is a rare disorder.

The body cannot break down oxalates once absorbed and they have to be excreted in the urine. If there are high amounts of oxalates in the urine, they can form crystals that can become kidney stones. If oxalate crystals accumulate in the bloodstream due to poor elimination through the kidneys, these crystals can be deposited in joints, heart tissue, skin, eyes, nerves, muscles and bones causing a variety of symptoms and conditions4. This level of oxalate toxicity is typically considered rare and mostly associated with primary hyperoxaluria, the genetic condition. 

In functional medicine, there is a lot of attention on oxalates causing pain, fatigue, and a myriad of other symptoms. Oxalates are being blamed for everything from depression to Hashimoto’s, but it is important to note that these claims have not been fully researched. If you are concerned about your oxalate levels, talk to your doctor about blood and urine testing for oxalates. 

 

Oxalates and the Microbiome 

Certain microorganisms are capable of producing and degrading oxalates. Many fungal species in soil produce oxalates, but the role of fungal species that produce oxalates in human health is not well researched or understood3 despite numerous claims that yeast overgrowth in the gut causes high oxalates. Some research suggests that certain bacterial species can make oxalates, but these, again, appear to be soil bacteria3.

When it comes to human health, oxalates, and the microbiome, the most well researched connection is Oxalobacter formigenes. This bacteria resides in the colon and can break down oxalates. O. formigenes breaks down oxalates because it uses oxalates as fuel6. And it doesn’t just use oxalates as fuel, oxalates are required for fuel and growth6. The presence of O. formigenes in the large intestine can reduce the amount of urinary oxalates, not just by breaking down oxalates in the gut but also by stimulating the gut cells to secrete absorbed oxalates back into the gut for elimination6. This may help prevent kidney stones and other symptoms of high oxalates.

However, not everyone has O. formigenes in their large intestine. Researchers are still working to understand the colonization of this bacteria in humans. Possibly only 30% of people in Western cultures have this bacteria, while in other parts of the world 65-80% of people may carry it6. While antibiotic use can definitely result in no O. formigenes, it seems like other factors of Western lifestyles negatively impact this bacteria6.  

If you are concerned about high oxalate levels, you first need to test your microbiome to see if you have O. formigenes. If you do have O. formigenes, you may be interested in how to increase it in order to reduce oxalates. However, we need more research to fully understand how to support this bacteria. For example, it is dependent on oxalates as its primary fuel source, so a low oxalate diet may decrease levels. Also, the research shows higher calcium intake associated with lower bacterial abundance6, and calcium supplements are often recommended to decrease oxalate absorption. Another consideration is fat consumption. Research in rats has demonstrated that fat may interfere with O. formigenes reducing oxalates, but it is not clear if this is also true of humans6. Further research is needed to fully understand the factors affecting O. formigenes colonization.

 

If you do not have O. formigenes in your microbiome, you may wonder if there is a probiotic. Researchers have been working on this with mixed results. Research shows that it doesn't always colonize, nor reduce urinary oxalate levels6. These probiotics are also not available outside of research currently.

 

So if you don’t have O. formigenes, you may consider supporting your Lactobacillus and Bifidobacterium species, some of which can also break down oxalates, but at a much lower level than O. formigenes6. Most prebiotics are excellent at supporting these species.

 

If you are concerned about your oxalate levels, your microbiome is only one part of the story. You need to consider if your liver is making too much oxalates (talk to your doctor about genetic testing) or if poor gut health is causing hyperabsorption. You may need to talk to your doctor about additional testing to investigate underlying causes of malabsorption:

 

  • A fecal fat test is a simple test to assess malabsorption
  • Consider a fecal calprotectin test to assess for GI inflammation
  • Consider a 3 hour lactulose breath test to assess for small intestine bacterial overgrowth
  • Consider blood testing to assess for celiac disease
  • Consider endoscopy or colonoscopy to further assess for celiac disease or inflammatory bowel disease

If you can address the malabsorption, that may be sufficient to reduce your oxalate levels without needing to modulate your microbiome or restrict your diet.

 

Other Ways to Decrease Oxalate Levels

Consume calcium with oxalate food. If dairy is tolerated, you can add dairy to your meals or you can take a calcium citrate supplement before your meal.
Reduce vitamin C supplementation to reduce endogenous production of oxalates
Consider using ox bile supplements with meals to better absorb fat

Talk to your doctor about testing, possible causes of high oxalates, and appropriate treatment options. 

 

References

  1. https://med.virginia.edu/ginutrition/wp-content/uploads/sites/199/2022/06/Oxalate-Foods-2022.pd
  2. Jaeger P, Robertson WG. Role of dietary intake and intestinal absorption of oxalate in calcium stone formation. Nephron Physiol. 2004;98(2):p64-71. doi:10.1159/00008026
  3. Palmieri F, Estoppey A, House GL, et al. Oxalic acid, a molecule at the crossroads of bacterial-fungal interactions. In: Advances in Applied Microbiology. Vol 106. Elsevier; 2019:49-77. doi:10.1016/bs.aambs.2018.10.001
  4. Crivelli JJ, Mitchell T, Knight J, et al. Contribution of Dietary Oxalate and Oxalate Precursors to Urinary Oxalate Excretion. Nutrients. 2020;13(1):62. doi:10.3390/nu13010062
  5. Lorenz EC, Michet CJ, Milliner DS, Lieske JC. Update on Oxalate Crystal Disease. Curr Rheumatol Rep. 2013;15(7):340. doi:10.1007/s11926-013-0340-4
  6. Daniel SL, Moradi L, Paiste H, et al. Forty Years of Oxalobacter formigenes, a Gutsy Oxalate-Degrading Specialist. Applied and Environmental Microbiology. 2021;87(18):e00544-21. doi:10.1128/AEM.00544-21

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