Vitamin C (also called ascorbic acid and ascorbate) is a vitamin present in varied meals and offered as a dietary complement.[9] It’s used to stop and deal with scurvy.[9] Vitamin C is an important nutrient concerned within the restore of tissue and the enzymatic manufacturing of sure neurotransmitters.[9][10] It’s required for the functioning of a number of enzymes and is essential for immune system perform.[10][11] It additionally features as an antioxidant.[12]
There may be some proof that common use of dietary supplements could scale back the period of the widespread chilly, but it surely doesn’t seem to stop an infection.[12][13][14] It’s unclear whether or not supplementation impacts the chance of most cancers, heart problems, or dementia.[15][16] It could be taken by mouth or by injection.[9]
Vitamin C is usually properly tolerated.[9] Giant doses could trigger gastrointestinal discomfort, headache, hassle sleeping, and flushing of the pores and skin.[9][13] Regular doses are protected throughout being pregnant.[8] The US Institute of Medication recommends in opposition to taking massive doses.[10]
Vitamin C was found in 1912, remoted in 1928, and, in 1933, was the primary vitamin to be chemically produced.[17] It’s on the World Well being Group’s Record of Important Medicines.[18] Vitamin C is obtainable as a cheap generic and over-the-counter medicine.[9][19] Partly for its discovery, Albert Szent-Györgyi and Walter Norman Haworth had been awarded the 1937 Nobel Prizes in Physiology and Medication and Chemistry, respectively.[20][21] Meals containing vitamin C embody citrus fruits, kiwifruit, guava, broccoli, Brussels sprouts, bell peppers and strawberries.[12] Extended storage or cooking could scale back vitamin C content material in meals.[12]
Contents
Biology[edit]
Vitamin C is an important nutrient for sure animals together with people. The time period vitamin C encompasses a number of vitamers which have vitamin C exercise in animals. Ascorbate salts equivalent to sodium ascorbate and calcium ascorbate are utilized in some dietary dietary supplements. These launch ascorbate upon digestion. Ascorbate and ascorbic acid are each naturally current within the physique, because the varieties interconvert in line with pH. Oxidized types of the molecule equivalent to dehydroascorbic acid are transformed again to ascorbic acid by decreasing brokers.[10][22]
Vitamin C features as a cofactor in lots of enzymatic reactions in animals (together with people) that mediate a wide range of important organic features, together with wound therapeutic and collagen synthesis. In people, vitamin C deficiency results in impaired collagen synthesis, contributing to the extra extreme signs of scurvy.[10] One other biochemical position of vitamin C is to behave as an antioxidant (a decreasing agent) by donating electrons to varied enzymatic and non-enzymatic reactions.[10] Doing so converts vitamin C to an oxidized state – both as semidehydroascorbic acid or dehydroascorbic acid. These compounds might be restored to a decreased state by glutathione and NADPH-dependent enzymatic mechanisms.[23][24][25]
In vegetation, vitamin C is a substrate for ascorbate peroxidase. This enzyme makes use of ascorbate to neutralize extra hydrogen peroxide (H2O2) by changing it to water (H2O) and oxygen.[11][22][26]
Deficiency[edit]
Vitamin C blood serum ranges are thought of saturated at ranges > 65 μmol/L (1.1 mg/dL), achieved by consuming quantities that are at, or above, the Really useful Dietary Allowance, whereas satisfactory ranges are outlined as ≥ 50 μmol/L. Hypovitaminosis within the case of vitamin C is outlined as ≤ 23 μmol/L and deficiency happens at ≤ 11.4 μmol/L.[27][28] For these 20 years of age or above, information from the U.S. 2003-04 NHANES survey confirmed imply and median serum concentrations of 49.0 and 54.4 μmol/L, respectively. The % of individuals reported as poor was 7.1%.[28]
Scurvy is a illness ensuing from a deficiency of vitamin C. With out this vitamin, collagen made by the physique is just too unstable to carry out its perform and several other different enzymes within the physique don’t function appropriately.[11] Scurvy is characterised by spots on and bleeding below the pores and skin, spongy gums, ‘corkscrew’ hair progress, and poor wound therapeutic. The pores and skin lesions are most plentiful on the thighs and legs, and an individual with the ailment appears to be like pale, feels depressed, and is partially immobilized. In superior scurvy there are open, suppurating wounds, lack of enamel, bone abnormalities and, ultimately, dying.[29]
