IngredientsGluconic acid (also known by its IUPAC name 2,3,4,5,6-pentahydroxypentane-1-carboxylic acid, or D-gluconic acid) is a naturally occurring, mild organic acid derived from the oxidation of the aldehyde group of D-glucose to a carboxylic acid. D-Gluconic acid (2,3,4,5,6-pentahydroxy pentane-1-carboxylic acid: C₆H₁₂O₇) is an oxidation product of D-glucose, which, in an aqueous solution, leads to a complex equilibrium between gluconic acid and its two lactones: 1,5-lactone (D-glucono-δ-lactone) and 1,4-lactone (D-glucono-γ-lactone). Its molecular formula is C₆H₁₂O₇ and it carries a PubChem CID of 10690.
Five hydroxyl groups and a carboxylic acid group characterize its chemical structure. D-Gluconic acid is commercially available as a 50% aqueous solution (with a density of 1230 kg/m³ at 20°C and a pH of 1.82). Its food-grade form is commonly a 50% solution in water with colourless to light-yellow color, and contains about 5% glucono delta-lactone at room temperature.
Gluconic acid is a multifunctional carbonic acid regarded as a bulk chemical in the food, feed, beverage, textile, pharmaceutical, and construction industries.
The salts of gluconic acid are referred to as gluconates. These are produced by the reaction of an anionic gluconate ion with the respective cationic mineral. The principal biologically and commercially relevant forms are:
Gluconic acid occurs naturally in fruit, honey, and wine. As a food additive it is designated E574 and is classified as an acidity regulator. In pure form it appears as a white or colorless crystalline powder with no odor, slightly acidic taste, highly soluble in water, and moderately soluble in ethanol.
Gluconic acid widely exists in nature, especially in fruits and in sucrose-containing substances such as honey. More specifically, glucono-delta-lactone (the equilibrium form of gluconic acid) occurs naturally in plants, fruits, wine (up to 0.5%), honey (up to 1%), and many fermented products. In honey, the amounts are higher due to the glucose oxidase enzyme present, where enzymatic conversion occurs.
Gluconic acid is a mild organic acid that has applications in the food industry; it is a natural constituent of fruit juices and honey and is used in the pickling of foods. In nature, it can also appear as an intermediate compound during fermentation. Foods that naturally contain gluconic acid or its lactone form include bean curd, yogurt, cottage cheese, bread, confectioneries, and meat.
Gluconic acid was first prepared by Hlasiwetz and Habermann in 1870 via the chemical oxidation of glucose. In 1880, Boutroux prepared and isolated gluconic acid using glucose fermentation. The production of gluconic acid by deep-tank fermentation (aerated, pH-controlled, and stirred tanks of >1,000 L) of the filamentous fungus Aspergillus niger in 1929, for use as a food acidity regulator and cleaning agent, was the first successful use of deep-tank fermentation by Pfizer. This technological milestone had profound implications beyond gluconic acid itself: this expertise later led to Pfizer's successful use of deep-tank fermentation of Penicillium fungi in February 1944, to rapidly scale up penicillin production, resulting in sufficient penicillin to treat American and British battle casualties of the D-Day invasion of World War II.
The favored industrial production process is submerged fermentation by Aspergillus niger utilizing glucose as a major carbohydrate source, which achieves a product yield of approximately 98%. Gluconic acid can generally be synthesized through chemical oxidation, electrolytic oxidation of glucose, or through the natural biological fermentation process.
Multiple microbial species are capable of producing gluconic acid. Aspergillus niger was the first reported fungal producer, along with other Aspergillus, Endomycopsis, Penicillium, Pillularia, and Scopulariopsis strains; bacterial species such as Pseudomonas, Gluconobacter, Acinetobacter, Acetobacter, Enterobacter, Micrococcus, and Moraxella are also used in gluconic acid synthesis. Among alternative carbohydrate sources, sugarcane molasses and grape must show the highest gluconic acid yield of approximately 95.8%, and banana must may assist in reducing the overall cost of production.
The traditional gluconic acid production with A. niger is named the "calcium gluconate process," which stems from the use of calcium carbonate for neutralization of the fermentation broth — a critical technological step to keep the extracellular glucose oxidase active. Commercially, it is produced by using microbes such as Aspergillus niger to oxidize glucose enzymatically.
