top of page
  • Writer's pictureTeresa Rodríguez

Xenobiotics and Oxalates

Updated: Feb 13

Xenobiotics and Oxalates – Harms of High Oxalate & Factors Influencing It.




What are Xenobiotics:


Xenobiotics are foreign to the human body or any biological system. Xenobiotics aren’t produced in the human body and should not exist either. Xenobiotics can be various chemicals, such as drugs, environmental pollutants, pesticides, industrial chemicals, and even some dietary compounds. Xenobiotics can also cover substances that are higher in concentration than usual. Xenobiotic nutritional intake is a global health concern today. They can alter the microbiota composition, leading to dysbiosis. Dysbiosis means disrupting the natural balance of microbiota, including changes in their functional design and metabolic activities. It causes various health issues such as digestive problems, chronic fatigue, trouble urinating, acid reflux, inflammation, skin issues, and increased toxicity of xenobiotics.


The gut microbiota can transform harmful xenobiotics into less toxic forms, potentially reducing the risk of dysbiosis effects. However, dietary contaminants and environmental toxins can still harm human health. The gut microbiota's role in xenobiotic metabolism can long-term impact the balance between a healthy gut and dysbiosis. Understanding these mechanisms requires a multidisciplinary approach. Xenobiotics that disrupt gut microbiota are called "microbiota-disrupting chemicals" (MDCs). These MDCs can alter the microbiota, which has been linked to various health issues in the host, such as intestinal, hormonal, and chronic diseases.


Xenobiotics are often metabolized and eliminated from the body by detoxification processes in the liver. Hepatic enzymes play an essential role in the metabolic transformation of xenobiotics. Initially, they activate these foreign compounds through oxidation, reduction, hydrolysis, or hydration. Then, the active secondary metabolite conjugates with substances like glucuronic acid, sulfuric acid, or glutathione. Finally, these conjugated compounds are excreted either in bile or through urine.





Oxalate as a Xenobiotic:


Oxalates are naturally organic compounds in many plant-based foods, such as spinach, rhubarb, beets, and nuts. In the context of xenobiotics, oxalates can be considered xenobiotics when consumed excessively or not well-tolerated by the human body. The symptoms of high oxalate include nausea, diarrhea, headache, fibromyalgia, burning eyes, mouth, ear, and throat, osteoporosis or brittle bones, kidney stones, difficulty in focusing, irritable bowel syndrome, etc.


Oxalate, in its dianionic form, is a potent chelating agent that readily binds to free metallic cations like calcium. Mammals including humans lack enzymes to transform oxalate and instead rely on its absorption, excretion, or microbial breakdown due to its widespread toxicity.


When oxalate concentration surpasses the limit, oxalate and calcium combine in the intestines and are expelled from the body through stool. When there's insufficient calcium, surplus oxalate has nothing to join within the intestines. As a result, it gets absorbed into the bloodstream and eventually ends up in the renal tubules, which can lead to calcium oxalate crystals. Calcium oxalate crystals can precipitate and accumulate in various tissues, including the kidneys, where they lead to the formation of kidney stones. These kidney stones, composed mainly of calcium oxalate, cause discomfort and medical complications.


When oxalates are consumed in large quantities or when an individual has a predisposition to oxalate-related health issues, they can act as xenobiotics, causing harm to the body. Only some people are equally sensitive to oxalates, and many people can consume oxalate-containing foods without any problems. However, if a person has certain medical conditions, such as hyperoxaluria or a history of kidney stones, they may need to limit their oxalate intake to prevent health issues.





The Relation Between Oxalate and pH:


The relationship between oxalate and pH is vital to understand, especially in the context of kidney stone formation. The pH level, or the acidity or alkalinity of the urine, plays a significant role in forming calcium oxalate crystals.


In general, urine pH can range from acidic (pH below 7) to alkaline (pH above 7). The solubility of calcium oxalate is highly dependent on the pH of the urine. When urine is more acidic (lower pH), it can increase the risk of calcium oxalate stone formation because acidic conditions promote the precipitation and crystallization of calcium oxalate. More precisely, if urine PH is less than 5.5, it increases the risk of uric acid crystal formation, which can act as heterogeneous nuclei of calcium oxalate crystals.


