IngredientsOxalic acid is an organic acid with the systematic (IUPAC) name ethanedioic acid and the chemical formula H2C2O4. It is the simplest dicarboxylic acid. It belongs to the family of carboxylic acids and is colourless and crystalline in its solid form. Its common name is derived from early investigators who isolated the compound from flowering plants of the genus Oxalis, commonly known as wood-sorrels. The ionized form, oxalate, is chemically denoted as C2O42â, and the two namesâoxalic acid and oxalateâare frequently used interchangeably in nutritional and biochemical literature.
Oxalic acid is a white crystalline solid that forms a colorless solution in water. It typically occurs as the dihydrate with the formula H2C2O4·2H2O. The dihydrate can be converted to the anhydrous form by heating or azeotropic distillation. Anhydrous oxalic acid exists as two polymorphs: in one, hydrogen-bonding results in a chain-like structure, whereas in the other form, the hydrogen bonding pattern defines a sheet-like structure.
Oxalic acid is a much stronger acid than acetic acid. It is a reducing agent, and its conjugate bases, hydrogenoxalate and oxalate, are chelating agents for metal cations. It exhibits strong acidity, chelating, and reducing abilities.
Oxalate can form soluble and insoluble salts in water. When binding with sodium, potassium, and ammonium ions, it forms soluble oxalates; whereas with calcium, iron, and magnesium it precipitates, forming insoluble compounds and making these minerals unavailable for absorption. Oxalic acid forms neutral and acid salts with monovalent metals and ammonia, including calcium oxalate, potassium oxalate, sodium oxalate, strontium oxalate, and magnesium oxalate.
Oxalic acid is among the most abundant organic acids found in different biospheres, including plants, as an end product of metabolism. It is an antinutrient present, commonly in trace amounts, in fruits, nuts, cereals, fungi, vegetables, aromatic plants, and beverages, with plant-based products being the main sources of dietary oxalates. However, some plants have high quantities of these compounds. In this matter, green leafy vegetables, such as spinach, Swiss chard, and rhubarb, are highlighted.
Published oxalate values include 329.6â2350 mg total oxalates per 100 g fresh weight for spinach, 1235 mg total oxalates per 100 g fresh weight for rhubarb, and 874â1458 mg total oxalates per 100 g fresh weight for Swiss chard. Spinach, New Zealand spinach, rhubarb, Swiss chard, taro leaves, sorrel, soybean, amaranth, parsley, and licorice are considered high-oxalate foods, especially some green leafy vegetables. In contrast, fruits (except for star fruit, elderberry, and dried fig), cabbage, broccoli, cauliflower, cucumber, kale, pumpkin, chickpeas, lentils, cowpea, arugula, cress, garlic, and green onion can be referred to as low-oxalate foods.
Spinach is considered healthful due to its high concentration of beta carotene, lutein, folate, vitamin C, calcium, iron, phosphorus, and potassium; however, it also contains higher concentrations of oxalic acid than most crops. Scientists have analyzed oxalate concentrations in 310 spinach varietiesâ300 USDA germplasm accessions and 10 commercial cultivarsâfinding that spinach varieties and cultivars displayed oxalate concentrations from 647.2 to 1286.9 mg/100 g on a fresh weight basis, suggesting that oxalate concentration is a complex trait controlled by multiple genes.
Oxalic acid can be found in soil, minerals, bacteria, fungi, and in plants. It is known that fungi excrete a significant amount of oxalic acid as a byproduct of carbohydrate metabolism. A number of molds produce oxalic acid as a major metabolic product. Some species of Penicillium and Aspergillus, for example, convert glucose into oxalic acid.
Oxalic acid and its salts are produced during the normal metabolism of mammals, including human beings. Oxaluria has two sources: oxalate formed endogenously from metabolism of its precursors, and oxalate absorbed from the gastrointestinal tract. The major precursors of oxalate under normal circumstances appear to be the amino acids hydroxyproline, glycine, and serine. Glycine and serine are present in all food proteins. The key player in the biosynthetic story is glyoxylate: it is the nexus of pathways that lead to and away from oxalate. Glyoxylate is the main precursor of oxalate, which combines spontaneously with calcium ions to form calcium oxalate.
Oxalate is formed in the body from a combination of dietary sources and endogenous synthesis from precursors such as ascorbate and various amino acids. Dietary sources (exogenous) account for approximately 20â40% of blood oxalate.
