Shocking Research about Oxalates: Are You in a Risk Group?

What are oxalates?

Oxalate, chemically known as oxalic acid salt, is a natural compound and a terminal toxic metabolite found in many plants, including leafy greens, vegetables, fruits, cocoa, nuts, and seeds.

There is no known physiological function of oxalates in humans, although they play various roles in plant metabolism. (1)

The typical rate of oxalate absorption in the intestines is about 10-15%, but this can vary depending on dietary factors, diseases or other dysfunctions of the organism (who especially needs to watch out for oxalates will be discussed later).

The primary route of oxalate elimination is through the kidneys, which remove oxalate using glomerular filtration and tubular secretion.

This is why high concentrations of oxalates are so often linked to kidney conditions.

Kidney problems

First and foremost, oxalates play a significant role in the formation of kidney stones, particularly calcium oxalate stones, which are the most common type of kidney stones.

Scientists have so far found several mechanisms by which oxalates are so harmful to the kidneys.

“The most studied consequence of increased urinary oxalate excretion is calcium oxalate nephrolithiasis (kidney stones), a condition caused by elevated urinary supersaturation for calcium oxalate, followed by crystal formation and deposition [1,2]. Hyperoxaluria has been also associated with both acute and chronic kidney disease [12,13].” (2)

As it turns out, oxalate and calcium oxalate crystals can induce oxidative stress in renal epithelial cells, leading to the production of reactive oxygen species (ROS).

The overproduction of ROS and associated decrease in antioxidant defenses leads to oxidative stress, inflammation, and renal cell injury, which all are involved in the pathogenesis of kidney stones.

Animal model and tissue culture studies have shown oxalates provoked renal cell reactive oxygen species mediated inflammatory responses. Furthermore, major inflammation markers are also usually detectable in stone patient urine. (3)

“High oxalate concentrations in urine can damage renal tubular epithelial cells through oxidative stress, and damaged renal tubular epithelial cells are more likely to cause crystal adhesion and aggregation.“ (4)

High concentrations of oxalate promote stone formation by inducing renal cell injury and altering cellular functions in a way that promotes the attachment of nascent crystals and affects the kinetics of crystal formation (nucleation), aggregation, and growth. (5)

A recent 2021 study additionally showed that oxalate can induce ferroptosis (a form of programmed cell death) in renal tubular epithelial cells through excessive activation of autophagy (self-degradative recycling process). (6)

“Renal tubular epithelial cell damage is the basis for the formation of kidney stones. Oxalate can induce human proximal tubular (HK-2) cells to undergo autophagy and ferroptosis.”

Chronic kidney disease

Moving on to the consequences of excess oxalate, some studies have found that high urinary oxalate excretion is linked to the progression of chronic kidney disease (CKD) towards kidney failure. (7)

“Higher oxalate excretion was independently associated with greater risks of both CKD progression and ESRD (end-stage renal disease): compared with quintile 1 (oxalate excretion, <11.5 mg/24 hours) those in quintile 5 (oxalate excretion, ≥27.8 mg/24 hours) had a 33% higher risk of CKD progression and a 45% higher risk of ESRD.”

Oxalate-induced renal inflammation and fibrosis contribute significantly to the progression of renal failure. (8) Researchers proposed:

“We propose that inhibiting oxalate-induced inflammasome activation, or lowering plasma oxalate, may prevent or mitigate progressive renal damage in CKD, and warrants clinical trials.”

Case reports

The medical literature also knows of cases of people whose habitual consumption of seemingly healthy products has led to serious health problems.

These people were predisposed to higher absorption of oxalates from food, but as I will show later, the group of people who should watch out for oxalates is much larger than it appears.

Case 1: A 59-year-old woman developed oxalate nephropathy after consuming a high-oxalate diet of six tablespoons of chia seeds and five handfuls of almonds daily to manage irritable bowel syndrome (IBS).

