Do you know or suspect that you have oxalate issues? A wide range of symptoms can be caused an elevation of oxalate in the body, such as allodynia (nerve pain caused by something that does not wouldn't normally cause pain), calcium oxalate kidney stones, thyroid conditions, or dysfunction of the energy-producing structures in our cells called mitochondria. But this is by no means a complete list of symptoms that can be caused by high oxalate levels in the body.

Primary and Secondary Oxaluria

An elevation of oxalate in the body leads to an elevation of oxalate in the urine, so this is referred to as "oxaluria". So for this article will use the term "oxaluria" to refer to an elevation of oxalate in the body and dig into seven causes of oxaluria.

Oxaluria is referred to as primary oxaluria when it is caused by genetic polymorphisms that impair the function of enzymes involved in the processing of metabolites that can be converted to oxalate. 

Oxaluria is referred to as secondary oxaluria when it is caused by anything other than genetic polymorphisms. Most of this article is devoted to discussing causes of secondary oxaluria.

Exogenous and Endogenous Oxalates

Oxalates can enter the body via food (exogenous oxalates), and oxalates can be formed by metabolic processes in the body (endogenous oxalates). Endogenous oxalates are primarily formed from carbohydrates, fats, and proteins via multiple steps that generate glyoxal, which can then be converted to glyoxalate. Glyoxalate can then be converted either to to oxalate by the enzyme lactate dehydrogenase or to the amino acid glycine by the enzyme alanine—glyoxylate transaminase (AGT) enzyme if it is working well, which means there is no primary oxaluria (genetic impairment of the AGT enzyme), no vitamin B6 deficiency, nor a deficiency of alanine, which is required in the reaction that converts glyoxalate to glycine.

Nine Causes of Oxaluria

There are nine main causes of oxaluria: 

1. Genetic causes (primary oxaluria)
2. Intestinal hyperpermeability ("leaky gut")
3. Alterations in the bacterial microbiome
4. Fungal growth in the body
5. Oxidized ascorbic acid (vitamin C) & deficiencies of glutathione and/or NADPH
6. Oxidative stress
7. Fat maldigestion / malabsorption
8. Sulfate deficiency
9. Eight Key Nutrient deficiencies

Genetic (Primary) Oxaluria

A high quantity of oxalate can be produced in the body if one or more of three particular enzymes are not working well. This is called "primary hyperoxaluria" (PH), which happens in people with a variant in one (or more) of the genes coding for these three enzymes that needs to function well in order to avoid the production of oxalate in the body. Primary hyperoxaluria (PH) is categorized as Type 1, Type 2, or Type 3, depending on which gene is involved. 

Intestinal Hyperpermeability / "Leaky Gut"

One common cause of secondary oxaluria is an intestinal lining that is more permeable than normal (intestinal hyperpermeability / "leaky gut"), which enables oxalate in food to enter the body instead of remaining in the gut and being eliminated in feces. Many factors can contribute to the development of intestinal hyperpermeability such as imbalances in the bacteria of the intestinal microbiome (dysbiosis) or deficiency of vitamin A.

Alterations in the Gut Microbiome

Secondary oxaluria can also be caused by the absence of bacterial species from the intestinal microbiome that are capable of metabolizing (breaking down) oxalate for us. One such species is Oxalobacter formigenes. Some species of bacteria in the genes Lactobacillus can also perform this feat.

Fungal Growth in the Body

Fungal organisms like Candida albicans (yeast) or Aspergillus fumigatus (mold) produce oxalate. So if there is an overgrowth of yeast organisms like Candida in the body, or if a mold like Aspergillus colonizes the nose / sinuses, lungs, and/or gastrointestinal tract (Aspergillosis, which can be a feature of mold illness), this can lead to secondary oxaluria. 

Oxidized Ascorbic Acid (Vitamin C) & Deficiencies of Glutathione, NADPH and/or Thioredoxin Reductase

When ascorbic acid (vitamin C) gets oxidized as a result of its antioxidant activity of neutralizing oxidants  (a.k.a. "free radicals"), the oxidized ascorbic acid can spontaneously convert to oxalate, potentially accumulating and causing secondary oxaluria. Vitamin C can be converted back to its antioxidant form by glutathione or by an enzyme called thioredoxin reductase that requires NADPH to perform this conversion. NADPH and an enzyme called glutathione reductase are required to recycle glutathione after it has recycled vitamin C. Glutathione, thioredoxin, and NADPH are essential to keeping oxidized vitamin C from converting to oxalate. 

Genetic polymorphisms in the genes that code for thioredoxin reductase and the enzymes that synthesize and recycle glutathione can cause deficiencies of these two antioxidant powerhouses. This is discussed in greater detail in How to Stop Vitamin C from Forming Oxalate with particular attention to the matter of avoiding the formation of calcium oxalate kidney stones.

