Vitamin C

Last Updated: February 1 2023

Vitamin C, or ascorbic acid, is an essential vitamin and a very popular supplement due to its antioxidant properties, safety profile, and low price. Many people supplement with vitamin C because it is believed to reduce symptoms of the common cold.

Vitamin C is most often used for.

Don't miss out on the latest research


Sources and Structure



Vitamin C (officially known as L-ascorbic acid, its prolonged name being 2-oxo-L-threo-hexono-1,4-lactone-2,3-enediol) is an Essential Vitamin, first structurally identified by Szent-Gyorgyi, Waugh, and King in 1932-1935[1][2] and first synthesized by Haworth and Hirst in 1933.[3] It has been popularized mostly by Linus Pauling for prevention of the common cold[4][5][6] and has since been said to be the most popular supplement in the world.[7]

Vitamin C is most commonly supplemented because of its potential protection against the common cold,[8] and purported anticancer effects.[9] Athletes report using vitamin C for both the antioxidant properties and potential immune support.[10]

The current recommendations for Vitamin C intake (according to the FDA) appears to be 75-90mg daily (females and males, respectively) for adults with increases of 10mg for pregnancy, 45mg for lactation, and 35mg for smokers.[11] Children require around 15-45mg daily and adolescents 65-75mg, while infants (12 months or less) appears to require 40-50mg daily; youth do not have differences in dosage based upon gender until adolescence is reached.[11]

Average dietary intakes have been reported to be 152+/-83.7mg in spain,[12]

Vitamin C is a relatively safe micronutrient that is a common supplement for its antioxidant properties and reported benefits against the common cold. Average dietary intakes are in the sufficiency range (above what the RDA recommends) although the lowest groups of vitamin C intake are under the recommendations

Particularly rich sources of Vitamin C include:

  • Kiwi fruits (290-800mg/kg in the deliciosa (common) species and 370-1850mg/kg in argutafruit[13])

Whereas the most common or significant dietary sources of Vitamin C include:

  • Citrus Fruits (29.6% in spain,[12] usually oranges[14]) and 9% in the US (all fruits inclusive[15])
  • Noncitrus fruits (21.5% in spain,[12] usually apples[14])
  • Juices (6.3% in spain[12] and 25-34% in the US[16][15])
  • Fruiting vegetables (usually peppers and sweet peppers) at 20% in spain[12] and 23% in the US (all vegetables inclusive[15])
  • Potatoes (3.9% in spain[12])
  • Leafy green vegetables (6.7% in spain[12])
  • Cruciferous vegetables (2.9% in spain[12])
  • Fortified cereals (4% in US[15])

Fruits tend to be the highest food source of vitamin C, and in mediterraean countries they also appear to be a predominant source of vitamin C in the average diet. In the US, juices appear to contribute a significant amount of vitamin C to the diet


Biological Significance

Vitamin C appears to be a cofactor for proper collagen synthesis, L-carnitine biosynthesis (interestingly not mandatory[17]), and some neurotransmitters (particularly catecholamines).[7] In the body it maintains an overall pool of around 1,500-2,000mg that can be maintained with 75mg daily intake and saturated with 140mg daily.[7] In the body, Vitamin C has a half-life of 10–20 days with a bodily turnover of 1mg/kg and at the serum concentration of 50μM it has a bodily pool of approximately 22mg/kg[18][19] (50μM is right in the middle of the 40-60μM range found in humans[20][21]).

The biosynthesis of L-Carnitine (β-hydroxy butyric acid) that requires Vitamin C is not as a substrate, but as a necessary cofactor (iron and alpha-ketoglutarate are also required cofactors).[22] This is similar to the biosynthesis of catecholamines, as the dopamine-β-hydroxylase enzyme that converts dopamine into noradrenaline (which subsequently converts into adrenaline) is Vitamin C dependent.[23] Other enzymes that Vitamin C is known to positively modulate include those involved in the synthesis of oxytocin, vasopressin, cholecystokinin and α-Melanocyte-stimulating hormone.[24]

Vitamin C is required in the human body since it is required by some critical enzymes, particular those that synthesize L-Carnitine and the neurotransmitters known as catecholamines (dopamine and adrenaline). It also influences a few other neurotransmitters, and is required for proper collagen (joint) synthesis rates

Biosynthesis of Vitamin C can normally occur from either glucose or galactose being converted to glucose-6-phosphate, which then is converted to uridine diphosphate glucose and (via uridine diphosphate glucuoronic acid) into L-glucuronic acid. This molecule is then converted into L-glucuronolactone, L-gulono-γ-lactone, and then via the enzyme known as gulonolactone oxidase it is converted into L-keto-gulono-γ-lactone and Vitamin C.[7] Humans (as well as guinea pigs, fruit eating bats, and apes) cannot follow the above biosynthetic pathway as the gulonolactone oxidase enzyme does not exist within us.[7][25]

Due to the inability to synthesize Vitamin C, it needs to be obtained via the diet. A failure to get sufficient Vitamin C in the diet results in scurvy,[26][27] and the ability of a molecule to prevent scurvy (of which Vitamin C is the reference drug) is known as being anti-scorbutic.[28]

Vitamin C can normally be synthesized in animals such as canines and felines, but humans do not have an ability to synthesize Vitamin C. If Vitamin C is not obtained via the diet, then a human will eventually get scurvy

While scurvy is the clinical deficiency state (and is true 'Vitamin C deficiency'), there are various states associated with excessive oxidation which serum vitamin C tends to be reduced (or at least the REDOX balanced altered suggesting a prooxidative state) relative to healthy cohorts. This includes fever and viral infections, stress, alcoholism,[7] smoking,[29][30] type II diabetes[31][32] despite consuming adequate vitamin C,[33] and in persons who have very recently suffered a myocardial infarction[34][35] or acute pancreatitis (these last two normalizing after some time).[36][37]

It has been noted[38] that it is still unclear whether the disease state causes a depletion in vitamin C or vice versa (vitamin C depletion exacerbates the progression of the above states) or whether it is merely a biomarker of a poor diet (this is seen in smokers[39]); at least in myocardial infarction[40] and acute pancreatitis,[41] there is a drastic increase in oxidation rapidly and both diabetes[42] and smoking[29] are associated with elevated chronic oxidation.