Initially presenting with elevated creatinine levels, her diagnosis was confirmed via renal biopsy showing calcium oxalate deposition. Switching to a low-oxalate diet improved her condition. (9)

Case 2: An 81-year-old man with well-controlled diabetes but no history of kidney disease experienced worsening kidney function after consuming a diet high in oxalate precursors.

We can read something that probably concerns many more people: “He was a health-minded individual who had read extensively about the benefits of antioxidants”.

His oxalate nephropathy was identified through kidney biopsy and improved after dietary oxalate restriction and hydration, avoiding the need for dialysis. (10)

Case 3: A 65-year-old woman with a history of gastric bypass and recent antibiotic use developed acute oxalate nephropathy leading to end-stage renal disease almost immediately after a "green smoothie cleanse" rich in oxalates.

We can read in a paper: “She had normal kidney function before using the cleanse and developed acute kidney injury that progressed to end-stage renal disease. Consumption of such juice cleanses increases oxalate absorption, causing hyperoxaluria and acute oxalate nephropathy in patients with predisposing risk factors.” (11)

Case 4: A 65-year-old male with underlying multiple myeloma and normal kidney function who developed acute kidney injury due to oxalate nephropathy after large ingestion of star fruit on an empty stomach. (12)

Case 5: A young male developed acute kidney injury following star fruit ingestion on an empty stomach. The patient was treated conservatively and recovered completely. (13)

Authors of other publications with patients with acute kidney injury and history of ingesting star fruit warned: “Taking star fruit in large amounts on an empty stomach and in a dehydrated state is a risk factor for nephrotoxicity.” (14)

Joint pain

Research and clinical cases have also suggested a link between calcium oxalates, specifically in the form of raphides (sharp, needle-shaped crystals of calcium oxalate) and joint pain.

It has been known for more than 40 years that calcium oxalate crystals are deposited in various tissues of the body, not only in the kidneys, but also in the joints and bones.

For example, a 1982 study by Hoffman et al. reported the identification of calcium oxalate crystals in the synovial fluid (that normally reduces friction between the articular cartilages) of patients with chronic renal failure, suggesting that these crystals can contribute to joint disease in this patient population.

They suggested: “Joint disease in chronic renal failure may be associated with calcium oxalate as well as the previously recognized apatite deposition.” (15)

In addition, oxalate arthropathy is sometimes encountered in clinical practice, which is a symptom of hyperoxaluria (increased urinary excretion of oxalate), associated with the deposition of calcium oxalate in tendons, cartilage, joint synovium and even blood vessels. (16)

Bone fractures

A limited number of studies have also shown that systemic oxalosis, a disorder characterized by the accumulation of calcium oxalate crystals in various tissues like visceral tissues, blood vessels, bones, and cartilage, is associated with substantial bone impairments.

In a 2015 study Bacchetta et al. highlighted calcium oxalate deposits in the bone marrow space, leading to recurrent low-trauma fractures, bone deformations, severe bone pains, and specific oxalate osteopathy observable on X-ray.

They found that these deposits were surrounded by a granulomatous reaction due to macrophage invasion. Moreover, bone quality analysis showed that the bones were harder and consequently more brittle than normal. (17)

Women's health

Some studies and case reports suggest that oxalates may be associated with vulvodynia (chronic pain in vulva, vagina).

The premise is that If oxalate crystals deposit on the external genitalia or within the vulvar tissue, they may trigger a local inflammatory response and cause microscopic abrasions, leading to irritation, inflammation, and pain.

Furthermore high levels of oxalates in the urine and potentially in the local vulvar area may disrupt the local microbiome and epithelial integrity. It should be noted, however, that a very limited number of studies have so far yielded inconclusive results. (18, 19)

Breast cancer

Similarly, in the preliminary stages of research is a potential link between oxalates and breast cancer. Oxalates, based on the existing data, could be seen as the initiators of cancer development.

Castellaro et al. found that breast tumor tissues contain higher concentrations of oxalates than non-pathological breast tissues.