Known as a constituent of wood sorrel as early as the 17th century, oxalic acid was first prepared synthetically in 1776. In 1776, Swedish chemists Carl Wilhelm Scheele and Torbern Olof Bergman produced oxalic acid by reacting sugar with concentrated nitric acid; Scheele called the resulting acid socker-syra (sugar acid). By 1784, Scheele had shown that "sugar acid" and oxalic acid from natural sources were identical. The modern name was introduced in 1787 by de Morveau, Lavoisier, and co-authors.
In 1824, the German chemist Friedrich Wöhler obtained oxalic acid by reacting cyanogen with ammonia in aqueous solution. This experiment may represent the first synthesis of a natural product.
Oxalic acid, a naturally occurring organic compound found in many plants such as spinach, rhubarb, and sorrel, has a notable historical presence in traditional and folk medicine. For centuries, it has been valued for its diverse properties when used in carefully controlled amounts. Ancient practitioners recognized oxalic acid's astringent quality, applying preparations from oxalate-rich plants to soothe sore throats, reduce inflammation, and as a topical remedy for skin irritations. Its mild antimicrobial effect was also harnessed for cleansing wounds and promoting healing.
As described in Oxalic Acid in Biology and Medicine by A. Hodgkinson (1977), oxalic acid was formerly used intravenously as a hemostatic agent and topically as an antiseptic in man and other animals, but this was discontinued because of its toxicity and the danger of precipitating insoluble calcium oxalate in the tissues.
In traditional cuisines, foods high in oxalic acid have been staples. Oxalic acid was first isolated in 1776 by Swedish chemist Carl Wilhelm Scheele from rhubarb juice, so it has been on scientists' radar for over two centuries. Mediterranean traditions involved blanching chard in olive oil and garlic; Chinese herbalists simmered rhubarb stalks for bitters. In India, spinach (palak) is a key ingredient in sabzis and dals, usually cooked with spices like cumin and asafoetida to aid digestion.
The journey of oxalic acid research began in the early 19th century when Swedish chemist Carl Wilhelm Scheele first isolated it from the juice of rhubarb in 1776. He named it "acidum oxalicum" after the Latin "oxalis" for sorrel, which was long used in European folk remedies for scurvy and digestive ailments.
Conventional uses of oxalic acid include as an analytical reagent, in calico printing and dyeing, for bleaching straw and leather, removing paint or varnish, rust or ink stains, cleaning wood, and manufacturing oxalates, blue ink, celluloid, intermediates and dyes, in metal polishes, in purifying methanol, for decolorizing crude glycerol, as a general reducing agent, in ceramics and pigments, in metallurgy as a cleanser, in the paper industry, in photography, in process engraving, in rubber manufacturing, in making glucose from starch, as a condensing agent in organic chemistry, and as a veterinary hemostatic agent.
Oxalates are referred to as anti-nutrients because they bind to certain minerals and prevent the body from absorbing and utilizing them. One prominent example is spinach: although rich in calcium and magnesium, the oxalate forms a complex with these minerals and can inhibit absorption. A high oxalate intake reduces the intestinal absorption of calcium because of the formation of insoluble calcium oxalate, and prolonged exposure to such a diet may lead to loss of bone mineral, particularly if the diet is also deficient in calcium or vitamin D.
Oxalic acid also inhibits the activity of a number of enzymes, possibly due to competition between oxalate and a structurally similar substrate of the enzyme.
The immediate metabolic precursor of the majority of the oxalate in human urine is glyoxylic acid. Much of the glyoxylic acid is in turn derived from glycolic acid. The enzyme glycolate oxidase (GAO) carries out the oxidation of glycolic acid, through glyoxylic acid, to oxalic acid.
Feeding experiments and radioisotope studies have indicated that a considerable number of compounds are precursors of oxalic acid in animals and humans, including glycine, glyoxylic acid, glycolic acid, ethylene glycol, ascorbic acid, and tryptophan. Studies with ascorbic acid have shown that the main excretory products of vitamin C in man are oxalate, ascorbic acid, and dehydroascorbic acid. From 17â40% of administered ascorbic acid was excreted as oxalic acid.
Oxalic acid has been shown in laboratory studies to suppress replication and migration of human endothelial cells and to inhibit thrombocyte aggregation, but it is not known if these findings have any relevance to uremic toxicity in vivo.
Oxalate found in humans mainly originates from dietary sources containing oxalate, including strawberries, spinach, tea, and coffee, while a small amount is formed by metabolizing glycine, ascorbic acid, and glyoxylate. Humans do not harbor enzymes to metabolize oxalate, but micro-organisms in the gut can degrade oxalate or assist its assimilation into the urinary system. Two key enzymes, formyl-coenzyme A transferase (FCR) and oxalyl-coenzyme A decarboxylase (OXC), play a critical role in oxalate degradation. FCR catalyzes the transfer of a CoA moiety to stimulate oxalic acid. Oxalyl-CoA is then transformed into formyl-CoA and CO2 by OXC in a thiamine PPi-dependent decarboxylation reaction.
