Vitamin C

{{anchor |Enantiomeric notation of vitamin C vitamers and their biological significance}}

{{Main|Chemistry of ascorbic acid}}

The name "vitamin C" always refers to the Enantiomer of ascorbic acid and its oxidized form, dehydroascorbate (DHA). Therefore, unless written otherwise, "ascorbate" and "ascorbic acid" refer in the nutritional literature to {{sm|l}}-ascorbate and {{sm|l}}-ascorbic acid respectively. Ascorbic acid is a weak sugar acid structurally related to glucose. In biological systems, ascorbic acid can be found only at low pH, but in solutions above pH 5 it is predominantly found in the ionized form, ascorbate.

Many analytical methods have been developed for ascorbic acid detection. For example, vitamin C content of a food sample such as fruit juice can be calculated by measuring the volume of the sample required to decolorize a solution of dichlorophenolindophenol (DCPIP) and then calibrating the results by comparison with a known concentration of vitamin C.{{cite web |url=http://www.foodafactoflife.org.uk/attachments/ff2caf4a-75e5-4aa129132873.pdf |title=Testing foods for vitamin C (ascorbic acid) |publisher=British Nutrition Foundation |date=2004 |url-status=live |archive-url=https://web.archive.org/web/20151123101705/http://www.foodafactoflife.org.uk/attachments/ff2caf4a-75e5-4aa129132873.pdf |archive-date=November 23, 2015 }}{{cite web |url=http://www.nuffieldfoundation.org/practical-biology/measuring-vitamin-c-content-foods-and-fruit-juices |title=Measuring the vitamin C content of foods and fruit juices |publisher=Nuffield Foundation |date=November 24, 2011 |url-status=live |archive-url=https://web.archive.org/web/20150721181046/http://www.nuffieldfoundation.org/practical-biology/measuring-vitamin-c-content-foods-and-fruit-juices |archive-date=July 21, 2015 }}

Plasma vitamin C is the most widely applied test for vitamin C status.{{cite book |title = Present Knowledge in Nutrition, Eleventh Edition |chapter = Vitamin C | veditors = Marriott MP, Birt DF, Stallings VA, Yates AA |publisher = Academic Press (Elsevier) |year=2020 |location = London, United Kingdom |pages = 155–70 |isbn=978-0-323-66162-1}} Adequate levels are defined as near 50 μmol/L. Hypovitaminosis of vitamin C is defined as less than 23 μmol/L, and deficiency as less than 11.4 μmol/L.{{cite journal |vauthors=Schleicher RL, Carroll MD, Ford ES, Lacher DA |title=Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES) |journal=The American Journal of Clinical Nutrition |volume=90 |issue=5 |pages=1252–63 |date=November 2009 |pmid=19675106 |doi=10.3945/ajcn.2008.27016 | doi-access = free | title-link = doi | issn = 0002-9165}} For people 20 years of age or above, data from the US 2017–18 National Health and Nutrition Examination Survey showed mean serum concentrations of 53.4 {{nbsp}}μmol/L. The percent of people reported as deficient was 5.9%.{{cite journal |vauthors=Narayanan S, Kumar SS, Manguvo A, Friedman E |title=Current estimates of serum vitamin C and vitamin C deficiency in the United States |journal=Curr Dev Nutr |volume=7 |issue=5 |pages=1067 |date=June 2021 |doi=10.1093/cdn/nzab053_060|pmc=8180804 }} Globally, vitamin C deficiency is common in low and middle-income countries, and not uncommon in high income countries. In the latter, prevalence is higher in males than in females.{{cite journal |vauthors=Rowe S, Carr AC |title=Global vitamin C status and prevalence of deficiency: A cause for concern? |journal=Nutrients |volume=12 |issue=7 |date=July 2020 |page=2008 |pmid=32640674 |pmc=7400810 |doi=10.3390/nu12072008 |doi-access=free |url=}}

Plasma levels are considered saturated at about 65 μmol/L, achieved by intakes of 100 to 200 mg/day, which are well above the recommended intakes. Even higher oral intake does not further raise plasma nor tissue concentrations because absorption efficiency decreases and any excess that is absorbed is excreted in urine.

Vitamin C content in plasma is used to determine vitamin status. For research purposes, concentrations can be assessed in leukocytes and tissues, which are normally maintained at an order of magnitude higher than in plasma via an energy-dependent transport system, depleted slower than plasma concentrations during dietary deficiency and restored faster during dietary repletion,{{rp|pages=103–109}} but these analysis are difficult to measure, and hence not part of standard diagnostic testing.{{cite journal | vauthors = Emadi-Konjin P, Verjee Z, Levin AV, Adeli K | title = Measurement of intracellular vitamin C levels in human lymphocytes by reverse phase high performance liquid chromatography (HPLC) | journal = Clinical Biochemistry | volume = 38 | issue = 5 | pages = 450–6 | date = May 2005 | pmid = 15820776 | doi = 10.1016/j.clinbiochem.2005.01.018 }}

Recommendations for vitamin C intake by adults have been set by various national agencies:

• 40 mg/day: India National Institute of Nutrition, Hyderabad{{cite web |url=http://ninindia.org/DietaryGuidelinesforNINwebsite.pdf |title=Dietary guidelines for Indians |publisher=National Institute of Nutrition, India |date=2011 |page=90 |access-date=February 10, 2019 |archive-date=December 22, 2018 |archive-url=https://web.archive.org/web/20181222101538/http://www.ninindia.org/DietaryGuidelinesforNINwebsite.pdf |url-status=dead }}
• 45 mg/day or 300 mg/week: the World Health Organization{{cite book | vauthors = ((World Health Organization)) | title = Vitamin and mineral requirements in human nutrition | edition = 2nd | publisher = World Health Organization | location = Geneva | year = 2005 | isbn = 978-92-4-154612-6 | chapter = Chapter 7: Vitamin C | hdl = 10665/42716 | author-link = World Health Organization}}
• 80 mg/day: the European Commission Council on nutrition labeling{{cite web |url=http://eur-lex.europa.eu/legal-content/en/TXT/?uri=CELEX%3A32008L0100 |title=Commission Directive 2008/100/EC of 28 October 2008 amending Council Directive 90/496/EEC on nutrition labeling for foodstuffs as regards recommended daily allowances, energy conversion factors and definitions |publisher=The Commission of the European Communities |url-status=live |archive-url=https://web.archive.org/web/20161002233059/http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32008L0100 |archive-date=October 2, 2016 |date=October 29, 2008 }}
• 90 mg/day (males) and 75 mg/day (females): Health Canada 2007{{cite web |url=http://www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licen-prod/monograph/mono_vitamin_c-eng.php |work=Natural Health Product Monograph |title=Vitamin C |publisher=Health Canada |url-status=dead |archive-url=https://web.archive.org/web/20130403150228/http://www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licen-prod/monograph/mono_vitamin_c-eng.php |archive-date=April 3, 2013 }}
• 90 mg/day (males) and 75 mg/day (females): United States National Academy of Sciences{{rp|pages=134–152}}
• 100 mg/day: Japan National Institute of Health and Nutrition{{cite web |url=https://www.mhlw.go.jp/file/06-Seisakujouhou-10900000-Kenkoukyoku/Overview.pdf |title=Overview of dietary reference intakes for Japanese |website=Ministry of Health, Labor and Welfare (Japan) |date=2015 |page=29 |access-date=August 19, 2021 |archive-date=October 21, 2022 |archive-url=https://web.archive.org/web/20221021004240/https://www.mhlw.go.jp/file/06-Seisakujouhou-10900000-Kenkoukyoku/Overview.pdf |url-status=live }}
• 110 mg/day (males) and 95 mg/day (females): European Food Safety Authority{{cite journal |title=Scientific Opinion on Dietary Reference Values for vitamin C |date=November 2013 |journal=EFSA Journal |volume=11 |issue=11 |doi=10.2903/j.efsa.2013.3418 |doi-access=free }}

In 2000, the chapter on Vitamin C in the North American Dietary Reference Intake was updated to give the Recommended Dietary Allowance (RDA) as 90 milligrams per day for adult men, 75 mg/day for adult women, and setting a Tolerable upper intake level (UL) for adults of 2,000 mg/day.{{rp|pages=134–152}} The table here shows RDAs for the United States and Canada for children, and for pregnant and lactating women,{{rp|pages=134–152}} as well as the ULs for adults.

For the European Union, the EFSA set higher recommendations for adults, and also for children: 20 mg/day for ages 1–3, 30 mg/day for ages 4–6, 45 mg/day for ages 7–10, 70 mg/day for ages 11–14, 100 mg/day for males ages 15–17, 90 mg/day for females ages 15–17. For pregnancy 100 mg/day; for lactation 155 mg/day.

Cigarette smokers and people exposed to secondhand smoke have lower serum vitamin C levels than nonsmokers. The thinking is that inhalation of smoke causes oxidative damage, depleting this antioxidant vitamin.{{rp|pages=152–153}} The US Institute of Medicine estimated that smokers need 35 mg more vitamin C per day than nonsmokers, but did not formally establish a higher RDA for smokers.{{rp|pages=152–153}}

The US National Center for Health Statistics conducts biannual National Health and Nutrition Examination Survey (NHANES) to assess the health and nutritional status of adults and children in the United States. Some results are reported as What We Eat In America. The 2013–2014 survey reported that for adults ages 20 years and older, men consumed on average 83.3 mg/d and women 75.1 mg/d. This means that half the women and more than half the men are not consuming the RDA for vitamin C.{{cite web | url = https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/1314/Table_1_NIN_GEN_13.pdf | title = TABLE 1: Nutrient intakes from food and beverages | work = National Health and Nutrition Examination Survey: What We Eat in America, DHHS-USDA Dietary Survey Integration | publisher = Centers for Disease Control and Prevention, U.S. Department of Health & Human Services| archive-url = https://web.archive.org/web/20170224042515/https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/1314/Table_1_NIN_GEN_13.pdf | archive-date=February 24, 2017 }} The same survey stated that about 30% of adults reported they consumed a vitamin C dietary supplement or a multi-vitamin/mineral supplement that included vitamin C, and that for these people total consumption was between 300 and 400 mg/d.{{cite web | url = https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/1314/Table_37_SUP_GEN_13.pdf | title = TABLE 37: Nutrient intakes from dietary supplements | work = National Health and Nutrition Examination Survey: What We Eat in America, DHHS-USDA Dietary Survey Integration | publisher = Centers for Disease Control and Prevention, U.S. Department of Health & Human Services | archive-url = https://web.archive.org/web/20171006162231/https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/1314/Table_37_SUP_GEN_13.pdf | archive-date=October 6, 2017 }}

In 2000, the Institute of Medicine of the US National Academy of Sciences set a Tolerable upper intake level (UL) for adults of 2,000 mg/day. The amount was chosen because human trials had reported diarrhea and other gastrointestinal disturbances at intakes of greater than 3,000 mg/day. This was the Lowest-Observed-Adverse-Effect Level (LOAEL), meaning that other adverse effects were observed at even higher intakes. ULs are progressively lower for younger and younger children.{{rp|pages=155–165}} In 2006, the European Food Safety Authority (EFSA) also pointed out the disturbances at that dose level, but reached the conclusion that there was not sufficient evidence to set a UL for vitamin C,{{cite web|year=2006|title=Tolerable upper intake levels for vitamins and minerals|url=http://www.efsa.europa.eu/sites/default/files/efsa_rep/blobserver_assets/ndatolerableuil.pdf|url-status=live|archive-url=https://web.archive.org/web/20160316225123/http://www.efsa.europa.eu/sites/default/files/efsa_rep/blobserver_assets/ndatolerableuil.pdf|archive-date=March 16, 2016|publisher=European Food Safety Authority}} as did the Japan National Institute of Health and Nutrition in 2010.

For US food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of Daily Value (%DV). For vitamin C labeling purposes, 100% of the Daily Value was 60 mg, but as of May 27, 2016, it was revised to 90 mg to bring it into agreement with the RDA.{{cite web |url=https://www.gpo.gov/fdsys/pkg/FR-2016-05-27/pdf/2016-11867.pdf |title=Federal Register May 27, 2016 food labeling: Revision of the nutrition and supplement facts labels. FR page 33982. |url-status=live |archive-url=https://web.archive.org/web/20160808164651/https://www.gpo.gov/fdsys/pkg/FR-2016-05-27/pdf/2016-11867.pdf |archive-date=August 8, 2016 }}{{cite web | title=Daily Value Reference of the Dietary Supplement Label Database (DSLD) | website=Dietary Supplement Label Database (DSLD) | url=https://www.dsld.nlm.nih.gov/dsld/dailyvalue.jsp | access-date=May 16, 2020 | archive-date=April 7, 2020 | archive-url=https://web.archive.org/web/20200407073956/https://dsld.nlm.nih.gov/dsld/dailyvalue.jsp | url-status=dead }} A table of the old and new adult daily values is provided at Reference Daily Intake.

European Union regulations require that labels declare energy, protein, fat, saturated fat, carbohydrates, sugars, and salt. Voluntary nutrients may be shown if present in significant amounts. Instead of Daily Values, amounts are shown as percent of Reference Intakes (RIs). For vitamin C, 100% RI was set at 80 mg in 2011.[http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2011:304:0018:0063:EN:PDF REGULATION (EU) No 1169/2011 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL] {{Webarchive|url=https://web.archive.org/web/20170726215901/http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ%3AL%3A2011%3A304%3A0018%3A0063%3AEN%3APDF |date=July 26, 2017 }} Official Journal of the European Union. page 304/61. (2009).

Although also present in other plant-derived foods, the richest natural sources of vitamin C are fruits and vegetables. Vitamin C is the most widely taken dietary supplement.

{{For|vitamin C content in ten common staple foods such as corn, rice, and wheat|Staple food#Nutrition}}

The following table is approximate and shows the relative abundance in different raw plant sources.{{cite web |url=https://fdc.nal.usda.gov/ |title=NDL/FNIC food composition database home page |access-date=30 November 2014 |publisher=USDA Nutrient Data Laboratory, the Food and Nutrition Information Center and Information Systems Division of the National Agricultural Library. |archive-date=January 15, 2023 |archive-url=https://web.archive.org/web/20230115162310/http://fdc.nal.usda.gov/ |url-status=live }} The amount is given in milligrams per 100 grams of the edible portion of the fruit or vegetable:

Animal-sourced foods do not generally provide much vitamin C, and what there is largely destroyed by heat during cooking. For example, raw chicken liver contains 17.9 mg/100 g, but fried, the content is reduced to 2.7 mg/100 g. Vitamin C is present in human breast milk at 5.0 mg/100 g. Cow's milk contains 1.0 mg/100 g, but the heat of pasteurization destroys it.{{cite web |url=http://www.saanendoah.com/compare.html |title= Comparing milk: human, cow, goat & commercial infant formula |access-date=February 28, 2007 |date=8 January 2007 | vauthors = Clark S |publisher=Washington State University |url-status=usurped |archive-url=https://web.archive.org/web/20070129024619/http://www.saanendoah.com/compare.html |archive-date=January 29, 2007}}

Vitamin C chemically decomposes under certain conditions, many of which may occur during the cooking of food. Vitamin C concentrations in various food substances decrease with time in proportion to the temperature at which they are stored.{{cite journal | vauthors = Roig MG, Rivera ZS, Kennedy JF | title = A model study on rate of degradation of L-ascorbic acid during processing using home-produced juice concentrates | journal = International Journal of Food Sciences and Nutrition | volume = 46 | issue = 2 | pages = 107–15 | date = May 1995 | pmid = 7621082 | doi = 10.3109/09637489509012538 }} Cooking can reduce the vitamin C content of vegetables by around 60%, possibly due to increased enzymatic destruction.{{cite journal | vauthors = Allen MA, Burgess SG | title = The losses of ascorbic acid during the large-scale cooking of green vegetables by different methods | journal = The British Journal of Nutrition | volume = 4 | issue = 2–3 | pages = 95–100 | year = 1950 | pmid = 14801407 | doi = 10.1079/BJN19500024 | doi-access = free | title-link = doi }} Longer cooking times may add to this effect.{{cite web |url=http://physchem.ox.ac.uk/MSDS/AS/ascorbic_acid.html |title=Safety (MSDS) data for ascorbic acid |access-date=February 21, 2007 |date=October 9, 2005 |publisher=Oxford University |url-status=live |archive-url=https://archive.today/20070209221915/http://physchem.ox.ac.uk/MSDS/AS/ascorbic_acid.html |archive-date=February 9, 2007 }} Another cause of vitamin{{nbsp}}C loss from food is leaching, which transfers vitamin{{nbsp}}C to the cooking water, which is decanted and not consumed.