In the food industry, glucono-delta-lactone is obtained by direct crystallization from aqueous gluconic acid solution. In dry form, glucono-delta-lactone is stable, while in aqueous media it slowly hydrolyzes to gluconic acid, providing a gradual pH decrease. In the food industry, GDL is produced biotechnologically: glucose is fermented by specific microorganisms (Aspergillus niger or Gluconobacter oxydans), which, through specific enzymes (glucose oxidase), gently oxidize the sugar to gluconic acid.
As a molecule that occurs naturally in widely consumed foods — honey, fruits, and fermented beverages — gluconic acid has been present in human diets throughout recorded history, though it was not isolated or chemically characterized until the nineteenth century. Its deliberate use as a distinct ingredient, therefore, belongs principally to the twentieth century.
Gluconic acid, a mild organic acid derived from the oxidation of glucose, has a longstanding history of use in food, pharmaceutical, and nutritional products. Its utility dates back to the early 20th century, where it was recognized for its ability to improve mineral solubility and stability, particularly for calcium and iron, in various formulations.
In food processing, the use of glucono-delta-lactone as a controlled acidulant was pioneered during the mid-twentieth century. The history of glucono-delta-lactone use is linked to the development of food technology in the 20th century, when manufacturers sought alternatives to strong acids (such as acetic or citric) and this mild-tasting, controlled-effect compound attracted attention. Its inner ester, glucono-δ-lactone, imparts an initially sweet taste, which later becomes slightly acidic. It is used in meat and dairy products, particularly in baked goods as a component of a leavening agent for pre-leavened products; it is also used as a flavoring agent (e.g., in sherbets), and finds application in reducing fat absorption in doughnuts and cones.
In traditional East Asian cuisines, glucono-delta-lactone has been used as a coagulant in tofu manufacture, producing a softer, silkier texture than salt-based coagulants. This use predates the formal chemical isolation of the compound, as naturally occurring gluconic acid from fermented substrates contributed to the acidity needed for protein coagulation in traditional tofu-making processes.
In pharmaceutical practice, gluconate is used most commonly as a biologically neutral carrier of minerals such as potassium (K⁺) to treat electrolyte imbalance. Calcium gluconate, in the form of a gel, has been used to treat burns from hydrofluoric acid; calcium gluconate injections may be used for more severe cases to avoid necrosis of deep tissues, as well as to treat hypocalcemia in hospitalized patients.
Gluconic acid is an oxidation product of glucose. Endogenously, the gluconate anion is produced as part of normal glucose catabolism. The sodium, potassium, and calcium salts of gluconic acid are expected to readily dissociate under environmentally and biologically relevant conditions to release gluconic acid and/or the gluconate anion, depending on ambient pH.
A closely related pathway in human metabolism is the pentose phosphate pathway, in which 6-phosphogluconate — a phosphorylated analog of gluconate — is a key intermediate. Glucose-6-phosphate is oxidized twice by the NADP⁺-dependent glucose-6-phosphate dehydrogenase to 6-phospho-glucono-δ-lactone as an intermediate, and by gluconolactonase to 6-phosphogluconate. The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism; the PPP is important to maintain carbon homeostasis, to provide precursors for nucleotide and amino acid biosynthesis, to provide reducing molecules for anabolism, and to defeat oxidative stress.
Gluconate, gluconic acid's conjugate base, is useful as a metal-chelating agent in alkaline solutions. This chelating property is central to gluconic acid's utility as a mineral supplement vehicle: by forming soluble complexes with calcium, magnesium, zinc, iron, and other minerals, it keeps these metals in solution in the gastrointestinal tract, potentially enhancing their absorption. Gluconic acid, with its high water solubility, can form metal complexes in food which enhance flavor and act as an acidity regulator.
A key proposed mechanism for gluconic acid's prebiotic and intestinal effects is its fermentability to short-chain fatty acids (SCFAs). Gluconic acid was shown to be poorly absorbed but readily fermented to butyrate in the gut, which in turn can improve gut function. Furthermore, the weight of cecal tissue and the concentrations of acetic acid and butyric acid in cecal digesta of rats fed calcium gluconate or gluconic acid diets were significantly increased. Butyrate is the primary energy source for colonocytes and has well-documented anti-inflammatory and barrier-protective effects in intestinal epithelium.
An oral gavage study on rats provided evidence that D-gluconic acid is likely to be absorbed through the intestine. When rats were dosed with U-¹⁴C-labeled glucono-delta-lactone or sodium gluconate via oral gavage, the chemicals were present in blood and the intestine within 5 hours of exposure, indicating these chemicals are rapidly absorbed through the gastrointestinal tract. However, intestinal absorption is incomplete: the absorption rate of gluconate from the ligated small intestinal loop in rats was 19.9% under conditions when 100% of glucose was absorbed, suggesting that the majority of orally ingested gluconate passes to the large intestine where it becomes available for microbial fermentation. From a nutritional standpoint, GDL is completely metabolized in the body like any other carbohydrate, providing 4 kcal/g.
