Chemistry of ascorbic acid

Last updated

l-Ascorbic acid
L-Ascorbic acid.svg
Ascorbic-acid-from-xtal-1997-3D-balls.png
Names
IUPAC name
(5R)-[(1S)-1,2-Dihydroxyethyl]-3,4-dihydroxyfuran-2(5H)-one
Other names
Vitamin C
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
EC Number
  • 200-066-2
E number E300 (antioxidants, ...)
KEGG
PubChem CID
UNII
  • InChI=1S/C6H8O6/c7-1-2(8)5-3(9)4(10)6(11)12-5/h2,5,7-10H,1H2/t2-,5+/m0/s1 X mark.svgN
    Key: CIWBSHSKHKDKBQ-JLAZNSOCSA-N X mark.svgN
  • OC=1C(OC(=O)C=1O)[C@@H](O)CO
  • C([C@@H]([C@@H]1C(=C(C(=O)O1)O)O)O)O
Properties
C6H8O6
Molar mass 176.124 g·mol−1
AppearanceWhite or light yellow solid
Density 1.65 g/cm3
Melting point 190 to 192 °C (374 to 378 °F; 463 to 465 K) decomposes
330 g/L
Solubility Insoluble in diethyl ether, chloroform, benzene, petroleum ether, oils, fats
Solubility in ethanol 20 g/L
Solubility in glycerol 10 g/L
Solubility in propylene glycol 50 g/L
Acidity (pKa)4.10 (first), 11.6 (second)
Pharmacology
A11GA01 ( WHO ) G01AD03 ( WHO ), S01XA15 ( WHO )
Hazards
NFPA 704 (fire diamond)
NFPA 704.svgHealth 1: Exposure would cause irritation but only minor residual injury. E.g. turpentineFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
1
0
Lethal dose or concentration (LD, LC):
11.9 g/kg (oral, rat) [1]
Safety data sheet (SDS) JT Baker
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Ascorbic acid is an organic compound with formula C
6H
8O
6, originally called hexuronic acid. It is a white solid, but impure samples can appear yellowish. It dissolves freely in water to give mildly acidic solutions. It is a mild reducing agent.

Contents

Ascorbic acid exists as two enantiomers (mirror-image isomers), commonly denoted "l" (for "levo") and "d" (for "dextro"). The l isomer is the one most often encountered: it occurs naturally in many foods, and is one form ("vitamer") of vitamin C, an essential nutrient for humans and many animals. Deficiency of vitamin C causes scurvy, formerly a major disease of sailors in long sea voyages. It is used as a food additive and a dietary supplement for its antioxidant properties. The "d" form (erythorbic acid) can be made by chemical synthesis, but has no significant biological role.

History

The antiscorbutic properties of certain foods were demonstrated in the 18th century by James Lind. In 1907, Axel Holst and Theodor Frølich discovered that the antiscorbutic factor was a water-soluble chemical substance, distinct from the one that prevented beriberi. Between 1928 and 1932, Albert Szent-Györgyi isolated a candidate for this substance, which he called "hexuronic acid", first from plants and later from animal adrenal glands. In 1932 Charles Glen King confirmed that it was indeed the antiscorbutic factor.

In 1933, sugar chemist Walter Norman Haworth, working with samples of "hexuronic acid" that Szent-Györgyi had isolated from paprika and sent him in the previous year, deduced the correct structure and optical-isomeric nature of the compound, and in 1934 reported its first synthesis. [2] [3] In reference to the compound's antiscorbutic properties, Haworth and Szent-Györgyi proposed to rename it "a-scorbic acid" for the compound, and later specifically l-ascorbic acid. [4] Because of their work, in 1937 two Nobel Prizes: in Chemistry and in Physiology or Medicine were awarded to Haworth and Szent-Györgyi, respectively.

Chemical properties

Acidity

Ascorbic acid is a furan-based lactone of 2-ketogluconic acid. It contains an adjacent enediol adjacent to the carbonyl. This −C(OH)=C(OH)−C(=O)− structural pattern is characteristic of reductones, and increases the acidity of one of the enol hydroxyl groups. The deprotonated conjugate base is the ascorbate anion, which is stabilized by electron delocalization that results from resonance between two forms:

Ascorbate resonance.png

For this reason, ascorbic acid is much more acidic than would be expected if the compound contained only isolated hydroxyl groups.

