CITRIC ACID MONOHYDRATE

CITRIC ACID MONOHYDRATE

CAS No. : 5949-29-1
EC No. : 201-069-1

Synonyms:
2-Hydroxypropane-1,2,3-tricarboxylic acid; Hydroxytricarballylic acid; CITRIC ACID; citric acid hydrate; 2-hydroxypropane-1,2,3-tricarboxylic acid hydrate; citric acid; monohydrate; unii-2968phw8qp; 1,2,3-propanetricarboxylic acid; 2-hydroxy-, monohydrate; citrate; acidum citricum monohydricum; citric acid monohydrate usp; Citric acid monohydrate; 5949-29-1; Citric acid hydrate; 2-hydroxypropane-1,2,3-tricarboxylic acid hydrate; CITRIC ACID, MONOHYDRATE; 1,2,3-Propanetricarboxylic acid, 2-hydroxy-, monohydrate; UNII-2968PHW8QP; Acidum citricum monohydricum; Citric acid monohydrate (USP); Citric acid monohydrate [USP]; 2-Hydroxy-1,2,3-propanetricarboxylic acid monohydrate; Citric acid monohydrate, 99+%, ACS reagent; Citric acid monohydrate, 99.5%, for analysis; 2-hydroxypropane-1,2,3-tricarboxylic acid;hydrate; citrate hydrate; C6H8O7.H2O; citric acid water; water citric acid; Citricacidmonohydrate; Citric acid (TN); ACMC-20alep; monohydrate citric acid; citric acid mono-hydrate; SCHEMBL22721; Citric acid hydrate (JP17); KSC147I0B; 1,2,3-Propanetricarboxylic acid, 2-hydroxy-, hydrate; Citric acid monohydrate, Ultrapure; Citric acid monohydrate, p.a., 99.5%; AK142751; BS-17269; Citric acid monohydrate, AR, >=99.5%; Citric acid monohydrate, BioXtra, >=99.5%; C12649; Citric acid monohydrate, LR, 99.5-100.5%; Citric acid monohydrate, technical, crystalline; D01222; Citric acid monohydrate, ACS reagent, >=99.0%; Citric Acid, Monohydrate, Crystal, Reagent, ACS; 2-hydroxypropane-1,2,3-tricarboxylic acid, hydrate; Citric acid monohydrate, JIS special grade, >=99.5%; Citric acid monohydrate, SAJ first grade, >=99.5%; Citric acid monohydrate, Vetec(TM) reagent grade, >=98%; 1,2,3-Propanetricarboxylic acid, 2-hydroxy-, hydrate (1:1); Citric acid monohydrate, reagent grade, >=98% (GC/titration); Citric acid monohydrate, >=99.5%, suitable for amino acid analysis; Citric acid monohydrate, European Pharmacopoeia (EP) Reference Standard; Citric acid monohydrate, p.a., ACS reagent, reag. ISO, reag. Ph. Eur., 99.5-100.5%; 15686-65-4; Citric acid monohydrate, puriss., meets analytical specification of Ph. Eur., BP, USP, E330, 99.5-100.5% (based on anhydrous substance), grit; Citric Acid, Anhydrous (sc-211113); Sodium Citrate, Dihydrate (sc-203383); Citric Acid Trisodium Salt (sc-214745); Sodium citrate monobasic (sc-215869); Sodium citrate tribasic hydrate (sc-236898); Citrate Concentrated Solution; citric acid; 77-92-9; 2-hydroxypropane-1,2,3-tricarboxylic acid; Citric acid, anhydrous; Anhydrous citric acid; Citro; Citretten; Aciletten; Chemfill; Hydrocerol A; 1,2,3-Propanetricarboxylic acid, 2-hydroxy-; Kyselina citronova; 2-hydroxy-1,2,3-propanetricarboxylic acid; 2-Hydroxytricarballylic acid; Citric acid anhydrous; Caswell No. 221C; F 0001 (polycarboxylic acid); 3-Carboxy-3-hydroxypentane-1,5-dioic acid; 2-Hydroxypropanetricarboxylic acid; beta-Hydroxytricarballylic acid; FEMA No. 2306; FEMA Number 2306; K-Lyte; Kyselina citronova [Czech]; K-Lyte DS; CCRIS 3292; HSDB 911; EPA Pesticide Chemical Code 021801; Uro-trainer; AI3-06286; UNII-XF417D3PSL; Citric acid [USAN:JAN]; Suby G; Kyselina 2-hydroxy-1,2,3-propantrikarbonova [Czech]; Kyselina 2-hydroxy-1,2,3-propantrikarbonova; CHEBI:30769; .beta.-Hydroxytricarballylic acid; citr; Citric acid, 99%; CITRATE ANION; Neodymium chloride citrate; Neodymium citrate chloride; Citric acid, 99%, pure, anhydrous; 2-hydroxy-1,2,3-propanetricarboxylic; Uralyt U; CAS-77-92-9; 1,3-Propanetricarboxylic acid, 2-hydroxy-; Citric acid, 99.5%, for analysis, anhydrous; NSC-112226; Citraclean; Citronensaeure; Citralite; Anhydrous citrate; citric acid group; Citric acid, anhydrous [USP:JAN]; Citric Acid,(S); Citric acid,anhydrous; Citric acid (8CI); K-Lyte (Salt/Mix); Citraclean (Salt/Mix); ACMC-209pcr; Citric Acid (Anhydrous); beta-Hydroxytricarballylate; HOC(CH2COOH)2COOH; EC 201-069-1; Citric Acid 77-92-9; Citric acid anhydrous (JAN); 4-03-00-01272 (Beilstein Handbook Reference); Citric Acid, anhydrous, USP; citric acid (Fragrance Grade); Citric acid, anhydrous (USP); Anhydrous citric acid (JP17); GTPL2478; INS NO.330; Citric Acid (Industrial Grade); Citric acid, analytical standard; Citric acid, p.a., 99.5%; Citric acid 5% solution in water; Pharmakon1600-01300013; ZINC895081; Citric acid 10% solution in water; Citric acid 50% solution in water; 1,2,3-Tricarboxy-2-hydroxypropane; Citric acid, LR, anhydrous, >=99%; 2-hydroxy-1,2,3-propanetricarboxylate; 3-Carboxy-3-hydroxypentane-1,5-dioate; Citric acid, >=99.5%, FCC, FG; Citric acid, ACS reagent, >=99.5%; Citric Acid, anhydrous powder, A.C.S.; 2-Hydroxy-1,3-propanetricarboxylic acid; Citric Acid, anhydrous granular, A.C.S.; 2-hydroxy-1,2,3-propanetricarboxyic acid; SBI-0206765.P001; Citric acid, SAJ first grade, >=99.5%; 2-Hydroxy-1,2,3-propane tricarboxylic acid; 2-Hydroxy-1,2,3-propanenetricarboxylic acid; Citric Acid, Aqueous Solution (Food Grade); Citric acid, Vetec(TM) reagent grade, 99%; Citric acid, 99.6%, ACS reagent, anhydrous; Citric acid, BioUltra, anhydrous, >=99.5% (T); IRRIGATING SOLUTION G IN PLASTIC CONTAINER; 1,2,3-Propanetricarboxylic acid, 2-hydroxy- (9CI); Citric acid, certified reference material, TraceCERT(R); Citric acid, meets USP testing specifications, anhydrous; Citrate standard for IC, 1000 mg/L, analytical standard; 1,2,3-PROPANETRICARBOXYLIC ACID,2-HYDROXY (CITRIC ACID); Citric acid, United States Pharmacopeia (USP) Reference Standard; Citric acid, anhydrous, cell culture tested, plant cell culture tested; Citric acid, anhydrous, European Pharmacopoeia (EP) Reference Standard; Citric acid, anhydrous, free-flowing, Redi-Dri(TM), ACS reagent, >=99.5%; Citric acid, for molecular biology, anhydrous, Rnase and Protease free; Citric acid, Anhydrous, Pharmaceutical Secondary Standard; Certified Reference Material; Citric acid, meets analytical specification of Ph. Eur., BP, USP, E330, anhydrous, 99.5-100.5% (based on anhydrous substance)

