Vitamin C

Vitamin C or ascorbate is a water-soluble vitamin found in citrus and other fruits, berries and vegetables. It is found as a form of ascorbic acid. It is an essential nutrient involved in the repair of tissue, the formation of collagen, and the enzymatic production of certain neurotransmitters. It is required for the functioning of several enzymes and is imp

Vitamin C or ascorbate is a water-soluble vitamin found in citrus and other fruits, berries and vegetables. It is found as a form of ascorbic acid. It is an essential nutrient involved in the repair of tissue, the formation of collagen, and the enzymatic production of certain neurotransmitters. It is required for the functioning of several enzymes and is important for immune system function.[6] It also functions as an antioxidant. Most animals are able to synthesize their own vitamin C. However, higher primates (including humans), most bats, guinea pigs, some fish species, and some bird species must acquire it from dietary sources because a gene for a synthesis enzyme has mutations that render it dysfunctional; humans obtain this vitamin from those fruits and vegetables.[7]

It is also a generic prescription medication and in some countries is sold as a non-prescription dietary supplement. As a therapy, it is used to prevent and treat scurvy, a disease caused by vitamin C deficiency. Vitamin C may be taken by mouth or by intramuscular, subcutaneous or intravenous injection. Various health claims exist on the supposition that moderate vitamin C deficiency increases disease risk, such as for the common cold, cancer or COVID-19.[8]: xi  There are also claims of benefits from vitamin C supplementation in excess of the recommended dietary intake for people who are not considered vitamin C deficient. Vitamin C is generally well tolerated. Large doses may cause gastrointestinal discomfort, headache, trouble sleeping, and flushing of the skin. The United States National Academy of Medicine recommends against consuming large amounts.[8]: 155–165 

Vitamin C was discovered in 1912, isolated in 1928, and in 1933, was the first vitamin to be chemically produced. Partly for its discovery, Albert Szent-Györgyi was awarded the 1937 Nobel Prize in Physiology or Medicine.

Chemistry

The name "vitamin C" always refers to the l-enantiomers of ascorbic acid and its oxidized form, dehydroascorbate (DHA). Therefore, unless written otherwise, "ascorbate" and "ascorbic acid" refer in the nutritional literature to l-ascorbate and 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.[9]

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.[10][11]

Deficiency

Plasma vitamin C is the most widely applied test for vitamin C status.[9] 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.[12] 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  μmol/L. The percent of people reported as deficient was 5.9%.[13] 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.[14]

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.[9]

Diagnostic testing

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,[8]: 103–109  but these analysis are difficult to measure, and hence not part of standard diagnostic testing.[9][15]

Diet

Recommended consumption

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

• 40 mg/day: India National Institute of Nutrition, Hyderabad[16]
• 45 mg/day or 300 mg/week: the World Health Organization[17]
• 80 mg/day: the European Commission Council on nutrition labeling[18]
• 90 mg/day (males) and 75 mg/day (females): Health Canada 2007[19]
• 90 mg/day (males) and 75 mg/day (females): United States National Academy of Sciences[8]: 134–152 
• 100 mg/day: Japan National Institute of Health and Nutrition[20]
• 110 mg/day (males) and 95 mg/day (females): European Food Safety Authority[21]

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.[8]: 134–152  The table here shows RDAs for the United States and Canada for children, and for pregnant and lactating women,[8]: 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.[21]

Cigarette smokers and people exposed to secondhand smoke have lower serum vitamin C levels than nonsmokers.[12] The reasoning is that inhalation of smoke causes oxidative damage, depleting this antioxidant vitamin.[8]: 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.[8]: 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.[22] 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.[23]

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.[8]: 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,[24] as did the Japan National Institute of Health and Nutrition in 2010.[20]