Vitamin C depletion (not to a clinical state where scurvey results) is associated with a variety of disease states. The reason for these observations is not fully clear, and the role vitamin C therapy could play in these states is similarly not clear


Structure and Properties

Vitamin C appears to stable in food (as the form of L-ascorbic acid) in the pH range of 4-6[7]


Supplement Variants and Specifications

European regulation state that any supplement with the label 'Vitamin C' may be one of five compounds; L-Ascorbic Acid (actual vitamin C), Sodium-L-Ascorbate, Potassium-L-Ascorbate, Calcium-L-Ascorbate, and L-Ascorbyl-6-Palmitate.[43] For vitamin-related purposes, they are equipotent.

They differ on some parameters such as DNA oxidation where Sodium Ascorbate and Ascorbic Acid (the main dietary form) could exert pro-oxidative effects on DNA, Calcium Ascorbate acting neutral on DNA and Ascorbyl-6-Palmitate being protective on DNA.[44] Due to this, it appears that Ascorbyl-6-Palmitate is used often in antioxidant supplements,[7] but does not have water solubility.

'Vitamin C' on the label may refer to one of five different molecules, but all of them are able to act as a vitamin in the body. There may be some small differences between the molecules

Ester-C is a brand name product (patented by Zila Nutraceuticals) for Vitamin C that consists of Vitamin C metabolites (the aldonic acids L-lyxonic, L-xylonic, and L-Threonic acid) with Calcium, and is labelled as Calcium Ascorbate. It is touted to be non-acidic and may be better tolerated by persons with acid reflux, as one study in persons sensitive to acidic foods noted that while 53.6% of the Vitamin C group experienced gastric upset, only 14.3% of the Ester-C group did.[45]

Beyond this, Ester-C appears to be more effective at treating scurvy (Vitamin C deficiency)[46] and at decreasing oxalate levels (a metabolite of Vitamin C),[47][48] Ester-C has been reported to reduce the common cold, but was not compared to basic Vitamin C and has not been replicated.[49]

Studies conducted using Ester-C that have been funded by Zila Nutraceuticals are cited following this sentence.[45]

Ester-C is a form of Vitamin C supplementation that may have benefit in persons who are sensitive to acid containing foods, but beyond that its supposed benefits over standard Vitamin C have not been thoroughly proven





Normal circulating concentrations of Vitamin C (as L-ascorbic acid) are in the range of 40-60μM while the reduced form of dehydroascorbate is around 2μM;[20][21] the difference is possibly due to a short half-life of dehydroasorbate of 2-6 minutes.[50] The half-life of ascorbate at a concentration below 70μM is much more prolonged (somewhere between 8 and 40 days) whereas a serum concentration of ascorbate above this threshold (seen with supplementation of over 1,000mg vitamin C) is met with a 30 minute half-life.[51]

Supplemental ascorbate appears to follow a dual phase pharmacokinetic profile. When serum levels are below (within the physiological range) the body tends to regulate ascorbate via resorption in the kidneys (via sodium dependent vitamin C transporters[52]) and have a prolonged half-life of 8-40 days.[53] Serum concentrations

Oral intake of 1,250mg vitamin c is able to increase plasma vitamin C to 134.8+/-20.6μM and is calculated to exceed 220μM when taken at 3,000mg every four hours (in accordance with megadosing therapy for the common cold).[54]



Supplementation of 500mg Vitamin C twice daily appears to increase expression of the transporter that mediates uptake of vitamin C in skeletal muscle (SVCT2) and subsequently Vitamin C concentrations after one week, maintaining over 42 days of supplementation, despite no alterations in oxidative balance.[55]



Vitamin C appears to be metabolized into primarly one of three metabolites after it turns into a free radical (ascrobyl radical); dehydroascorbic acid, 2,3-diketogulonic acid and oxalic acid which convert into one another in that order. Dietary supplementation does not necessarily increase urinary levels of these metabolites, as there is a lack of metabolism of L-ascorbic acid before it is urinated out.[7][50]

As the first stage of metabolism is turning into a free radical, conditions characterized by excessive oxidation deplete circulating L-ascorbic acid (which acts in a protective but sacrifical manner); this is best shown with studies on smoking[56][57] which usually requires a higher Vitamin C intake.