Citric Acid Monohydrate

Citric Acid Monohydrate is a tricarboxylic acid found in citrus fruits. Citric acid monohydrate is used as an excipient in pharmaceutical preparations due to its antioxidant properties. Citric acid monohydrate maintains stability of active ingredients and is used as a preservative. Citric acid monohydrate is also used as an acidulant to control pH and acts as an anticoagulant by chelating calcium in blood.

General description of Citric Acid Monohydrate
Citric acid monohydrate is an organic acid. Its molar enthalpy of solution in water has been reported to be ΔsolHm (298.15K, m = 0.0203molkg-1) = (29061±123)Jmol-1.[2] It can be produced by crystallization from mother liquor of citric acid solution at 20-25°C during citric acid synthesis. An investigation of its crystal growth kinetics indicates that growth is linearly dependent on size.

Application of Citric Acid Monohydrate
Citric acid monohydrate was used in the preparation of citric acid solution employed in the acetone method of 68Ga pre-purification and radiolabeling technique.
Citric Acid Monohydrate may be used:
• As release-modifying agent to improve the release of diltiazem hydrochloride from melt extruded Eudragit RS PO tablets.
• To prepare citrate buffer for use in the preparation of platelets for intravital microscopy.
• To prepare Tris-citrate buffer employed for the electrophoresis of bacterial enzymes.