Notable human dietary research of experimentally induced scurvy had been carried out on conscientious objectors throughout World Warfare II in Britain and on Iowa state prisoners within the late Nineteen Sixties to the Nineteen Eighties. Males within the jail examine developed the primary indicators of scurvy about 4 weeks after beginning the vitamin C-free weight-reduction plan, whereas within the earlier British examine, six to eight months had been required, presumably as a result of pre-loading of this group with a 70 mg/day complement for six weeks earlier than the scorbutic weight-reduction plan was fed. Males in each research had blood ranges of ascorbic acid too low to be precisely measured by the point they developed indicators of scurvy. These research each reported that every one apparent signs of scurvy may very well be fully reversed by supplementation of solely 10 mg a day.[30][31]
Makes use of[edit]
Vitamin C has a definitive position in treating scurvy, which is a illness brought on by vitamin C deficiency. Past that, a task for vitamin C as prevention or remedy for varied ailments is disputed, with evaluations reporting conflicting outcomes. A 2012 Cochrane evaluate reported no impact of vitamin C supplementation on total mortality.[32] It’s on the World Well being Group’s Record of Important Medicines.[18]
Scurvy[edit]
The illness scurvy is brought on by vitamin C deficiency and might be prevented and handled with vitamin C-containing meals or dietary dietary supplements.[9][10] It takes a minimum of a month of little to no vitamin C earlier than signs happen.[30] Early signs are malaise and lethargy, progressing to shortness of breath, bone ache, bleeding gums, susceptibility to bruising, poor wound therapeutic, and eventually fever, convulsions and eventual dying.[9] Till fairly late within the illness the harm is reversible, as wholesome collagen replaces the faulty collagen with vitamin C repletion. Remedy might be oral supplementation of the vitamin or by intramuscular or intravenous injection.[9] Scurvy was identified to Hippocrates within the classical period. The illness was proven to be prevented by citrus fruits in an early managed trial by a Royal Navy surgeon, James Lind, in 1747, on board HMS Salisbury[33] and from 1796 lemon juice was issued to all Royal Navy crewmen.[34][33]
An infection[edit]
Analysis on vitamin C within the widespread chilly has been divided into results on prevention, period, and severity. A Cochrane evaluate which checked out a minimum of 200 mg/day concluded that vitamin C taken regularly was not efficient in prevention of the widespread chilly. Proscribing evaluation to trials that used a minimum of 1000 mg/day additionally noticed no prevention profit. Nevertheless, taking vitamin C regularly did scale back the typical period by 8% in adults and 14% in youngsters, and likewise decreased severity of colds.[14] A subsequent meta-analysis in youngsters discovered that vitamin C approached statistical significance for prevention and decreased the period of higher respiratory tract infections.[35] A subset of trials in adults reported that supplementation decreased the incidence of colds by half in marathon runners, skiers, or troopers in subarctic situations.[14] One other subset of trials checked out therapeutic use, that means that vitamin C was not began until the folks began to really feel the beginnings of a chilly. In these, vitamin C didn’t have an effect on period or severity.[14] An earlier evaluate acknowledged that vitamin C didn’t forestall colds, did scale back period, didn’t scale back severity.[36] The authors of the Cochrane evaluate concluded that:
Vitamin C distributes readily in excessive concentrations into immune cells, has antimicrobial and pure killer cell actions, promotes lymphocyte proliferation, and is consumed shortly throughout infections, results indicating a distinguished position in immune system regulation.[37] The European Meals Security Authority discovered a trigger and impact relationship exists between the dietary consumption of vitamin C and functioning of a standard immune system in adults and in youngsters below three years of age.[38][39]
Most cancers[edit]
There are two approaches to the query of whether or not vitamin C has an impact on most cancers. First, throughout the regular vary of dietary consumption with out extra dietary supplementation, are individuals who eat extra vitamin C at decrease danger for creating most cancers, and if that’s the case, does an orally consumed complement have the identical profit? Second, for folks recognized with most cancers, will massive quantities of ascorbic acid administered intravenously deal with the most cancers, scale back the opposed results of different remedies, and so delay survival and enhance high quality of life? A 2013 Cochrane evaluate discovered no proof that vitamin C supplementation reduces the chance of lung most cancers in wholesome folks or these at excessive danger as a consequence of smoking or asbestos publicity.[40] A second meta-analysis discovered no impact on the chance of prostate most cancers.[41] Two meta-analyses evaluated the impact of vitamin C supplementation on the chance of colorectal most cancers. One discovered a weak affiliation between vitamin C consumption and decreased danger, and the opposite discovered no impact from supplementation.[42][43] A 2011 meta-analysis failed to search out help for the prevention of breast most cancers with vitamin C supplementation,[44] however a second examine concluded that vitamin C could also be related to elevated survival in these already recognized.[45]