Vitamin C dietary supplements are available as tablets, capsules, drink mix packets, in multi-vitamin/mineral formulations, in antioxidant formulations, and as crystalline powder.{{cite web |title=Ascorbic acid (Monograph) |url=https://www.drugs.com/monograph/ascorbic-acid.html |publisher=The American Society of Health-System Pharmacists |access-date=December 8, 2016 |url-status=live |archive-url=https://web.archive.org/web/20161230161611/https://www.drugs.com/monograph/ascorbic-acid.html |archive-date=December 30, 2016 }} Vitamin C is also added to some fruit juices and juice drinks. Tablet and capsule content ranges from 25 mg to 1500 mg per serving. The most commonly used supplement compounds are ascorbic acid, sodium ascorbate and calcium ascorbate. Vitamin C molecules can also be bound to the fatty acid palmitate, creating ascorbyl palmitate, or else incorporated into liposomes.{{cite journal | vauthors = Davis JL, Paris HL, Beals JW, Binns SE, Giordano GR, Scalzo RL, Schweder MM, Blair E, Bell C | title = Liposomal-encapsulated ascorbic acid: influence on vitamin C bioavailability and capacity to protect against ischemia-reperfusion injury | journal = Nutrition and Metabolic Insights | volume = 9 | pages = 25–30 | year = 2016 | pmid = 27375360 | pmc = 4915787 | doi = 10.4137/NMI.S39764 }}

Countries fortify foods with nutrients to address known deficiencies.{{cite web |url=https://www.ffinetwork.org/savelives |title=Why fortify? |website=Food Fortification Initiative |date=December 2023 |access-date=January 3, 2024 |archive-date=March 8, 2023 |archive-url=https://web.archive.org/web/20230308151817/https://www.ffinetwork.org/savelives |url-status=live }} While many countries mandate or have voluntary programs to fortify wheat flour, maize (corn) flour or rice with vitamins,{{cite web|url=https://fortificationdata.org/map-number-of-nutrients/|title=Map: Count of nutrients in fortification standards|website=Global Fortification Data Exchange|access-date=January 3, 2024|archive-date=April 11, 2019|archive-url=https://web.archive.org/web/20190411123853/https://fortificationdata.org/map-number-of-nutrients/|url-status=live}} none include vitamin C in those programs. As described in Vitamin C Fortification of Food Aid Commodities (1997), the United States provides rations to international food relief programs, later under the auspices of the Food for Peace Act and the Bureau for Humanitarian Assistance.{{cite web|title=USAID's Bureau for Humanitarian Assistance website|date=November 21, 2023 |url=https://www.usaid.gov/who-we-are/organization/bureaus/bureau-humanitarian-assistance|archive-url=https://web.archive.org/web/20200813170934/https://www.usaid.gov/who-we-are/organization/bureaus/bureau-humanitarian-assistance|url-status=dead|archive-date=August 13, 2020}} Vitamin C is added to corn-soy blend and wheat-soy blend products at 40 mg/100 grams. (along with minerals and other vitamins). Supplemental rations of these highly fortified, blended foods are provided to refugees and displaced persons in camps and to beneficiaries of development feeding programs that are targeted largely toward mothers and children.{{cite book |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK230149/ |title=Vitamin C fortification of food aid commodities: final report |chapter=Introduction |date=1997 |publisher=National Academies Press (US) |access-date=January 3, 2024 |archive-date=January 21, 2024 |archive-url=https://web.archive.org/web/20240121044202/https://www.ncbi.nlm.nih.gov/books/NBK230149/ |url-status=live }} The report adds: "The stability of vitamin C (L-ascorbic acid) is of concern because this is one of the most labile vitamins in foods. Its main loss during processing and storage is from oxidation, which is accelerated by light, oxygen, heat, increased pH, high moisture content (water activity), and the presence of copper or ferrous salts. To reduce oxidation, the vitamin C used in commodity fortification is coated with ethyl cellulose (2.5 percent). Oxidative losses also occur during food processing and preparation, and additional vitamin C may be lost if it dissolves into cooking liquid and is then discarded."

Ascorbic acid and some of its salts and esters are common additives added to foods such as canned fruits, mostly to slow oxidation and enzymatic browning.{{cite web|url=https://digitalcommons.usu.edu/cgi/viewcontent.cgi?article=2781&context=extension_curall|title=Pretreatments to prevent darkening of fruits prior to canning or dehydrating|vauthors=Washburn C, Jensen C|date=2017|publisher=Utah State University|access-date=January 26, 2020|archive-date=December 15, 2020|archive-url=https://web.archive.org/web/20201215135857/https://digitalcommons.usu.edu/cgi/viewcontent.cgi?article=2781&context=extension_curall|url-status=live}}{{cite journal |vauthors=Yin X, Chen K, Cheng H, Chen X, Feng S, Song Y, Liang L |title=Chemical Stability of Ascorbic Acid Integrated into Commercial Products: A Review on Bioactivity and Delivery Technology |journal=Antioxidants |volume=11 |issue=1 |date=January 2022 |page=153 |pmid=35052657 |pmc=8773188 |doi=10.3390/antiox11010153|doi-access=free }} It may be used as a flour treatment agent used in breadmaking.{{cite news |title=Ingredients |url=https://www.fob.uk.com/about-the-bread-industry/how-bread-is-made/ingredients/ |access-date=April 3, 2021 |publisher=The Federation of Bakers |archive-date=February 26, 2021 |archive-url=https://web.archive.org/web/20210226064815/https://www.fob.uk.com/about-the-bread-industry/how-bread-is-made/ingredients/ |url-status=live }} As food additives, they are assigned E numbers, with safety assessment and approval the responsibility of the European Food Safety Authority.{{cite web|url=http://www.faia.org.uk/faq2_4.php|title=Frequently asked questions {{!}} why food additives|website=Food Additives and Ingredients Association UK & Ireland- Making life taste better|access-date=October 27, 2010|url-status=live |archive-url=https://web.archive.org/web/20190601015633/https://www.faia.org.uk/faqs/|archive-date=June 1, 2019}} The relevant E numbers are:

1. E300 ascorbic acid (approved for use as a food additive in the UK,UK Food Standards Agency: {{cite web |url=http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist |title=Approved additives and their E numbers |access-date=October 27, 2011 |archive-date=October 7, 2010 |archive-url=https://web.archive.org/web/20101007124435/http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist |url-status=live }} USUS Food and Drug Administration:{{cite web|url=https://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/FoodAdditiveListings/ucm091048.htm |title=Listing of food additives status part I |website=Food and Drug Administration |access-date=October 27, 2011 |url-status=dead |archive-url=https://web.archive.org/web/20120117060614/https://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/FoodAdditiveListings/ucm091048.htm |archive-date=January 17, 2012 }} Canada,Health Canada {{cite web |title=List of permitted preservatives (lists of permitted food additives) - Government of Canada |url=https://www.canada.ca/en/health-canada/services/food-nutrition/food-safety/food-additives/lists-permitted/11-preservatives.html |website=Government of Canada |date=November 27, 2006 |access-date=October 27, 2022 |archive-date=October 27, 2022 |archive-url=https://web.archive.org/web/20221027020735/https://www.canada.ca/en/health-canada/services/food-nutrition/food-safety/food-additives/lists-permitted/11-preservatives.html |url-status=live }} Australia and New ZealandAustralia New Zealand Food Standards Code{{cite web |url=http://www.comlaw.gov.au/Details/F2011C00827 |title=Standard 1.2.4 – labeling of ingredients |date=September 8, 2011 |access-date=October 27, 2011 |archive-date=September 2, 2013 |archive-url=https://web.archive.org/web/20130902084805/http://www.comlaw.gov.au/Details/F2011C00827 |url-status=live }})
2. E301 sodium ascorbate (approved for use as a food additive in the UK, US,{{cite web |url=https://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/ucm191033.htm#ftnT |title=Listing of food additives status part II |website=US Food and Drug Administration |access-date=October 27, 2011 |archive-date=November 8, 2011 |archive-url=https://web.archive.org/web/20111108002304/https://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/ucm191033.htm#ftnT |url-status=live }} Canada, Australia and New Zealand)
3. E302 calcium ascorbate (approved for use as a food additive in the UK, US Canada, Australia and New Zealand)
4. E303 potassium ascorbate (approved in Australia and New Zealand, but not in the UK, US or Canada)
5. E304 fatty acid esters of ascorbic acid such as ascorbyl palmitate (approved for use as a food additive in the UK, US, Canada, Australia and New Zealand)

The stereoisomers of Vitamin C have a similar effect in food despite their lack of efficacy in human scurvy. They include erythorbic acid and its sodium salt (E315, E316).

{{See also|Chemistry of ascorbic acid}}

Pharmacodynamics is the study of how the drug – in this instance vitamin C – affects the organism, whereas pharmacokinetics is the study of how an organism affects the drug.

Pharmacodynamics includes enzymes for which vitamin C is a cofactor, with function potentially compromised in a deficiency state, and any enzyme cofactor or other physiological function affected by administration of vitamin C, orally or injected, in excess of normal requirements. At normal physiological concentrations, vitamin C serves as an enzyme substrate or cofactor and an electron donor antioxidant. The enzymatic functions include the synthesis of collagen, carnitine, and neurotransmitters; the synthesis and catabolism of tyrosine; and the metabolism of microsomes. In nonenzymatic functions it acts as a reducing agent, donating electrons to oxidized molecules and preventing oxidation in order to keep iron and copper atoms in their reduced states. At non-physiological concentrations achieved by intravenous dosing, vitamin C may function as a pro-oxidant, with therapeutic toxicity against cancer cells.{{cite journal |vauthors=Böttger F, Vallés-Martí A, Cahn L, Jimenez CR |title=High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer |journal=J Exp Clin Cancer Res |volume=40 |issue=1 |pages=343 |date=October 2021 |pmid=34717701 |pmc=8557029 |doi=10.1186/s13046-021-02134-y |doi-access=free |url=}}{{cite journal |vauthors=Park S, Ahn S, Shin Y, Yang Y, Yeom CH |title=Vitamin C in cancer: a metabolomics perspective |journal=Front Physiol |volume=9 |issue= |pages=762 |date=2018 |pmid=29971019 |pmc=6018397 |doi=10.3389/fphys.2018.00762 |doi-access=free |url=}}

Vitamin C functions as a cofactor for the following enzymes:

• Three groups of enzymes (prolyl-3-hydroxylases, prolyl-4-hydroxylases, and lysyl hydroxylases) that are required for the hydroxylation of proline and lysine in the synthesis of collagen. These reactions add hydroxyl groups to the amino acids proline or lysine in the collagen molecule via prolyl hydroxylase and lysyl hydroxylase, both requiring vitamin C as a cofactor. The role of vitamin C as a cofactor is to oxidize prolyl hydroxylase and lysyl hydroxylase from Fe{{sup|2+}} to Fe{{sup|3+}} and to reduce it from Fe{{sup|3+}} to Fe{{sup|2+}}. Hydroxylation allows the collagen molecule to assume its triple helix structure, and thus vitamin C is essential to the development and maintenance of scar tissue, blood vessels, and cartilage.
• Two enzymes (ε-N-trimethyl-L-lysine hydroxylase and γ-butyrobetaine hydroxylase) are necessary for synthesis of carnitine. Carnitine is essential for the transport of fatty acids into mitochondria for ATP generation.
• Hypoxia-inducible factor-proline dioxygenase enzymes (isoforms: EGLN1, EGLN2, and EGLN3) allows cells to respond physiologically to low concentrations of oxygen.
• Dopamine beta-hydroxylase participates in the biosynthesis of norepinephrine from dopamine.
• Peptidylglycine alpha-amidating monooxygenase amidates peptide hormones by removing the glyoxylate residue from their c-terminal glycine residues. This increases peptide hormone stability and activity.