Citric acid monohydrate is a weak organic acid that has the molecular formula C6H8O7. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the Citric acid monohydrate cycle, which occurs in the metabolism of all aerobic organisms.
More than two million tons of Citric acid monohydrate are manufactured every year. It is used widely as an acidifier, as a flavoring and a chelating agent.
A citrate is a derivative of Citric acid monohydrate; that is, the salts, esters, and the polyatomic anion found in solution. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate. When part of a salt, the formula of the citrate anion is written as C6H5O3−7 or C3H5O(COO)3−3.

Natural occurrence and industrial production of Citric acid monohydrate
Lemons, oranges, limes, and other citrus fruits possess high concentrations of Citric acid monohydrate
Citric acid monohydrate exists in a variety of fruits and vegetables, most notably citrus fruits. Lemons and limes have particularly high concentrations of the acid; it can constitute as much as 8% of the dry weight of these fruits (about 47 g/l in the juices[10]).[a] The concentrations of Citric acid monohydrate in citrus fruits range from 0.005 mol/L for oranges and grapefruits to 0.30 mol/L in lemons and limes; these values vary within species depending upon the cultivar and the circumstances in which the fruit was grown.
Citric acid monohydrate was first isolated in 1784 by the chemist Carl Wilhelm Scheele, who crystallized it from lemon juice.
Industrial-scale Citric acid monohydrate production first began in 1890 based on the Italian citrus fruit industry, where the juice was treated with hydrated lime (calcium hydroxide) to precipitate calcium citrate, which was isolated and converted back to the acid using diluted sulfuric acid. In 1893, C. Wehmer discovered Penicillium mold could produce Citric acid monohydrate from sugar. However, microbial production of Citric acid monohydrate did not become industrially important until World War I disrupted Italian citrus exports.

In 1917, American food chemist James Currie discovered certain strains of the mold Aspergillus niger could be efficient Citric acid monohydrate producers, and the pharmaceutical company Pfizer began industrial-level production using this technique two years later, followed by Citrique Belge in 1929. In this production technique, which is still the major industrial route to Citric acid monohydrate used today, cultures of A. niger are fed on a sucrose or glucose-containing medium to produce Citric acid monohydrate. The source of sugar is corn steep liquor, molasses, hydrolyzed corn starch, or other inexpensive, sugary solution.[14] After the mold is filtered out of the resulting solution, Citric acid monohydrate is isolated by precipitating it with calcium hydroxide to yield calcium citrate salt, from which Citric acid monohydrate is regenerated by treatment with sulfuric acid, as in the direct extraction from citrus fruit juice.
In 1977, a patent was granted to Lever Brothers for the chemical synthesis of Citric acid monohydrate starting either from aconitic or isocitrate/alloisocitrate calcium salts under high pressure conditions; this produced Citric acid monohydrate in near quantitative conversion under what appeared to be a reverse, non-enzymatic Krebs cycle reaction.
Global production was in excess of 2,000,000 tons in 2018. More than 50% of this volume was produced in China. More than 50% was used as an acidity regulator in beverages, some 20% in other food applications, 20% for detergent applications, and 10% for applications other than food, such as cosmetics, pharmaceuticals, and in the chemical industry.

Chemical characteristics of Citric acid monohydrate
Speciation diagram for a 10-millimolar solution of Citric acid monohydrate
Citric acid monohydrate can be obtained as an anhydrous (water-free) form or as a monohydrate. The anhydrous form crystallizes from hot water, while the monohydrate forms when Citric acid monohydrate is crystallized from cold water. The monohydrate can be converted to the anhydrous form at about 78 °C. Citric acid monohydrate also dissolves in absolute (anhydrous) ethanol (76 parts of Citric acid monohydrate per 100 parts of ethanol) at 15 °C. It decomposes with loss of carbon dioxide above about 175 °C.
Citric acid monohydrate is a tribasic acid, with pKa values, extrapolated to zero ionic strength, of 2.92, 4.28, and 5.21 at 25 °C.[17] The pKa of the hydroxyl group has been found, by means of 13C NMR spectroscopy, to be 14.4.[18] The speciation diagram shows that solutions of Citric acid monohydrate are buffer solutions between about pH 2 and pH 8. In biological systems around pH 7, the two species present are the citrate ion and mono-hydrogen citrate ion. The SSC 20X hybridization buffer is an example in common use.[19] Tables compiled for biochemical studies[20] are available.
On the other hand, the pH of a 1 mM solution of Citric acid monohydrate will be about 3.2. The pH of fruit juices from citrus fruits like oranges and lemons depends on the Citric acid monohydrate concentration, being lower for higher acid concentration and conversely.
Acid salts of Citric acid monohydrate can be prepared by careful adjustment of the pH before crystallizing the compound. See, for example, sodium citrate.