Vitamin C is metabolized into a free radical (via a sacrifical and protective antioxidant effect) and then converted into dehydroascobic acid. From here, vitamin C then proceeds along to produce oxalic acid via 2,3-diketogulonic acid




Kinetics and Distribution

Vitamin C is actively transported into the brain via the Sodium-dependent Vitamin C Transporter-2 (SVCT2 or Slc23a1) transporter, whereas the oxidized version of Vitamin C (Dehydroascorbic acid) is transported by GLUT transporters.[58][59] Due to this, it is known to be transported across the blood brain barrier.[60][61] While from systemic circulation (through the blood brain barrier) the oxidized form of dehydroascorbate appears to be required to be transported through GLUT transporters,[61] the choroid plexus epithelium (connection of cerebrospinal fluid to the brain) expresses SVCT2[62][63] and this appears to be the majority route of entry.[63][64][65]

There appears to be a 4-fold higher cerebrospinal fluid concentration of ascorbate relative to plasma in rats,[66][65] resulting in a cerebrospinal concentration of around 200-400μM when plasma are 60μM or less[67][68] although human measurements are more modest at 160μM relative to the same plasma level of 40-60μM.[69][70]

Vitamin C can cross the blood brain barrier, but the rate of entry is somewhat limited and and it needs to be in the oxidized form of dehydroascorbate for this to occur. The majority of Vitamin C entry into the brain occurs via cerebrospinal fluid

Within the brain, Vitamin C appears to be in highest concentrations in the hippocampus, parietal cortex, and the cerebellum[71][72][73] with slightly lower concentrations in the frontal cortex, thalamic nuclei, olfactoy bulb, and striatum with lowest detected in the spinal cord and pons (lowest).[71][74] It is thought that distribution of Vitamin C in the brain mirrors that of where the SVCT2 transport is expressed (noted to be high in the cerebellum, hippocampus, olfactory bulb[75] and frontal cortex[76]), although this does not fully explain the distribution as the parietal cortex does not possess SVCT2.[76]

Vitamin C seems to be in highest concentrations in the hippocampus, cerebellum, and frontal/parietal cortices



As mentioned elsewhere (Biological Significance), Vitamin C is a cofactor in the production of catecholamines (via the enzyme dopamine-β-hydroxylase[23][77][78]) and other neurohormones such as oxytocin, vasopressin, and α-Melanocyte-stimulating hormone.[24][79] Another area that Vitamin C facilitates is supporting HIF-1α production, which uses a prolyl and lysyl hydroxylation similar to what is seen with collagen.[58][80] These enzymatic interactions rely on the ability of L-ascorbic acid to transfer a single electron, and may involve the Vitamin C metabolites as well.

Vitamin C interacts with a variety of enzymes involved in cognition. It does not inherently induce these enzymes (increase their activity or the amount of them), but its existence is required for optimal enzyme functioning; this likely means that for enzymatic benefits perhaps only avoiding a deficiency is required



In isolated rat synaptic vesicles, vitamin C appears to cause acetylcholine release with an EC50 value of 2-2.5µM and appears to be dependent on calcium as it was inhibited with EGTA.[81]

Injections of 60mg/kg vitamin C to mice appears to have acetylcholinesterase inhibiting properties by reducing its activity 17.1% (comparable to 50mg/kg Metrifonate and 150mg/kg oral licorice).[82]



Vitamin C has been found to, in vitro, protect cerebellar granule cells from glutamate induced excitotoxicity[83][84] which is thought to be related to how NDMA receptors can respond to REDOX modulation.[85][86] This is more of a general phenomena that applies to reducing agents (antioxidants), and is abolished by prooxidants.[86]

Vitamin C appears to have putative neuroprotective roles against excitotoxicity (toxicity from excessive cell stimulation) through inhibiting the NMDA receptor. This does not appear to be a unique role for Vitamin C, but something that is attributable to antioxidants in general



There appears to be an increase in oxidative stress within cells following percieved stressors (both physical[87] and mental[88][89]), and this increased oxidative state is known to lead to cellular death.

A rat study has noted that oral ingestion of low dose vitamin C (1mg/kg; 0.16mg/kg in humans) was able to suppress an increase in biomarkers of stress in rats, namely oxidation.[90]



Vitamin C appears to have antidepressant effects, associated with potassium channels (can be read up on under the depression section on the agmatine page).[91] In short, potassium channel blockers appear to have anti-depressant effects[92] while potassium channel openers have pro-depressive effects and inhibit the actions of potassium channel blockers[93][92] and vitamin C appears to be synergistically antidepressive with potassium channel blockers.[91]

Vitamin C appears to have antidepressant effects. While the direct mechanism of action is not known, it appears to ultimately work via potassium channels (like most antidepressants) and is synergistic with potassium channel blockers

In regards to animal research, administration of Vitamin C has shown an antidepressant effect in a tail suspension test,[94][91] chronic unpredictable manageable stress,[95] and acute stress[90] at a dosage range of 1-10mg/kg oral administration.

In humans, there is an old case study where depression in a child (induced by ACTH administration) was alleviated with vitamin C[96] but more importantly, a study using a product known as Cetebe (3,000mg vitamin C) in otherwise healthy adults for two weeks noted a reduction in depressive symptoms (Becks Depression Inventory) and increase in the frequency of intercourse (no influence on masturbation);[97] this study was funded by the producer of Cetebe, GlaxoSmithKline.

Preliminary evidence in humans to support antidepressant effects in humans, with the lone controlled trial having a notable conflict of interest



Serum concentrations of Vitamin C appear to be inversely related with risk of Dementia, with an Odds Ratio (OR) of 0.29 after controlling for school education, intake of dietary supplements, smoking habits, body mass index, and alcohol consumption.[98]



In regards to Alzheimer's, oxidative stress is thought to play a major role in the pathogenesis of the disease[99] with byproducts of peroxidation being detected in higher than normal levels in neurofibrillary tangles[100][101][102] and lower serum vitamin C concentrations despite adequate dietary intake[103] although due to a higher cerebrospinal fluid to plasma ratio in alzheimer's (5.1 relative to 3.1 in controls[104]) it is thought the lower serum concentration reflects increased uptake by the brain to counter increaed oxidative stress;[105] this would position the decrease in Vitamin C as a consequence of Alzheimer's rather than a cause.