On the other hand, more alkaline urine (pH above 7) can make it less likely for calcium oxalate to crystallize and form stones. However, calcium phosphate supersaturation boosts rapidly when the urine pH rises above 6. Lately, there has been a rise in calcium phosphate stone cases, and the combination of (hypercalciuria) (and hypocitraturia) is the primary urinary condition that favors crystal formation.


B Complex and Magnesium on Control of Oxalate:



Vitamin B1 (Thiamine), B2 (Riboflavin), B6 (Pyridoxine), and B12 (Cobalamin) do have a direct or indirect role in controlling oxalate levels in the body. Oxalates are primarily handled through dietary management, adequate hydration, and certain medical conditions that affect oxalate metabolism.


Vitamin B6, also known as pyridoxine, can decrease the urinary excretion of oxalate, a critical factor in forming calcium oxalate kidney stones. This effect is linked to vitamin B6's role as a cofactor for the enzyme alanine-glyoxylate aminotransferase, which converts glyoxylate to glycine. A deficiency in vitamin B6 may lead to an increased conversion of glyoxylate into oxalate through lactate dehydrogenase. Studies have reported that a lack of vitamin B6 can result in higher oxalate production and excretion, while supplementation with vitamin B6 has shown the potential to reduce urinary oxalate excretion.


Additionally, magnesium prevents the formation of calcium oxalate crystals in the urine. It does this by binding to oxalate in the intestines, reducing its absorption and excretion in the urine. When there is less oxalate available in the urine, it is less likely to combine with calcium and form crystals, which are the building blocks of kidney stones.




How Epsom Salt and Baking Soda Can Help to Control Oxalate?


Epsom salt (magnesium sulfate) and baking soda (sodium bicarbonate) are sometimes suggested as dietary supplements or home remedies to help control oxalate levels in the body, particularly in people prone to calcium oxalate kidney stones. Epsom Salt (Magnesium Sulfate) is a powerful source of magnesium. It can potentially reduce the risk of calcium oxalate stone formation. Magnesium may bind to oxalate in the intestines, reducing its absorption into the bloodstream. Less oxalate in the bloodstream means less available for excretion in the kidneys. Magnesium can also contribute to urine alkalinization (raising urine pH), which may inhibit the formation of calcium oxalate crystals, as they are less likely to form in alkaline conditions.


Baking soda or sodium bicarbonate is an alkaline substance, and when ingested, it can raise the urine pH. This increased alkalinity may help prevent the formation of calcium oxalate stones, as they are less likely to crystallize in alkaline urine. However, it's important to note that using Epsom salt or baking soda to control oxalate levels should be done under the guidance of a healthcare professional. Excessive intake of these substances can have side effects and may not be suitable for everyone. Additionally, dietary modifications, such as reducing high-oxalate foods and staying well-hydrated, remain fundamental strategies for managing oxalate levels and preventing kidney stones.







Etiology of high oxalate (candida overgrowth, high fat intake, mold like Aspergillus and Penicillium, etc.


Various factors, including dietary choices and certain medical conditions, can influence high oxalate levels in the body. Consumption of foods rich in oxalates, such as spinach, rhubarb, beets, nuts, and chocolate still comes at the top. A diet high in fat may increase oxalate absorption in the intestines, potentially raising oxalate levels in the urine.


Hyperoxaluria is a medical condition characterized by excess oxalate in the urine. It has two main types: primary (genetic) and secondary (acquired). Secondary hyperoxaluria can result from various factors, including certain gastrointestinal disorders that affect oxalate absorption. Some people with candida overgrowth or fungal infections may have altered gut flora, which can sabotage oxalate metabolism and lead to higher oxalate absorption. Moreover; exposure to molds like Aspergillus and Penicillium can lead to the production of oxalates in the body. This has been observed in some cases.


However; high oxalate levels alone may not necessarily lead to kidney stones or other health issues. Various factors, including other substances in the urine, urinary pH, and individual susceptibility, influence the risk of kidney stone formation. If you suspect you have high oxalate levels or are concerned about kidney stones, it's essential to consult a healthcare professional. They can assess your situation, conduct appropriate tests, and guide dietary modifications and treatment options tailored to your needs.