Salts

The ascorbate anion forms salts, such as sodium ascorbate, calcium ascorbate, and potassium ascorbate.

Esters

Ascorbic acid can also react with organic acids as an alcohol forming esters such as ascorbyl palmitate and ascorbyl stearate.

Nucleophilic attack

Nucleophilic attack of ascorbic acid on a proton results in a 1,3-diketone:

Ascorbic diketone.png

Oxidation

Semidehydroascorbate acid radical L-Semidehydroascorbinsaure.svg
Semidehydroascorbate acid radical
Pseudodehydroascorbate Dehydroascorbic acid 2.svg
Pseudodehydroascorbate
Ascorbic acid all.svg
Dehydroascorbate

The ascorbate ion is the predominant species at typical biological pH values. It is a mild reducing agent and antioxidant, typically reacting with oxidants of the reactive oxygen species, such as the hydroxyl radical.

Reactive oxygen species are damaging to animals and plants at the molecular level due to their possible interaction with nucleic acids, proteins, and lipids. Sometimes these radicals initiate chain reactions. Ascorbate can terminate these chain radical reactions by electron transfer. The oxidized forms of ascorbate are relatively unreactive and do not cause cellular damage.

Ascorbic acid and its sodium, potassium, and calcium salts are commonly used as antioxidant food additives. These compounds are water-soluble and, thus, cannot protect fats from oxidation: For this purpose, the fat-soluble esters of ascorbic acid with long-chain fatty acids (ascorbyl palmitate or ascorbyl stearate) can be used as antioxidant food additives. Sodium-dependent active transport process enables absorption of Ascorbic acid from the intestine. [5]

Ascorbate readily donates a hydrogen atom to free radicals, forming the radical anion semidehydroascorbate (also known as monodehydroascorbate), a resonance-stabilized semitrione: [6]

C6H7O−6 + L• → C6H6O6•− + LH

Loss of an electron from semidehydroascorbate to produce the 1,2,3-tricarbonyl pseudodehydroascorbate is thermodynamically disfavored, which helps prevent propagation of free radical chain reactions such as autoxidation: [6]

C6H6O6•− + O2C6H6O6 + O2•−

However, being a good electron donor, excess ascorbate in the presence of free metal ions can not only promote but also initiate free radical reactions, thus making it a potentially dangerous pro-oxidative compound in certain metabolic contexts.

Semidehydroascorbate oxidation instead occurs in conjunction with hydration, yielding the bicyclic hemiketal dehydroascorbate. In particular, semidehydroascorbate undergoes disproportionation to ascorbate and dehydroascorbate: [6]

C6H6O6•− + L• + H2O + H+ → C6H8O7 + LH
2 C6H6O6•− + H2O + H+ → C6H8O7 + C6H7O−6

Aqueous solutions of dehydroascorbate are unstable, undergoing hydrolysis with a half-life of 5–15 minutes at 37 °C (99 °F). Decomposition products include diketogulonic acid, xylonic acid, threonic acid and oxalic acid. [7] [8] : 14 

Other reactions

It creates volatile compounds when mixed with glucose and amino acids at 90 °C. [9]

It is a cofactor in tyrosine oxidation, though because a crude extract of animal liver is used, it is unclear which reaction catalyzed by which enzyme is being helped here. [10] For known roles in enzymatic reactions, see Vitamin C § Pharmacodynamics.