Vitamin C and oxidative kinetics appear to be altered in persons with Alzheimer's disease

In rat studies, orally ingested Vitamin C (25mg/kg in rats) alongside intracerebral injections of fibrillar amyloid-β was able to reduce oxidative and inflammatory biomarkers (the former comparable to melatonin at 20mg/kg but weaker than vitamin E at 50mg/kg; the latter similar to vitamin E but less than melatonin)[106] although elsewhere in an older APP/PSEN1 transgenic mouse model injected with 125mg/kg vitamin C failed to find evidence for neuroprotection or beneficial changes in oxidation (despite slightly improving memory).[107]

Mixed evidence as to whether vitamin C can be of help. It may be neuroprotective but not rehabilitative, and the benefits appear to extend to other antioxidant compounds as well


Cardiovascular Health


Blood Flow

There appear to be several disease states or metabolic conditions of which ascorbate deficiency in the endothelium is associated with endothelial dysfunction.[108]

The endothelial variant of the NOS enzyme (eNOS) appears to be susceptible to oxidative damage, including both translation of the enzyme itself[109] and the required cofactor tetrahydrobiopterin is readily oxidized and rendered inactive.[110] Due to this, supplemental antioxidants are thought to preserve the actions of eNOS in instances of excessive oxidative stress and vitamin C has been said to augment nitric oxide production[111] secondary to 'recycling' (preserving) tetrahydrobiopterin.[112][113] As this is an antioxidative effect and other studies in animals have noted comparable benefits with other antioxidants (such as melatonin[114][115]) this is likely just an antioxidative effect rather than a unique property of vitamin C.

Other possible mechanisms that may contribute (also general to antioxidants) include scavenging superoxide[116] which would otherwise reduce nitric oxide into peroxynitrate[117] and directly reducing nitrite (product of nitrate) into nitric oxide[118] or producing nitric oxide from S-nitrosothiols.[119]

Vitamin C appears to promote nitric oxide secondary to its antioxidant properties preventing a unnecessarily rapid decline of nitric oxide. This is not a unique mechanism of action, and is thought to underlie the effects of other potent antioxidants such as melatonin or pycnogenol (both demonstrated to act similarly)



Vitamin C is known to be required for microsomal 7α-hydroxylation (rate limiting step of the catabolism of cholesterol), and a deficiency of Vitamin C results in excess cholesterol in the liver and increased risk for gallstones.[7][120][121] This increase in cholesterol retention (by reducing its elimination rate) also appears to be a risk factor for cardiovascular diseases and particularly atherosclerosis.[122][123]


Interactions with Glucose Metabolism



Ascorbate appears to be important to a pancreatic β-cell due in part to its antioxidant properties[124] (these cells tend to have low levels of antioxidant enzymes[125][126]) and its presence is required for proper secretion of insulin.[127] In rats that are able to synthesize vitamin C, it accumulates to high levels in these cells.[128] Furthermore, there is possible competitive inhibition of ascorbate acid metabolites (dehydroascorbate) with glucose as they use the same transporter.[129]

Two grams of vitamin C daily for 2 weeks in otherwise healthy adults has been noted to delay the postprandial insulin spike and prolong the increase in serum glucose when measured at one hour (but not beyond that),[130] hypothesized to be due to competitive inhibition with glucose into pancreatic β-cells.

Not substantial amounts of evidence at this moment in time, but vitamin C may be protective of pancreatic beta-cells. However, supplementation of vitamin C with glucose may cause a transient state of insulin resistance by increasing circulating glucose and suppressing insulin secretion


Blood Glucose and Insulin

Many studies have examined the potential role of vitamin C supplementation in reducing glucose levels (fasting and postprandial) and the results have been mixed, with only a few studies finding a statistically significant reduction,[131][132][133] a handful finding a nonsignificant reduction,[134][135][136][137][138] and many not finding a reduction.[139][140][141][142][143][144][145][146][147][148][149][150] A meta-analysis found that, across all studies, there was no significant effect of vitamin C supplementation on blood glucose levels, however among 15 studies in 597 type 2 diabetics, vitamin C supplementation led to a modest, significant reduction of -0.41 (-0.78, -0.04 95% CI) mmol/L.[151] Studies lasting more than than 30 days yielded greater effects than shorter studies, of which some only gave a single dose on the day of examination. Overall, there didn’t seem to be a great risk of bias, though there wasn't an abundance of particularly well-designed studies with large sample sizes that treated vitamin C as their primary outcome. While there’s a lot of data on the effects of vitamin C, it can’t be said that vitamin C has been properly researched for its effects on blood glucose levels.

Overall, there was a reduction in fasting insulin, but there was no change in HbA1c, and no subgroup analyses were able to find a statistically significant difference.[151]

Vitamin C supplementation may modestly reduce blood glucose and insulin in type 2 diabetics, however, it can't be said that vitamin C is well-researched for this purpose. Further research with this possible interaction specifically in mind is needed.



Recent[152] research has shown that vitamin C interactions with glucose metabolism may make it useful as a potential anti-cancer agent.[153] Although Vitamin C anti-cancer effects were proposed as early as the 1970s by the Nobel prize winning chemist Dr. Linus Pauling,[154] later clinical trials failed to demonstrate any efficacy as a cancer treatment.[155][152]

This cast doubt on any anti-cancer properties for vitamin C, which was further reinforced by studies suggesting that antioxidants may actually give cancer cells an advantage by promoting, rather than inhibiting tumorigenesis.[156] It turns out that Linus Pauling may have been right after all about vitamin C and cancer, but not for the reasons he originally envisioned. At high doses vitamin C promotes, rather than reduces oxidative stress in cancer cells, leading to cytotoxic effects.[157]

The mechanism behind the selective toxicity of vitamin C against cancer cells was unknown until only recently, when a recent study found that vitamin C-induced oxidative stress inhibits GAPDH, an important metabolic enzyme in the glycolytic pathway.[153] Because cancer cells tend to rely on high rates of glycolysis for survival,[158] the ability of high-dose vitamin C to suppress glycolytic metabolism confer anti-tumorigenic activity in certain types of cancer cells.[153]

By suppressing an important enzyme in the glycolytic pathway, high dose vitamin C may have selectively kill certain types of cancer cells. Clinical trials are currently under way to evaluate the efficacy of vitamin C as a cancer treatment in humans.


