IngredientsFormic acid (from Latin formica, meaning "ant"), systematically named methanoic acid, is the simplest carboxylic acid, with the chemical formula HCOOH and structure H−C(=O)−O−H. It is a weak acid with a pKa of 3.76. At room temperature, formic acid is a colorless liquid with a pungent, penetrating odor comparable to that of the related compound acetic acid. Esters, salts, and the anion derived from formic acid are collectively called formates.
In nature, formic acid is found in the stings and bites of many insects of the order Hymenoptera, most notably ants. Ants are named after this compound — the family Formicidae — and produce formic acid as a defense mechanism and to combat pathogens. Formic acid is also found in honeybees (Apis mellifera) and other related species, where it is a component of their venom used for defense. Formic acid is additionally present in the stinging hairs (trichomes) of stinging nettles (Urtica dioica); when these hairs contact skin they release a mixture containing formic acid, producing the characteristic stinging sensation.
Formic acid naturally occurs in a wide range of plant-derived foods and botanicals including carrots, soybean roots, carob, yarrow, aloe, bearberries, wormwood, ylang-ylang, celandine, water mint, apples, tomatoes, bay leaves, common juniper, ginkgo, corn mint, European pennyroyal, and bananas. Formic acid is also a naturally occurring component of the atmosphere, due primarily to forest emissions.
Formic acid (methanoic acid, HCOOH) is a simple carboxylic acid with a pungent odor and strong antiseptic properties. In industrial and regulatory contexts it is encountered in several forms:
As early as the 15th century, some alchemists and naturalists were aware that ant hills give off an acidic vapor. The first person to describe the isolation of this substance, by the distillation of large numbers of ants, was English naturalist John Ray in 1671. Formic acid was first synthesized from hydrocyanic acid by French chemist Joseph Gay-Lussac. In 1855, another French chemist, Marcellin Berthelot, developed a synthesis from carbon monoxide, a process similar to the one used today.
The mound-building red wood ant, Formica rufa L., was widely used in Sweden and neighboring countries for its perceived healing properties. It was a widespread belief that formic acid could cure various diseases, especially gout and rheumatism; both anthills and the ants themselves were used for that purpose. It was also common to flavor distilled liquor (brännvin) with ants as a medicinal remedy. Spirits seasoned with live ants are documented at least from the seventeenth century, and formic acid and ant oil were available in the pharmacy until the end of the nineteenth century.
In the Stockholm Pharmacopoeia of 1686 and in the Swedish Pharmacopoeia of 1775, remedies derived from the red wood ant (Formica rufa) were listed alongside preparations from other insects including the stag beetle, Spanish fly, European honeybee, and others. Treatment of rheumatic and other diseases through immersion in an anthill is reported in German folk medicine.
In the first half of the twentieth century, the physicians Eduard and Egon Krull (1842–1914 and 1879–1936, respectively) as well as Albrecht Reuter (1863–1937) recommended injections of diluted formic acid to treat tuberculosis, gout, arthritis, renal disorders, and other complaints. Between 1930 and 1960, more than 15 different commercial preparations were marketed, and Egon Krull invented a drug series called "Myrmekan." Formic acid inhalations were recommended by Sigmund von Kapff (1864–1946), and by the 1950s the injection of formic acid was regarded as one of the most important procedures in alternative medicine.
In the late 1960s, significant quantities of formic acid became available as a by-product of acetic acid production, and it found increasing use as a preservative and antibacterial agent in livestock feed. Following the European ban on antibiotic growth promoters in 2006 (EC Regulation No. 1831/2003), the use of organic acids including formic acid in animal feed gained considerable importance; their positive effects on feed quality and animal performance had been known for decades.
The molecular formula of formic acid is HCOOH, making it the simplest carboxylic acid with notable acidity and antibacterial properties. Due to the −CHO group, formic acid imparts some of the chemical character of an aldehyde.
Formic acid and its conjugate base formate are essential endogenous one-carbon metabolites in virtually all living organisms. Formate is an essential intermediary metabolite in folate-mediated one-carbon metabolism; despite its importance, knowledge of its detailed metabolism remains limited. Formate can be produced from several substrates, including methanol and branched-chain fatty acids, some reactions being folate-dependent while others are not.