Close to 70% of kidney stones in man are composed partially or predominantly of calcium oxalate. Nephrolithiasis (kidney stones) affects up to 9% of the US population, affecting both males and females, with incidence increasing in children and adults.
The role of dietary oxalate in calcium oxalate kidney stone formation remains unclear. However, due to the risk for stone disease that is associated with a low calcium intake, dietary oxalate is believed to be an important contributing factor. The only difference identified to date between normal individuals and those who form stones is in the intestinal absorption of oxalate. Differences in dietary oxalate intake and in renal oxalate excretion are two other parameters likely to receive close scrutiny, and such research should help clarify the role of dietary oxalate in stone formation.
The other concern with oxalate is that it can contribute to kidney stones. Most people have a small amount of oxalate and calcium in the urinary tract at some point. Research has shown that this is a particular problem if oxalate levels are high and urinary volume is low.
Evidence strength: The relationship between elevated urinary oxalate (hyperoxaluria) and calcium oxalate nephrolithiasis is well established in the literature; however, whether dietary restriction of oxalate alone substantially reduces stone recurrence in the general stone-forming population remains debated. Dietary intervention trials have shown mixed results on whether low-oxalate diets significantly reduce stone recurrence compared to calcium supplementation. Preliminary animal data show high dietary oxalates might alter gut permeability. Limitations include small sample sizes, short durations, and variability in measuring soluble versus insoluble oxalates.
Oxalate homeostasis is maintained through a combination of endogenous biosynthesis, exogenous supply, and renal and faecal excretion. Novel studies have shed light on the essential roles of metabolic pathways, the microbiome, epithelial oxalate transporters, and adequate oxalate excretion in maintaining oxalate homeostasis. In patients with primary or secondary hyperoxaluria, nephrolithiasis, acute or chronic oxalate nephropathy, or chronic kidney disease, one or more of these elements are disrupted. The consequent impairment in oxalate homeostasis can trigger localized and systemic inflammation, progressive kidney disease, and cardiovascular complications, including sudden cardiac death.
There is emerging evidence that increased concentrations of oxalate could be a driver of chronic kidney disease progression. Furthermore, oxalate has been implicated in cardiovascular disease. Mounting evidence suggests that impaired oxalate metabolism is an important factor in the development of cardiovascular disease, not only in patients with kidney disease requiring dialysis but also in those with metabolic syndrome. There are also indications that oxalate plays a role in inflammatory processes above and beyond those mediating chronic kidney disease.
Evidence strength: Evidence on oxalate's role in CKD progression and cardiovascular disease is preliminary and largely derived from epidemiological associations and animal models. Clearly, further research is needed: preclinical findings need to be reported in organ-appropriate tissue in vitro and in vivo, and population studies focusing on relevant risk phenotypes would also be beneficial.
The primary hyperoxalurias (PHs) are a group of rare but underdiagnosed disorders of hepatic glyoxylate metabolism resulting in excessive endogenous oxalate production, which is their common biochemical hallmark. Three types (PH1â3) can be distinguished according to their specific enzymatic defect in glyoxylate metabolism.
Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that results in oxalate overproduction leading to nephrolithiasis, nephrocalcinosis, kidney failure, and systemic oxalosis. Infantile PH1 is its most severe form and may require intensive hemodialysis followed by a liver-kidney transplant.
Lumasiran (Oxlumoâą, developed by Alnylam Pharmaceuticals), an investigational RNA interference (RNAi) therapeutic agent, is the first drug approved for the treatment of PH1, officially approved by the US Food and Drug Administration and the European Union in November 2020. Lumasiran is a subcutaneously administered RNA interference (RNAi) therapeutic agent targeting the molecular pathway of glyoxylate metabolism, specifically directed at hepatic cells. Lumasiran reduces glycolate oxidase (GO) by degrading the mRNA-encoding GO. The reduction in GO results in a decline in liver-produced oxalates.
In 2019, the double-blind phase 3 clinical trial ILLUMINATE-A evaluated the efficacy and safety of lumasiran in 39 patients with PH1 older than 6 years of age with no end-stage renal disease. Lumasiran reduced urinary oxalate excretion and most patients reached normal or near-normal levels after 6 months of treatment. In the ILLUMINATE-B trial (infants and young children), lumasiran treatment reduced spot urinary oxalate:creatinine ratio by 72% at month 6, maintained at 72% at month 12. The mean reduction from baseline in plasma oxalate level was 32% at month 6 and improved to 47% at month 12. Additional improvements were seen in nephrocalcinosis grade, and kidney stone event rates remained low. The most common adverse events were mild, transient injection-site reactions in 3 patients (17%).