Exercise and Physical Performance



Skeletal muscle is known to be a large store of bodily vitamin C (around two thirds[159]) and responsive to dietary vitamin C intake, with one study noting baseline concentrations of 19nmol/g being increased to 53 and 61nmol/g following consumption of 0.5 or 2 kiwi fruits (conferring 53 and 212mg respectively[160]). Vitamin C is readily taken up via SVCT transporters in skeletal muscle tissue.[161]

The main mechanism of concern with Vitamin C supplementation and muscle metabolism would be the antioxidant properties of Vitamin C,[162] although both the collagen and carnitine synthesis roles are thought to be useful.

Vitamin C appears to be readily taken up and stored in skeletal muscle tissue, where it is thought to confer antioxidant protection and support carnitine and collagen biosynthesis


Exercise Immunology

The post exercise spike in cortisol is known to suppress activity of T-cells and B-cells, which would limit antibody production such as IgA.[163] Despite an interaction with cortisol following exercise with Vitamin C supplemenation (1,500mg for 7-12 days)[164][165][166][167] a few studies measuring IgA have failed to find any significant influence, with similar decreases in both placebo and Vitamin C.[165][166] One study has noted a significant increase in post-exercise lymphocyte counts associated with a decrease in cortisol,[167] whereas another has reported a relative suppression.[164]

For studies measuring cytokines, there has been no reported influence on IL-6, IL-10, IL-1ra, IL-2, IFN-γ, and IL-8 following an ultramarathon[168] nor any influence on IL-6 following short-term exercise.[167] IL-6 is particularly notable as despite there being no significant influence on circulating levels following oral supplementation of Vitamin C (1,000-1,500mg), a combination supplement of Vitamin C (500mg) and Vitamin E (400 IU) for 28 days has once been shown to prevent IL-6 release from contracting skeletal muscle (associated with antioxidant effects).[169]

Although the combination of vitamin E and vitamin C can suppress IL-6 production in response to exercise,[170] this may or may not be helpful, given other work that suggesting that IL-6 may play a positive role in exercise adaptation. IL-6 has been noted to function as a sort of “fuel gage” for muscle tissue, where it is released when muscle glucose levels are low, causing an increase in glucose production in the liver while also increasing lipolysis during exercise.[171][172] Acute increases in IL-6 may also be responsible for much of the direct fat-burning effects from of exercise training, amplifying fat oxidation in intramuscular[173][174][175] and whole body fat stores.[176]

Vitamin C was shown in one study to decrease IL-6 production from skeletal muscle in response to exercise. Although IL-6 is a pro-inflammatory cytokine, other studies suggest that it may play a role in exercise adaptation, in part by increasing fat oxidation. More research is needed to determine whether possible vitamin C-induced suppression of IL-6 could affect exercise performance of adaptation in humans.

For studies that measure upper respitatory tract infection risk following exercise, no significant effects are seen with 1,500mg Vitamin C for 12 days prior to a simulated half marathon in the heat.[166]

Usage of supplemental vitamin C in the 1,500-2,000mg range before short duration exercise is able to attenuate the increase in cortisol. However, this does not appear to significantly mediate immune responses to exercise.

In contrast to the suppression of cortisol mentioned above with short term exercise, longer and more strenuous exercise such as ultramarathons are known to have an augmentation of cortisol with vitamin C.[168][165] This is thought to be related to the observation that the risk of colds is only reduced in populations subject to strenous exercise (where vitamin C halves the risk of cold symptoms) according to meta-analyses on the topic.[177][178]

Strenous and prolonged exercise such as marathons or skiing appear to be affected differently with supplemental vitamin C, as they increase cortisol rather than decrease it. This type of exercise also appears to be the type that does experience reductions in cold frequency with supplemental vitamin C


Delayed Onset Muscle Soreness (DOMS)

DOMS is a soreness and tenderness of the muscle tissue that arises after exercise, usually with a delay where it does not suface immediately but usually the next day or 48 hours afterwards.

One study using Vitamin C at 400mg (with Vitamin E at 264mg) failed to notice any benefit to soreness with treatment relative to placebo.[179]


Power Output

Vitamin C (400mg), in conjunction with Vitamin E (286mg) as a mixed anti-oxidant supplement for 6 weeks in otherwise healthy men, is not significantly better than placebo at attenuating an exercise-induced reduction of power output seen during the recovery phase of exercise.[179]


Endurance Performance

There is mixed evidence in the literature on the effects of vitamin C on endurance performance. It is generally accepted that the state of obesity, relative to a non-obese state, makes the same amount of exercise more tiring to the body (perception) and uses more caloric reserves for the same amount of work.[180] Ingestion of 500mg Vitamin C via supplementation when paired with both an exercise regimen and a caloric restriction diet was able to significantly reduce heart rate during exercise and the rate of perceived exertion, although it didn't affect success on the diet.[181]

In another study, 11 health men took 500 mg vitamin C twice daily along with 400 IU vitamin E once daily or placebo for four weeks. They were then subject to a strenuous 60 minute exercise routine on a stationary bicycle. The VO2peak of the vitamin group did not differ from placebo, nor did the rate of perceived exertion or maximal power output.[182]