Because it reduces iron(III) and chelates iron ions, it enhances the oral absorption of non-heme iron. [11] This property also applies to its enantiomer. [12]

Conversion to oxalate

In 1958, it was discovered that ascorbic acid can be converted to oxalate, a key component of calcium oxalate kidney stones. [13] [14] [15] The process begins with the formation of dehydroascorbic acid (DHA) from the ascorbyl radical. While DHA can be recycled back to ascorbic acid, a portion irreversibly degrades to 2,3-diketogulonic acid (DKG), which then breaks down to both oxalate and the sugars L-erythrulose and threosone. [14] [15] [16] Research conducted in the 1960s suggested ascorbic acid could substantially contribute to urinary oxalate content (possibly over 40%), but these estimates have been questioned due to methodological limitations. [14] [15] [17] Subsequent large cohort studies have yielded conflicting results regarding the link between vitamin C intake and kidney stone formation. The overall clinical significance of ascorbic acid consumption to kidney stone risk, however, remains inconclusive, although several studies have suggested a potential association, especially with high-dose supplementation in men. [14] [15] [18] [19]

Uses

Food additive

The main use of l-ascorbic acid and its salts is as food additives, mostly to combat oxidation and prevent discoloration of the product during storage. [20] It is approved for this purpose in the EU with E number E300, [21] the US, [22] Australia, and New Zealand. [23]

The "d" enantiomer (erythorbic acid) shares all of the non-biological chemical properties with the more common l enantiomer. As a result, it is an equally effective food antioxidant, and is also approved in processed foods. [24]

Dietary supplement

Another major use of l-ascorbic acid is as a dietary supplement. It is on the World Health Organization's List of Essential Medicines. [25] [26] It's deficiency over a prolonged period of time could cause scurvy, which is characterized by fatigue, widespread weakness in connective tissues and capillary fragility. [27] It affects multiple organ systems due to its role in the biochemical reactions of connective tissue synthesis. [28]

Niche, non-food uses

Synthesis

Natural biosynthesis of vitamin C occurs through various processes in many plants and animals.

Industrial preparation

The outdated but historically significant industrial synthesis of ascorbic acid from glucose via the Reichstein process Synthesis ascorbic acid.svg
The outdated but historically significant industrial synthesis of ascorbic acid from glucose via the Reichstein process

Seventy percent of the world's supply of ascorbic acid is produced in China. [36] Ascorbic acid is prepared in industry from glucose in a method based on the historical Reichstein process. In the first of a five-step process, glucose is catalytically hydrogenated to sorbitol, which is then oxidized by the microorganism Acetobacter suboxydans to sorbose. Only one of the six hydroxy groups is oxidized by this enzymatic reaction. From this point, two routes are available. Treatment of the product with acetone in the presence of an acid catalyst converts four of the remaining hydroxyl groups to acetals. The unprotected hydroxyl group is oxidized to the carboxylic acid by reaction with the catalytic oxidant TEMPO (regenerated by sodium hypochlorite  – bleaching solution). Historically, industrial preparation via the Reichstein process used potassium permanganate as the bleaching solution. Acid-catalyzed hydrolysis of this product performs the dual function of removing the two acetal groups and ring-closing lactonization. This step yields ascorbic acid. Each of the five steps has a yield larger than 90%. [37]

A biotechnological process, first developed in China in the 1960s but further developed in the 1990s, bypassing acetone-protecting groups. A second genetically modified microbe species, such as mutant Erwinia , among others, oxidises sorbose into 2-ketogluconic acid (2-KGA), which can then undergo ring-closing lactonization via dehydration. This method is used in the predominant process used by the ascorbic acid industry in China, which supplies 70% of the world's ascorbic acid. [36] Researchers are exploring means for one-step fermentation. [38] [39]

Determination

The traditional way to analyze the ascorbic acid content is by titration with an oxidizing agent, and several procedures have been developed.

The popular iodometry approach uses iodine in the presence of a starch indicator. Iodine is reduced by ascorbic acid, and when all the ascorbic acid has reacted, the iodine is in excess, forming a blue-black complex with the starch indicator. This indicates the end-point of the titration.

As an alternative, ascorbic acid can be treated with iodine in excess, followed by back titration with sodium thiosulfate using starch as an indicator. [40]

This iodometric method has been revised to exploit the reaction of ascorbic acid with iodate and iodide in acid solution. Electrolyzing the potassium iodide solution produces iodine, which reacts with ascorbic acid. The end of the process is determined by potentiometric titration like Karl Fischer titration. The amount of ascorbic acid can be calculated by Faraday's law.