10-formylTHF is formed from tetrahydrofolate (THF), ATP, and formate catalyzed by methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) in the cytosol and nucleus. Formate is a major source of one-carbon units, derived primarily from THF-dependent serine and glycine catabolism in the mitochondria. THF-mediated one-carbon metabolism is a network of interdependent biosynthetic pathways compartmentalized in the cytoplasm, mitochondria, and nucleus; one-carbon metabolism in the cytoplasm is required for the synthesis of purines and thymidylate and the remethylation of homocysteine to methionine.
Formaldehyde, which is generated from oxidative decomposition of the folate backbone, is converted in human cells to formate, thereby promoting nucleotide synthesis. Formate removal proceeds via two pathways, the major one being folate-dependent; formate is a potentially toxic molecule, and may play a role in some of the pathologies associated with defective one-carbon metabolism.
Research using human skin fibroblasts demonstrated that the major water-soluble product formed from alpha-oxidation of phytanic acid is formic acid; as phytanic acid contains beta-methyl groups and cannot be degraded by beta-oxidation, formic acid is postulated to be formed by alpha-oxidation. Marked reduction in formic acid production in peroxisome-deficient skin fibroblasts suggests that peroxisomes are involved in the generation of C1 units.
Once within a bacterial cell, in which the pH is approximately 7, formic acid dissociates and lowers the cytoplasmic pH, inactivating decarboxylases and catalases. The mechanism is dependent on the pKa of the acid to infiltrate the bacterial cell, since the acid may enter the surrounding bacterium in its undissociated state. The main mechanisms by which acidifiers including formic acid improve livestock performance and health are related to the regulation of gastrointestinal pH, improvement in intestinal digestibility and mineral utilization, and antimicrobial properties against specific pathogens.
Metabolism of methanol, methyl ethers, esters, and amides gives rise to formic acid. This acid is an inhibitor of mitochondrial cytochrome oxidase, causing histotoxic hypoxia; it is a weaker inhibitor than cyanide and hydrosulfide anions. The development of anion gap metabolic acidosis from formate accumulation is multifactorial, driven by the buildup of poorly eliminated organic acids (e.g., formic acid and formate) and disruption of oxidative phosphorylation due to formate's inhibition of cytochrome oxidase. This mechanism is discussed in detail in the Safety section below, as it is toxicologically relevant rather than therapeutically intentional.
Based on in vitro investigations, formic acid has been shown to be a reasonably efficient antibacterial agent against Salmonella spp. and other infections. Formic acid is authorized by the FDA and listed in the European Union register of food additives for use in the organic production of agricultural food and as a food packaging additive. The Joint FAO/WHO Expert Committee on Food Additives established an acceptable daily intake (ADI) of formic acid of 0–3 mg/kg body weight.
Under U.S. FDA regulations, formic acid may be used as a preservative in hay crop silage at amounts not to exceed 2.25% of the silage on a dry weight basis (or 0.45% when direct-cut), and as a feed acidifying agent to lower pH in complete feed for swine and poultry at levels not to exceed 1.2% of the complete feed. In the European Union Feed Additives List, formic acid can be added up to 10 g/kg in livestock animal rations.
Evidence strength (antimicrobial/feed): The evidence base for antimicrobial efficacy in animal feed is well established at the regulatory level (FDA, EFSA, FAO/WHO) and in numerous animal studies. EFSA has addressed the re-authorization of formic acid for use as a preservative in feed and water for drinking and as a silage additive in feed for all animal species and categories. However, even if there is some evidence which excludes the occurrence of resistance of bacteria to formic acid, few data are available to support or refute the "resistance hypothesis" against acidifiers, and additional research is necessary. A complicating finding from in vitro research is that formic acid can induce a viable-but-non-culturable (VBNC) state in pathogenic Gram-negative bacteria such as Acinetobacter baumannii and Klebsiella pneumoniae at food-processing, storage, and distribution temperatures. Furthermore, removal of formic acid was able to resuscitate VBNC bacteria, with increased expression of multiple virulence and antimicrobial resistance genes in both pathogens. This finding raises important questions about resistance emergence that require further study.