Vitamin C has also been observed to decrease endurance performance in certain experimental models. One study noted that giving greyhounds 1g of vitamin C before racing significantly slowed racing time relative to dogs that did not receive supplementation.[183] Five adult female racing greyhounds received one of three treatments for four weeks per treatment: no vitamin C, 1g vitamin C immediately after racing, or 1g vitamin C immediately before racing. On average, when dogs were supplemented with vitamin C , their 500m racing time was 0.2 seconds slower.[183]

While studies in greyhounds have limited relevance to humans, a later human study further suggested that antioxidants may limit endurance in humans.[184] 14 men age 27-36 received either a 1000mg daily dose of vitamin C or a placebo during an 8-week endurance training program. The study found that vitamin C suppressed endurance capacity, which was associated with a decrease in mitochondrial biogenesis,[184] driven by decreased expression of a number of different proteins important for the process.

There is mixed evidence of the effects of vitamin C on endurance performance, with results ranging from possible positive effects to possible negative effects. The study that suggested vitamin C has a negative affect on endurance performance attributed this effect to decreased mitochondrial biogenesis.


Insulin sensitivity

Since exercise-induced increases in insulin sensitivity are in part driven by increased reactive oxygen species production (ROS)[1], a study in 2009 by Ristow et al, examined the effects of supplementation with vitamin C (500mg twice/day) and vitamin E (400IU/day) on changes in insulin sensitivity caused by exercise.[185] Subjects were enrolled in a 5 day per week training program for 4 weeks that consisted of both cardio and weight training. To rule out any possible “beginner effects” (i.e. the well-known result in exercise-science studies where those with little to no training experience tend to respond better), participants included beginners, as well as those with more extensive training experience. In subject that took a placebo, insulin sensitivity increased over the course of the training program. This occured in beginners as well as those with more extensive training experience. Subjects that took vitamin C/E supplements during the 4-week training period showed no increases in insulin sensitivity, however, indicating that the antioxidant supplementation negated the exercise-induced increase in insulin sensitivity.[185]

Vitamin C at 500mg twice per day in combination with 400 IU vitamin E was shown in one study to negate the insulin-sensitivity increasing effects of exercise in both trained and untrained individuals. Further studies are needed to explore the effects of antioxidant supplementation on exercise-induced increases in insulin sensitivity in different populations and exercise protocols.


Skeletal and Bone Metabolism


Bone Mass

At least one rat study notes that supplementation with Vitamin C (5mg) is associated with an attenuation of bone loss due to ovariectomy, an animal model of menopause.[186] After 8 weeks of supplementation, the control ovariectomy group experienced bone loss while the ovariectomy group with Vitamin C was not significantly different than control.[186]


Inflammation and Immunology


Cold and Flu

According to meta-analyses on the topic assessing doses of 200mg vitamin C or more, vitamin C has failed to reduce the frequency of colds in the normal population but was successful in reducing the duration of colds (on average 8-14%);[187][178] when looking at studies investigating extreme physical stress (marathoners and skiiers), the risk of getting a cold was halved (which has been noted in past meta-analyses[177])

It has been noted[188] that the observations from Linus Pauling on vitamin C interactions with the common cold may have been influenced by athletic cohorts, as one of the more convincing studies he wrote about[189] was in regards to children in a skiing school (German PDF[190]).

Most of the literature uses dosages within the range of 200mg to 2,000mg, and while this does appears to be ineffective for preventing or reducing the occurrence of the common cold it does appear to slightly reduce the duration thereof. There are more marked benefits in athletic populations, where risk may be halved


Bacterial Interactions

One study has noted that drug resistant Mycobacterium tuberculosis (bacteria that causes tuberculosis) is highly sensitive to being destroyed by Vitamin C, which was fairly unique as other bacteria tested were not affected.[191] This was due to a large iron content in this bacteria, which is reduced (from Fe3+ to Fe2+) and causes prooxidative effects after reacting with oxygen.

Although there is no human evidence at this moment in time, Vitamin C supplementation holds promise for being able to destroy the tuberculosis bacteria despite being drug resistant


Interactions with Oxidation



Vitamin C (L-Ascorbic acid) is a single electron donor, and can be reduced into an ascorbyl radical (AFR) via either oxidative stressors or being used as a cofactor in enzymes. This sacrificial antioxidant activity (antioxidant being somewhat synonymous with 'reduction' when looking at REDOX equations) can be reversed by NADH and NADPH dependent reductases.[192][193][194] Another possible reaction occurs when excessive accumulation of AFR occurs, where two molecules of AFR react with one another to form L-ascorbic acid and Dehydroascorbic acid.[195] Although conversion of the two AFR molecules into dehydroascorbic acid is also reversible (various antioxidant enzymes such as glutathione or thiol reductases[196]), it can possibly not occur due to a short half-life of around 2-6 minutes under physiological conditions[50] the dehydroascorbic molecule and spontaenous formation of 2,3-diketogulonic acid which is irreversible and cannot be converted back into L-ascorbic acid.[50] Production of 2,3-diketogulonic acid then proceeds to create oxalic acid and get excreted from the body via urine.