Another alternative uses N-bromosuccinimide (NBS) as the oxidizing agent in the presence of potassium iodide and starch. The NBS first oxidizes the ascorbic acid; when the latter is exhausted, the NBS liberates the iodine from the potassium iodide, which then forms the blue-black complex with starch.

See also

Related Research Articles

Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants are frequently added to industrial products, such as polymers, fuels, and lubricants, to extend their usable lifetimes. Foods are also treated with antioxidants to forestall spoilage, in particular the rancidification of oils and fats. In cells, antioxidants such as glutathione, mycothiol, or bacillithiol, and enzyme systems like superoxide dismutase, can prevent damage from oxidative stress.

A preservative is a substance or a chemical that is added to products such as food products, beverages, pharmaceutical drugs, paints, biological samples, cosmetics, wood, and many other products to prevent decomposition by microbial growth or by undesirable chemical changes. In general, preservation is implemented in two modes, chemical and physical. Chemical preservation entails adding chemical compounds to the product. Physical preservation entails processes such as refrigeration or drying. Preservative food additives reduce the risk of foodborne infections, decrease microbial spoilage, and preserve fresh attributes and nutritional quality. Some physical techniques for food preservation include dehydration, UV-C radiation, freeze-drying, and refrigeration. Chemical preservation and physical preservation techniques are sometimes combined.

<span class="mw-page-title-main">Titration</span> Laboratory method for determining the concentration of an analyte

Titration is a common laboratory method of quantitative chemical analysis to determine the concentration of an identified analyte. A reagent, termed the titrant or titrator, is prepared as a standard solution of known concentration and volume. The titrant reacts with a solution of analyte to determine the analyte's concentration. The volume of titrant that reacted with the analyte is termed the titration volume.

<span class="mw-page-title-main">Vitamin C</span> Essential nutrient found in citrus fruits and other foods

Vitamin C is a water-soluble vitamin found in citrus and other fruits, berries and vegetables. It is also a generic prescription medication and in some countries is sold as a non-prescription dietary supplement. As a therapy, it is used to prevent and treat scurvy, a disease caused by vitamin C deficiency.

<span class="mw-page-title-main">Nitrosamine</span> Organic compounds of the form >N–N=O

Nitrosamines are organic compounds produced by industrial processes.

<span class="mw-page-title-main">Erythorbic acid</span> Chemical compound

Erythorbic acid is a stereoisomer of ascorbic acid. It is synthesized by a reaction between methyl 2-keto-D-gluconate and sodium methoxide. It can also be synthesized from sucrose or by strains of Penicillium that have been selected for this feature. It is denoted by E number E315, and is widely used as an antioxidant in processed foods.

Dehydroascorbic acid (DHA) is an oxidized form of ascorbic acid. It is actively imported into the endoplasmic reticulum of cells via glucose transporters. It is trapped therein by reduction back to ascorbic acid by glutathione and other thiols. The (free) chemical radical semidehydroascorbic acid (SDA) also belongs to the group of oxidized ascorbic acids.

<span class="mw-page-title-main">Mineral ascorbates</span>

Mineral ascorbates are a group of salts of ascorbic acid. They are composed of a mineral cation bonded to ascorbate.

Irwin Stone (1907–1984) was an American biochemist, chemical engineer, and writer. He was the first to use ascorbic acid in the food processing industry as a preservative, and originated and published the hypothesis that humans require much larger amounts of Vitamin C for optimal health than is necessary to prevent scurvy.

<span class="mw-page-title-main">Ascorbyl palmitate</span> Chemical compound

Ascorbyl palmitate is an ester formed from ascorbic acid and palmitic acid creating a fat-soluble form of vitamin C. In addition to its use as a source of vitamin C, it is also used as an antioxidant food additive. It is approved for use as a food additive in the EU, the U.S., Canada, Australia, and New Zealand.

Ascorbyl stearate (C24H42O7) is an ester formed from ascorbic acid and stearic acid. In addition to its use as a source of vitamin C, it is used as an antioxidant food additive in margarine (E number E305). The USDA limits its use to 0.02% individually or in conjunction with other antioxidants.