Underneath the rubric of orthomolecular medication, “Intravenous vitamin C is a contentious adjunctive cancer therapy, widely used in naturopathic and integrative oncology settings.”[46] With oral administration absorption effectivity decreases as quantities improve. Intravenous administration bypasses this.[47] Doing so makes it potential to attain plasma concentrations of 5 to 10 millimoles/liter (mmol/L), which far exceed the roughly 0.2 mmol/L restrict from oral consumption.[48] The theories of mechanism are contradictory. At excessive tissue concentrations ascorbic acid is described as appearing as a pro-oxidant, producing hydrogen peroxide (H2O2) to kill tumor cells. The identical literature claims that ascorbic acid acts as an antioxidant, thereby decreasing the opposed results of chemotherapy and radiation remedy.[46][47] Analysis continues on this discipline, however a 2014 evaluate concluded: “Currently, the use of high-dose intravenous vitamin C [as an anticancer agent] cannot be recommended outside of a clinical trial.”[49] A 2015 evaluate added: “There is no high-quality evidence to suggest that ascorbate supplementation in cancer patients either enhances the antitumor effects of chemotherapy or reduces its toxicity. Evidence for ascorbate’s anti-tumor effects was limited to case reports and observational and uncontrolled studies.”[50]
Heart problems[edit]
There is no such thing as a proof as of 2017 that taking vitamin C decreases heart problems.[51] One 2013 evaluate discovered no proof that antioxidant vitamin supplementation reduces the chance of myocardial infarction, stroke, cardiovascular mortality, or all-cause mortality (it didn’t present subset evaluation for trials that simply used vitamin C).[15] One other 2013 evaluate discovered an affiliation between larger circulating vitamin C ranges or dietary vitamin C and a decrease danger of stroke.[52]
A 2014 evaluate discovered a optimistic impact of vitamin C on endothelial dysfunction when taken at doses higher than 500 mg per day. The endothelium is a layer of cells that line the inside floor of blood vessels.[53]
Mind perform[edit]
A 2017 systematic evaluate discovered decrease vitamin C concentrations in folks with cognitive impairment, together with Alzheimer’s illness and dementia, in comparison with folks with regular cognition.[54] The cognitive testing, nonetheless, relied on the Mini-Psychological State Examination, which is just a basic take a look at of cognition, indicating an total low high quality of analysis assessing the potential significance of vitamin C on cognition in regular and impaired folks.[54] A evaluate of nutrient standing in folks with Alzheimer’s illness reported low plasma vitamin C, but in addition low blood ranges of folate, vitamin B12, and vitamin E.[55]
Different ailments[edit]
Research analyzing the consequences of vitamin C consumption on the chance of Alzheimer’s illness have reached conflicting conclusions.[56][57] Sustaining a wholesome dietary consumption might be extra essential than supplementation for attaining any potential profit.[58] A 2010 evaluate discovered no position for vitamin C supplementation within the remedy of rheumatoid arthritis.[59] Vitamin C supplementation doesn’t forestall or gradual the development of age-related cataract.[60]
Throughout March by way of July 2020, vitamin C was the topic of extra US FDA warning letters than another ingredient for prevention and/or remedy of COVID-19.[61]
Uncomfortable side effects[edit]
Vitamin C is a water-soluble vitamin,[62] with dietary excesses not absorbed, and excesses within the blood quickly excreted within the urine, so it reveals remarkably low acute toxicity.[11] Greater than two to a few grams could trigger indigestion, notably when taken on an empty abdomen. Nevertheless, taking vitamin C within the type of sodium ascorbate and calcium ascorbate could reduce this impact.[63] Different signs reported for big doses embody nausea, belly cramps and diarrhea. These results are attributed to the osmotic impact of unabsorbed vitamin C passing by way of the gut.[10] In concept, excessive vitamin C consumption could trigger extreme absorption of iron. A abstract of evaluations of supplementation in wholesome topics didn’t report this downside, however left as untested the chance that people with hereditary hemochromatosis could be adversely affected.[10]