As an antioxidant, ascorbate scavenges reactive oxygen and nitrogen compounds, thus neutralizing the potential tissue damage of these free radical compounds. Dehydroascorbate, the oxidized form, is then recycled back to ascorbate by endogenous antioxidants such as glutathione.{{rp|pages=98–99}} In the eye, ascorbate is thought to protect against photolytically generated free-radical damage; higher plasma ascorbate is associated with lower risk of cataracts. Ascorbate may also provide antioxidant protection indirectly by regenerating other biological antioxidants such as α-tocopherol back to an active state.{{rp|pages=98–99}} In addition, ascorbate also functions as a non-enzymatic reducing agent for mixed-function oxidases in the microsomal drug-metabolizing system that inactivates a wide variety of substrates such as drugs and environmental carcinogens.{{rp|pages=98–99}}

Ascorbic acid is absorbed in the body by both active transport and passive diffusion.{{cite journal |vauthors=Lykkesfeldt J, Tveden-Nyborg P |title=The pharmacokinetics of vitamin C |journal=Nutrients |volume=11 |issue=10 |date=October 2019 |page=2412 |pmid=31601028 |pmc=6835439 |doi=10.3390/nu11102412 |doi-access=free |url=}} Approximately 70%–90% of vitamin C is active-transport absorbed when intakes of 30–180 mg/day from a combination of food sources and moderate-dose dietary supplements such as a multi-vitamin/mineral product are consumed. However, when large amounts are consumed, such as a vitamin C dietary supplement, the active transport system becomes saturated, and while the total amount being absorbed continues to increase with dose, absorption efficiency falls to less than 50%. Active transport is managed by Sodium-Ascorbate Co-Transporter proteins (SVCTs) and Hexose Transporter proteins (GLUTs). SVCT1 and SVCT2 import ascorbate across plasma membranes.{{cite journal | vauthors = Savini I, Rossi A, Pierro C, Avigliano L, Catani MV | title = SVCT1 and SVCT2: key proteins for vitamin C uptake | journal = Amino Acids | volume = 34 | issue = 3 | pages = 347–55 | date = April 2008 | pmid = 17541511 | doi = 10.1007/s00726-007-0555-7 | s2cid = 312905 }} The Hexose Transporter proteins GLUT1, GLUT3 and GLUT4 transfer only the oxydized dehydroascorbic acid (DHA) form of vitamin C.{{cite journal | vauthors = Rumsey SC, Kwon O, Xu GW, Burant CF, Simpson I, Levine M | title = Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid | journal = The Journal of Biological Chemistry | volume = 272 | issue = 30 | pages = 18982–9 | date = July 1997 | pmid = 9228080 | doi = 10.1074/jbc.272.30.18982 | doi-access = free | title-link = doi }} The amount of DHA found in plasma and tissues under normal conditions is low, as cells rapidly reduce DHA to ascorbate.{{cite journal | vauthors = May JM, Qu ZC, Neel DR, Li X | title = Recycling of vitamin C from its oxidized forms by human endothelial cells | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1640 | issue = 2–3 | pages = 153–61 | date = May 2003 | pmid = 12729925 | doi = 10.1016/S0167-4889(03)00043-0 | doi-access = | title-link = doi }}

SVCTs are the predominant system for vitamin C transport within the body. In both vitamin C synthesizers (example: rat) and non-synthesizers (example: human) cells maintain ascorbic acid concentrations much higher than the approximately 50 micromoles/liter (μmol/L) found in plasma. For example, the ascorbic acid content of pituitary and adrenal glands can exceed 2,000 μmol/L, and muscle is at 200–300 μmol/L.{{cite journal | vauthors = Padayatty SJ, Levine M | title = Vitamin C: the known and the unknown and Goldilocks | journal = Oral Diseases | volume = 22 | issue = 6 | pages = 463–93 | date = September 2016 | pmid = 26808119 | pmc = 4959991 | doi = 10.1111/odi.12446 }} The known coenzymatic functions of ascorbic acid do not require such high concentrations, so there may be other, as yet unknown functions. A consequence of all this high concentration organ content is that plasma vitamin C is not a good indicator of whole-body status, and people may vary in the amount of time needed to show symptoms of deficiency when consuming a diet very low in vitamin C.

Excretion (via urine) is as ascorbic acid and metabolites. The fraction that is excreted as unmetabolized ascorbic acid increases as intake increases. In addition, ascorbic acid converts (reversibly) to DHA and from that compound non-reversibly to 2,3-diketogulonate and then oxalate. These three metabolites are also excreted via urine. During times of low dietary intake, vitamin C is reabsorbed by the kidneys rather than excreted. This salvage process delays onset of deficiency. Humans are better than guinea pigs at converting DHA back to ascorbate, and thus take much longer to become vitamin C deficient.

Most animals and plants are able to synthesize vitamin C through a sequence of enzyme-driven steps, which convert monosaccharides to vitamin C. Yeasts do not make {{sm|l}}-ascorbic acid but rather its stereoisomer, erythorbic acid.{{cite journal | vauthors = Branduardi P, Fossati T, Sauer M, Pagani R, Mattanovich D, Porro D | title = Biosynthesis of vitamin C by yeast leads to increased stress resistance | journal = PLOS ONE | volume = 2 | issue = 10 | pages = e1092 | date = October 2007 | pmid = 17971855 | pmc = 2034532 | doi = 10.1371/journal.pone.0001092 | bibcode = 2007PLoSO...2.1092B | doi-access = free | title-link = doi }} In plants, synthesis is accomplished through the conversion of mannose or galactose to ascorbic acid.{{cite journal | vauthors = Wheeler GL, Jones MA, Smirnoff N | title = The biosynthetic pathway of vitamin C in higher plants | journal = Nature | volume = 393 | issue = 6683 | pages = 365–9 | date = May 1998 | pmid = 9620799 | doi = 10.1038/30728 | bibcode = 1998Natur.393..365W | s2cid = 4421568 }}{{cite journal | url = http://orthomolecular.org/library/jom/1972/pdf/1972-v01n02%2603-p082.pdf | title = The natural history of ascorbic acid in the evolution of the mammals and primates and is significance for present-day man evolution of mammals and primates | vauthors = Stone I | year = 1972 | journal = Journal of Orthomolecular Psychiatry | volume = 1 | issue = 2 | pages = 82–9 | access-date = December 31, 2023 | archive-date = October 2, 2023 | archive-url = https://web.archive.org/web/20231002185424/http://orthomolecular.org/library/jom/1972/pdf/1972-v01n02%2603-p082.pdf | url-status = live }} In animals, the starting material is glucose. In some species that synthesize ascorbate in the liver (including mammals and perching birds), the glucose is extracted from glycogen; ascorbate synthesis is a glycogenolysis-dependent process.{{cite journal | vauthors = Bánhegyi G, Mándl J | title = The hepatic glycogenoreticular system | journal = Pathology & Oncology Research | volume = 7 | issue = 2 | pages = 107–10 | year = 2001 | pmid = 11458272 | doi = 10.1007/BF03032575 | citeseerx = 10.1.1.602.5659 | s2cid = 20139913 }} In humans and in animals that cannot synthesize vitamin C, the enzyme gulonolactone oxidase (GULO), which catalyzes the last step in the biosynthesis, is highly mutated and non-functional.{{cite journal | title = Biosynthesis of L-ascorbic acid in plants: new pathways for an old antioxidant | vauthors = Valpuesta V, Botella MA | journal = Trends in Plant Science | year = 2004 | volume = 9 | issue = 12 | pages = 573–7 | pmid = 15564123 | doi = 10.1016/j.tplants.2004.10.002 | bibcode = 2004TPS.....9..573V | url = http://www.bmbq.uma.es/lbbv/index_archivos/pdf/Valpuesta%202004.pdf | access-date = October 8, 2018 | archive-date = December 25, 2020 | archive-url = https://web.archive.org/web/20201225062850/http://www.bmbq.uma.es/lbbv/index_archivos/pdf/Valpuesta%202004.pdf | url-status = live }}{{cite journal | vauthors = Nishikimi M, Yagi K | title = Molecular basis for the deficiency in humans of gulonolactone oxidase, a key enzyme for ascorbic acid biosynthesis | journal = Am J Clin Nutr | volume = 54 | issue = 6 Suppl | pages = 1203S–8S | date = December 1991 | pmid = 1962571 | doi = 10.1093/ajcn/54.6.1203s| doi-access = free | title-link = doi }}{{cite journal | vauthors = Nishikimi M, Kawai T, Yagi K | title = Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species | journal = The Journal of Biological Chemistry | volume = 267 | issue = 30 | pages = 21967–72 | date = October 1992 | doi = 10.1016/S0021-9258(19)36707-9 | pmid = 1400507 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Ohta Y, Nishikimi M | title = Random nucleotide substitutions in primate nonfunctional gene for L-gulono-gamma-lactone oxidase, the missing enzyme in L-ascorbic acid biosynthesis | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1472 | issue = 1–2 | pages = 408–11 | date = October 1999 | pmid = 10572964 | doi = 10.1016/S0304-4165(99)00123-3 }}

There is some information on serum vitamin C concentrations maintained in animal species that are able to synthesize vitamin C. One study of several breeds of dogs reported an average of 35.9 μmol/L.{{cite journal |vauthors=Wang S, Berge GE, Sund RB |title=Plasma ascorbic acid concentrations in healthy dogs |journal=Res. Vet. Sci. |volume=71 |issue=1 |pages=33–5 |date=August 2001 |pmid=11666145 |doi=10.1053/rvsc.2001.0481 }} A report on goats, sheep and cattle reported ranges of 100–110, 265–270 and 160–350 μmol/L, respectively.{{cite journal |vauthors=Ranjan R, Ranjan A, Dhaliwal GS, Patra RC |s2cid=1674389 |title=l-Ascorbic acid (vitamin C) supplementation to optimize health and reproduction in cattle |journal=Vet Q |volume=32 |issue=3–4 |pages=145–50 |date=2012 |pmid=23078207 |doi=10.1080/01652176.2012.734640 }}

The biosynthesis of ascorbic acid in vertebrates starts with the formation of UDP-glucuronic acid. UDP-glucuronic acid is formed when UDP-glucose undergoes two oxidations catalyzed by the enzyme UDP-glucose 6-dehydrogenase. UDP-glucose 6-dehydrogenase uses the co-factor NAD⁺ as the electron acceptor. The transferase UDP-glucuronate pyrophosphorylase removes a UMP and glucuronokinase, with the cofactor ADP, removes the final phosphate leading to glucuronic acid. The aldehyde group of this compound is reduced to a primary alcohol using the enzyme glucuronate reductase and the cofactor NADPH, yielding {{sm|l}}-gulonic acid. This is followed by lactone formation{{Em dash}}utilizing the hydrolase gluconolactonase{{Em dash}}between the carbonyl on C1 and hydroxyl group on C4. {{sm|l}}-Gulonolactone then reacts with oxygen, catalyzed by the enzyme L-gulonolactone oxidase (which is nonfunctional in humans and other Haplorrhini primates; see Unitary pseudogenes) and the cofactor FAD+. This reaction produces 2-oxogulonolactone (2-keto-gulonolactone), which spontaneously undergoes enolization to form ascorbic acid.{{cite book | vauthors = Dewick PM | title = Medicinal natural products: a biosynthetic approach | edition = 3rd | year = 2009 | isbn = 978-0-470-74167-2 | publisher = John Wiley and Sons | page = 493}}{{cite journal | vauthors = Linster CL, Van Schaftingen E | title = Vitamin C. Biosynthesis, recycling and degradation in mammals | journal = The FEBS Journal | volume = 274 | issue = 1 | pages = 1–22 | date = January 2007 | pmid = 17222174 | doi = 10.1111/j.1742-4658.2006.05607.x | s2cid = 21345196 | doi-access = free | title-link = doi }} Reptiles and older orders of birds make ascorbic acid in their kidneys. Recent orders of birds and most mammals make ascorbic acid in their liver.

Some mammals have lost the ability to synthesize vitamin C, including simians and tarsiers, which together make up one of two major primate suborders, Haplorhini. This group includes humans. The other more primitive primates (Strepsirrhini) have the ability to make vitamin C. Synthesis does not occur in some species in the rodent family Caviidae, which includes guinea pigs and capybaras, but does occur in other rodents, including rats and mice.{{cite book | vauthors = Miller RE, Fowler ME | title = Fowler's zoo and wild animal medicine, volume 8 | page = 389 | url = https://books.google.com/books?id=llBcBAAAQBAJ&q=Caviidae+%22vitamin+C%22&pg=PA389 |access-date=2 June 2016 |url-status=live |archive-url=https://web.archive.org/web/20161207032904/https://books.google.com/books?id=llBcBAAAQBAJ&pg=PA389&lpg=PA389&dq=Caviidae+%22vitamin+C%22&source=bl&ots=ofF-Bu-mx-&sig=nPEZZ68O7v26lmGS9eAGfmaUZ1o&hl=en&sa=X&ved=0ahUKEwiIk471gInNAhUT0WMKHWlpAqAQ6AEISDAH#v=onepage&q=Caviidae%20%22vitamin%20C%22&f=false |archive-date=December 7, 2016 | isbn = 978-1-4557-7399-2 |date=2014 | publisher = Elsevier Health Sciences }}

Synthesis does not occur in most bat species,{{cite journal |doi=10.1016/0305-0491(80)90131-5 |title=Variation of l-gulonolactone oxidase activity in placental mammals |year=1980 |vauthors=Jenness R, Birney E, Ayaz K |journal=Comparative Biochemistry and Physiology B |volume=67 |issue=2 |pages=195–204 }} but there are at least two species, frugivorous bat Rousettus leschenaultii and insectivorous bat Hipposideros armiger, that retain (or regained) their ability of vitamin C production.{{cite journal | vauthors = Cui J, Pan YH, Zhang Y, Jones G, Zhang S | title = Progressive pseudogenization: vitamin C synthesis and its loss in bats | journal = Molecular Biology and Evolution | volume = 28 | issue = 2 | pages = 1025–31 | date = February 2011 | pmid = 21037206 | doi = 10.1093/molbev/msq286 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Cui J, Yuan X, Wang L, Jones G, Zhang S | title = Recent loss of vitamin C biosynthesis ability in bats | journal = PLOS ONE | volume = 6 | issue = 11 | pages = e27114 | date = Nov 2011 | pmid = 22069493 | pmc = 3206078 | doi = 10.1371/journal.pone.0027114 | doi-access = free | title-link = doi | bibcode = 2011PLoSO...627114C }} A number of species of passerine birds also do not synthesize, but not all of them, and those that do not are not clearly related; it has been proposed that the ability was lost separately a number of times in birds.{{cite journal |title=Can passerines synthesize vitamin C? | vauthors = Martinez del Rio C |journal= The Auk |date=July 1997 |volume=114 |issue=3 |pages=513–6 |jstor=4089257 |doi=10.2307/4089257 | doi-access = free | title-link = doi }} In particular, the ability to synthesize vitamin C is presumed to have been lost and then later re-acquired in at least two cases.{{cite journal | vauthors = Drouin G, Godin JR, Pagé B | title = The genetics of vitamin C loss in vertebrates | journal = Current Genomics | volume = 12 | issue = 5 | pages = 371–8 | date = August 2011 | pmid = 22294879 | pmc = 3145266 | doi = 10.2174/138920211796429736 }} The ability to synthesize vitamin{{nbsp}}C has also been lost in about 96% of extant fish{{cite book | vauthors = Berra TM |title=Freshwater fish distribution |url=https://books.google.com/books?id=K-1Ygw6XwFQC&pg=PA55 |year=2008 |publisher=University of Chicago Press |isbn=978-0-226-04443-9|page=55}} (the teleosts).

On a milligram consumed per kilogram of body weight basis, simian non-synthesizer species consume the vitamin in amounts 10 to 20 times higher than what is recommended by governments for humans.{{cite journal | vauthors = Milton K | title = Nutritional characteristics of wild primate foods: do the diets of our closest living relatives have lessons for us? | journal = Nutrition | volume = 15 | issue = 6 | pages = 488–98 | date = June 1999 | pmid = 10378206 | doi = 10.1016/S0899-9007(99)00078-7 | url = http://www.direct-ms.org/pdf/EvolutionPaleolithic/primaten.pdf | archive-url = https://web.archive.org/web/20170810090049/http://www.direct-ms.org/pdf/EvolutionPaleolithic/primaten.pdf | df = mdy-all | url-status = live | archive-date = 10 August 2017 | citeseerx = 10.1.1.564.1533}} This discrepancy constituted some of the basis of the controversy on human recommended dietary allowances being set too low. However, simian consumption does not indicate simian requirements. Merck's veterinary manual states that daily intake of vitamin C at 3–6 mg/kg prevents scurvy in non-human primates.{{cite web |url=https://www.msdvetmanual.com/exotic-and-laboratory-animals/nonhuman-primates/nutritional-diseases-of-nonhuman-primates |title=Nutritional diseases of nonhuman primates | vauthors = Parrott T |date=October 2022 |website=Merck Veterinary Manual |access-date=24 December 2023 |archive-date=December 24, 2023 |archive-url=https://web.archive.org/web/20231224173242/https://www.msdvetmanual.com/exotic-and-laboratory-animals/nonhuman-primates/nutritional-diseases-of-nonhuman-primates |url-status=live }} By way of comparison, across several countries, the recommended dietary intake for adult humans is in the range of 1–2 mg/kg.