<span class="mw-page-title-main">Sodium ascorbate</span> Chemical compound

Sodium ascorbate is one of a number of mineral salts of ascorbic acid (vitamin C). The molecular formula of this chemical compound is C6H7NaO6. As the sodium salt of ascorbic acid, it is known as a mineral ascorbate. It has not been demonstrated to be more bioavailable than any other form of vitamin C supplement.

<span class="mw-page-title-main">Potassium ascorbate</span> Chemical compound

Potassium ascorbate is a compound with formula KC6H7O6. It is the potassium salt of ascorbic acid (vitamin C) and a mineral ascorbate. As a food additive, it has E number E303, INS number 303. Although it is not a permitted food additive in the UK, USA and the EU, it is approved for use in Australia and New Zealand. According to some studies, it has shown a strong antioxidant activity and antitumoral properties.

<span class="mw-page-title-main">Potassium iodate</span> Chemical compound

Potassium iodate (KIO3) is an ionic inorganic compound with the formula KIO3. It is a white salt that is soluble in water.

<span class="mw-page-title-main">Ascorbate peroxidase</span> Enzyme

Ascorbate peroxidase (or L-ascorbate peroxidase, APX or APEX) (EC 1.11.1.11) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Dichlorophenolindophenol</span> Chemical compound

2,6-Dichlorophenolindophenol is a chemical compound used as a redox dye. When oxidized, DCPIP is blue with a maximal absorption at 600 nm; when reduced, DCPIP is colorless.

<span class="mw-page-title-main">Dough conditioner</span> Substance added to bread dough to strengthen its texture

A dough conditioner, flour treatment agent, improving agent or bread improver is any ingredient or chemical added to bread dough to strengthen its texture or otherwise improve it in some way. Dough conditioners may include enzymes, yeast nutrients, mineral salts, oxidants and reductants, bleaching agents and emulsifiers. They are food additives combined with flour to improve baking functionality. Flour treatment agents are used to increase the speed of dough rising and to improve the strength and workability of the dough.

<span class="mw-page-title-main">Intravenous ascorbic acid</span> Nonmedical procedure

Intravenous Ascorbic Acid or PAA, pharmacologic ascorbic acid, is a process that delivers soluble ascorbic acid directly into the bloodstream. It is not approved for use to treat any medical condition.

In biochemistry, nitrosamines are a class of compounds that can form during food digestion. The presence of their precursors, nitrites, in cured meats, is controversial, because of a small connection to cancer risk.