The citrate ion forms complexes with metallic cations. The stability constants for the formation of these complexes are quite large because of the chelate effect. Consequently, it forms complexes even with alkali metal cations. However, when a chelate complex is formed using all three carboxylate groups, the chelate rings have 7 and 8 members, which are generally less stable thermodynamically than smaller chelate rings. In consequence, the hydroxyl group can be deprotonated, forming part of a more stable 5-membered ring, as in ammonium ferric citrate, (NH4)5Fe(C6H4O7)2·2H2O.
Citric acid monohydrate can be esterified at one or more of its three carboxylic acid groups to form any of a variety of mono-, di-, tri-, and mixed esters.

Biochemistry of Citric acid monohydrate
Citric acid monohydrate cycle
Main article: Citric acid monohydrate cycle
Citrate is an intermediate in the TCA cycle (aka TriCarboxylic Acid cycle, or Krebs cycle, Szent-Györgyi), a central metabolic pathway for animals, plants, and bacteria. Citrate synthase catalyzes the condensation of oxaloacetate with acetyl CoA to form citrate. Citrate then acts as the substrate for aconitase and is converted into aconitic acid. The cycle ends with regeneration of oxaloacetate. This series of chemical reactions is the source of two-thirds of the food-derived energy in higher organisms. Hans Adolf Krebs received the 1953 Nobel Prize in Physiology or Medicine for the discovery.
Some bacteria (notably E. coli) can produce and consume citrate internally as part of their TCA cycle, but are unable to use it as food because they lack the enzymes required to import it into the cell. After tens of thousand of evolutions in a minimal glucose medium that also contained citrate during Richard Lenski's Long-Term Evolution Experiment, a variant E. coli evolved with the ability to grow aerobically on citrate. Zachary Blount, a student of Lenski's, and colleagues studied these "Cit+" E. coli[23][24] as a model for how novel traits evolve. They found evidence that, in this case, the innovation was caused by a rare duplication mutation due to the accumulation of several prior "potentiating" mutations, the identity and effects of which are still under study. The evolution of the Cit+ trait has been considered a notable example of the role of historical contingency in evolution.

Other biological roles of Citric acid monohydrate
Citrate can be transported out of the mitochondria and into the cytoplasm, then broken down into acetyl-CoA for fatty acid synthesis, and into oxaloacetate. Citrate is a positive modulator of this conversion, and allosterically regulates the enzyme acetyl-CoA carboxylase, which is the regulating enzyme in the conversion of acetyl-CoA into malonyl-CoA (the commitment step in fatty acid synthesis). In short, citrate is transported into the cytoplasm, converted into acetyl CoA, which is then converted into malonyl CoA by acetyl CoA carboxylase, which is allosterically modulated by citrate.
High concentrations of cytosolic citrate can inhibit phosphofructokinase, the catalyst of a rate-limiting step of glycolysis. This effect is advantageous: high concentrations of citrate indicate that there is a large supply of biosynthetic precursor molecules, so there is no need for phosphofructokinase to continue to send molecules of its substrate, fructose 6-phosphate, into glycolysis. Citrate acts by augmenting the inhibitory effect of high concentrations of ATP, another sign that there is no need to carry out glycolysis.[25]
Citrate is a vital component of bone, helping to regulate the size of apatite crystals.[26]

Applications of Citric acid monohydrate
Food and drink
Powdered Citric acid monohydrate being used to prepare lemon pepper seasoning
Because it is one of the stronger edible acids, the dominant use of Citric acid monohydrate is as a flavoring and preservative in food and beverages, especially soft drinks and candies.[13] Within the European Union it is denoted by E number E330. Citrate salts of various metals are used to deliver those minerals in a biologically available form in many dietary supplements. Citric acid monohydrate has 247 kcal per 100 g.[27] In the United States the purity requirements for Citric acid monohydrate as a food additive are defined by the Food Chemicals Codex, which is published by the United States Pharmacopoeia (USP).

Citric acid monohydrate can be added to ice cream as an emulsifying agent to keep fats from separating, to caramel to prevent sucrose crystallization, or in recipes in place of fresh lemon juice. Citric acid monohydrate is used with sodium bicarbonate in a wide range of effervescent formulae, both for ingestion (e.g., powders and tablets) and for personal care (e.g., bath salts, bath bombs, and cleaning of grease). Citric acid monohydrate sold in a dry powdered form is commonly sold in markets and groceries as "sour salt", due to its physical resemblance to table salt. It has use in culinary applications, as an alternative to vinegar or lemon juice, where a pure acid is needed. Citric acid monohydrate can be used in food coloring to balance the pH level of a normally basic dye.

Cleaning and chelating agent of Citric acid monohydrate
Structure of an iron(III) citrate complex.
Citric acid monohydrate is an excellent chelating agent, binding metals by making them soluble. It is used to remove and discourage the buildup of limescale from boilers and evaporators.[13] It can be used to treat water, which makes it useful in improving the effectiveness of soaps and laundry detergents. By chelating the metals in hard water, it lets these cleaners produce foam and work better without need for water softening. Citric acid monohydrate is the active ingredient in some bathroom and kitchen cleaning solutions. A solution with a six percent concentration of Citric acid monohydrate will remove hard water stains from glass without scrubbing. Citric acid monohydrate can be used in shampoo to wash out wax and coloring from the hair. Illustrative of its chelating abilities, Citric acid monohydrate was the first successful eluant used for total ion-exchange separation of the lanthanides, during the Manhattan Project in the 1940s. In the 1950s, it was replaced by the far more efficient EDTA.
In industry, it is used to dissolve rust from steel and passivate stainless steels.