Ascorbic acid is a common enzymatic cofactor in mammals used in the synthesis of collagen, as well as a powerful reducing agent capable of rapidly scavenging a number of reactive oxygen species (ROS). Given that ascorbate has these important functions, it is surprising that the ability to synthesize this molecule has not always been conserved. In fact, anthropoid primates, Cavia porcellus (guinea pigs), teleost fishes, most bats, and some passerine birds have all independently lost the ability to internally synthesize vitamin C in either the kidney or the liver.{{cite journal | vauthors = Lachapelle MY, Drouin G | title = Inactivation dates of the human and guinea pig vitamin C genes | journal = Genetica | volume = 139 | issue = 2 | pages = 199–207 | date = February 2011 | pmid = 21140195 | doi = 10.1007/s10709-010-9537-x | s2cid = 7747147 }} In all of the cases where genomic analysis was done on an ascorbic acid auxotroph, the origin of the change was found to be a result of loss-of-function mutations in the gene that encodes L-gulono-γ-lactone oxidase, the enzyme that catalyzes the last step of the ascorbic acid pathway outlined above.{{cite journal | vauthors = Yang H | s2cid = 14393449 | title = Conserved or lost: molecular evolution of the key gene GULO in vertebrate vitamin C biosynthesis | journal = Biochemical Genetics | volume = 51 | issue = 5–6 | pages = 413–25 | date = June 2013 | pmid = 23404229 | doi = 10.1007/s10528-013-9574-0 }} One explanation for the repeated loss of the ability to synthesize vitamin C is that it was the result of genetic drift; assuming that the diet was rich in vitamin{{nbsp}}C, natural selection would not act to preserve it.{{cite journal | vauthors = Zhang ZD, Frankish A, Hunt T, Harrow J, Gerstein M | title = Identification and analysis of unitary pseudogenes: historic and contemporary gene losses in humans and other primates | journal = Genome Biology | volume = 11 | issue = 3 | pages = R26 | date = 2010 | pmid = 20210993 | pmc = 2864566 | doi = 10.1186/gb-2010-11-3-r26 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Koshizaka T, Nishikimi M, Ozawa T, Yagi K | title = Isolation and sequence analysis of a complementary DNA encoding rat liver L-gulono-gamma-lactone oxidase, a key enzyme for L-ascorbic acid biosynthesis | journal = The Journal of Biological Chemistry | volume = 263 | issue = 4 | pages = 1619–21 | date = February 1988 | doi = 10.1016/S0021-9258(19)77923-X | pmid = 3338984 | doi-access = free | title-link = doi }}

In the case of the simians, it is thought that the loss of the ability to make vitamin C may have occurred much farther back in evolutionary history than the emergence of humans or even apes, since it evidently occurred soon after the appearance of the first primates, yet sometime after the split of early primates into the two major suborders Haplorrhini (which cannot make vitamin C) and its sister suborder of non-tarsier prosimians, the Strepsirrhini ("wet-nosed" primates), which retained the ability to make vitamin C.{{cite journal | vauthors = Pollock JI, Mullin RJ | title = Vitamin C biosynthesis in prosimians: evidence for the anthropoid affinity of Tarsius | journal = American Journal of Physical Anthropology | volume = 73 | issue = 1 | pages = 65–70 | date=1987 | pmid = 3113259 | doi = 10.1002/ajpa.1330730106 }} According to molecular clock dating, these two suborder primate branches parted ways about 63 to 60 million years ago.{{cite journal | vauthors = Poux C, Douzery EJ | title = Primate phylogeny, evolutionary rate variations, and divergence times: a contribution from the nuclear gene IRBP | journal = American Journal of Physical Anthropology | volume = 124 | issue = 1 | pages = 01–16 | date=2004 | pmid = 15085543 | doi = 10.1002/ajpa.10322 }} Approximately three to five million years later (58 million years ago), only a short time afterward from an evolutionary perspective, the infraorder Tarsiiformes, whose only remaining family is that of the tarsier (Tarsiidae), branched off from the other haplorrhines.{{cite journal | vauthors = Goodman M, Porter CA, Czelusniak J, Page SL, Schneider H, Shoshani J, Gunnell G, Groves CP | title = Toward a phylogenetic classification of Primates based on DNA evidence complemented by fossil evidence | journal = Molecular Phylogenetics and Evolution | volume = 9 | issue = 3 | pages = 585–98 | date=June 1998 | pmid = 9668008 | doi = 10.1006/mpev.1998.0495 | bibcode = 1998MolPE...9..585G | s2cid = 23525774 }}{{cite journal |vauthors=Porter CA, Page SL, Czelusniak J, Schneider H, Schneider MP, Sampaio I, Goodman M |s2cid=1851788 |title=Phylogeny and evolution of selected primates as determined by sequences of the ε-globin locus and 5′ flanking regions |journal=Int J Primatol |date= April 1997 |volume=18 |issue=2 |pages=261–95 |doi=10.1023/A:1026328804319 |hdl=2027.42/44561 |hdl-access=free }} Since tarsiers also cannot make vitamin C, this implies the mutation had already occurred, and thus must have occurred between these two marker points (63 to 58 million years ago).

It has also been noted that the loss of the ability to synthesize ascorbate strikingly parallels the inability to break down uric acid, also a characteristic of primates. Uric acid and ascorbate are both strong reducing agents. This has led to the suggestion that, in higher primates, uric acid has taken over some of the functions of ascorbate.{{cite journal | vauthors = Proctor P | s2cid = 4146946 | title = Similar functions of uric acid and ascorbate in man? | journal = Nature | volume = 228 | issue = 5274 | pages = 868 | date = 1970 | pmid = 5477017 | doi = 10.1038/228868a0 | bibcode = 1970Natur.228..868P | doi-access = free | title-link = doi }}

File:Vitamin C Biosynthesis in Plants.svg

There are many different biosynthesis pathways to ascorbic acid in plants. Most proceed through products of glycolysis and other metabolic pathways. For example, one pathway utilizes plant cell wall polymers. The principal plant ascorbic acid biosynthesis pathway seems to be via {{sm|l}}-galactose. The enzyme L-galactose 1-dehydrogenase catalyzes the overall oxidation to the lactone and isomerization of the lactone to the C4-hydroxyl group, resulting in {{sm|l}}-galactono-1,4-lactone. {{sm|l}}-Galactono-1,4-lactone then reacts with the mitochondrial flavoenzyme Galactonolactone dehydrogenase{{cite journal | vauthors = Leferink NG, van den Berg WA, van Berkel WJ | title = l-Galactono-gamma-lactone dehydrogenase from Arabidopsis thaliana, a flavoprotein involved in vitamin C biosynthesis | journal = The FEBS Journal | volume = 275 | issue = 4 | pages = 713–26 | date = February 2008 | pmid = 18190525 | doi = 10.1111/j.1742-4658.2007.06233.x | s2cid = 25096297 | doi-access = free | title-link = doi }} to produce ascorbic acid. {{sm|l}}-Ascorbic acid has a negative feedback on {{sm|l}}-galactose dehydrogenase in spinach.{{cite journal | vauthors = Mieda T, Yabuta Y, Rapolu M, Motoki T, Takeda T, Yoshimura K, Ishikawa T, Shigeoka S | title = Feedback inhibition of spinach L-galactose dehydrogenase by L-ascorbate | journal = Plant & Cell Physiology | volume = 45 | issue = 9 | pages = 1271–9 | date = September 2004 | pmid = 15509850 | doi = 10.1093/pcp/pch152 | doi-access = free | title-link = doi }} Ascorbic acid efflux by embryos of dicot plants is a well-established mechanism of iron reduction and a step obligatory for iron uptake.{{efn| Dicot plants transport only ferrous iron (Fe²⁺), but if the iron circulates as ferric complexes (Fe³⁺), it has to undergo a reduction before it can be actively transported. Plant embryos efflux high amounts of ascorbate that chemically reduce iron(III) from ferric complexes.{{cite journal | vauthors = Grillet L, Ouerdane L, Flis P, Hoang MT, Isaure MP, Lobinski R, Curie C, Mari S | title = Ascorbate efflux as a new strategy for iron reduction and transport in plants | journal = The Journal of Biological Chemistry | volume = 289 | issue = 5 | pages = 2515–25 | date = January 2014 | pmid = 24347170 | pmc = 3908387 | doi = 10.1074/jbc.M113.514828 | doi-access = free | title-link = doi }}}}

All plants synthesize ascorbic acid. Ascorbic acid functions as a cofactor for enzymes involved in photosynthesis, synthesis of plant hormones, as an antioxidant and regenerator of other antioxidants.{{cite journal | vauthors = Gallie DR | title = L-ascorbic acid: a multifunctional molecule supporting plant growth and development | journal = Scientifica | volume = 2013 | pages = 1–24 | year = 2013 | pmid = 24278786 | pmc = 3820358 | doi = 10.1155/2013/795964 | doi-access = free | title-link = doi }} Plants use multiple pathways to synthesize vitamin C. The major pathway starts with glucose, fructose or mannose (all simple sugars) and proceeds to {{sm|l}}-galactose, {{sm|l}}-galactonolactone and ascorbic acid. This biosynthesis is regulated following a diurnal rhythm. Enzyme expression peaks in the morning to supporting biosynthesis for when mid-day sunlight intensity demands high ascorbic acid concentrations.{{cite journal | vauthors = Mellidou I, Kanellis AK | title = Genetic control of ascorbic acid biosynthesis and recycling in horticultural crops | journal = Frontiers in Chemistry | volume = 5 | pages = 50 | year = 2017 | pmid = 28744455 | pmc = 5504230 | doi = 10.3389/fchem.2017.00050 | bibcode = 2017FrCh....5...50M | doi-access = free | title-link = doi }}{{cite journal | vauthors = Bulley S, Laing W | title = The regulation of ascorbate biosynthesis | journal = Current Opinion in Plant Biology | volume = 33 | pages = 15–22 | date = October 2016 | pmid = 27179323 | doi = 10.1016/j.pbi.2016.04.010 | series = SI: 33: Cell signalling and gene regulation 2016 | bibcode = 2016COPB...33...15B }} Minor pathways may be specific to certain parts of plants; these can be either identical to the vertebrate pathway (including the GLO enzyme), or start with inositol and get to ascorbic acid via {{sm|l}}-galactonic acid to {{sm|l}}-galactonolactone.

{{Main|Chemistry of ascorbic acid}}

Vitamin C can be produced from glucose by two main routes. The no longer utilized Reichstein process, developed in the 1930s, used a single fermentation followed by a purely chemical route. The modern two-step fermentation process, originally developed in China in the 1960s, uses additional fermentation to replace part of the later chemical stages. The Reichstein process and the modern two-step fermentation processes both use glucose as the starting material, convert that to sorbitol, and then to sorbose using fermentation.{{cite journal | vauthors = Eggersdorfer M, Laudert D, Létinois U, McClymont T, Medlock J, Netscher T, Bonrath W | title = One hundred years of vitamins-a success story of the natural sciences | journal = Angewandte Chemie | volume = 51 | issue = 52 | pages = 12960–12990 | date = December 2012 | pmid = 23208776 | doi = 10.1002/anie.201205886 }} The two-step fermentation process then converts sorbose to 2-keto-l-gulonic acid (KGA) through another fermentation step, avoiding an extra intermediate. Both processes yield approximately 60% vitamin C from the glucose starting point.{{cite web |url=http://www.competition-commission.org.uk/rep_pub/reports/2001/fulltext/456a4.2.pdf |archive-url=http://webarchive.nationalarchives.gov.uk/20120119194657/http://www.competition-commission.org.uk/rep_pub/reports/2001/fulltext/456a4.2.pdf |url-status=usurped |archive-date=January 19, 2012 |title=The production of vitamin C |access-date=February 20, 2007 |year=2001 |publisher=Competition Commission }} Researchers are exploring means for one-step fermentation.{{cite journal |vauthors=Zhou M, Bi Y, Ding M, Yuan Y |title=One-step biosynthesis of vitamin C in Saccharomyces cerevisiae |journal=Front Microbiol |volume=12 |issue= |pages=643472 |date=2021 |pmid=33717042 |pmc=7947327 |doi=10.3389/fmicb.2021.643472 |url= | doi-access = free | title-link = doi }}{{cite journal |vauthors=Tian YS, Deng YD, Zhang WH, Yu-Wang, Xu J, Gao JJ, Bo-Wang, Fu XY, Han HJ, Li ZJ, Wang LJ, Peng RH, Yao QH |title=Metabolic engineering of Escherichia coli for direct production of vitamin C from D-glucose |journal=Biotechnol Biofuels Bioprod |volume=15 |issue=1 |pages=86 |date=August 2022 |pmid=35996146 |pmc=9396866 |doi=10.1186/s13068-022-02184-0 |url= | doi-access = free | title-link = doi |bibcode=2022BBB....15...86T }}

China produces about 70% of the global vitamin C market. The rest is split among European Union, India and North America. The global market is expected to exceed 141 thousand metric tons in 2024.{{cite press release |url=https://www.globenewswire.com/en/news-release/2022/11/08/2550571/0/en/Global-Vitamin-C-Market-Size-Share-to-Surpass-1-8-Bn-by-2028-China-Produces-80-of-Commercial-Vitamin-C-Vantage-Market-Research.html |title=Vantage market research: global vitamin C market size & share to surpass $1.8 Bn by 2028 |date=November 8, 2022 |website=Globe Newswire |access-date=December 21, 2023 |archive-date=December 21, 2023 |archive-url=https://web.archive.org/web/20231221215223/https://www.globenewswire.com/en/news-release/2022/11/08/2550571/0/en/Global-Vitamin-C-Market-Size-Share-to-Surpass-1-8-Bn-by-2028-China-Produces-80-of-Commercial-Vitamin-C-Vantage-Market-Research.html |url-status=live }} Cost per metric ton (1000 kg) in US dollars was $2,220 in Shanghai, $2,850 in Hamburg and $3,490 in the US.{{cite web |url=https://www.chemanalyst.com/Pricing-data/vitamin-c-1258 |title=Vitamin C price trend and forecast |date=September 2023 |website=ChemAnalyst |access-date=December 21, 2023 |archive-date=December 21, 2023 |archive-url=https://web.archive.org/web/20231221215224/https://www.chemanalyst.com/Pricing-data/vitamin-c-1258 |url-status=live }}

File:VitaminSupplementPills2.jpg

Vitamin C has a definitive role in treating scurvy, which is a disease caused by vitamin{{nbsp}}C deficiency. Beyond that, a role for vitamin{{nbsp}}C as prevention or treatment for various diseases is disputed, with reviews often reporting conflicting results. No effect of vitamin{{nbsp}}C supplementation reported for overall mortality.{{cite journal | vauthors = Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C | title = Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases | journal = The Cochrane Database of Systematic Reviews | volume = 2012 | issue = 3 | pages = CD007176 | date = March 2012 | pmid = 22419320 | doi = 10.1002/14651858.CD007176.pub2 | pmc = 8407395 | hdl = 10138/136201 | hdl-access = free }} It is on the World Health Organization's List of Essential Medicines{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }} and on the World Health Organization's Model Forumulary.{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 978-92-4-154765-9 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free }} In 2022, it was the 226th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}{{cite web | title = Ascorbic Acid Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/AscorbicAcid | access-date = 30 August 2024 }}