References

  1. ↑ Safety (MSDS) data for ascorbic acid. University of Oxford
  2. ↑ Story of Vitamin C's chemical discovery. Profiles.nlm.nih.gov. Retrieved on 2012-12-04.
  3. ↑ Davies MB, Austin J, Partridge DA (1991). Vitamin C: Its Chemistry and Biochemistry. The Royal Society of Chemistry. p. 48. ISBN   0-85186-333-7.
  4. ↑ Svirbelf JL, Szent-Györgyi A (April 25, 1932). "The Chemical Nature Of Vitamin C" (PDF). Science. 75 (1944): 357–8. Bibcode:1932Sci....75..357K. doi:10.1126/science.75.1944.357-a. PMID   17750032. S2CID   33277683.. Part of the National Library of Medicine collection. Accessed January 2007
  5. ↑ "Re-evaluation of ascorbic acid, sodium ascorbate and calcium ascorbate as food additives | EFSA". www.efsa.europa.eu. European Food Safety Authority. 6 May 2015.
  6. 1 2 3 Njus D, Kelley PM, Tu YJ, Schlegel HB (November 2020). "Ascorbic acid: The chemistry underlying its antioxidant properties". Free Radical Biology and Medicine. 159: 37–43. doi:10.1016/j.freeradbiomed.2020.07.013. PMID   32738399.
  7. ↑ Gaonkar AG, McPherson A (2016-04-19). Ingredient Interactions: Effects on Food Quality, Second Edition. CRC Press. ISBN   9781420028133.
  8. ↑ Linster CL [in Luxembourgish], Van Schaftingen E (January 2007). "Vitamin C: Biosynthesis, recycling and degradation in mammals". The FEBS Journal. 274 (1): 1–22. doi:10.1111/j.1742-4658.2006.05607.x. PMID   17222174.
  9. ↑ Seck, S., Crouzet, J. (1981). "Formation of Volatile Compounds in Sugar-Phenylalanine and Ascorbic Acid-Phenylalanine Model Systems during Heat Treatment". Journal of Food Science. 46 (3): 790–793. doi:10.1111/j.1365-2621.1981.tb15349.x.
  10. ↑ Sealock RR, Goodland RL, Sumerwell WN, Brierly JM (May 1952). "The role of ascorbic acid in the oxidation of L-Tyrosine by guinea pig liver extracts" (PDF). The Journal of Biological Chemistry. 196 (2): 761–7. doi: 10.1016/S0021-9258(19)52407-3 . PMID   12981016.
  11. ↑ DeLoughery TG (March 2017). "Iron deficiency anemia". Med Clin North Am (Review). 101 (2): 319–32. doi:10.1016/j.mcna.2016.09.004. PMID   28189173.
  12. ↑ Fidler MC, Davidsson L, Zeder C, Hurrell RF (January 2004). "Erythorbic acid is a potent enhancer of nonheme-iron absorption". American Journal of Clinical Nutrition. 79 (1): 99–102. doi: 10.1093/ajcn/79.1.99 . PMID   14684404.
  13. ↑ Hellman L, Burns JJ (February 1958). "Metabolism of L-ascorbic acid-1-C14 in man". The Journal of Biological Chemistry. 230 (2): 923–30. doi: 10.1016/S0021-9258(18)70515-2 . PMID   13525409.
  14. 1 2 3 4 Knight J, Madduma-Liyanage K, Mobley JA, Assimos DG, Holmes RP (August 2016). "Ascorbic acid intake and oxalate synthesis". Urolithiasis. 44 (4): 289–97. doi:10.1007/s00240-016-0868-7. PMC   4946963 . PMID   27002809.
  15. 1 2 3 4 Kayis C (2024). "Effect of Ascorbic Acid on the Kidneys". Ascorbic Acid - Biochemistry and Functions. IntechOpen. doi: 10.5772/intechopen.111913 . ISBN   978-1-83768-562-2 . Retrieved 12 January 2025.
  16. ↑ Bao D, Wang Y, Zhao MH (December 2023). "Oxalate Nephropathy and the Mechanism of Oxalate-Induced Kidney Injury". Kidney Diseases (Basel, Switzerland). 9 (6): 459–468. doi:10.1159/000533295. PMC   10712969 . PMID   38089442.
  17. ↑ Atkins GL, Dean BM, Griffin WJ, Watts RW (September 1964). "Quantitative Aspects Of Ascorbic Acid Metabolism In Man". The Journal of Biological Chemistry. 239 (9): 2975–80. doi: 10.1016/S0021-9258(18)93840-8 . PMID   14217884.
  18. ↑ Cupisti A, Giannese D, D'Alessandro C, Benedetti A, Panichi V, Alfieri C, Castellano G, Messa P (February 2023). "Kidney Stone Prevention: Is There a Role for Complementary and Alternative Medicine?". Nutrients. 15 (4): 877. doi: 10.3390/nu15040877 . PMC   9959749 . PMID   36839235.
  19. ↑ Jiang K, Tang K, Liu H, Xu H, Ye Z, Chen Z (May 2019). "Ascorbic Acid Supplements and Kidney Stones Incidence Among Men and Women: A systematic review and meta-analysis". Urology Journal. 16 (2): 115–120. doi:10.22037/uj.v0i0.4275. PMID   30178451.