Cosmetics, pharmaceuticals, dietary supplements, and foods
Citric acid monohydrate is used as an acidulant in creams, gels, and liquids. Used in foods and dietary supplements, it may be classified as a processing aid if it was added for a technical or functional effect (e.g. acidulent, chelator, viscosifier, etc.). If it is still present in insignificant amounts, and the technical or functional effect is no longer present, it may be exempt from labeling <21 CFR §101.100(c)>.
Citric acid monohydrate is an alpha hydroxy acid and is an active ingredient in chemical skin peels.
Citric acid monohydrate is commonly used as a buffer to increase the solubility of brown heroin.[31]
Citric acid monohydrate is used as one of the active ingredients in the production of facial tissues with antiviral properties.[32]

Other uses of Citric acid monohydrate
The buffering properties of citrates are used to control pH in household cleaners and pharmaceuticals.
Citric acid monohydrate is used as an odorless alternative to white vinegar for home dyeing with acid dyes.
Sodium citrate is a component of Benedict's reagent, used for identification both qualitatively and quantitatively of reducing sugars.
Citric acid monohydrate can be used as an alternative to nitric acid in passivation of stainless steel.[33]
Citric acid monohydrate can be used as a lower-odor stop bath as part of the process for developing photographic film. Photographic developers are alkaline, so a mild acid is used to neutralize and stop their action quickly, but commonly used acetic acid leaves a strong vinegar odor in the darkroom.
Citric acid monohydrate/potassium-sodium citrate can be used as a blood acid regulator.
Soldering flux. Citric acid monohydrate is an excellent soldering flux,[35] either dry or as a concentrated solution in water. It should be removed after soldering, especially with fine wires, as it is mildly corrosive. It dissolves and rinses quickly in hot water.

Synthesis of solid materials from small molecules
In materials science, the Citrate-gel method is a process similar to the sol-gel method, which is a method for producing solid materials from small molecules. During the synthetic process, metal salts or alkoxides are introduced into a Citric acid monohydrate solution. The formation of citric complexes is believed to balance the difference in individual behavior of ions in solution, which results in a better distribution of ions and prevents the separation of components at later process stages. The polycondensation of ethylene glycol and Citric acid monohydrate starts above 100°С, resulting in polymer citrate gel formation.

Safety of Citric acid monohydrate
Although a weak acid, exposure to pure Citric acid monohydrate can cause adverse effects. Inhalation may cause cough, shortness of breath, or sore throat. Over-ingestion may cause abdominal pain and sore throat. Exposure of concentrated solutions to skin and eyes can cause redness and pain.[36] Long-term or repeated consumption may cause erosion of tooth enamel.
Citric Acid Monohydrate is an acidic compound from citrus fruits; as a starting point in the Krebs cycle, citrate is a key intermediate in metabolism. Citric acid is one of a series of compounds responsible for the physiological oxidation of fats, carbohydrates, and proteins to carbon dioxide and water. It has been used to prepare citrate buffer for antigen retrieval of tissue samples. The citrate solution is designed to break protein cross-links, thus unmasking antigens and epitopes in formalin-fixed and paraffin embedded tissue sections, and resulting in enhanced staining intensity of antibodies. Citrate has anticoagulant activity; as a calcium chelator, it forms complexes that disrupt the tendency of blood to clot. May be used to adjust pH and as a sequestering agent for the removal of trace metals.
Additional forms available:
Citric Acid, Anhydrous (sc-211113)
Sodium Citrate, Dihydrate (sc-203383)
Citric Acid Trisodium Salt (sc-214745)
Sodium citrate monobasic (sc-215869)
Sodium citrate tribasic hydrate (sc-236898)
Citrate Concentrated Solution (sc-294091)
This monograph for Citric Acid, Anhydrous, and Citric Acid, Monohydrate provides, in addition to common physical constants, a general description including typical appearance, applications, change in state (approximate), and aqueous solubility. The monograph also details the following specifications, corresponding tests for verifying that a substance meets ACS Reagent Grade specifications including: Assay, Insoluble Matter, Residue after Ignition, Chloride, Oxalate, Phosphate, Sulfur Compounds (as SO, Iron, Lead, and Substances Carbonizable by Hot Sulfuric Acid (Tartrates, etc.).