There’s a longstanding perception among the many mainstream medical neighborhood that vitamin C will increase danger of kidney stones.[64] “Reports of kidney stone formation associated with excess ascorbic acid intake are limited to individuals with renal disease”.[10] Critiques state that “data from epidemiological studies do not support an association between excess ascorbic acid intake and kidney stone formation in apparently healthy individuals”,[10][65] though one massive, multi-year trial did report a virtually two-fold improve in kidney stones in males who usually consumed a vitamin C complement.[66]
Weight-reduction plan[edit] – “vitamin c food sources”
Really useful ranges[edit]
Suggestions for vitamin C consumption by adults have been set by varied nationwide businesses:
In 2000 the North American Dietary Reference Consumption chapter on vitamin C up to date the Really useful Dietary Allowance (RDA) to 90 milligrams per day for grownup males and 75 mg/day for grownup girls, and set a Tolerable higher consumption stage (UL) for adults of two,000 mg/day.[10] The desk reveals RDAs for america and Canada for youngsters, and for pregnant and lactating girls.[10] For the European Union, the EFSA set larger suggestions for adults, and likewise for youngsters: 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 being pregnant 100 mg/day; for lactation 155 mg/day.[72] India, then again, has set suggestions a lot decrease: 40 mg/day for ages 1 by way of grownup, 60 mg/day for being pregnant, and 80 mg/day for lactation.[67] Clearly, there’s not consensus amongst international locations.
Cigarette people who smoke and other people uncovered to secondhand smoke have decrease serum vitamin C ranges than nonsmokers.[28] The considering is that inhalation of smoke causes oxidative harm, depleting this antioxidant vitamin.[10][71] The U.S. Institute of Medication estimated that people who smoke want 35 mg extra vitamin C per day than nonsmokers, however didn’t formally set up the next RDA for people who smoke.[10] One meta-analysis confirmed an inverse relationship between vitamin C consumption and lung most cancers, though it concluded that extra analysis is required to substantiate this commentary.[73]
The U.S. Nationwide Middle for Well being Statistics conducts biannual Nationwide Well being and Diet Examination Survey (NHANES) to evaluate the well being and dietary standing of adults and youngsters in america. Some outcomes are reported as What We Eat In America. The 2013-2014 survey reported that for adults ages 20 years and older, males consumed on common 83.3 mg/d and girls 75.1 mg/d. Because of this half the ladies and greater than half the boys aren’t consuming the RDA for vitamin C.[74] The identical survey acknowledged that about 30% of adults reported they consumed a vitamin C dietary complement or a multi-vitamin/mineral complement that included vitamin C, and that for these folks complete consumption was between 300 and 400 mg/d.[75]
Tolerable higher consumption stage[edit]
In 2000 the Institute of Medication of the U.S. Nationwide Academy of Sciences set a Tolerable higher consumption stage (UL) for adults of two,000 mg/day. The quantity was chosen as a result of human trials had reported diarrhea and different gastrointestinal disturbances at intakes of higher than 3,000 mg/day. This was the Lowest-Noticed-Hostile-Impact Stage (LOAEL), that means that different opposed results had been noticed at larger intakes. ULs are progressively decrease for youthful and youthful youngsters.[10] The European Meals Security Authority (EFSA) reviewed the protection query in 2006 and reached the conclusion that there was not enough proof to set a UL for vitamin C.[76] The Japan Nationwide Institute of Well being and Diet reviewed the identical query in 2010 and likewise reached the conclusion that there was not enough proof to set a UL.[71]
Meals labeling[edit]
For U.S. meals and dietary complement labeling functions, the quantity in a serving is expressed as a % of Every day Worth (%DV). For vitamin C labeling functions, 100% of the Every day Worth was 60 mg, however as of Might 27, 2016 it was revised to 90 mg to convey it into settlement with the RDA.[77][78] Compliance with the up to date labeling rules was required by 1 January 2020 for producers with US$10 million or extra in annual meals gross sales, and by 1 January 2021 for producers with decrease quantity meals gross sales.[79][80] A desk of the previous and new grownup day by day values is supplied at Reference Every day Consumption.