Oxalate was shown to induce proliferation of breast cells and stimulate the expression of the pro-tumorigenic gene c-fos. Furthermore, oxalate generated highly malignant and undifferentiated tumors when injected into the mammary fat pad in female mice.

In conclusion, the study suggested chronic exposure to oxalate may promote the transformation of breast cells from normal to tumor cells. (20)

“Surprisingly, the mice that were injected with oxalate generated very aggressive tumors.”

In another study oxalate was found to induce DNA synthesis and overexpression of immediate early genes (IEG) in human breast cancer cells in culture. The study found a strict correlation between oxalate concentration and overexpression of aforementioned pro-tumorigenic markers c-Fos and Fra-1 (high Fra-1 levels are associated with enhanced cell proliferation and invasion) in human breast cancer tissues.

Thus, this is the second study that highlights oxalates excreted from cells could induce alterations in normal breast epithelial cells, providing an environment for the transformation from normal to fully developed breast tumors. (21)

Who should be especially careful with oxalates?

“Secondary hyperoxaluria is a more common disorder which can be caused by enteric conditions and increased dietary intake of oxalate. In enteric hyperoxaluria, increased absorption of oxalic acid occurs. These are mostly patients with malabsorption as a result of e.g. small bowel resections, pancreatic insufficiency or gastric bypass.” (22)

Predispositions include:

• intestinal problems (inflammatory bowel disease, irritable bowel syndrome, SIBO, Crohn's disease, etc.)
• antibiotic therapies (antibiotics kill oxalate-degrading bacteria).
• fat absorption problems (pancreatic and/or bile problems).

Note: Even if you don't have these predispositions, high consumption of oxalates is not advisable, because although cases of sudden acute renal failure in people without predispositions and normal kidney function are rare, kidney stones in the long run are not a nice thing either.

We can read: “Oxalate nephropathy may also occur in individuals with normal gastrointestinal function when they consume foods with a high content of oxalate, especially in its soluble form (1, 7, 10, 16, 49).” (23)

Recommended doses and tips

In the literature we can find that the daily intake of oxalates for a healthy person should not exceed 250 mg per day. When we consider that raw spinach can have as much as 900 mg/100g, rhubarb 540 mg/100g, star fruit 730 mg/100g, almonds 490 mg/100g, cashew 260 mg/100g, peanuts 150 mg/100g or dark chocolate 500 mg/100g this is not a difficult limit to exceed.

“Moreover, when a diet contains more than 50 mg of oxalate per day, the absorption of dietary oxalate increases more steeply, which can further elevate urinary oxalate levels [13].” (24)

In contrast, in people with the aforementioned predispositions or already present problems with kidney function, daily dose of less than 50 mg or complete elimination of oxalates may be recommended.

Tips

Meals low in calcium may increase the absorption of oxalates. Calcium binds to oxalate in the gastrointestinal tract, consequently reducing oxalate absorption.

Studies have shown that a higher dietary calcium intake is associated with lower oxalate absorption, suggesting that consuming calcium-rich foods or supplements during meals can help minimize oxalate absorption and its urinary excretion. (25)

Cooking can significantly reduce the oxalate content of foods, especially methods like boiling, which allow oxalates to leach into the water.

One study has found: “Boiling markedly reduced soluble oxalate content by 30-87% and was more effective than steaming (5-53%) and baking (used only for potatoes, no oxalate loss).” (26)

In addition, juicing products rich in oxalates increases their absorption in the intestines, as in our earlier case of "healthy" green juices.

Bottom line

Oxalate is a terminal toxic metabolite found mainly in plants but lacking physiological functions in humans.

The problems associated with it are mainly related to kidney function, which is connected with its main route of excretion. However, early studies suggest a link between oxalates and joint pain, weaker bones, vulvodynia or even cancer.

More and more studies suggest that oxalates may be more problematic than previously thought even for people without various predispositions to over-absorb them: “Accumulating evidence from animal and human studies suggests that dietary oxalate may have a greater impact on kidney function than previously recognized.“ (27), which indicates that the popular slogan “the more plants the better for health” may not be true.