Oxidative Stress

Aside from the fact that oxidative stress would increase the formation of oxidized vitamin C, which can then form oxalate, oxidative stress can set up conditions in which oxalate gets formed from carbohydrates, fats, and proteins. Oxidative stress causes protein glycation, glucose autoxidation, and lipid peroxidation, all of which can result in the formation of glyoxal, which can be converted to glyoxalate, which can then be converted to oxalate if there is a deficiency of the active form of vitamin B6, or if there is a genetic polymorphisms in the AGT/AGXT gene for the enzyme that converts glyoxalate to glycine (so that it does not get converted to oxalate).

Oxidative stress also depletes glutathione and NADPH, which serve as cofactors for enzymes (glyoxalase and aldo-keto reductase) that metabolize glyoxal and methylglyoxal, preventing them form being converted to glyoxalate and oxalate.

Fat Maldigestion / Malabsorption

When fat is not properly digested and absorbed, it remains as fatty acids in the gut that "saponify" with minerals (binds to them), especially sodium, potassium, calcium, and magnesium, and to a lesser degree iron, copper, zinc, and manganese. 

Some of these minerals, especially calcium, can bind to oxalate from food, forming calcium oxalate, which is insoluble and cannot be absorbed into the body and therefore passes out of the body in the stool. So when fatty acids saponify with calcium, calcium is no longer available to bind to oxalate to keep the oxalate from being absorbed into the bloodstream. 

Fat malabsorption can be related to cholestasis (reduced bile secretion by the liver and gallbladder), Crohn’s disease, celiac disease, cystic fibrosis, and various disorders of the liver, gallbladder, pancreas, and small intestine. 

However, fat malabsorption and saponification of minerals does not necessarily cause oxalate issues because intestinal hyperpermeability would probably also need to be present in order for unbound oxalate to enter the bloodstream from the gut.

Even if you do not develop oxalate issues as a result of fat malabsorption, it would contribute to malabsorption of the minerals mentioned above and of fat-soluble nutrients like essential fatty acids and vitamins A, D, E, and K2. Since a deficiency of vitamin A can contribute to intestinal hyperpermeability, malabsorption of fat-soluble nutrients could ultimately promote secondary oxaluria.

Sulfate Deficiency

Oxalate can use the sulfate transporter to enter cells, so when sulfate is deficient, the sulfate transporter is less occupied by sulfate and more available for use by oxalate to enter cells. 

Low sulfate can also cause problems with oxalates via the kidneys. According to Susan Owens, who heads the Autism Oxalate Project at the Autism Research Institute, insufficient sulfate inside the kidney tubule cells interferes with the ability of the kidneys to remove oxalate from the blood and deliver it to the urine. This could cause higher levels of oxalate in the system.

Eight Nutrient Deficiencies

Deficiencies in one or more of eight nutrients (and perhaps others) can also lead to secondary oxaluria. These eight nutrients include:

• Vitamin B6
• Vitamin B1, vitamin B2, and magnesium (and low thyroid and adrenal function)
• Vitamin A
• Glutathione (not technically a "nutrient")
• Vitamin B2
• Vitamin B3
• Biotin

Vitamin B6

Vitamin B6 is the coenzyme for one of the three enzymes that need to work well in order to avoid oxalate being produced in the body. Specifically, it is the enzyme / gene (AGT / AGXT) involved in Type 1 primary hyperoxaluria (PH). If B6 (in its active form, pyridoxal-5-phosphate, P5) is deficient, restoring sufficiency of B6 in the body treats this cause of secondary hyperoxaluria. And in some people with Type 1 primary hyperoxaluria, supplementation with B6 can also reduce oxalate production by helping their defective AGT enzyme function better.

Some common causes of B6 deficiency include oxidative stress, chronic inflammation, sulfites, medications, malabsorption, or a diet low or very high in animal foods. 

Vitamin B1, Vitamin B2, and Magnesium (and Low Thyroid and Adrenal Function)

Vitamin B1, thiamine (in its active form, thiamine pyrophosphate, TPP, a.k.a. thiamine diphosphate, TDP), is required by the enzyme (pyridoxal kinase, which also goes by numerous other names) that completes the first step in converting B6 from its inactive form to its active form, pyridoxal-5-phosphate (P5P).

Vitamin B2, riboflavin (in one of its active forms, flavin adenine mononucleotide, FMN) is required for the enzyme (pyridoxine 5’-phosphate oxidase) that completes the second and final step of converting B6 from its inactive form to its active form, P5P. 

So deficiency of thiamine (in its active form) or riboflavin (in one of its active form)s could lead to a deficiency of active B6, potentially causing secondary oxaluria. Genetic variants in the genes that code for pyridoxal kinase (PDXK gene) or pyridoxine 5’-phosphate oxidase (PNPO) could also lead to secondary oxaluria by reducing the body's ability to convert the form of B6 found in plants and some nutritional supplements (pyridoxine HCl) to the active form that the body uses (P5P).