Citric acid is a naturally occurring fruit acid, produced commercially by microbial fermentation of a carbohydrate substrate. Citric acid is the most widely used organic acid and pH-control agent in foods, beverages, pharmaceuticals and technical applications.
Citric acid monohydrate occurs as colourless crystals or as white, crystalline powder with a strongly acidic taste. It is efflorescent in dry air, very soluble in water, freely soluble in ethanol (96 %) and sparingly soluble in ether.
Citric acid monohydrate is non-toxic and has a low reactivity. It is chemically stable if stored at ambient temperatures. Citric acid monohydrate is fully biodegradable and can be disposed of with regular waste or sewage.

Citric acid monohydrate is found naturally in citrus fruits, especially lemons and limes. It’s what gives them their tart, sour taste.
A manufactured form of Citric acid monohydrate is commonly used as an additive in food, cleaning agents, and nutritional supplements.
However, this manufactured form differs from what’s found naturally in citrus fruits.
For this reason, you may wonder whether it’s good or bad for you.
This article explains the differences between natural and manufactured Citric acid monohydrate, and explores its benefits, uses, and safety.
What Is Citric acid monohydrate?
Citric acid monohydrate was first derived from lemon juice by a Swedish researcher in 1784.
The odorless and colorless compound was produced from lemon juice until the early 1900s when researchers discovered that it could also be made from the black mold, Aspergillus niger, which creates Citric acid monohydrate when it feeds on sugar.
Because of its acidic, sour-tasting nature, Citric acid monohydrate is predominantly used as a flavoring and preserving agent — especially in soft drinks and candies.
It’s also used to stabilize or preserve medicines and as a disinfectant against viruses and bacteria.
Citric acid monohydrate is a compound originally derived from lemon juice. It’s produced today from a specific type of mold and used in a variety of applications.

Natural Food Sources
Citrus fruits and their juices are the best natural sources of Citric acid monohydrate.
In fact, the word citric originates from the Latin word citrus.
Examples of citrus fruits include:
lemons, limes, oranges, grapefruits, tangerines, pomelos
Other fruits also contain Citric acid monohydrate but in lesser amounts. These include:
pineapple, strawberries, raspberries, cranberries, cherries, tomatoes
Beverages or food products that contain these fruits — such as ketchup in the case of tomatoes — also contain Citric acid monohydrate.
While not naturally occurring, Citric acid monohydrate is also a byproduct of cheese, wine, and sourdough bread production.
The Citric acid monohydrate listed in the ingredients of foods and supplements is manufactured — not what’s naturally found in citrus fruits.
This is because producing this additive from citrus fruits is too expensive and the demand far exceeds the supply.
Lemons, limes, and other citrus fruits are the predominant natural sources of Citric acid monohydrate. Other fruits that contain much less include certain berries, cherries, and tomatoes.
Artificial Sources and Uses
The characteristics of Citric acid monohydrate make it an important additive for a variety of industries.
Food and beverages use an estimated 70% of manufactured Citric acid monohydrate, pharmaceutical and dietary supplements use 20%, and the remaining 10% goes into cleaning agents.

Food Industry
Manufactured Citric acid monohydrate is one of the most common food additives in the world.
It’s used to boost acidity, enhance flavor, and preserve ingredients (5).
Sodas, juices, powdered beverages, candies, frozen foods, and some dairy products often contain manufactured Citric acid monohydrate.
It’s also added to canned fruits and vegetables to protect against botulism, a rare but serious illness caused by the toxin-producing Clostridium botulinum bacteria.

Medicines and Dietary Supplements
Citric acid monohydrate is an industrial staple in medicines and dietary supplements.
It’s added to medicines to help stabilize and preserve the active ingredients and used to enhance or mask the taste of chewable and syrup-based medications.
Mineral supplements, such as magnesium and calcium, may contain Citric acid monohydrate — in the form of citrate — as well to enhance absorption.

Disinfecting and Cleaning
Citric acid monohydrate is a useful disinfectant against a variety of bacteria and viruses.
A test-tube study showed that it may be effective in treating or preventing human norovirus, a leading cause of foodborne illness.
Citric acid monohydrate is commercially sold as a general disinfectant and cleaning agent for removing soap scum, hard water stains, lime, and rust.
It’s viewed as a safer alternative to conventional disinfectant and cleaning products, such as quat and chlorine bleach.
Citric acid monohydrate is a versatile additive for food, beverages, medicines, and dietary supplements, as well as cleaning and disinfecting products.

Health Benefits and Body Uses
Citric acid monohydrate has many impressive health benefits and functions.
Metabolizes Energy
Citrate — a closely related molecule of Citric acid monohydrate — is the first molecule that forms during a process called the Citric acid monohydrate cycle.
Also known as the tricarboxylic acid (TCA) or Krebs cycle, these chemical reactions in your body help transform food into usable energy.
Humans and other organisms derive the majority of their energy from this cycle.