References:



Abdelsalam N.A., Ramadan A.T., ElRakaiby M.T., Aziz R.K. Toxicomicrobiomics: The Human Microbiome vs. Pharmaceutical, Dietary, and Environmental Xenobiotics. Front. Pharmacol. 2020;11:390. doi: 10.3389/fphar.2020.00390. [PMC free article] [PubMed] [CrossRef] [Google Scholar]


Aziz R.K. Toxicomicrobiomics: Narrowing the Gap between Environmental and Medicinal Toxicogenomics. OMICS A J. Integr. Biol. 2018;22:788–789. doi: 10.1089/omi.2018.0183. [PubMed] [CrossRef] [Google Scholar]


Lu, Kun; Mahbub, Ridwan; Fox, James G. (31 August 2015). "Xenobiotics: Interaction with the Intestinal Microflora". ILAR Journal. 56 (2): 218–227. doi:10.1093/ilar/ilv018. ISSN 1084-2020. PMC 4654756. PMID 26323631


Hoppe B., Beck B., Gatter N., von Unruh G., Tischer A., Hesse A., Laube N., Kaul P., Sidhu H. Oxalobacter formigenes: A potential tool for the treatment of primary hyperoxaluria type I. Kidney Int. 2006;70:1305–1311. doi: 10.1038/sj.ki.5001707. [PubMed] [CrossRef] [Google Scholar]


James L.F., Butcher J.E. Halogeton poisoning of sheep: Effect of the high level of oxalate intake. J. Anim. Sci. 1972;35:1233–1238. [PubMed] [Google Scholar]


Kamel KS, Cheema-Dhadli S, Halperin ML. Studies on the pathophysiology of the low urine pH in patients with uric acid stones. Kidney Int. 2002;61:988–994. [PubMed] [Google Scholar]


Maalouf NM, Cameron MA, Moe OW, Sakhaee K. Metabolic basis for low urine pH in type 2 diabetes. Clin J Am Soc Nephrol. 2010;5:1277–1281. [PMC free article] [PubMed] [Google Scholar]


Oliveira LM, Hauschild DB, Leite Cde M, Baptista DR, Carvalho M. Adequate dietary intake and nutritional status in patients with nephrolithiasis: new targets and objectives. J Ren Nutr. 2014;24:417–422. [PubMed] [Google Scholar]


Curhan GC, Taylor EN. 24-h uric acid excretion and the risk of kidney stones. Kidney Int. 2008;73:489–96. [PubMed] [Google Scholar]


Williams HE, Smith LH. Disorders of oxalate metabolism. Am J Med. 1968;45:715–35. [PubMed] [Google Scholar]


Balcke P, Schmidt P, Zazgornik J, Kopsa H, Minar E. Pyridoxine therapy in patients with renal calcium oxalate calculi. Proc Eur Dial Transpl Assoc Eur Dial Transpl Assoc. 1983;20:417–21. [PubMed] [Google Scholar]


Yendt ER, Cohanim M. Response to a physiologic dose of pyridoxine in type I primary hyperoxaluria. N Engl J Med. 1985;312:953–7. [PubMed] [Google Scholar]


Grases, F., Garcia-Gonzalez, R., Genestar, C., Torres, J. J. & March, J. G. Vitamin A and urolithiasis. Clin. Chim. Acta 269, 147–157 (1998).Return to ref 51 in article Article CAS PubMed Google Scholar


Munday, J. S. et al. Cystitis, pyelonephritis, and urolithiasis in rats accidentally fed a diet deficient in vitamin A. J. Am. Assoc. Lab. Anim. Sci. 48, 790–794 (2009). CAS PubMed PubMed Central Google Scholar


Bardaoui, M., Sakly, R., Neffati, F., Najjar, M. F. & El Hani, A. Effect of vitamin A supplemented diet on calcium oxalate renal stone formation in rats. Exp. Toxicol. Pathol. 62, 573–576 (2010). Article CAS PubMed Google Scholar


Schwille PO, Schmiedl A, Herrmann U, et al.. Magnesium, citrate, magnesium citrate and magnesium-alkali citrate as modulators of calcium oxalate crystallisation in urine: Observations in patients with recurrent idiopathic calcium urolithiasis. Urol Res 1999;27:117–126 [PubMed] [Google Scholar]


79 views0 comments

Comments


bottom of page