Pyridoxal kinase, one of the enzymes involved in converting B6 to its active form, not only requires B1 as its cofactor, it also appears to be regulated (possibly upregulated) by various active forms of B1. So, it is worth mentioning that the enzyme (thiamine pyrophosphokinase-1, TPK1 gene) that converts inactive thiamine to its main active form (thiamine pyrophosphate, TPP) requires magnesium and ATP as cofactors, making magnesium and ATP indirectly relevant to the conversion of B6 from its inactive form to its active form.

Riboflavin kinase, the enzyme that converts riboflavin to one of its active forms (FMN) , which is required for the function of the second enzyme (pyridoxine 5’-phosphate oxidase) in the 2-step activation of vitamin B6, also requires ATP and magnesium as cofactors.

So magnesium deficiency or low ATP production might also play a role in a deficiency of the active form of B6 via a deficiency in the active forms of B1 or B2. Furthermore, the conversion of riboflavin to FMN is impaired by low thyroid function and adrenal insufficiency (R, R, R, R). Perhaps the effects of low thyroid and adrenal function on FMN synthesis are mediated at least in part by reduced ATP production.

On another front, vitamin B1 and magnesium are heavily involved in one of the processes (pentose phosphate pathway) that supplies electrons to recycle oxidized NADPH (NADP+) back to NADPH so that it can donate an electron to recycle oxidized glutathione, so that glutathione can donate an electron to oxidized ascorbic acid, so that oxidized ascorbic acid does not form oxalate. Think of it as an electron "bucket brigade".

NADPH is also required by the enzyme (aldo-keto reductase) that converts glyoxal to glyceraldehyde so that it does not become glyoxalate and then oxalate.

B1 deficiency impairs the function of B1-dependent enzymes in the metabolism of glucose (pyruvate dehydrogenase, alpha ketoglutarate dehydrogenase, branched chain keto-acid dehydrogenase) that when impaired can lead to upstream metabolites in the glycolysis pathway backing up and being converted to glyoxal (which can be converted to glyoxalate and then oxalate).

Common causes of B1 deficiency include diets high in sugar and/or refined carbohydrates, sulfites, medications, mycotoxins, and consuming tea with meals (tannins bind B1).

Vitamin A

Vitamin A deficiency can cause intestinal hyperpermeability, which can increase absorption of oxalate from the gut, as described previously. Some people have genetic variants that do not enable them to efficiently form vitamin A from the beta carotene in plant foods, which is the main source of vitamin A for most people.

Glutathione (Not Technically a Nutrient)

Glutathione, an antioxidant enzyme produced by our bodies, normally recycles oxidized ascorbic acid back to its non-oxidized, fully-functional antioxidant form. However, a low level of glutathione can result in oxidized ascorbic acid accumulating, and forming oxalate.

Vitamin B2

Vitamin B2 is the precursor to the coenzyme that is required by the enzyme that recycles glutathione. After giving an electron to oxidized ascorbic acid to recycle it back to functional ascorbic acid, glutathione needs to be recycled from its oxidized form back to its functional form.  Glutathione needs to be recycled so that it is available to recycle ascorbic acid, thereby preventing the formation of oxalate from oxidized ascorbic acid. Deficiency of vitamin B2 can lead to less recycling of glutathione, resulting in less recycling of vitamin C, causing greater formation of oxalate from oxidized vitamin C.

Vitamin B3

Vitamin B3 is the precursor to NADPH, the source of electrons that glutathione reductase uses to recycle oxidized glutathione. So a deficiency of vitamin B3 could lead to less recycling of glutathione, resulting in less recycling of vitamin C, causing greater formation of oxalate from oxidized vitamin C.

Biotin

Biotin is perhaps the most intersting nutritient to consider in relation to  the level of oxalate in the body. According to an intriguing analysis by Chris Masterjohn, PhD, pyruvate dehydrogenase might be able to initiate a process of transforming oxalate to other compounds that do not cause the problems that oxalate can cause. This was discussed in the article entitled How To Stop Vitamin C From Forming Oxalate.

Five Key Takeaways and Actions

If you have secondary oxaluria, there is a lot that you can do to resolve it by simply doing the following five things:

1. Resolve intestinal hyperpermeability.
2. Increase the diversity of your intestinal microbiome and/or supplement with oxalate-metabolizing probiotics.
3. Test your levels of glutathione, magnesium, and vitamins A, B1, B2, B3, B6, and biotin.
4. Increase your intake of any deficient nutrients.
5. Promote glutathione production and recycling.

There are a variety of ways to accomplish these four steps that are built into the Bio-Individual Blueprint system. If you would like to discuss how I might be able to help you overcome oxalate issues or other health challenges, or simply get to the next level of health, download the Bio-Individual Blueprint Roadmap, watch the walkthrough video, and schedule a complimentary consultation with me to ...

1. Go over your situation
2. Review what you've done so far
3. Identify some potential next steps for you to take
4. Discuss whether it might be a fit for us to work together

If you have already downloaded the Roadmap and watched the walkthrough video, you can go here to schedule a complimentary consultation.