  20. ↑ Varvara M, Bozzo G, Celano G, Disanto C, Pagliarone CN, Celano GV (2016). "The Use of Ascorbic Acid as a Food Additive: Technical-Legal Issues". National Library of Medicine. Vol. 5, no. 1. National Center for Biotechnology Information. p. 4313. doi:10.4081/ijfs.2016.4313. PMC   5076701 . PMID   27800425.
  21. ↑ UK Food Standards Agency: "Current EU approved additives and their E Numbers" . Retrieved 2011-10-27.
  22. ↑ US Food and Drug Administration: "Listing of Food Additives Status Part I". Food and Drug Administration . Archived from the original on 2012-01-17. Retrieved 2011-10-27.
  23. ↑ Australia New Zealand Food Standards Code "Standard 1.2.4 – Labelling of ingredients". 8 September 2011. Retrieved 2011-10-27.
  24. ↑ Current EU approved additives and their E Numbers, Food Standards Agency
  25. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  26. ↑ "World Health Organization Model list of essential medicines" (PDF). World Health Organization.
  27. ↑ "Office of Dietary Supplements - Vitamin C". ods.od.nih.gov. National Institue of Health.
  28. ↑ "Scurvy: Rediscovering a Forgotten Disease". National Library of Medicine.
  29. ↑ Widengren J, Chmyrov A, Eggeling C, Löfdahl PA, Seidel CA (January 2007). "Strategies to improve photostabilities in ultrasensitive fluorescence spectroscopy". The Journal of Physical Chemistry A. 111 (3): 429–40. Bibcode:2007JPCA..111..429W. doi:10.1021/jp0646325. PMID   17228891.
  30. ↑ Vitamin C, water have benefits for plastic manufacturing. Reliable Plant Magazine. 2007. Archived from the original on 2007-09-27. Retrieved 2007-06-25.
  31. ↑ Beynon CM, McVeigh J, Chandler M, Wareing M, Bellis MA (December 2007). "The impact of citrate introduction at UK syringe exchange programmes: a retrospective cohort study in Cheshire and Merseyside, UK". Harm Reduction Journal. 4 (1): 21. doi: 10.1186/1477-7517-4-21 . PMC   2245922 . PMID   18072971.
  32. ↑ "The Riordan IVC Protocol for Adjunctive Cancer Care: Intravenous Ascorbate as a Chemotherapeutic and Biological Response Modifying Agent" (PDF). Riordan Clinic Research Institut. February 2013. Archived (PDF) from the original on 2022-10-09. Retrieved 2 February 2014.
  33. ↑ "High-Dose Vitamin C (PDQ): Human/Clinical Studies". National Cancer Institute. 2013-02-08. Retrieved 2 February 2014.
  34. ↑ Strom JG, Jun HW (1993). "Effect of urine pH and ascorbic acid on the rate of conversion of methenamine to formaldehyde". Biopharmaceutics & Drug Disposition. 14 (1): 61–69. doi:10.1002/bdd.2510140106. PMID   8427945. S2CID   11151179.
  35. ↑ Nahata MC, Cummins BA, McLeod DC, Schondelmeyer SW, Butler R (1982). "Effect of urinary acidifiers on formaldehyde concentration and efficacy with methenamine therapy". European Journal of Clinical Pharmacology. 22 (3): 281–284. doi:10.1007/bf00545228. PMID   7106162. S2CID   31796137.
  36. 1 2 "Vantage Market Research: Global Vitamin C Market Size & Share to Surpass $1.8 Bn by 2028". Globe Newswire (Press release). 8 November 2022. Retrieved 21 December 2023.
  37. ↑ Eggersdorfer, M., et al. "Vitamins". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a27_443. ISBN   978-3527306732.
  38. ↑ Zhou M, Bi Y, Ding M, Yuan Y (2021). "One-Step Biosynthesis of Vitamin C in Saccharomyces cerevisiae". Front Microbiol. 12: 643472. doi: 10.3389/fmicb.2021.643472 . PMC   7947327 . PMID   33717042.
  39. ↑ Tian YS, Deng YD, Zhang WH, Yu-Wang, Xu J, et al. (August 2022). "Metabolic engineering of Escherichia coli for direct production of vitamin C from D-glucose". Biotechnol Biofuels Bioprod. 15 (1): 86. Bibcode:2022BBB....15...86T. doi: 10.1186/s13068-022-02184-0 . PMC   9396866 . PMID   35996146.
  40. ↑ "A Simple Test for Vitamin C" (PDF). School Science Review. 83 (305): 131. 2002. Archived from the original (PDF) on July 4, 2016.

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