European Union rules require that labels declare power, protein, fats, saturated fats, carbohydrates, sugars, and salt. Voluntary vitamins could also be proven if current in vital quantities. As an alternative of Every day Values, quantities are proven as % of Reference Intakes (RIs). For vitamin C, 100% RI was set at 80 mg in 2011.[81]
Sources[edit]
The richest pure sources of vitamin C are vegetables and fruit.[11] The vitamin is probably the most extensively taken dietary complement and is obtainable in a wide range of varieties,[11] together with tablets, drink mixes, and in capsules.[citation needed]
Plant sources[edit]
Whereas plant meals are usually supply of vitamin C, the quantity in meals of plant origin depends upon the number of the plant, soil situation, local weather the place it grew, size of time because it was picked, storage situations, and technique of preparation.[82][83] The next desk is approximate and reveals the relative abundance in numerous uncooked plant sources.[84][85] As some vegetation had been analyzed contemporary whereas others had been dried (thus, artificially growing focus of particular person constituents like vitamin C), the information are topic to potential variation and difficulties for comparability. The quantity is given in milligrams per 100 grams of the edible portion of the fruit or vegetable:
Animal sources[edit]
Animal-sourced meals don’t present a lot vitamin C, and what there’s, is essentially destroyed by the warmth of cooking. For instance, uncooked hen liver comprises 17.9 mg/100 g, however fried, the content material is decreased to 2.7 mg/100 g. Hen eggs include no vitamin C, uncooked or cooked.[86] Vitamin C is current in human breast milk at 5.0 mg/100 g and 6.1 mg/100 g in a single examined pattern of toddler system, however cow’s milk comprises just one.0 mg/ 100 g.[92]
Meals preparation[edit]
Vitamin C chemically decomposes below sure situations, lots of which can happen in the course of the cooking of meals. Vitamin C concentrations in varied meals substances lower with time in proportion to the temperature at which they’re saved.[93] Cooking can scale back the vitamin C content material of greens by round 60%, presumably as a consequence of elevated enzymatic destruction.[94] Longer cooking occasions could add to this impact.[95]
One other reason behind vitamin C loss from meals is leaching, which transfers vitamin C to the cooking water, which is decanted and never consumed. Broccoli could retain vitamin C throughout cooking or storage greater than most greens.[96]
Dietary supplements[edit]
Vitamin C dietary dietary supplements can be found as tablets, capsules, drink combine packets, in multi-vitamin/mineral formulations, in antioxidant formulations, and as crystalline powder.[9] Vitamin C can be added to some fruit juices and juice drinks. Pill and capsule content material ranges from 25 mg to 1500 mg per serving. Essentially the most generally used complement compounds are ascorbic acid, sodium ascorbate and calcium ascorbate.[9] Vitamin C molecules may also be certain to the fatty acid palmitate, creating ascorbyl palmitate, or else integrated into liposomes.[97]
Meals fortification[edit]
In 2014, the Canadian Meals Inspection Company evaluated the impact of fortification of meals with ascorbate within the steering doc, Meals to Which Nutritional vitamins, Mineral Vitamins and Amino Acids Might or Should be Added.[98] Voluntary and necessary fortification was described for varied lessons of meals. Amongst meals labeled for necessary fortification with vitamin C had been fruit-flavored drinks, mixes, and concentrates, meals for a low-energy weight-reduction plan, meal substitute merchandise, and evaporated milk.[98]
Meals components[edit]
Ascorbic acid and a few of its salts and esters are widespread components added to varied meals, equivalent to canned fruits, principally to retard oxidation and enzymatic browning.[99] It could be used as a flour remedy agent utilized in breadmaking.[100] As meals components, they’re assigned E numbers, with security evaluation and approval the duty of the European Meals Security Authority.[101] The related E numbers are:
The stereoisomers of Vitamin C have an analogous impact in meals regardless of their lack of efficacy in people. They embody erythorbic acid and its sodium salt (E315, E316).[102]
Pharmacology[edit]
Pharmacodynamics[edit]
Vitamin C – particularly, within the type of ascorbate – performs quite a few physiological features within the human physique by serving as an enzyme substrate and/or cofactor and an electron donor. These features embody the synthesis of collagen, carnitine, and neurotransmitters; the synthesis and catabolism of tyrosine; and the metabolism of microsome.[25] Throughout biosynthesis, ascorbate acts as a decreasing agent, donating electrons and stopping oxidation to maintain iron and copper atoms of their decreased states.