The above reduction conducted by L-ascorbic acid that converts it to AFR is the main antioxidative effect of Vitamin C, and is known to be 'sacrificial' as the L-ascorbic acid molecule is changed when the reaction occurs. This scavenging applies to most reactive oxygen species (ROS) including superoxide (O2-)[197] and some reactive nitrogen species such as peroxynitrate either directly[198] or reducing an O2- induced conversion of nitric oxide into peroxynitrate.[197]

Vitamin C gets reduced (absorbs oxidation) in a sacrifical manner to either protect other things from being oxidized or to facilitate enzymes in the body. The molecules created have the potential to be restored back into Vitamin C, and if this does not occur then Vitamin C is metablized to oxalic acid and then urinated out

It is wholly possible for Vitamin C to also act as a prooxidant depending on context, although the ascorbyl radical itself (technically a prooxidant) is not overly potent due to the position of the free radical group.[199][200] Dietary minerals in vitro are able to oxidize ascorbate as ascorbate is oxidized in the presence of minerals such as iron or copper[201][202] while chelating the minerals prevents autooxidation;[203] this reduction of minerals via ascorbate produces reduced minerals that are better able to exert prooxidative effects. It has been noted[200] that prooxidative effects appear to predominate in vitro at low concentrations of vitamin C relative to minerals (usually iron), and antioxidative effects at higher concentrations of vitamin C relative to minerals.


Antioxidant Enzymes

Exercise is known to reduce oxidation levels in serum[204][205] possibly associated with an increase in antioxidant enzymes,[206][207] which is said to be an adaptation to the initial increase in oxidative damage induced by exercise. Vitamin C supplementation has been reported to increase activity of these antioxidant enzymes (when acting as a prooxidant).[208]

In a study where 11 healthy men took 500 mg of vitamin C twice daily plus 400 IU vitamin E for 4 weeks before being subject to strenuous aerobic exercise, the vitamin group had lower superoxide dismutase activity in their muscles versus the placebo group measured through a muscle biopsy. However, markers of oxidative stress in the muscle biopsy was ultimately unaffected.[182]


Interactions with Hormones



A deficiency of vitamin C in rodents tends to result in elevated plasma cortisol without influencing ACTH concentrations,[209][210] and ACTH stimulation appears to be somewhat hindered despite higher serum cortisol concentrations.[211]

In rats unable to synthesize vitamin C, injections (500mg per rat) are able to delay the turnover of cortisol and enhance its actions in the body[212] and has been found to enhance ACTH-induced cortisol production.[213]

In animal studies, injections of vitamin C can enhance glucocorticoid activity by delaying turnover and enhancing secretion while cortisol activity is also enhanced during deficiency

Supplementation of Vitamin C has been shown to reduce exercise-induced spikes in cortisol after both acute[164][167] and up to 12 days supplementation[166] in the dosage range of 1,000-1,500mg. These studies tend to note either no significant changes in lipid peroxides (a parameter of oxidation in the body) relative to placebo,[166] or a relative decrease.[167] These results are not unanimous as some studies note only a trend towards a reduction in cortisol that fails to reach significance,[214] and similar effects have been noted when a Vitamin C and Vitamin E combination supplement has reduced oxidative parameters.[179]

Elsewhere, an increase in cortisol has been noted with ultramarathons using similar doses of Vitamin C (1,500mg for 7 days).[168][165] These studies either fail to report an increase in oxidative damage[165] or actually note increases in some oxidative biomarkers such as F2-Isoprostane,[168] and one study using Vitamin E alongside Vitamin C (400IU and 500mg, respectively) has noted the same effects.[208]

Vitamin C appears to have a bidirectional relationship with cortisol, with increases noted when Vitamin C is able to be a prooxidant and decreases noted when Vitamin C is able to be an antioxidant. The addition of Vitamin E does not appear to significantly influence the actions of Vitamin C

One study using 3,000mg Vitamin C prior to a non-exercise stressor has failed to find a significant influence on cortisol concentrations relative to control.[215]

Minimal studies assessing cortisol concentrations outside of exercise, none of which are promising



In instances where oxidative stressors damage testicular function (usually rat studies), vitamin C supplementation has been shown to preserve testosterone concentrations secondary to its antioxidant properties. This has been noted in response to lead toxicity,[216] alcohol ingestion,[217] stressors such as noise or burns,[218][219] and various research toxins that act via pro-oxidative means.[220] These protective effects have been noted at oral doses as low as 20-40mg/kg in rats[220][216] and similar protective effects on the testicles has been noted in human males at 1,000mg vitamin C daily.[221]

It should be noted that these protective effects may not be unique to vitamin C, as various other antioxidant compounds have also been noted to exert protection against oxidative toxins (including but not limited to quercetin, vitamin E, selenium, and panax ginseng).

There may be protective effects of vitamin C (any antioxidant, actually) on testicular function. An impairment of testicular function normally suppresses testosterone concentrations, and preserving function would preserve testosterone concentrations; while this is a relative increase, it does not suggest that superloading Vitamin C increases testosterone beyond basal levels


Interactions with Lungs




Interactions with other Organ Systems



Vitamin C is known to be metabolized into oxalic acid, which is known to contribute to the formation of calcium oxalate kidney stones.

It appears that men who take higher doses of Vitamin C (1,000mg) appear to be at a greater relative risk (approximate doubling) of forming kidney stones than do persons who are not deficient in vitamin C but who do not supplement.[222]


Adrenal Glands

Vitamin C appears to be involved in regulation of catecholamines (dopamine, adrenaline, noradrenaline) in the adrenal glands, as ascorbate in the chromaffin granule is oxidized (to ascorbyl radical) and gets reduced back to ascorbate when it reaches the granule membrane (via cytochrome b561)[194][223][224] where it is then secreted alongside catecholamines,[225] which has been detected in humans when stimulated by ACTH.[226] As mentioned elsewhere, vitamin C is also a requirement for the dopamine-β-hydroxylase enzyme which is in the catecholamine biosynthetic pathway, and vitamin C can support earlier stages of catecholamine biosynthesis by recycling tetrahydrobiopterin which is a cofactor for tyrosine hydroxylase (converts L-Tyrosine into L-DOPA).[227]