Evidence grade: Moderate (clinical) for calcium gluconate as a mineral supplement vehicle; strong for IV use in hypocalcemia.
Calcium gluconate is a calcium salt crucial in managing hypocalcemia, cardiac arrest, and cardiotoxicity arising from hyperkalemia or hypermagnesemia. Calcium gluconate is a mineral supplement of calcium; IV administration of calcium gluconate increases serum ionized calcium level rapidly and effectively.
For oral supplementation, the high water solubility of the gluconate form confers advantages in specific populations. There is 93 mg of elemental calcium in a 10 mL ampule of 10% calcium gluconate; in comparison, there is 272 mg of elemental calcium in 10 mL of 10% solution of calcium chloride, another calcium salt. Calcium gluconate is typically preferred over calcium chloride due to the lower risk of tissue necrosis if the fluid is extravasated.
Regarding bone outcomes, calcium lactate gluconate, when administered to 19 non-menopausal women with osteoporosis during or after hormone therapy, significantly reduced bone fracture rate (Almustafa et al., 1992). Moreover, in a study in 50 Chinese women aged 62–92 years, calcium lactate gluconate increased bone mineral density (BMD) of the hip more than exercise (Lau et al., 1992). These are small, older trials and the benefit is attributed primarily to the calcium delivered rather than the gluconate moiety specifically. The superior effect on fractional absorption rate of calcium, calcium bioavailability biomarkers (urinary and serum ionized calcium and PTH), and BMD with calcium lactate gluconate have been reviewed previously (Gerstner, 2003).
Supplementation with calcium gluconate may be done to treat or prevent osteoporosis or rickets. However, these indications are driven by calcium deficiency correction, with the gluconate anion serving as the delivery vehicle.
Evidence grade: Preclinical (animal) only; no confirmed human RCTs.
A key mechanistic observation comes from a 30-day rat study: the effects of commercially available calcium supplements (calcium carbonate, calcium gluconate, oyster shell preparation, and bovine bone preparation) and gluconic acid on the absorption of calcium and magnesium were evaluated. There were no differences in the apparent absorption ratio of calcium among rats fed each calcium supplement; however, the rats fed the calcium gluconate diet had a higher apparent absorption ratio of magnesium than the rats fed the other calcium supplements. Dietary gluconic acid also more markedly stimulated magnesium absorption than the calcium carbonate diet, and the bone (femur and tibia) magnesium contents of rats fed the gluconic acid diet were significantly higher than those fed the calcium carbonate diet. The authors speculate that the stimulation of magnesium absorption in rats fed the calcium gluconate diet is a result of the gluconic acid component and that the effect on magnesium absorption probably results from cecal hypertrophy, magnesium solubility in the large intestine, and the effects of volatile fatty acids on magnesium absorption.
This mechanism — fermentation of gluconate to SCFAs lowering luminal pH and increasing mineral solubility — is consistent with the broader prebiotic literature, but direct human evidence for gluconic acid specifically enhancing magnesium absorption is lacking.
Evidence grade: Moderate — human clinical data exist but comparisons with other forms are mixed.
Zinc is an essential micronutrient needed for numerous critical health functions in the body. Several trials have compared different zinc salt forms in humans. A 2024 narrative review of the clinical evidence (Devarshi et al., Nutrients 2024) concluded that zinc glycinate and zinc gluconate are better absorbed than other forms of zinc. However, the picture is not uniform: zinc sulfate, gluconate, and citrate show comparable bioavailability in healthy adults (60–71% range), and individual variation matters more than form for many subjects. A separate animal study found that zinc-enriched yeast was 3.7 times more bioavailable than zinc gluconate in a rat depletion-repletion model, underscoring that bioavailability comparisons are format- and context-dependent.
Evidence grade: Preliminary — animal data and in vitro / small human studies only; promising but not conclusive.