{{Main|Scurvy}}

Scurvy is a disease resulting from a deficiency of vitamin C. Without this vitamin, collagen made by the body is too unstable to perform its function and several other enzymes in the body do not operate correctly. Early symptoms are malaise and lethargy, progressing to shortness of breath, bone pain and susceptibility to bruising. As the disease progressed, it is characterized by spots on and bleeding under the skin and bleeding gums. The skin lesions are most abundant on the thighs and legs. A person with the ailment looks pale, feels depressed, and is partially immobilized. In advanced scurvy there is fever, old wounds may become open and suppurating, loss of teeth, convulsions and, eventually, death. Until quite late in the disease the damage is reversible, as healthy collagen replaces the defective collagen with vitamin{{nbsp}}C repletion.{{cite journal | vauthors = Magiorkinis E, Beloukas A, Diamantis A | title = Scurvy: past, present and future. | journal = The European Journal of Internal Medicine | volume = 22 | issue = 2 | pages = 147–52 | date = April 2011 | pmid = 21402244 | doi = 10.1016/j.ejim.2010.10.006}}

Notable human dietary studies of experimentally induced scurvy were conducted on conscientious objectors during World War II in Britain and on Iowa state prisoners in the late 1960s to the 1980s. Men in the prison study developed the first signs of scurvy about four weeks after starting the vitamin C-free diet, whereas in the earlier British study, six to eight months were required, possibly due to the pre-loading of this group with a 70 mg/day supplement for six weeks before the scorbutic diet was fed. Men in both studies had blood levels of ascorbic acid too low to be accurately measured by the time they developed signs of scurvy. These studies both reported that all obvious symptoms of scurvy could be completely reversed by supplementation of only 10 mg a day.{{cite journal | vauthors = Hodges RE, Baker EM, Hood J, Sauberlich HE, March SC | title = Experimental scurvy in man | journal = The American Journal of Clinical Nutrition | volume = 22 | issue = 5 | pages = 535–48 | date = May 1969 | pmid = 4977512 | doi = 10.1093/ajcn/22.5.535}}{{cite journal | vauthors = Pemberton J | title = Medical experiments carried out in Sheffield on conscientious objectors to military service during the 1939-45 war | journal = International Journal of Epidemiology | volume = 35 | issue = 3 | pages = 556–8 | date = June 2006 | pmid = 16510534 | doi = 10.1093/ije/dyl020 | doi-access = free | title-link = doi }} Treatment of scurvy can be with vitamin{{nbsp}}C-containing foods or dietary supplements or injection.{{rp|page=101}}

People in sepsis may have micronutrient deficiencies, including low levels of vitamin C.{{cite journal | vauthors = Belsky JB, Wira CR, Jacob V, Sather JE, Lee PJ | title = A review of micronutrients in sepsis: the role of thiamine, L-carnitine, vitamin C, selenium and vitamin D | journal = Nutrition Research Reviews | volume = 31 | issue = 2 | pages = 281–90 | date = December 2018 | pmid = 29984680 | doi = 10.1017/S0954422418000124 | s2cid = 51599526 }} An intravenous intake of doses much higher than the RDA, such as {{val|3|u=g/day}} or more, appears to be needed to maintain normal plasma concentrations in people with sepsis, as the body's demand for vitamin C may increase significantly due to the heightened inflammatory response and oxidative stress.{{cite journal |vauthors=Langlois PL, Manzanares W, Adhikari NK, Lamontagne F, Stoppe C, Hill A, Heyland DK |title=Vitamin C Administration to the Critically Ill: A Systematic Review and Meta-Analysis |journal=JPEN J Parenter Enteral Nutr |volume=43 |issue=3 |pages=335–346 |date=March 2019 |pmid=30452091 |doi=10.1002/jpen.1471 |url=}}{{cite journal |vauthors=Berger MM, Oudemans-van Straaten HM |title=Vitamin C supplementation in the critically ill patient |journal=Curr Opin Clin Nutr Metab Care |volume=18 |issue=2 |pages=193–201 |date=March 2015 |pmid=25635594 |doi=10.1097/MCO.0000000000000148 |s2cid=37895257 |url=}} Sepsis mortality may be reduced with administration of intravenous vitamin C.{{cite journal |vauthors=Xu C, Yi T, Tan S, Xu H, Hu Y, Ma J, Xu J |title=Association of oral or intravenous vitamin C supplementation with mortality: A systematic review and meta-analysis |journal=Nutrients |volume=15 |issue=8 |date=April 2023 |page=1848 |pmid=37111066 |pmc=10146309 |doi=10.3390/nu15081848 |doi-access=free |url=}}{{cite journal |vauthors=Liang H, Mu Q, Sun W, Liu L, Qiu S, Xu Z, Cui Y, Yan Y, Sun T |title=Effect of intravenous vitamin C on adult septic patients: a systematic review and meta-analysis |journal=Front Nutr |volume=10 |issue= |pages=1211194 |date=2023 |pmid=37599680 |pmc=10437115 |doi=10.3389/fnut.2023.1211194 |doi-access=free |url=}}

File:Linus Pauling.jpg advocated taking vitamin C for the common cold in a 1970 book.]]

Research on vitamin{{nbsp}}C in the common cold has been divided into effects on prevention, duration, and severity. Oral intakes of more than 200 mg/day taken on a regular basis was not effective in prevention of the common cold. Restricting analysis to trials that used at least 1000 mg/day also saw no prevention benefit. However, taking a vitamin{{nbsp}}C supplement on a regular basis did reduce the average duration of the illness by 8% in adults and 14% in children, and also reduced the severity of colds.{{cite journal |vauthors = Hemilä H, Chalker E |title = Vitamin C for preventing and treating the common cold |journal = The Cochrane Database of Systematic Reviews |issue = 1 |pages = CD000980 |date = January 2013 |volume = 2013 |pmid = 23440782 |doi = 10.1002/14651858.CD000980.pub4 |pmc = 1160577}} Vitamin C taken on a regular basis reduced the duration of severe symptoms but had no effect on the duration of mild symptoms.{{cite journal |vauthors=Hemilä H, Chalker E |title=Vitamin C reduces the severity of common colds: a meta-analysis |journal=BMC Public Health |volume=23 |issue=1 |pages=2468 |date=December 2023 |pmid=38082300 |pmc=10712193 |doi=10.1186/s12889-023-17229-8 |url= | doi-access = free | title-link = doi }} Therapeutic use, meaning that the vitamin was not started unless people started to feel the beginnings of a cold, had no effect on the duration or severity of the illness.

Vitamin C distributes readily in high concentrations into immune cells, promotes natural killer cell activities, promotes lymphocyte proliferation, and is depleted quickly during infections, effects suggesting a prominent role in immune system function.{{cite journal | vauthors = Wintergerst ES, Maggini S, Hornig DH | s2cid = 21756498 | title = Immune-enhancing role of vitamin C and zinc and effect on clinical conditions | journal = Annals of Nutrition & Metabolism | volume = 50 | issue = 2 | pages = 85–94 | year = 2006 | pmid = 16373990 | doi = 10.1159/000090495 | url = http://doc.rero.ch/record/303675/files/S0029665108006927.pdf | access-date = August 25, 2019 | archive-date = July 22, 2018 | archive-url = https://web.archive.org/web/20180722160530/http://doc.rero.ch/record/303675/files/S0029665108006927.pdf | url-status = live }} The European Food Safety Authority concluded there is a cause and effect relationship between the dietary intake of vitamin C and functioning of a normal immune system in adults and in children under three years of age.{{cite journal |author=EFSA Panel on Dietetic Products, Nutrition and Allergies |title=Scientific Opinion on the substantiation of health claims related to vitamin C and protection of DNA, proteins and lipids from oxidative damage (ID 129, 138, 143, 148), antioxidant function of lutein (ID 146), maintenance of vision (ID 141, 142), collagen formation (ID 130, 131, 136, 137, 149), function of the nervous system (ID 133), function of the immune system (ID 134), function of the immune system during and after extreme physical exercise (ID 144), non-haem iron absorption (ID 132, 147), energy-yielding metabolism (ID 135), and relief in case of irritation in the upper respiratory tract (ID 1714, 1715) pursuant to Article 13(1) of Regulation (EC) No 1924/2006 |journal=EFSA Journal |volume=7 |issue=9 |year=2009 |page=1226 |doi=10.2903/j.efsa.2009.1226| doi-access = free | title-link = doi }}{{cite journal |author=EFSA Panel on Dietetic Products, Nutrition and Allergies |title=Vitamin C and contribution to the normal function of the immune system: evaluation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 |journal=EFSA Journal |year=2015 |volume=13 |issue=11 |page=4298 |doi=10.2903/j.efsa.2015.4298| doi-access = free | title-link = doi |hdl=11380/1296052 |hdl-access=free }}

{{see also|COVID-19 drug repurposing research#Vitamin C|COVID-19 misinformation#Vitamin C}}

During March through July 2020, vitamin C was the subject of more US FDA warning letters than any other ingredient for claims for prevention and/or treatment of COVID-19.{{cite journal |vauthors=Bramstedt KA |title=Unicorn poo and blessed waters: COVID-19 quackery and FDA Warning Letters |journal=Ther Innov Regul Sci |date=October 2020 |volume=55 |issue=1 |pages=239–44 |pmid=33001378 |pmc=7528445 |doi=10.1007/s43441-020-00224-1 }} In April 2021, the US National Institutes of Health (NIH) COVID-19 Treatment Guidelines stated that "there are insufficient data to recommend either for or against the use of vitamin{{nbsp}}C for the prevention or treatment of COVID-19."{{cite web |title=Vitamin C |url=https://www.covid19treatmentguidelines.nih.gov/therapies/supplements/vitamin-c/ |website=COVID-19 Treatment Guidelines |date=April 21, 2021 |access-date=January 2, 2022 |archive-date=November 20, 2021 |archive-url=https://web.archive.org/web/20211120131306/https://www.covid19treatmentguidelines.nih.gov/therapies/supplements/vitamin-c/ |url-status=live }} In an update posted December 2022, the NIH position was unchanged:

• There is insufficient evidence for the COVID-19 Treatment Guidelines Panel (the Panel) to recommend either for or against the use of vitamin C for the treatment of COVID-19 in nonhospitalized patients.
• There is insufficient evidence for the Panel to recommend either for or against the use of vitamin C for the treatment of COVID-19 in hospitalized patients.{{cite web |url=https://www.covid19treatmentguidelines.nih.gov/therapies/supplements/vitamin-c/ |title=COVID-19 treatment guidelines |date=December 26, 2022 |website=U.S. National Institutes of Health |access-date=December 18, 2023 |archive-date=November 20, 2021 |archive-url=https://web.archive.org/web/20211120131306/https://www.covid19treatmentguidelines.nih.gov/therapies/supplements/vitamin-c/ |url-status=live }}

For people hospitalized with severe COVID-19 there are reports of a significant reduction in the risk of all-cause, in-hospital mortality with the administration of vitamin C relative to no vitamin C. There were no significant differences in ventilation incidence, hospitalization duration or length of intensive care unit stay between the two groups. The majority of the trials incorporated into these meta-analyses used intravenous administration of the vitamin.{{cite journal |vauthors=Kow CS, Hasan SS, Ramachandram DS |title=The effect of vitamin C on the risk of mortality in patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials | journal=Inflammopharmacology |volume=31 |issue=6 |pages=3357–62 |date=December 2023 |pmid= 37071316|pmc=10111321 |doi=10.1007/s10787-023-01200-5 |url=}}{{cite journal |vauthors=Huang WY, Hong J, Ahn SI, Han BK, Kim YJ |title=Association of vitamin C treatment with clinical outcomes for COVID-19 patients: A systematic review and meta-analysis |journal=Healthcare |volume=10 |issue=12 |date=December 2022 |page=2456 |pmid=36553979 |pmc=9777834 |doi=10.3390/healthcare10122456 |url= | doi-access = free | title-link = doi }}{{cite journal |vauthors=Olczak-Pruc M, Swieczkowski D, Ladny JR, Pruc M, Juarez-Vela R, Rafique Z, Peacock FW, Szarpak L |title=Vitamin C supplementation for the treatment of COVID-19: A systematic review and meta-analysis |journal=Nutrients |volume=14 |issue=19 |date=October 2022 |page=4217 |pmid=36235869 |pmc=9570769 |doi=10.3390/nu14194217 |url= | doi-access = free | title-link = doi }} Acute kidney injury was lower in people treated with vitamin C treatment. There were no differences in the frequency of other adverse events due to the vitamin. The conclusion was that further large-scale studies are needed to affirm its mortality benefits before issuing updated guidelines and recommendations.