Beekeepers use organic acids, including formic acid, to control the invasive parasitic mite Varroa destructor in honey bee colonies (Apis mellifera), as an alternative to synthetic acaricides to which Varroa mites can develop resistance. Multiple field studies have evaluated the efficacy of different formic acid delivery systems.
In a controlled field study comparing two formic acid treatments: both a solid matrix product (Formic Pro) and a liquid product (Formivar 60%) effectively killed Varroa mites at greater than 95% efficacy. Despite this high efficacy, the results also highlighted several negative effects, including increased worker bee and brood mortality and induction of queen supersedure. Specifically, both formic acid treatments killed more than 95% of the mites, but the use of formic acid also resulted in 1.6 times more brood loss and 30% queen loss relative to control colonies.
A separate field study using a Nassenheider Professional® evaporator filled with 290 ml of formic acid 60% found that mean acaricide efficacy varied from a minimum of 57.0 ± 21.8% to a maximum of 72.7 ± 12.5%, and was always statistically higher relative to natural mite fall observed in untreated groups. Efficacy against Varroa destructor and the impact of formic acid treatment on honey bee colonies can vary depending on the commercial product applied, the evaporator chosen, environmental temperature and humidity, hive size, presence of brood, and the position of the evaporator.
A study of the commercial Formic Pro™ product under Serbian field conditions found that Formic Pro™ achieved varroacidal efficacy of 88.37% without causing queen losses or significant brood disruption, and that the hygienic behavior of worker bees was significantly stimulated, suggesting the product can both control Varroa populations and support colony health as part of integrated pest management strategies.
Evidence strength (varroa control): Multiple controlled field trials support the varroacidal efficacy of formic acid preparations (>57%–95% mite kill depending on application method and conditions). Evidence is reasonably strong and sufficiently consistent for regulatory approval in numerous countries. However, risk of adverse effects on bee colonies, particularly brood and queen mortality, is a documented trade-off requiring careful protocol adherence.
The historical use of formic acid in rheumatic and joint disease is well documented. "Ant medicine" was used especially for rheumatism and back pain in Scandinavian tradition. It was a widespread historical belief that formic acid could be used to cure various diseases, especially gout and rheumatism, and both anthills and the ants themselves were used for this purpose.
In the modern period, a clinical study published in 2024 in the European Review for Medical and Pharmacological Sciences examined the combination of formic acid with conventional disease-modifying antirheumatic drugs (cDMARDs) in rheumatoid arthritis: The study examined the potential enhancement of conventional RA treatments specifically by the addition of formic acid, a naturally occurring substance that may possess anti-inflammatory properties. A total of 90 children diagnosed with rheumatoid arthritis were examined from 2020 to 2022 and segregated into two cohorts of 45 children each; one cohort was administered cDMARDs (methotrexate and leflunomide). While the study represents an area of active investigation, the details of outcomes and effect sizes were not fully accessible from available sources.
Evidence strength (musculoskeletal): Evidence from controlled human clinical trials is very limited. Historical use for rheumatism is extensively documented but represents traditional knowledge, not controlled evidence. The 2024 pediatric RA study is a small single-center trial. No large-scale randomized controlled trials or systematic reviews in humans were identified in the sources consulted. This area should currently be regarded as preliminary.
It has been proposed that formate may be a valuable biomarker of impaired one-carbon metabolism; formate is an essential intermediary metabolite in folate-mediated one-carbon metabolism, and despite its importance, knowledge of its metabolism remains limited. Elevated plasma formate concentrations and decreased rates of de novo formate production were observed in rats fed a folate-deficient diet compared with rats fed a folate-replete diet. Research has proposed that formate supplementation (as calcium formate) could potentially bypass certain steps in folate-dependent one-carbon metabolism to support nucleotide synthesis. However, this research has been largely conducted at the preclinical or theoretical level; no large human clinical trials on formate supplementation for this purpose were identified in the sources consulted.