Vitamin C features as a cofactor for the next enzymes:
Pharmacokinetics[edit]
Absorption[edit]
From the U.S. Nationwide Institutes of Well being: [In humans] “Approximately 70%–90% of vitamin C is absorbed at moderate intakes of 30–180 mg/day. However, at doses above 1,000 mg/day, absorption falls to less than 50%.”[12] It’s transported by way of the gut by way of each glucose-sensitive and glucose-insensitive mechanisms, so the presence of huge portions of sugar within the gut can gradual absorption.[115]
Ascorbic acid is absorbed within the physique by each lively transport and easy diffusion. Sodium-Dependent Lively Transport—Sodium-Ascorbate Co-Transporters (SVCTs) and Hexose transporters (GLUTs)—are the 2 transporter proteins required for lively absorption. SVCT1 and SVCT2 import the decreased type of ascorbate throughout plasma membranes.[116] GLUT1 and GLUT3 are glucose transporters, and switch solely the dehydroascorbic acid (DHA) type of vitamin C.[117] Though dehydroascorbic acid is absorbed in larger price than ascorbate, the quantity of dehydroascorbic acid present in plasma and tissues below regular situations is low, as cells quickly scale back dehydroascorbic acid to ascorbate.[118]
Transport[edit]
SVCTs look like the predominant system for vitamin C transport within the physique,[116] the notable exception being crimson blood cells, which lose SVCT proteins throughout maturation.[119] In each vitamin C synthesizers (instance: rat) and non-synthesizers (instance: human) cells with few exceptions keep ascorbic acid concentrations a lot larger than the roughly 50 micromoles/liter (µmol/L) present in plasma. For instance, the ascorbic acid content material of pituitary and adrenal glands can exceed 2,000 µmol/L, and muscle is at 200-300 µmol/L.[120] The identified coenzymatic features of ascorbic acid don’t require such excessive concentrations, so there could also be different, as but unknown features. Penalties of all this organ content material is that plasma vitamin C isn’t indicator of whole-body standing, and other people could fluctuate within the period of time wanted to indicate signs of deficiency when consuming a weight-reduction plan very low in vitamin C.[120]
Excretion[edit]
Excretion might be as ascorbic acid, by way of urine. In people, throughout occasions of low dietary consumption, vitamin C is reabsorbed by the kidneys moderately than excreted. Solely when plasma concentrations are 1.4 mg/dL or larger does re-absorption decline and the surplus quantities cross freely into the urine. This salvage course of delays onset of deficiency.[121] Ascorbic acid additionally converts (reversibly) to dehydroascorbate (DHA) and from that compound non-reversibly to 2,3-diketogluonate after which oxalate. These three compounds are additionally excreted by way of urine. People are higher than guinea pigs at changing DHA again to ascorbate, and thus take for much longer to turn out to be vitamin C poor.[122]
Chemistry[edit]
The title “vitamin C” at all times refers back to the l-enantiomer of ascorbic acid and its oxidized varieties, equivalent to dehydroascorbate (DHA). Due to this fact, until written in any other case, “ascorbate” and “ascorbic acid” refer within the dietary literature to l-ascorbate and l-ascorbic acid respectively. Ascorbic acid is a weak sugar acid structurally associated to glucose. In organic methods, ascorbic acid might be discovered solely at low pH, however in options above pH 5 is predominantly discovered within the ionized kind, ascorbate. All of those molecules have vitamin C exercise and thus are used synonymously with vitamin C, until in any other case specified.[citation needed]
Quite a few analytical strategies have been developed for ascorbic acid detection. For instance, vitamin C content material of a meals pattern equivalent to fruit juice might be calculated by measuring the amount of the pattern required to decolorize an answer of dichlorophenolindophenol (DCPIP) after which calibrating the outcomes by comparability with a identified focus of vitamin C.[123][124]