Higher vitamin C intake appears to reduce the risk for lung cancer.{{cite journal | vauthors = Luo J, Shen L, Zheng D | title = Association between vitamin C intake and lung cancer: a dose-response meta-analysis | journal = Scientific Reports | volume = 4 | pages = 6161 | date = 2014 | pmid = 25145261 | pmc = 5381428 | doi = 10.1038/srep06161 | bibcode = 2014NatSR...4.6161L }} There is no evidence that vitamin C supplementation reduces the risk of prostate cancer,{{cite journal | vauthors = Stratton J, Godwin M | title = The effect of supplemental vitamins and minerals on the development of prostate cancer: a systematic review and meta-analysis | journal = Family Practice | volume = 28 | issue = 3 | pages = 243–52 | date = June 2011 | pmid = 21273283 | doi = 10.1093/fampra/cmq115 | doi-access = free | title-link = doi }} colorectal cancer{{cite journal |vauthors=Heine-Bröring RC, Winkels RM, Renkema JM, Kragt L, van Orten-Luiten AC, Tigchelaar EF, Chan DS, Norat T, Kampman E |title=Dietary supplement use and colorectal cancer risk: a systematic review and meta-analyses of prospective cohort studies |journal=Int J Cancer |volume=136 |issue=10 |pages=2388–401 |date=May 2015 |pmid=25335850 |doi=10.1002/ijc.29277 |s2cid=44706004 |url=}} or breast cancer.{{cite journal | vauthors = Fulan H, Changxing J, Baina WY, Wencui Z, Chunqing L, Fan W, Dandan L, Dianjun S, Tong W, Da P, Yashuang Z | title = Retinol, vitamins A, C, and E and breast cancer risk: a meta-analysis and meta-regression | journal = Cancer Causes & Control | volume = 22 | issue = 10 | pages = 1383–96 | date = October 2011 | pmid = 21761132 | doi = 10.1007/s10552-011-9811-y | s2cid = 24867472 }}

There is no evidence that vitamin C supplementation decreases the risk cardiovascular disease,{{cite journal | vauthors = Al-Khudairy L, Flowers N, Wheelhouse R, Ghannam O, Hartley L, Stranges S, Eres K | title = Vitamin C supplementation for the primary prevention of cardiovascular disease | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | pages = CD011114 | date = March 2017 | issue = 3 | pmid = 28301692 | doi = 10.1002/14651858.CD011114.pub2 | pmc = 6464316 }} although there may be an association between higher circulating vitamin C levels or dietary vitamin C and a lower risk of stroke.{{cite journal | vauthors = Chen GC, Lu DB, Pang Z, Liu QF | title = Vitamin C intake, circulating vitamin C and risk of stroke: a meta-analysis of prospective studies | journal = J Am Heart Assoc | volume = 2 | issue = 6 | pages = e000329 | date = November 2013 | pmid = 24284213 | pmc = 3886767 | doi = 10.1161/JAHA.113.000329 }} There is a positive effect of vitamin C on endothelial dysfunction when taken at doses greater than 500 mg per day. (The endothelium is a layer of cells that line the interior surface of blood vessels.){{cite journal | vauthors = Ashor AW, Lara J, Mathers JC, Siervo M | title = Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomized controlled trials | journal = Atherosclerosis | volume = 235 | issue = 1 | pages = 9–20 | date = July 2014 | pmid = 24792921 | doi = 10.1016/j.atherosclerosis.2014.04.004 }}

Serum vitamin C was reported to be 15.13 μmol/L lower in people with hypertension compared to normotensives. The vitamin was inversely associated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP).{{cite journal |vauthors=Ran L, Zhao W, Tan X, Wang H, Mizuno K, Takagi K, Zhao Y, Bu H |title=Association between serum vitamin C and the blood pressure: A systematic review and meta-analysis of observational studies |journal=Cardiovasc Ther |volume=2020 |issue= |pages=4940673 |date=April 2020 |pmid=32426036 |pmc=7211237 |doi=10.1155/2020/4940673 |url= | doi-access = free | title-link = doi }} Oral supplementation of the vitamin resulted in a very modest but statistically significant decrease in SBP in people with hypertension.{{cite journal |vauthors=Guan Y, Dai P, Wang H |title=Effects of vitamin C supplementation on essential hypertension: A systematic review and meta-analysis |journal=Medicine (Baltimore) |volume=99 |issue=8 |pages=e19274 |date=February 2020 |pmid=32080138 |pmc=7034722 |doi=10.1097/MD.0000000000019274 |url=}}{{cite journal |vauthors=Lbban E, Kwon K, Ashor A, Stephan B, Idris I, Tsintzas K, Siervo M |title=Vitamin C supplementation showed greater effects on systolic blood pressure in hypertensive and diabetic patients: an updated systematic review and meta-analysis of randomized clinical trials |journal=Int J Food Sci Nutr |volume=74 |issue=8 |pages=814–25 |date=December 2023 |pmid=37791386 |doi=10.1080/09637486.2023.2264549 |s2cid=263621742 |url=https://figshare.com/articles/journal_contribution/24241426 |access-date=December 23, 2023 |archive-date=January 21, 2024 |archive-url=https://web.archive.org/web/20240121044305/https://figshare.com/articles/journal_contribution/Vitamin_C_supplementation_showed_greater_effects_on_systolic_blood_pressure_in_hypertensive_and_diabetic_patients_an_updated_systematic_review_and_meta-analysis_of_randomised_clinical_trials/24241426 |url-status=live }} The proposed explanation is that vitamin C increases intracellular concentrations of tetrahydrobiopterin, an endothelial nitric oxide synthase cofactor that promotes the production of nitric oxide, which is a potent vasodilator. Vitamin C supplementation might also reverse the nitric oxide synthase inhibitor NG-monomethyl-L-arginine 1, and there is also evidence cited that vitamin C directly enhances the biological activity of nitric oxide

There are contradictory reviews. From one, vitamin C supplementation cannot be recommended for management of type 2 diabetes.{{cite journal |vauthors=Mason SA, Keske MA, Wadley GD |title=Effects of vitamin C supplementation on glycemic control and cardiovascular risk factors in people With type 2 diabetes: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials |journal=Diabetes Care |volume=44 |issue=2 |pages=618–30 |date=February 2021 |pmid=33472962 |doi=10.2337/dc20-1893 |url=https://diabetesjournals.org/care/article/44/2/618/35482/Effects-of-Vitamin-C-Supplementation-on-Glycemic |doi-access=free |title-link=doi |hdl=10536/DRO/DU:30147432 |hdl-access=free |access-date=December 21, 2023 |archive-date=January 21, 2024 |archive-url=https://web.archive.org/web/20240121044253/https://diabetesjournals.org/care/article/44/2/618/35482/Effects-of-Vitamin-C-Supplementation-on-Glycemic |url-status=live }} However, another reported that supplementation with high doses of vitamin C can decrease blood glucose, insulin and hemoglobin A1c.{{cite journal |vauthors=Nosratabadi S, Ashtary-Larky D, Hosseini F, Namkhah Z, Mohammadi S, Salamat S, Nadery M, Yarmand S, Zamani M, Wong A, Asbaghi O |title=The effects of vitamin C supplementation on glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis |journal=Diabetes and Metabolic Syndrome |volume=17 |issue=8 |pages=102824 |date=August 2023 |pmid=37523928 |doi=10.1016/j.dsx.2023.102824 |s2cid=259581695 }}

One of the causes of iron-deficiency anemia is reduced absorption of iron. Iron absorption can be enhanced through ingestion of vitamin C alongside iron-containing food or supplements. Vitamin C helps to keep iron in the reduced ferrous state, which is more soluble and more easily absorbed. It also chelates iron into a soluble complex.{{cite journal | vauthors = DeLoughery TG | title = Iron Deficiency Anemia | journal = The Medical Clinics of North America | volume = 101 | issue = 2 | pages = 319–332 | date = March 2017 | pmid = 28189173 | doi = 10.1016/j.mcna.2016.09.004 | type = Review }} It specifically helps the absorption of non-heme iron,{{cite journal | vauthors = Heffernan A, Evans C, Holmes M, Moore J |title=The Regulation of Dietary Iron Bioavailability by Vitamin C: A Systematic Review and Meta-Analysis |journal=Proceedings of the Nutrition Society |date=2017 |volume=76 |issue=OCE4 |doi=10.1017/S0029665117003445}} which is found in non-meat sources and absorbed via DMT1.

Lower plasma vitamin C concentrations were reported in people with Alzheimer's disease. Reviews do not present reporting on supplement intervention clinical trials.{{cite journal | vauthors = Harrison FE | title = A critical review of vitamin C for the prevention of age-related cognitive decline and Alzheimer's disease | journal = Journal of Alzheimer's Disease | volume = 29 | issue = 4 | pages = 711–26 | year = 2012 | pmid = 22366772 | pmc = 3727637 | doi = 10.3233/JAD-2012-111853 }}{{cite journal |vauthors=Hamid M, Mansoor S, Amber S, Zahid S |title=A quantitative meta-analysis of vitamin C in the pathophysiology of Alzheimer's disease |journal=Front Aging Neurosci |volume=14 |issue= |pages=970263 |date=2022 |pmid=36158537 |pmc=9490219 |doi=10.3389/fnagi.2022.970263 |doi-access=free |url=}}

Higher dietary intake of vitamin C was associated with lower risk of age-related cataracts.{{cite journal |vauthors=Sideri O, Tsaousis KT, Li HJ, Viskadouraki M, Tsinopoulos IT |title=The potential role of nutrition on lens pathology: a systematic review and meta-analysis |journal=Surv Ophthalmol |volume=64 |issue=5 |pages=668–78 |date=2019 |pmid=30878580 |doi=10.1016/j.survophthal.2019.03.003 |s2cid=81981938 |url=}}{{cite journal |vauthors=Jiang H, Yin Y, Wu CR, Liu Y, Guo F, Li M, Ma L |title=Dietary vitamin and carotenoid intake and risk of age-related cataract |journal=Am J Clin Nutr |volume=109 |issue=1 |pages=43–54 |date=January 2019 |pmid=30624584 |doi=10.1093/ajcn/nqy270 |url=|doi-access=free }} Vitamin C supplementation did not prevent age-related macular degeneration.{{cite journal |vauthors=Evans JR, Lawrenson JG |title=Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration |journal=Cochrane Database Syst Rev |volume=2017 |issue=7 |pages=CD000253 |date=July 2017 |pmid=28756617 |pmc=6483250 |doi=10.1002/14651858.CD000253.pub4 |url=}}

Low intake and low serum concentration were associated with greater progression of periodontal disease.{{cite journal |vauthors=Mi N, Zhang M, Ying Z, Lin X, Jin Y |title=Vitamin intake and periodontal disease: a meta-analysis of observational studies |journal=BMC Oral Health |volume=24 |issue=1 |pages=117 |date=January 2024 |pmid=38245765 |pmc=10799494 |doi=10.1186/s12903-024-03850-5 |doi-access=free |url=}}{{cite journal |vauthors=Tada A, Miura H |title=The relationship between vitamin C and periodontal diseases: A systematic review |journal=Int J Environ Res Public Health |volume=16 |issue=14 |date=July 2019 |page=2472 |pmid=31336735 |pmc=6678404 |doi=10.3390/ijerph16142472 |doi-access=free |url=}}

Oral intake of dietary supplements vitamin C in excess of requirements is poorly absorbed,{{cite web |title=Vitamin C: Fact sheet for health professionals |url=https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/ |publisher=Office of Dietary Supplements, US National Institutes of Health |date=March 26, 2021 |accessdate=25 February 2024 |archive-date=July 30, 2017 |archive-url=https://web.archive.org/web/20170730052126/https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/ |url-status=live }} and excess amounts in the blood are rapidly excreted in the urine, so it exhibits low acute toxicity. More than two to three grams, consumed orally, may cause nausea, abdominal cramps and diarrhea. These effects are attributed to the osmotic effect of unabsorbed vitamin C passing through the intestine.{{rp|page=156}} In theory, high vitamin C intake may cause excessive absorption of iron. A summary of reviews of supplementation in healthy subjects did not report this problem, but left as untested the possibility that individuals with hereditary hemochromatosis might be adversely affected.{{rp|page=158}}

There is a longstanding belief among the mainstream medical community that vitamin C increases risk of kidney stones.{{cite journal | vauthors = Goodwin JS, Tangum MR | title = Battling quackery: attitudes about micronutrient supplements in American academic medicine | journal = Archives of Internal Medicine | volume = 158 | issue = 20 | pages = 2187–91 | date = November 1998 | pmid = 9818798 | doi = 10.1001/archinte.158.20.2187 }} "Reports of kidney stone formation associated with excess ascorbic acid intake are limited to individuals with renal disease".{{rp|pages=156–157}} A 2003 review stated that "data from epidemiological studies do not support an association between excess ascorbic acid intake and kidney stone formation in apparently healthy individuals",{{cite journal | vauthors = Naidu KA | title = Vitamin C in human health and disease is still a mystery? An overview | journal = Nutrition Journal | volume = 2 | issue = 7 | pages = 7 | date = August 2003 | pmid = 14498993 | pmc = 201008 | doi = 10.1186/1475-2891-2-7 | url = http://www.nutritionj.com/content/pdf/1475-2891-2-7.pdf | archive-url = https://web.archive.org/web/20120918153239/http://www.nutritionj.com/content/pdf/1475-2891-2-7.pdf | df = mdy-all | url-status = live | archive-date = September 18, 2012 | doi-access = free | title-link = doi }} although one large, multi-year trial published in 2013 did report a nearly two-fold increase in kidney stones in men who regularly consumed a vitamin C supplement.{{cite journal | vauthors = Thomas LD, Elinder CG, Tiselius HG, Wolk A, Akesson A | title = Ascorbic acid supplements and kidney stone incidence among men: a prospective study | journal = JAMA Internal Medicine | volume = 173 | issue = 5 | pages = 386–8 | date = March 2013 | pmid = 23381591 | doi = 10.1001/jamainternmed.2013.2296 | doi-access = free | title-link = doi }}

There is extensive research on the purported benefits of intravenous vitamin C for treatment of sepsis,{{cite journal |vauthors=Liang B, Su J, Shao H, Chen H, Xie B |title=The outcome of IV vitamin C therapy in patients with sepsis or septic shock: a meta-analysis of randomized controlled trials |journal=Crit Care |volume=27 |issue=1 |pages=109 |date=March 2023 |pmid=36915173 |pmc=10012592 |doi=10.1186/s13054-023-04392-y |url= | doi-access = free | title-link = doi }} severe COVID-19 and cancer.{{cite journal |vauthors=Jacobs C, Hutton B, Ng T, Shorr R, Clemons M |date=February 2015 |title=Is there a role for oral or intravenous ascorbate (vitamin C) in treating patients with cancer? A systematic review |journal=The Oncologist |volume=20 |issue=2 |pages=210–23 |doi=10.1634/theoncologist.2014-0381 |pmc=4319640 |pmid=25601965}} Reviews list trials with doses as high as 24 grams per day. Concerns about possible adverse effects are that intravenous high-dose vitamin C leads to a supraphysiological level of vitamin C followed by oxidative degradation to dehydroascorbic acid and hence to oxalate, increasing the risk of oxalate kidney stones and oxalate nephropathy. The risk may be higher in people with renal impairment, as kidneys efficiently excrete excess vitamin C. Second, treatment with high dose vitamin C should be avoided in patients with glucose-6-phosphate dehydrogenase deficiency as it can lead to acute hemolysis. Third, treatment might interfere with the accuracy of glucometer measurement of blood glucose levels, as both vitamin C and glucose have similar molecular structure, which could lead to false high blood glucose readings. Despite all these concerns, meta-analyses of patients in intensive care for sepsis, septic shock, COVID-19 and other acute conditions reported no increase in new-onset kidney stones, acute kidney injury or requirement for renal replacement therapy for patients receiving short-term, high-dose, intravenous vitamin C treatment. This suggests that intravenous vitamin C is safe under these short-term applications.{{cite journal |vauthors=Shrestha DB, Budhathoki P, Sedhai YR, Mandal SK, Shikhrakar S, Karki S, Baniya RK, Kashiouris MG, Qiao X, Fowler AA |title=Vitamin C in critically ill patients: An updated systematic review and meta-analysis |journal=Nutrients |volume=13 |issue=10 |date=October 2021 |page=3564 |pmid=34684565 |pmc=8539952 |doi=10.3390/nu13103564 | doi-access = free | title-link = doi |url=}}{{cite journal |vauthors=Holford P, Carr AC, Zawari M, Vizcaychipi MP |title=Vitamin C intervention for critical COVID-19: A pragmatic review of the current level of evidence |journal=Life |volume=11 |issue=11 |date=November 2021 |page=1166 |pmid=34833042 |pmc=8624950 |doi=10.3390/life11111166 | doi-access = free | title-link = doi |bibcode=2021Life...11.1166H |url=}}{{cite journal |vauthors=Abobaker A, Alzwi A, Alraied AH |title=Overview of the possible role of vitamin C in management of COVID-19 |journal=Pharmacol Rep |volume=72 |issue=6 |pages=1517–28 |date=December 2020 |pmid=33113146 |pmc=7592143 |doi=10.1007/s43440-020-00176-1 |url=}}