Enhances Nutrient Absorption
Supplemental minerals are available in a variety of forms.
But not all forms are created equal, as your body uses some more effectively.
Citric acid monohydrate enhances the bioavailability of minerals, allowing your body to better absorb them.
For example, calcium citrate doesn’t require stomach acid for absorption. It also has fewer side effects — such as gas, bloating, or constipation — than another form called calcium carbonate.
Thus, calcium citrate is a better option for people with less stomach acid, like older adults.
Similarly, magnesium in the citrate form is absorbed more completely and is more bioavailable than magnesium oxide and magnesium sulfate.
Citric acid monohydrate also enhances the absorption of zinc supplements.

May Protect Against Kidney Stones
Citric acid monohydrate — in the form of potassium citrate — prevents new kidney stone formation and breaks apart those already formed.
Citric acid monohydrate protects against kidney stones by making your urine less favorable for the formation of stones.
Kidney stones are often treated with Citric acid monohydrate as potassium citrate. However, consuming foods high in this natural acid — like citrus fruits — can offer similar stone-preventing benefits.
Safety and Risks
Manufactured Citric acid monohydrate is generally recognized as safe (GRAS) by the Food and Drug Administration (FDA) (5).
No scientific studies exist investigating the safety of manufactured Citric acid monohydrate when consumed in large amounts for long periods.
Still, there have been reports of sickness and allergic reactions to the additive.
One report found joint pain with swelling and stiffness, muscular and stomach pain, as well as shortness of breath in four people after they consumed foods containing manufactured Citric acid monohydrate.
These same symptoms were not observed in people consuming natural forms of the acid, such as lemons and limes.
Researchers acknowledged that they couldn’t prove the manufactured Citric acid monohydrate was responsible for those symptoms but recommended that its use in foods and beverages be further studied.
In either case, the scientists suggested that the symptoms were most likely related to the mold used to produce the Citric acid monohydrate rather than the compound itself.
The Bottom Line
Citric acid monohydrate is naturally found in citrus fruits, but synthetic versions — produced from a type of mold — are commonly added to foods, medicines, supplements, and cleaning agents.
While mold residues from the manufacturing process may trigger allergies in rare cases, Citric acid monohydrate is generally deemed safe.

Anhydrous Citric acid monohydrate is a tricarboxylic acid found in citrus fruits. Citric acid monohydrate is used as an excipient in pharmaceutical preparations due to its antioxidant properties. It maintains stability of active ingredients and is used as a preservative. It is also used as an acidulant to control pH and acts as an anticoagulant by chelating calcium in blood.
Citric acid monohydrate and its salts are naturally occurring constituents and common metabolites in plants and animal tissues. Citric acid monohydrate is an intermediary compound in the Krebs cycle linking oxidative metabolism of carbohydrate, protein and fat. The concentration of naturally occurring citrate is relatively higher in fruits, particularly citrus fruits and juices than vegetables and animal tissues.
In human (as well as in animal and plant) physiology, Citric acid monohydrate is a very common intermediate in one of the central biochemical cycles, the Krebs or tricarboxylic acid cycle, which takes place in every cell. It completes the breakdown of pyruvate formed from glucose through glycolysis, thereby liberating carbon dioxide and a further four hydrogen atoms which are picked up by electron transport molecules. Thus, in man approximately 2 kg of Citric acid monohydrate are formed and metabolised every day. This physiological pathway is very well developed and capable of processing very high amounts of Citric acid monohydrate as long as it occurs in low concentrations.
The NK(2), and to a lesser extent the NK(1), receptors have been shown to be involved with Citric acid monohydrate-induced bronchoconstriction in the guinea pig, which is in part mediated by endogenously released bradykinin. Tachykinins and bradykinin could also modulate Citric acid monohydrate-induced bronchoconstriction. ... Bronchoconstriction induced by Citric acid monohydrate inhalation in the guinea pig, mainly caused by the tachykinin NK(2) receptor, is counteracted by bronchoprotective NO after activation of bradykinin B(2) and tachykinin NK(1) receptors in airway epithelium.