Gluconic acid is only partially absorbed in the small intestine, and the remainder reaches the colon where it serves as a substrate for microbial fermentation. Gluconate was fermented selectively by the Bifidobacterium adolescentis group and some species of other genera, including Clostridium clostridiiforme, C. innocuum, Propionibacterium acnes, Megasphaera elsdenii, Enterococcus faecium, and Klebsiella pneumoniae; however, it was not utilized by most other bacteria including the Bacteroidaceae. The effects of ingestion of gluconate on human fecal bacteria were studied in ten healthy adult males, who ingested 9 g/d or 3 g/d of glucono-δ-lactone (anhydride of gluconic acid).
More recent research has focused on gluconic acid's role in cross-feeding pathways in the gut. Using in vitro fecal cultures and a human intervention study (n = 27), researchers identified maltobionic acid and lactobionic acid (both gluconic acid-containing oligosaccharides) as compounds that specifically promoted Faecalibacterium growth in vitro and in vivo, without significantly affecting Bifidobacterium. A significant increase in Faecalibacterium abundance following maltobionic acid supplementation was observed, with effectiveness correlating with initial Parabacteroides abundance. Mechanistic investigations revealed a cross-feeding pathway in which Parabacteroides species converted the gluconic acid moiety of maltobionic and lactobionic acids to glucuronic acid, which was then preferentially utilized by Faecalibacterium. Faecalibacterium prausnitzii is regarded as a beneficial intestinal commensal with anti-inflammatory properties.
An animal study in weaned piglets provides further mechanistic data. A total of 144 weaning pigs were fed experimental diets for 42 days; three treatments were replicated in 8 pens with 6 piglets each: control; low dietary dose of gluconic acid, 9 g/kg; and high dietary dose, 18 g/kg. Feeding gluconic acid enhanced performance in the period of 0–14 days post-weaning — in particular, feed intake was increased (P = 0.028), though the high dose did not show benefits over the low dose. For the full 0–42 day period, feed intake was elevated (P = 0.026). Increased dietary gluconic acid resulted in higher presence of Lactobacillaceae and Lactobacillus (P < 0.05) in the distal small intestine. These are animal data and cannot be directly extrapolated to human supplementation outcomes.
Evidence grade: Strong — well-established clinical practice supported by extensive controlled use and FDA-approved indications.
Calcium gluconate is the calcium salt of gluconic acid; as an intravenous medication it is used to treat conditions arising from calcium deficiencies such as hypocalcemic tetany, hypocalcemia related to hypoparathyroidism, and hypocalcemia due to rapid growth or pregnancy. As a medication it is used by injection into a vein to treat low blood calcium, high blood potassium, and magnesium toxicity.
It is also used in the treatment of black widow spider bites to relieve muscle cramping, and as an adjunct in the treatment of rickets, osteomalacia, lead colic, and magnesium sulfate overdose. Calcium gluconate has also been employed to decrease capillary permeability in allergic conditions, non-thrombocytopenic purpura, and exudative dermatoses such as dermatitis herpetiformis, and for pruritus of eruptions caused by certain drugs.
Evidence grade: Moderate — clinical case series and standard-of-care use, not RCT-proven.
Calcium gluconate, in the form of a gel, is used to treat burns from hydrofluoric acid; calcium gluconate injections may be used for more severe cases to avoid necrosis of deep tissues. This application exploits the calcium ion's ability to chelate the extremely toxic fluoride ion at the wound site, preventing its deeper tissue penetration.
Evidence grade: Limited — only preliminary human data available.
A study assessing its effects on skin condition and inflammation found that dietary intake of GDL attenuated skin inflammation and modulated skin condition in healthy human subjects. Clinical-dermatological examinations have reported no intolerances, such as skin irritation or allergic reactions, following the application of formulations containing GDL. Therefore, GDL is considered safe for use in cosmetic applications, even among individuals with sensitive skin. Gluconolactone (GDL) is also applied topically in skincare as a polyhydroxy acid (PHA) for mild exfoliation. GDL is commonly called gluconolactone when used in cosmetics and personal care products; it is generally used for its chelating and skin-conditioning properties as suggested by the European Commission database for information on cosmetic substances and ingredients.
The following dosages are those reported in cited sources and should not be taken as prescriptive recommendations.
The usual dosage of calcium gluconate in adults is 500 mg to 2 grams (5–20 mL); in children 200–500 mg (2–5 mL); and in infants not more than 200 mg (not more than 2 mL). There is 93 mg of elemental calcium in a 10 mL ampule of 10% calcium gluconate. For management of cardiac arrest associated with hyperkalemia, hypocalcemia, or hypermagnesemia, a dose of 1.5–3 g intravenously over 2–5 minutes has been used (routine use in cardiac arrest is not recommended, as it yields no improvement in survival).