Scurvy was known to Hippocrates, described in book two of his Prorrheticorum and in his Liber de internis affectionibus, and cited by James Lind.{{cite book | vauthors = Lind J | title = A Treatise on the Scurvy | location = London, England | publisher = G. Pearch and W. Woodfall | date= 1772 | edition = 3rd | url = https://archive.org/details/treatiseonscurvy1772lind/page/285 | page = 285 | archive-url=https://web.archive.org/web/20160101135046/https://books.google.com/books?id=T1OT3tYmh5wC&pg=PA285&lpg=PA285 | archive-date=January 1, 2016 }} Symptoms of scurvy were also described by Pliny the Elder: (i) {{cite book | vauthors = Pliny | title = Naturalis historiae | volume = 3 | chapter = 49 }}; and (ii) Strabo, in Geographicorum, book 16, cited in the 1881 International Encyclopedia of Surgery.{{cite encyclopedia | veditors = Ashhurst J | title = The International Encyclopedia of Surgery | volume = 1 | location = New York, New York | publisher = William Wood and Co. | date = 1881 | url = https://books.google.com/books?id=mDV11NpZyNgC&pg=PA278 | page = 278 | archive-url = https://web.archive.org/web/20160505051643/https://books.google.com/books?id=mDV11NpZyNgC&pg=PA278&lpg=PA278 | archive-date=May 5, 2016}}

File:Wiki Loves Cocktails at WikiCon 2016, 2017 (1Y7A1464).jpg

In the 1497 expedition of Vasco da Gama, the curative effects of citrus fruit were known.{{cite journal | vauthors = Rajakumar K | title = Infantile scurvy: a historical perspective | journal = Pediatrics | volume = 108 | issue = 4 | pages = E76 | date = October 2001 | pmid = 11581484 | doi = 10.1542/peds.108.4.e76 | url = http://pediatrics.aappublications.org/content/108/4/e76.full | archive-url = https://web.archive.org/web/20150904021206/http://pediatrics.aappublications.org/content/108/4/e76.full | archive-date=September 4, 2015 | quote = As they sailed farther up the east coast of Africa, they met local traders, who traded them fresh oranges. Within six days of eating the oranges, da Gama's crew recovered fully | citeseerx = 10.1.1.566.5857 }} In the 1500s, Portuguese sailors put in to the island of Saint Helena to avail themselves of planted vegetable gardens and wild-growing fruit trees.{{cite journal | vauthors = Livermore H | title = Santa Helena, a forgotten Portuguese discovery | journal = Estudos Em Homenagem a Luis Antonio de Oliveira Ramos | trans-journal = Studies in Homage to Luis Antonio de Oliveira Ramos. | date = 2004 | pages = 623–631 | url = http://ler.letras.up.pt/uploads/ficheiros/4999.pdf | archive-url= https://web.archive.org/web/20110529065201/http://ler.letras.up.pt/uploads/ficheiros/4999.pdf | archive-date = May 29, 2011 | quote = On returning, Lopes' ship had left him on St Helena, where with admirable sagacity and industry he planted vegetables and nurseries with which passing ships were marvelously sustained. [...] There were 'wild groves' of oranges, lemons and other fruits that ripened all the year round, large pomegranates and figs. }} Authorities occasionally recommended plant food to prevent scurvy during long sea voyages. John Woodall, the first surgeon to the British East India Company, recommended the preventive and curative use of lemon juice in his 1617 book, The Surgeon's Mate.{{cite book | vauthors = Woodall J | title = The Surgion's Mate | location = London, England | publisher = Edward Griffin | date = 1617 | page = 89 | url = https://archive.org/stream/surgionsmateortr00wood#page/89/mode/1up | archive-url = https://web.archive.org/web/20160411083503/https://archive.org/stream/surgionsmateortr00wood | archive-date=April 11, 2016 | quote = Succus Limonum, or juice of Lemons ... [is] the most precious help that ever was discovered against the Scurvy[;] to be drunk at all times; ... }} In 1734, the Dutch writer Johann Bachstrom gave the firm opinion, "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens."{{cite journal | vauthors = Armstrong A |journal=British and Foreign Medico-chirurgical Review: Or, Quarterly Journal of Practical Medicine and Surgery |title=Observation on naval hygiene and scurvy, more particularly as the later appeared during the Polar voyage |volume=22 |pages=295–305 |year=1858 |url =https://books.google.com/books?id=7VJYAAAAMAAJ&pg=PA295 }}{{cite book | vauthors = Bachstrom JF | title = Observationes circa scorbutum | trans-title = Observations on scurvy | language = Latin | location = Leiden (Lugdunum Batavorum), Netherlands | publisher = Conrad Wishof | date = 1734 | page = 16 | url = https://books.google.com/books?id=bj8_AAAAcAAJ&pg=PA16 | archive-url = https://web.archive.org/web/20160101135046/https://books.google.com/books?id=bj8_AAAAcAAJ&pg=PA16 | archive-date = January 1, 2016 | quote = ... sed ex nostra causa optime explicatur, que est absentia, carentia & abstinentia a vegetabilibus recentibus, ... ( ... but [this misfortune] is explained very well by our [supposed] cause, which is the absence of, lack of, and abstinence from fresh vegetables, ... }} Scurvy had long been a principal killer of sailors during the long sea voyages.{{cite web |url=https://www.bbc.co.uk/history/british/empire_seapower/captaincook_scurvy_01.shtml |title=Captain Cook and the scourge of scurvy |publisher=BBC |work=British History in depth | vauthors = Lamb J |date=February 17, 2011 |url-status=live |archive-url=https://web.archive.org/web/20110221073823/http://www.bbc.co.uk/history/british/empire_seapower/captaincook_scurvy_01.shtml |archive-date=February 21, 2011 }} According to Jonathan Lamb, "In 1499, Vasco da Gama lost 116 of his crew of 170; In 1520, Magellan lost 208 out of 230; ... all mainly to scurvy."{{cite book | vauthors = Lamb J |title=Preserving the self in the south seas, 1680–1840 |publisher=University of Chicago Press |year=2001 |page=117 |isbn=978-0-226-46849-5 |url=https://books.google.com/books?id=hSoj1DR4ZSMC |url-status=live |archive-url=https://web.archive.org/web/20160430065803/https://books.google.com/books?id=hSoj1DR4ZSMC&pg=&dq |archive-date=April 30, 2016 }}

File:James Lind by Chalmers.jpg, a British Royal Navy surgeon who, in 1747, identified that a quality in fruit prevented scurvy in one of the first recorded controlled experiments{{cite journal | vauthors = Baron JH | title = Sailors' scurvy before and after James Lind--a reassessment | journal = Nutrition Reviews | volume = 67 | issue = 6 | pages = 315–32 | date = June 2009 | pmid = 19519673 | doi = 10.1111/j.1753-4887.2009.00205.x | s2cid = 20435128 }}]]

The first attempt to give scientific basis for the cause of this disease was by a ship's surgeon in the Royal Navy, James Lind. While at sea in May 1747, Lind provided some crew members with two oranges and one lemon per day, in addition to normal rations, while others continued on cider, vinegar, sulfuric acid or seawater, along with their normal rations, in one of the world's first controlled experiments. The results showed that citrus fruits prevented the disease. Lind published his work in 1753 in his Treatise on the Scurvy.{{cite book | vauthors = Lind J |title=A treatise of the scurvy |publisher=A. Millar |location=London |year=1753 }} In the 1757 edition of his work, Lind discusses his experiment starting on {{cite web |title=A treatise of the scurvy | url = https://archive.org/stream/treatiseonscurvy00lind#page/149/mode/1up | page = 149 | archive-url = https://web.archive.org/web/20160320155753/https://archive.org/stream/treatiseonscurvy00lind | archive-date=March 20, 2016 }}

Fresh fruit was expensive to keep on board, whereas boiling it down to juice allowed easy storage, but destroyed the vitamin (especially if it was boiled in copper kettles). It was 1796 before the British navy adopted lemon juice as standard issue at sea. In 1845, ships in the West Indies were provided with lime juice instead, and in 1860 lime juice was used throughout the Royal Navy, giving rise to the American use of the nickname "limey" for the British. Captain James Cook had previously demonstrated the advantages of carrying "Sour krout" on board by taking his crew on a 1772–75 Pacific Ocean voyage without losing any of his men to scurvy.{{cite book |vauthors=Beaglehole JH, Cook JD, Edwards PR |title=The journals of Captain Cook |publisher=Penguin |location=Harmondsworth [Eng.] |year=1999 |isbn=978-0-14-043647-1 |url=https://archive.org/details/journalsofcaptai00jame }} For his report on his methods the British Royal Society awarded him the Copley Medal in 1776.{{cite web |url=https://royalsociety.org/grants-schemes-awards/awards/copley-medal/ |title=Copley Medal, past winners |date= |website=The Royal Society |access-date=January 1, 2024 |archive-date=September 6, 2015 |archive-url=https://web.archive.org/web/20150906190948/https://royalsociety.org/grants-schemes-awards/awards/copley-medal/ |url-status=live }}

The name antiscorbutic was used in the eighteenth and nineteenth centuries for foods known to prevent scurvy. These foods included lemons, limes, oranges, sauerkraut, cabbage, malt, and portable soup.{{cite book |vauthors=Reeve J, Stevens DA |title=Navy and the nation: the influence of the navy on modern Australia |publisher=Allen & Unwin Academic |year=2006 |page=74 |isbn=978-1-74114-200-6 |chapter-url=https://books.google.com/books?id=BGs6__kbqKIC&pg=PA74 |chapter=Cook's Voyages 1768–1780 }} In 1928, the Canadian Arctic anthropologist Vilhjalmur Stefansson showed that the Inuit avoided scurvy on a diet largely of raw meat. Later studies on traditional food diets of the Yukon First Nations, Dene, Inuit, and Métis of Northern Canada showed that their daily intake of vitamin C averaged between 52 and 62 mg/day.{{cite journal | vauthors = Kuhnlein HV, Receveur O, Soueida R, Egeland GM | title = Arctic indigenous peoples experience the nutrition transition with changing dietary patterns and obesity | journal = The Journal of Nutrition | volume = 134 | issue = 6 | pages = 1447–53 | date = June 2004 | pmid = 15173410 | doi = 10.1093/jn/134.6.1447| df = mdy-all | doi-access = free | title-link = doi }}

{{Further|Vitamin#History}}

Vitamin C was discovered in 1912, isolated in 1928 and synthesized in 1933, making it the first vitamin to be synthesized.{{cite book |vauthors=Squires VR |title=The role of food, agriculture, forestry and fisheries in human nutrition - Volume IV |date=2011 |publisher=EOLSS Publications |isbn=978-1-84826-195-2 |page=121 |url=https://books.google.com/books?id=VJWoCwAAQBAJ&pg=PA121 |access-date=September 17, 2017 |archive-date=January 11, 2023 |archive-url=https://web.archive.org/web/20230111085247/https://books.google.com/books?id=VJWoCwAAQBAJ&pg=PA121 |url-status=live }} Shortly thereafter Tadeus Reichstein succeeded in synthesizing the vitamin in bulk by what is now called the Reichstein process.{{cite book | vauthors = Stacey M, Manners DJ | title = Advances in carbohydrate chemistry and biochemistry | chapter = Edmund Langley Hirst | volume = 35 | pages = 1–29 | year = 1978 | pmid = 356548 | doi = 10.1016/S0065-2318(08)60217-6 | isbn = 978-0-12-007235-4 }} This made possible the inexpensive mass-production of vitamin C. In 1934, Hoffmann–La Roche bought the Reichstein process patent, trademarked synthetic vitamin C under the brand name Redoxon, and began to market it as a dietary supplement.{{cite web|url=http://www.trademarkia.com/redoxon-71350953.html|title=Redoxon trademark information by Hoffman-la Roche, Inc. (1934)|access-date=December 25, 2017|archive-date=November 16, 2018|archive-url=https://web.archive.org/web/20181116044212/https://www.trademarkia.com/redoxon-71350953.html|url-status=live}}{{cite book | chapter-url = https://books.google.com/books?id=WgamCgAAQBAJ&pg=PA161 | chapter = Industrial fermentation of Vitamin C | vauthors = Wang W, Xu H | year = 2016 | page = 161 | title = Industrial biotechnology of vitamins, biopigments, and antioxidants | veditors = Vandamme EJ, Revuelta JI | publisher = Wiley-VCH Verlag GmbH & Co. KGaA. | isbn = 978-3-527-33734-7 }}

In 1907, a laboratory animal model which would help to identify the antiscorbutic factor was serendipitously discovered by the Norwegian physicians Axel Holst and Theodor Frølich, who when studying shipboard beriberi, fed guinea pigs their test diet of grains and flour and were surprised when scurvy resulted instead of beriberi. Unknown at that time, this species did not make its own vitamin C (being a caviomorph), whereas mice and rats do.{{cite journal | vauthors = Norum KR, Grav HJ | title = [Axel Holst and Theodor Frolich--pioneers in the combat of scurvy] | language = no | journal = Tidsskrift for den Norske Laegeforening | volume = 122 | issue = 17 | pages = 1686–7 | date = June 2002 | pmid = 12555613 }} In 1912, the Polish biochemist Casimir Funk developed the concept of vitamins. One of these was thought to be the anti-scorbutic factor. In 1928, this was referred to as "water-soluble C", although its chemical structure had not been determined.{{cite journal | vauthors = Rosenfeld L | title = Vitamine--vitamin. The early years of discovery | journal = Clinical Chemistry | volume = 43 | issue = 4 | pages = 680–5 | date = April 1997 | doi = 10.1093/clinchem/43.4.680 | pmid = 9105273 | doi-access = free | title-link = doi }}

File:GyorgyiNIH.jpg, pictured here in 1948, was awarded the 1937 Nobel Prize in Medicine "for his discoveries in connection with the biological combustion processes, with special reference to vitamin{{nbsp}}C and the catalysis of fumaric acid".|alt=Albert Szent-Györgyi was awarded the Nobel Prize in Medicine in part for his research on vitamin C]]