A concentration of 47.6 mmol/L of Citric acid monohydrate (pH 2.3) in water led to total cell death within three minutes of incubation /with gingival fibroblasts (GF)/. Media containing 23.8 mmol/L and 47.6 mmol/L of Citric acid monohydrate exerted strong cytotoxicity (47 to 90 per cent of cell death) and inhibited protein synthesis (IC50 = 0.28 per cent) of GF within three hours of incubation. Incubation of cells in a medium containing 11.9 mmol/L of Citric acid monohydrate also suppressed the attachment and spreading of fibroblasts on culture plates and Type I collagen, with 58 per cent and 22 per cent of inhibition, respectively. Culture medium supplemented with 11.9, 23.8 and 47.6 mmol/L of Citric acid monohydrate also led to extracellular acidosis by decreasing the pH value from 7.5 to 6.3, 5.2 and 3.8, respectively.
Malic acid and deferoxamine mesylate were the most effective in increasing the urinary excretion of aluminum. Citric acid monohydrate was the most effective in increasing the fecal excretion of aluminum. Malonic, oxalic and succinic acids had no overall beneficial effects. Citric acid monohydrate would appear to be the most effective agent of those tested in the prevention of acute aluminium intoxication.
The entomopathogenic fungus, Beauveria bassiana, produced Citric acid monohydrates in liquid cultures containing grasshopper (Melanoplus sanguinipes) cuticle as the sole nutrient source. Citric acid monohydrates solubilized cuticular proteins as well as commercial preparations of elastin and collagen. Melanoplus sanguinipes treated with Beauveria bassiana showed a LT50 of 7.33 days, while Melanoplus sanguinipes treated with Citric acid monohydrate showed a LT50 of 7.25 and 13.28 days, respectively. Melanoplus sanguinipes treated with Citric acid monohydrate followed by a Beauveria bassiana conidia treatment showed a LT50 of 3.88 days. Analysis of the bioassay data revealed that the relationship between Citric acid monohydrate together with Beauveria bassiana conidia in grasshopper mortality was markedly synergistic. It is suggested that acid metabolites produced by Beauveria bassiana may play a role in cuticle solubilization and subsequent hyphal penetration.

Citric acid monohydrate's production and use as an acidulant in beverages, confectionery, effervescent salts, in pharmaceutical syrups, elixirs; in processing cheese, in chemical manufacture, a foam inhibitor, a sequestering agent, a mordant, in electroplating, in special inks, an anticoagulant, and in water-conditioning agent and detergent builder may result in its release to the environment through various waste streams. Citric acid monohydrate is widely distributed in plants and in animal tissues and fluids. If released to air, a vapor pressure of 1.66X10-8 mm Hg at 25 °C indicates Citric acid monohydrate will exist solely in the particulate phase in the atmosphere. Particulate-phase Citric acid monohydrate will be removed from the atmosphere by wet and dry deposition. Citric acid monohydrate absorbs light at wavelengths up to 260 nm and, therefore, is not expected to be susceptible to direct photolysis since sunlight consists of wavelengths above 290 nm. If released to soil, Citric acid monohydrate is expected to have very high mobility based upon an estimated Koc of 10. The pKa of Citric acid monohydrate is 2.79, indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Citric acid monohydrate is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Citric acid monohydrate reached 53% of its theoretical BOD in 5 days using a sludge inoculum, suggesting that biodegradation may be an important environmental fate process in soil. If released into water, Citric acid monohydrate is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Theoretical biodegradation values of 66.4% and 67.3% after 5 days using freshwater and seawater inoculums, respectively, indicate that biodegradation is an important environmental fate process in water. The pKa indicates Citric acid monohydrate will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to Citric acid monohydrate may occur through dermal contact with this compound at workplaces where Citric acid monohydrate is produced or used. Monitoring data indicate that the general population may be exposed to Citric acid monohydrate via ingestion of food and dermal contact with consumer products containing Citric acid monohydrate. 

The biodegradability of Citric acid monohydrate was determined in six different tests and results found it to be well degraded in all tests(1). Citric acid monohydrate achieved 93% DOC removal in a coupled units test (sludge inoculum), 85% DOC removal after 1 day in a Zahn-Wellens test (sludge inoculum), 100% DOC removal in an AFNOR test (42 days, germs inoculum simulating polluted river water), 100% DOC removal in a Sturm test (42 days, sewage treatment plant effluent), 100% DOC removal in an OECD screening test (19 days, effluent simulating surface water), and 90% BODT in a closed bottle test (30 days, effluent simulating surface water)(1). Citric acid monohydrate reached 53% of its theoretical BOD in 5 days using a sludge inoculum(2). Citric acid monohydrate, present at 500 mg/L, reached 46% of its theoretical oxygen demand in 12 hours using a phenol acclimated activated sludge inoculum(3).Citric acid monohydrate, present at 500 mg/L, reached 98.4% of its theoretical BOD in 22 to 24 hours using an activated sludge inoculum at 2,228 mg/L(4). Citric acid monohydrate (1% w/v) displayed BOD values of 6,410 and 6,040 mg/L using a defined microbial mixture and sewage inoculums, respectively(5). Citric acid monohydrate, present at 10 mg/L, reached 66.4% and 67.3% of its theoretical BOD after 5 days using freshwater and seawater inoculums, respectively(6).
A Citric acid monohydrate aqueous solution (pH 1), with a hydroxy radical concentration of 1X10-17 mol/L, had a reaction rate constant of 3.0X10+7 L/mol-sec at room temperature(1). This corresponds to a calculated half-life of 73 years(1). Citric acid monohydrate is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Citric acid monohydrate absorbs light at wavelengths up to 260 nm(3) and, therefore, is not expected to be susceptible to direct photolysis since sunlight consists of wavelengths above 290 nm(SRC).