Nedosiran is currently being developed for the treatment of three types of PH as a siRNA-based modality. Through specific inhibition of lactate dehydrogenase enzyme, the key enzyme in biosynthesis of oxalate in the liver, phase 1, 2, and 3 clinical trials of nedosiran have achieved the desired primary endpoint of reduction of urinary oxalate levels in patients with PH1.
Consumption of oxalic acid-rich foods in human diets, particularly leafy vegetables such as spinach, tea, and rhubarb, affects mineral absorption such as calcium. Its high level in blood is associated with many diseases such as hyperoxaluria and systemic oxalosis, and it is thus classified among potential anti-nutrients.
Oxalate can react with calcium, iron, and other minerals to form crystals that inhibit mineral absorption. Notably, the impact on mineral status in healthy individuals consuming typical Western diets is considered modest; major concerns arise primarily in settings of very high oxalate intake, low calcium intake, or compromised renal function.
Evidence strength: The anti-nutritional effect of oxalate on calcium absorption is well documented in biochemical and observational studies. Human intervention data on bone mineral density outcomes specifically attributable to dietary oxalate are limited.
Oxalobacter formigenes, a unique anaerobic bacterium that relies solely on oxalate for growth, is a key oxalate-degrading bacterium in the mammalian intestinal tract. Degradation of oxalate in the gut by O. formigenes plays a critical role in preventing renal toxicity in animals that feed on oxalate-rich plants. The role of O. formigenes in reducing the risk of calcium oxalate kidney stone disease and oxalate nephropathy in humans is less clear, in part due to difficulties in culturing this organism and the lack of studies which have utilized diets in which the oxalate content is controlled.
Intestinal O. formigenes colonization has been associated with a lower risk for recurrent kidney stones in humans. Two recent large-scale epidemiological studies associated antibiotic use with increased nephrolithiasis risk, presumably via a perturbed microbiota.
One study examining microbial factors that influence the effectiveness of O. formigenes in lowering urinary oxalate analyzed gut microbiota from a controlled diet study involving 26 healthy, nonâstone-forming adults who were initially uncolonized and then colonized with O. formigenes. Stool samples were profiled for 16S rRNA and oxalate-degrading genes.
Patients with inflammatory bowel disease (IBD) frequently suffer from disrupted oxalate homeostasis and calcium oxalate nephrolithiasis. Enteric oxalate levels are elevated in IBD patients, with the highest levels in Crohn's disease patients with both ileal and colonic involvement, consistent with known nephrolithiasis risk.
Evidence strength: The role of the oxalobiome in regulating systemic oxalate is supported by observational human studies and animal experiments, but direct clinical trial evidence for probiotic-based oxalate reduction in humans remains limited and preliminary.
Api-Bioxal Oxalic Acid Varroa Mite Treatment is registered by the USDA and approved by the EPA for the treatment of Varroa mites in honey bee colonies. Oxalic acid has been used against Varroa mites since the early 1980s. Oxalic acid (OA) is a natural chemical that has been shown to reduce the incidence of Varroa destructor within bee colonies, while maintaining safety for bees.
Short-acting oxalic acid applications can have over 99% efficacy against Varroa under broodless conditions, but only approximately 40â50% efficacy when brood is present. The varroacidal activity of oxalic acid is related to its acidic nature, although the specific mode of action remains unknown. This chemical can kill mites during their dispersal phase, but unlike formic acid it cannot penetrate wax cappings to kill mites inside cells. To date, there are no records of Varroa mites developing resistance to oxalic acid.
There are some procedures to reduce oxalate content in foods, in particular soluble oxalate, such as boiling, steaming, soaking, and processing with calcium sources. Boiling or blanching can reduce soluble oxalates by 50â70%. Steaming preserves more oxalates but also more vitamins.
Employing cooking techniques that greatly reduce soluble oxalate presents a potential strategy for lowering oxaluria in those prone to the development of kidney stones, since soluble forms of oxalate seem to be more bioavailable than insoluble sources. The addition of calcium salts (e.g., calcium carbonate and calcium chloride) to oxalate-rich food sources upon cooking could also lead to oxalate reduction, particularly by converting soluble oxalates into insoluble form.