Evidence strength (one-carbon metabolism): Mechanistic and biochemical evidence is well established, supporting formate as an endogenous one-carbon donor. Clinical evidence for supplementation strategies in humans is not yet established; this area is at the preclinical stage.
Reported dosages vary widely by application context. The following are drawn directly from cited sources and regulatory documents:
No confirmed human clinical dosages for dietary supplementation or therapeutic injection were identified in peer-reviewed sources. The historical German alternative medicine preparations involved injections of diluted formic acid, but no standardized dose from peer-reviewed human trial data could be verified.
Eye contact with formic acid liquid or high vapor concentrations produces irritation and conjunctivitis and may cause corneal burns. The liquid causes skin and eye burns; vapors are irritating and painful to breathe; vapor exposure may cause nausea and vomiting. Repeated or prolonged exposure may result in erosion of teeth, swelling, and ulceration of the mouth lining.
A critical safety consideration is the role of formic acid as the principal toxic metabolite in methanol poisoning. Formic acid is responsible for the anion gap metabolic acidosis and end-organ damage in methanol poisoning. Formic acid, the product of methanol's serial oxidation, directly damages multiple organ systems, most notably the central nervous system. It is responsible for the elevated anion gap metabolic acidosis observed late in methanol poisoning; the retina appears to be particularly sensitive, and the basal ganglia are especially vulnerable, with bilateral basal ganglia necrosis being a characteristic finding.
The metabolic acidosis and blindness associated with methanol poisoning are due to formic acid accumulation in humans and monkeys — a feature not seen in lower animals. This accumulation is due to a deficiency in formate metabolism, related in part to low hepatic tetrahydrofolate (H4 folate). In documented fatal cases of methanol ingestion, formic acid levels in blood at admission ranged from 302 to 680 mg/L.
Chronic occupational exposures to formic acid may produce nausea and albumin or blood in the urine. Chronic absorption of formic acid may cause damage to the kidneys, indicated by albuminuria and hematuria; chronic skin contact may cause sensitization dermatitis, particularly in workers previously sensitized to formaldehyde. Occupational exposure to vapors of methanol and formic acid can be quantitatively monitored by urinary formic acid determinations.
The European Food Safety Authority (EFSA) and other international regulatory bodies have assessed formic acid as safe for human consumption at approved levels. EFSA has specifically addressed the re-authorization of formic acid for use as a preservative in feed and water for drinking and as a silage additive in feed for all animal species and categories.
A significant pharmacological interaction exists between formic acid levels and folate status. Formate accumulation in methanol poisoning is due to deficiency in formate metabolism that is related in part to low hepatic tetrahydrofolate (H4 folate); an excellent correlation between hepatic H4 folate and formate oxidation rates has been demonstrated within and across species, with humans and monkeys having low hepatic H4 folate levels, low rates of formate oxidation, and consequent accumulation of formate. This implies that individuals with folate deficiency may be at increased risk from formate accumulation. Folic acid may be of benefit in formic acid toxicity by hastening the metabolism of formic acid to carbon dioxide.
A safety concern in the food preservation context is the potential for formate to drive antimicrobial resistance. Research has demonstrated that removal of formic acid from bacteria that had been placed in a viable-but-non-culturable (VBNC) state was able to resuscitate those bacteria with increased expression of multiple virulence and antimicrobial resistance genes in both A. baumannii and K. pneumoniae. This area is an active subject of scientific investigation.
While the soft acaricides oxalic acid, thymol, and formic acid 65% are generally considered safe for honey bee colonies and beekeepers when handled appropriately, caution is essential. Documented negative effects of formic acid in apiculture include brood, queen, and drone mortality; larval and pupal tissue damage; colony weakening; and triggering of physiological stress responses. To prevent adverse impacts on honey bee survival and queens, it is crucial to adhere to the appropriate dosage and follow product label instructions; doing so is also essential to prevent negative impacts on colony health, beekeeper safety, and the quality of honey for consumers.
Health conditions that Formic acid may help support.
Body systems that Formic acid may help support.
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