From 1928 to 1932, Albert Szent-Györgyi and Joseph L. Svirbely's Hungarian team, and Charles Glen King's American team, identified the anti-scorbutic factor. Szent-Györgyi isolated hexuronic acid from animal adrenal glands, and suspected it to be the antiscorbutic factor.{{cite journal | vauthors = Svirbely JL, Szent-Györgyi A | title = The chemical nature of vitamin C | journal = The Biochemical Journal | volume = 26 | issue = 3 | pages = 865–70 | year = 1932 | pmid = 16744896 | pmc = 1260981 | doi = 10.1126/science.75.1944.357-a | bibcode = 1932Sci....75..357K }} In late 1931, Szent-Györgyi gave Svirbely the last of his adrenal-derived hexuronic acid with the suggestion that it might be the anti-scorbutic factor. By the spring of 1932, King's laboratory had proven this, but published the result without giving Szent-Györgyi credit for it. This led to a bitter dispute over priority. In 1933, Walter Norman Haworth chemically identified the vitamin as {{sm|l}}-hexuronic acid, proving this by synthesis in 1933.{{cite journal | vauthors = Juhász-Nagy S | title = [Albert Szent-Györgyi--biography of a free genius] | language = hu | journal = Orvosi Hetilap | volume = 143 | issue = 12 | pages = 611–4 | date = March 2002 | pmid = 11963399 }}{{cite journal | vauthors = Kenéz J | title = [Eventful life of a scientist. 80th birthday of Nobel prize winner Albert Szent-Györgyi] | language = de | journal = Munchener Medizinische Wochenschrift | volume = 115 | issue = 51 | pages = 2324–6 | date = December 1973 | pmid = 4589872 }}{{cite journal | vauthors = Szállási A | title = [2 interesting early articles by Albert Szent-Györgyi] | language = hu | journal = Orvosi Hetilap | volume = 115 | issue = 52 | pages = 3118–9 | date = December 1974 | pmid = 4612454 }}{{cite web |url=http://profiles.nlm.nih.gov/WG/Views/Exhibit/narrative/szeged.html |title=The Albert Szent-Gyorgyi Papers: Szeged, 1931-1947: Vitamin C, Muscles, and WWII |work=Profiles in Science |publisher=United States National Library of Medicine |url-status=live |archive-url=https://web.archive.org/web/20090505232208/http://profiles.nlm.nih.gov/WG/Views/Exhibit/narrative/szeged.html |archive-date=May 5, 2009 }} Haworth and Szent-Györgyi proposed that L-hexuronic acid be named a-scorbic acid, and chemically {{sm|l}}-ascorbic acid, in honor of its activity against scurvy. The term's etymology is from Latin, "a-" meaning away, or off from, while -scorbic is from Medieval Latin scorbuticus (pertaining to scurvy), cognate with Old Norse skyrbjugr, French scorbut, Dutch scheurbuik and Low German scharbock.{{cite web |url=https://www.etymonline.com/word/scurvy |title=Scurvy |publisher=Online Entymology Dictionary |access-date=November 19, 2017 |archive-date=December 15, 2020 |archive-url=https://web.archive.org/web/20201215135611/https://www.etymonline.com/word/scurvy |url-status=live }} Partly for this discovery, Szent-Györgyi was awarded the 1937 Nobel Prize in Medicine,{{cite journal | vauthors = Zetterström R | title = Nobel Prize 1937 to Albert von Szent-Györgyi: identification of vitamin C as the anti-scorbutic factor | journal = Acta Paediatrica | volume = 98 | issue = 5 | pages = 915–19 | date = May 2009 | pmid = 19239412 | doi = 10.1111/j.1651-2227.2009.01239.x | s2cid = 11077461 }} and Haworth shared that year's Nobel Prize in Chemistry.{{cite journal |vauthors=Hirst EL |title=Sir Norman Haworth |journal=Nature |volume=165 |issue=4198 |pages=587 |date=April 1950 |pmid=15416703 |doi=10.1038/165587a0 |bibcode=1950Natur.165..587H |url=}}

In 1957, J. J. Burns showed that some mammals are susceptible to scurvy as their liver does not produce the enzyme L-gulonolactone oxidase, the last of the chain of four enzymes that synthesize vitamin C.{{cite journal | vauthors = Burns JJ, Evans C | title = The synthesis of L-ascorbic acid in the rat from D-glucuronolactone and L-gulonolactone | journal = The Journal of Biological Chemistry | volume = 223 | issue = 2 | pages = 897–905 | date = December 1956 | doi = 10.1016/S0021-9258(18)65088-4 | pmid = 13385237 | url = https://www.jbc.org/article/S0021-9258(18)65088-4/pdf | doi-access = free | title-link = doi | format = PDF | access-date = December 3, 2022 | archive-date = December 3, 2022 | archive-url = https://web.archive.org/web/20221203231846/https://www.jbc.org/article/S0021-9258(18)65088-4/pdf | url-status = live }}{{cite journal | vauthors = Burns JJ, Moltz A, Peyser P | title = Missing step in guinea pigs required for the biosynthesis of L-ascorbic acid | journal = Science | volume = 124 | issue = 3232 | pages = 1148–9 | date = December 1956 | pmid = 13380431 | doi = 10.1126/science.124.3232.1148-a | bibcode = 1956Sci...124.1148B }} American biochemist Irwin Stone was the first to exploit vitamin C for its food preservative properties. He later developed the idea that humans possess a mutated form of the {{sm|l}}-gulonolactone oxidase coding gene.{{cite journal | vauthors = Henson DE, Block G, Levine M | title = Ascorbic acid: biologic functions and relation to cancer | journal = Journal of the National Cancer Institute | volume = 83 | issue = 8 | pages = 547–50 | date = April 1991 | pmid = 1672383 | doi = 10.1093/jnci/83.8.547 | url = https://zenodo.org/record/1234351 | access-date = March 18, 2020 | archive-date = December 25, 2020 | archive-url = https://web.archive.org/web/20201225062602/https://zenodo.org/record/1234351 | url-status = live | doi-access = free | title-link = doi }}

Stone introduced Linus Pauling to the theory that humans needed to consume vitamin C in quantities far higher than what was considered a recommended daily intake in order to optimize health.{{cite web |url=http://www.orthomolecular.org/history/index.shtml |title=Orthomolecular Medicine Hall of fame - Irwin Stone, Ph.D. | vauthors = Saul A |date= |website=Orthomolecular Organization |access-date=December 25, 2023 |archive-date=August 9, 2011 |archive-url=https://web.archive.org/web/20110809145751/http://www.orthomolecular.org/history/index.shtml |url-status=live }}

In 2008, researchers discovered that in humans and other primates the red blood cells have evolved a mechanism to more efficiently utilize the vitamin C present in the body by recycling oxidized {{sm|l}}-dehydroascorbic acid (DHA) back into ascorbic acid for reuse by the body. The mechanism was not found to be present in mammals that synthesize their own vitamin C.{{cite journal | vauthors = Montel-Hagen A, Kinet S, Manel N, Mongellaz C, Prohaska R, Battini JL, Delaunay J, Sitbon M, Taylor N |s2cid = 18128118 |title = Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C |journal = Cell |volume = 132 |issue = 6 |pages = 1039–48 |date = March 2008 |pmid = 18358815 |doi = 10.1016/j.cell.2008.01.042| doi-access = | title-link = doi }}

{{Further|Vitamin C megadosage|Intravenous ascorbic acid}}

Vitamin C megadosage is a term describing the consumption or injection of vitamin C in doses comparable to or higher than the amounts produced by the livers of mammals which are able to synthesize vitamin C. An argument for this, although not the actual term, was described in 1970 in an article by Linus Pauling. Briefly, his position was that for optimal health, humans should be consuming at least 2,300 mg/day to compensate for the inability to synthesize vitamin C. The recommendation also fell into the consumption range for gorillas — a non-synthesizing near-relative to humans.{{cite journal | vauthors = Pauling L | title = Evolution and the need for ascorbic acid | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 67 | issue = 4 | pages = 1643–8 | date = December 1970 | pmid = 5275366 | pmc = 283405 | doi = 10.1073/pnas.67.4.1643 | bibcode = 1970PNAS...67.1643P | doi-access = free | title-link = doi }} A second argument for high intake is that serum ascorbic acid concentrations increase as intake increases until it plateaus at about 190 to 200 micromoles per liter (μmol/L) once consumption exceeds 1,250 milligrams.{{cite journal | vauthors = Mandl J, Szarka A, Bánhegyi G | title = Vitamin C: update on physiology and pharmacology | journal = British Journal of Pharmacology | volume = 157 | issue = 7 | pages = 1097–110 | date = August 2009 | pmid = 19508394 | pmc = 2743829 | doi = 10.1111/j.1476-5381.2009.00282.x }} As noted, government recommendations are a range of 40 to 110 mg/day and normal plasma is approximately 50 μmol/L, so "normal" is about 25% of what can be achieved when oral consumption is in the proposed megadose range.

Pauling popularized the concept of high dose vitamin C as prevention and treatment of the common cold in 1970. A few years later he proposed that vitamin C would prevent cardiovascular disease, and that 10 grams/day, initially administered intravenously and thereafter orally, would cure late-stage cancer.{{cite journal | vauthors = Cameron E, Pauling L | title = Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 73 | issue = 10 | pages = 3685–9 | date = October 1976 | pmid = 1068480 | pmc = 431183 | doi = 10.1073/pnas.73.10.3685| bibcode = 1976PNAS...73.3685C | doi-access = free | title-link = doi }} Mega-dosing with ascorbic acid has other champions, among them chemist Irwin Stone and the controversial Matthias Rath and Patrick Holford, who both have been accused of making unsubstantiated treatment claims for treating cancer and HIV infection.{{cite web |url= https://www.theguardian.com/world/2008/sep/12/matthiasrath.aids2 |title=Fall of the vitamin doctor: Matthias Rath drops libel action | vauthors = Boseley S |date=September 12, 2008 |website=The Guardian |access-date=January 5, 2024 |archive-date=December 1, 2016 |archive-url=https://web.archive.org/web/20161201225117/https://www.theguardian.com/world/2008/sep/12/matthiasrath.aids2 |url-status=live }}{{cite news |url=https://www.theguardian.com/science/2007/aug/15/endarkenment |title=The age of endarkenment | Science | guardian.co.uk |newspaper=Guardian |date=August 15, 2007 |access-date=January 5, 2024 | vauthors = Colquhoun D |archive-date=March 6, 2023 |archive-url=https://web.archive.org/web/20230306023533/https://www.theguardian.com/science/2007/aug/15/endarkenment |url-status=live }} The idea that large amounts of intravenous ascorbic acid can be used to treat late-stage cancer or ameliorate the toxicity of chemotherapy is — some forty years after Pauling's seminal paper — still considered unproven and still in need of high quality research.{{cite web|url=https://www.quackwatch.org/01QuackeryRelatedTopics/pauling.html |title=The dark side of Linus Pauling's legacy| vauthors = Barret S |date=September 14, 2014|website=www.quackwatch.org|archive-url= https://web.archive.org/web/20180904155649/https://www.quackwatch.org/01QuackeryRelatedTopics/pauling.html |archive-date=September 4, 2018|access-date=December 18, 2018}}{{Unreliable source?|date=April 2024}}{{cite journal | vauthors = Wilson MK, Baguley BC, Wall C, Jameson MB, Findlay MP | title = Review of high-dose intravenous vitamin C as an anticancer agent | journal = Asia-Pacific Journal of Clinical Oncology | volume = 10 | issue = 1 | pages = 22–37 | date = March 2014 | pmid = 24571058 | doi = 10.1111/ajco.12173 | s2cid = 206983069 | doi-access = free | title-link = doi }}

There is research investigating whether high dose intravenous vitamin C administration as a co-treatment will suppress cancer stem cells, which are responsible for tumor recurrence, metastasis and chemoresistance.{{cite journal |vauthors=Lee Y |title=Role of vitamin C in targeting cancer stem cells and cellular plasticity |journal=Cancers |volume=15 |issue=23 |date=November 2023 |page=5657 |pmid=38067361 |pmc=10705783 |doi=10.3390/cancers15235657 |doi-access=free |url=}}{{cite journal |vauthors=Satheesh NJ, Samuel SM, Büsselberg D |title=Combination therapy with vitamin C could eradicate cancer stem cells |journal=Biomolecules |volume=10 |issue=1 |date=January 2020 |page=79 |pmid=31947879 |pmc=7022456 |doi=10.3390/biom10010079 |doi-access=free}}

There is also ongoing research on topical application of vitamin C to prevent signs of skin aging. Human skin physiologically contains small amounts of vitamin C, which supports collagen synthesis, decreases collagen degradation, and assists in antioxidant protection against UV-induced photo-aging, including photocarcinogenesis. This knowledge is often used as a rationale for the marketing of vitamin C as a topical "serum" ingredient to prevent or treat facial skin aging, melasma (dark pigmented spots), and wrinkles; however, these claims are unsubstantiated and are not supported by research conducted so far; the supposed efficacy of topical treatment as opposed to oral intake is poorly understood.{{cite journal |vauthors=Pullar JM, Carr AC, Vissers MC |title=The roles of vitamin C in skin health |journal=Nutrients |volume=9 |issue=8 |date=August 2017 |page=866 |pmid=28805671 |pmc=5579659 |doi=10.3390/nu9080866 |url= | doi-access = free | title-link = doi }}{{cite journal |vauthors=Al-Niaimi F, Chiang NY |title=Topical vitamin C and the skin: Mechanisms of action and clinical applications |journal=J Clin Aesthet Dermatol |volume=10 |issue=7 |pages=14–17 |date=July 2017 |pmid=29104718 |pmc=5605218 |doi= |url=}} The purported mechanism on supposed benefit of topical vitamin C application to slow skin aging is that vitamin C functions as an antioxidant, neutralizing free radicals from sunlight exposure, air pollutants or normal metabolic processes.{{cite web |url=https://www.health.harvard.edu/blog/why-is-topical-vitamin-c-important-for-skin-health-202111102635 |title=Why is topical vitamin C important for skin health? |vauthors=Nathan N, Patel P |date=10 November 2021 |website=Harvard Health Publishing, Harvard Medical School |access-date=October 14, 2022 |archive-date=October 14, 2022 |archive-url=https://web.archive.org/web/20221014100454/https://www.health.harvard.edu/blog/why-is-topical-vitamin-c-important-for-skin-health-202111102635 |url-status=live }} The clinical trial literature is characterized as insufficient to support health claims; one reason being put forward was that "All the studies used vitamin C in combination with other ingredients or therapeutic mechanisms, thereby complicating any specific conclusions regarding the efficacy of vitamin C."{{cite journal |vauthors=Sanabria B, Berger LE, Mohd H, Benoit L, Truong TM, Michniak-Kohn BB, Rao BK |title=Clinical efficacy of topical vitamin C on the appearance of wrinkles: A systematic literature review |journal=Journal of Drugs in Dermatology |volume=22 |issue=9 |pages=898–904 |date=September 2023 |pmid=37683066 |doi=10.36849/JDD.7332 |doi-broken-date=November 1, 2024 |doi-access=free |url=https://jddonline.com/articles/clinical-efficacy-of-topical-vitamin-c-on-the-appearance-of-wrinkles-a-systematic-literature-review-S1545961623P0898X/ |access-date=February 25, 2024 |archive-date=February 25, 2024 |archive-url=https://web.archive.org/web/20240225202726/https://jddonline.com/articles/clinical-efficacy-of-topical-vitamin-c-on-the-appearance-of-wrinkles-a-systematic-literature-review-S1545961623P0898X/ |url-status=live }}{{cite journal |vauthors=Correia G, Magina S |title=Efficacy of topical vitamin C in melasma and photoaging: A systematic review |journal=J Cosmet Dermatol |volume=22 |issue=7 |pages=1938–45 |date=July 2023 |pmid=37128827 |doi=10.1111/jocd.15748 |s2cid=258439047 |url=| doi-access = free | title-link = doi }}

Further research is needed to determine if prophylactic vitamin C treatment is helpful for preventing or treating pneumonia.{{cite journal |vauthors=Padhani ZA, Moazzam Z, Ashraf A, Bilal H, Salam RA, Das JK, Bhutta ZA |date=18 Nov 2021 |title=Vitamin C supplementation for prevention and treatment of pneumonia |journal=The Cochrane Database of Systematic Reviews |volume= 2021|issue= 11|pages= CD013134|doi=10.1002/14651858.CD013134.pub3 |pmc=8599445 |pmid=34791642}}

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