Traditionally, oxalic acid has been extracted from natural products by treating them with an alkaline solution, followed by crystallization of the acid. Sodium hydroxide is the alkaline material most commonly used for this procedure.
If an average serving (60 g) of spinach or rhubarb is included, the oxalate intake rises to between 400 and 600 mg/day. Wide variations in oxalate intake may occur in countries such as India, where vegetables rather than dairy products provide the main source of minerals, and where many of the plants used as vegetables contain high concentrations of oxalate. A study found intakes ranging from 78â2045 mg/day depending on the season in the rural population of Udaipur, India.
A double-blinded randomized trial in PH1 patients aged six years or older demonstrated a 53.5% reduction in 24-hour urinary oxalate excretion and a substantial decrease in plasma oxalate levels with lumasiran. Nedosiran is subcutaneously injected in a fixed dose of 170 mg on a monthly basis in adult patients.
A significant increase of 61% and 41% was observed in mean urinary oxalate after supplementation with 1 or 2 g of vitamin C, respectively, in calcium stone-forming patients. The lack of a further increase on urinary oxalate after 2 g of vitamin C may be ascribed to a saturable transport mechanism leading to a reduced relative absorption capacity with increasing intakes.
For the dribble method, 35 g of Api-Bioxal is mixed in 1:1 liter of sugar syrup, with 5 ml of the solution dribbled onto the bees in each occupied bee space. For the vaporization sublimation method, 4 g of Api-Bioxal is used per hive.
Oxalic acid can be toxic when eaten in significant quantities, and contact with concentrated forms can cause chemical burns. As reported in the literature including Oxalic Acid in Biology and Medicine, poisoning from oxalic acid in animals and man has been recognized since the beginning of the 19th century. The death rate from oxalate poisoning has declined, supposedly because of a decreased use of oxalic acid in domestic cleaning fluids. Examples of chronic poisoning by absorption of oxalic acid through the skin and by inhalation have been reported.
The reported average lethal dose for oxalate is estimated at 170 mg per pound (375 mg per kg) of body weight, which is approximately 26.3 grams for a 154-pound (70-kg) person. This means a person would have to eat between 5.7â11.7 pounds (2.6â5.3 kg) of rhubarb leaves for a potentially lethal dose of oxalate. During World War I, people were advised to eat rhubarb leaves as a substitute for vegetables that were unavailable, leading to reports of several poisonings and deaths.
High levels of oxalate in the blood are associated with diseases such as hyperoxaluria, systemic oxalosis, and are classified among potential anti-nutrients. Risk factors for secondary oxalate nephropathy due to excessive intake of oxalate or its precursor are likely to be age, diabetes, dehydration, and underlying chronic kidney disease. Most of the patients do not have a complete recovery of kidney function, and many become dependent on dialysis.
In 1958, it was discovered that ascorbic acid can be converted to oxalate, a key component of calcium oxalate kidney stones. The process begins with the formation of dehydroascorbic acid (DHA) from the ascorbyl radical. Despite newer assays that mitigate the in vitro conversion of ascorbic acid to oxalate, controversy still remains, with some studies suggesting that vitamin C leads to an increase in oxaluria, whereas others do not support this observation. Caution should be exercised before supplementing vitamin C either in its natural form or as a drug, particularly in individuals with risk factors for nephrolithiasis or impaired renal function.
When taken with food, ingested oxalate is poorly absorbed from the gastrointestinal tract. Low amounts of calcium in the diet can increase chances of forming calcium oxalate kidney stones. Calcium binds with oxalate in the intestines, thereby reducing free oxalate available for absorption. This is why dietary calcium restriction, paradoxically, can increase stone risk by allowing more luminal oxalate to be absorbed.
Prior antibiotic use has been associated with kidney stone development months or even years later. O. formigenes presence is a marker for a richer microbiome, and its loss is a marker of important antibiotic-induced microbiome alterations. No significant recolonization was detected by 6 months, while overall diversity recovered, consistent with persistent microbiome disturbance.
Increased rate of formation or increased rate of absorption of oxalate can lead to hyperoxaluria. Groups with elevated risk include individuals with primary hyperoxaluria (genetic), inflammatory bowel disease, short bowel syndrome, bariatric surgery history, chronic kidney disease, and those taking high-dose supplemental vitamin C. A much smaller number of people are afflicted with primary hyperoxaluria, a genetic metabolic disorder in which oxalate is deposited in the kidneys. Nephrolithiasis and nephrocalcinosis are usually present in patients suffering from this condition before the age of 5.
Health conditions that Oxalic acid may help support.
Body systems that Oxalic acid may help support.
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