The effects of ingestion of gluconate on human fecal bacteria were studied in ten healthy adult males, who ingested 9 g/d or 3 g/d of glucono-δ-lactone.
Three dietary treatments were tested: control; low dietary dose of gluconic acid, 9 g/kg; and high dietary dose of gluconic acid, 18 g/kg. As noted above, these are animal data.
The clinical bone studies cited above used calcium in the form of commercial Calcium Sandoz® preparations containing calcium lactate gluconate; specific elemental calcium doses in these trials were not reported in the sources retrieved.
Gluconic acid is sold as δ-lactone or gluconate and serves in the food industry as a mild acidulant. Sodium gluconate is used in food at concentrations typically ranging from 0.1% to 0.3% by weight of the final product, depending on the specific application and local regulatory guidelines.
The U.S. Food and Drug Administration (FDA) has affirmed glucono-delta-lactone (GDL) as Generally Recognized As Safe (GRAS) under 21 CFR 184.1318, permitting its use as a curing and pickling agent, leavening agent, pH control agent, and sequestrant. Gluconic acid itself (E574) and its related salt additives (E575–E579) are authorized food additives in the European Union. According to Regulation (EC) No 1333/2008, food additives permitted for use in the EU before 20 January 2009 need to be re-evaluated by EFSA. The programme was defined by Regulation (EU) No 257/2010; among the additives that remain to be re-evaluated, EFSA is actively collecting documented information supporting the re-evaluation of gluconic acid (E 574) and related food additives (E 575–579).
GDL has been approved as a safe preservative by the U.S. FDA, the European Food Safety Authority (EFSA), as well as the Joint FAO/WHO Expert Committee on Food Additives (JECFA).
The EPA has found that D-gluconic acid's endogenous nature, transformation profile, lack of structural alerts in the parent chemical substance, and experimental genotoxicity studies provide sufficient information to indicate that this chemical has low concern for carcinogenicity.
Glucono-delta-lactone has undergone various toxicological evaluations, including assessments for mutagenicity and teratogenicity. Studies have demonstrated that GDL is neither carcinogenic nor teratogenic, and does not exhibit mutagenic effects in bacterial assays. GDL is generally recognized as safe by the U.S. FDA and is well-tolerated by most individuals, with minimal reported side effects. However, excessive consumption may lead to mild gastrointestinal discomfort in sensitive individuals.
Side effects when injected include slow heart rate, pain at the site of injection, and low blood pressure. When taken by mouth, side effects may include constipation and nausea. Blood calcium levels should be measured when used, and extra care should be taken in those with a history of kidney stones. Adverse cardiovascular reactions include vasodilation, decreased blood pressure, bradycardia, cardiac arrhythmia, and syncope; administration site reactions include local soft tissue inflammation, local necrosis, calcinosis cutis, and calcification.
Calcium gluconate may interact with digoxin, antacids or other calcium supplements, calcitriol or vitamin D supplements, doxycycline, minocycline, or tetracycline. More specifically:
At normal doses, use of calcium gluconate is regarded as safe in pregnancy and breastfeeding. Limited available data with calcium gluconate injection use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes.
Blood calcium levels should be measured when calcium gluconate is used, and extra care should be taken in those with a history of kidney stones. Studies have demonstrated an acute relationship between urinary calcium excretion and IV administration of calcium gluconate, with renal clearance for calcium increased multiple-fold during and after calcium gluconate infusion.
The body of evidence for gluconic acid and its salts as dietary supplements is characterized by several important limitations. First, the vast majority of mechanistic data on intestinal mineral absorption enhancement and prebiotic effects comes from animal models (especially rodents and pigs), and has not been replicated in adequately powered human randomized controlled trials. Second, clinical evidence for calcium gluconate is strong but relates almost entirely to the calcium content it delivers, not to any independent biological action of the gluconate anion per se. Third, the human gut microbiome intervention study (n = 27) on gluconic acid-containing oligosaccharides was small, short-term, and industry-affiliated, requiring replication in independent cohorts. Fourth, EFSA's ongoing re-evaluation of gluconic acid (E574) and related additives acknowledges that data supporting safety conclusions at food-use levels remain incomplete and are actively being solicited. Fifth, the relative bioavailability of zinc gluconate versus other zinc forms shows inconsistencies across studies, suggesting that dose, food matrix, and individual zinc status are confounding variables that have not been systematically controlled.
Health conditions that Gluconic acid may help support.
Body systems that Gluconic acid may help support.
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