The importance of vitamin C in maintaining adrenal gland function and catecholamine secretion is thought to underlie why scurvy (Vitamin C deficiency) is associated with fatigue (the earliest observable symptom).[228][229][230] In rodent models where vitamin C deficiencies are induced, circulating catecholamines do appear to be reduced.[231]

Vitamin C is a mandatory cofactor for the synthesis of noradrenaline from dopamine, and subsequently adrenaline from noradrenaline. It is thought that a deficiency of vitamin C and lack of catecholamine secretion underlies fatigue symptoms associated with scurvy

Incubating adrenal chromaffin cells with vitamin C does not appear to increase the activity of the enzyme[232] but has been found to increase noradrenaline production from dopamine in SH-SY5Y neuroblastoma cells (50% increase with 1mM ascorbate over 6 hours,[233] with a later study noting 100-1000µM of ascorbate or 100-300µM dehydroascrobate also causing a similar increase but a plateau at around 500µM[234]). This reaction appeared to be unique to vitamin C (the other antioxidants trolox and N-acetylcysteine failed to mimic the results).[234]

In otherwise healthy humans with a relatively low intake of dietary vitamin C (did not have scurvy), oral ingestion of vitamin C (3,000mg) has been shown to reduce adrenaline secretion in response to stress without affecting noradrenaline nor dopamine.[215]

Vitamin C dose-dependently increases noradrenaline production from dopamine in the adrenalins up until around 0.5mM concentration, where it then plateaus. It appears that this concentration is near physiological concentrations already, as adding additional vitamin C to the diet does not appear to further increase urinary catecholamines



In rats simultaneously exposed to lead, 40mg/kg vitamin C over 6 weeks is able to attenuate changes in oxidative parameters (to approximately half of the way between lead only and no lead control) which was associated with a minimization of lead accumulation and preservation of testicular zinc content. Perhaps secondary to preserving zinc concentrations and testicular function (zinc playing important roles in testicular function[235][236]), vitamin C supplementation preserved testosterone concentrations that dropped with lead.[216]


Pregnancy and Infancy



In rat brains, Vitamin C concentrations in the brain approximately double during the last portion of pregnancy[237][238] which does not further increase after birth (slight decline);[237] this appears to extend to human infants.[239] Lower cerebral ascorbic acid concentrations during development appear to be biomarkers of increased oxidative stress,[240][241] and the importance of vitamin C in neural development is further demonstrated in studies that block vitamin C transport to the brain and causes perinatal death.[59][242]

Dietary requirements (FDA numbers) appear to be increased from 75mg up to 85mg (pregnancy) and 120mg (lactation)[11] and a maternal deficiency of Vitamin C (rodent studies, mostly guinea pigs) appears to deletiriously affect offspring with effects such as; reduced hippocampal neurogenesis and memory formation.[243][244]

Vitamin C is outright vital for cognitive development of infants during pregnancy, and there are higher dietary requirements of Vitamin C during pregnancy and lactation; these increased needs are still wholly feasible through dietary intake of Vitamin C, and a deficiency (however impractical in human life) may result in cognitive impairment to the child


Various other Clinical Usages


Mineral Accumulation and Chelation

In animal studies, vitamin C has been found to reduce cadmium toxicity[245][246][247][248][249] and is implicated in aiding elimination of both lead[250][216] and mercury (although there is mixed evidence on mercury, with a reduction of bioaccumulation,[250] exacerbation of accumulation,[251][252] and no effects on bioaccumulation (despite some protective effects)[253] being reported in animals).

Lead, in particular, appears to be chelated by vitamin C with a potency lesser than EDTA despite requiring a higher dose to match carboxylic acid groups (40mg/kg injections of EDTA being equivalent to 1,750-2,333mg/kg vitamin C per rat).[254] EDTA and vitamin C are, however, additive.[254]

In animal research, supplementation of vitamin C appears to reduce the accumulation of toxic heavy metals and partially normalize the adverse changes. The protection does not appear to be absolute, although statistically significant

In humans not subject to lead toxicity (non-concernable serum and hair concentrations) given 500-1000mg vitamin C for three months, there was no significant influence of Vitamin C on lead accumulation.[255]

One study in psychiatric outpatients noted that combination therapy with vitamin C (2,000mg) and zinc (30mg as gluconate) was found to reduce serum lead concentrations, but copper was also reduced.[256] Industrial workers exposed to lead have also noted a beneficial trend in sperm parameters with 1,000mg for 3 months[221] (lead is known to be adverse to testicular function at concentrations in industrial work utilizing lead[257][258]).

There is mixed evidence for oral supplementation of Vitamin C at doses exceeding 500mg for the removal of lead from the body, with suggestions that this may only affect persons already in a state of lead toxicity and not inherently to otherwise normal persons



In patients with gout given vitamin C supplementation (500mg) either in isolation or in addition to allopurinol for 8 weeks, supplementation has failed to significantly reduce plasma urate in either condition.[259]


Nutrient-Nutrient Interactions


Vitamin E

Vitamin E is a very common addition to Vitamin C supplements, and the combination is marketed as an antioxidant blend. Vitamin C appears to have an ability to recycle and/or spare the oxidation of Vitamin E (in reference to α-tocopherol) in lipid membranes,[260][261] and this preservation of Vitamin E has been noted to probably be the reason lipid peroxidation (a type of oxidation to cellular membranes that Vitamin C does not effectively counter, but Vitamin E does) is reduced with cellular incubation of Vitamin C[262][263] and is synergistic with coincubation with α-tocopherol.[264][265]

In cellular cultures, Vitamin C appears to preserve Vitamin E (since Vitamin C is oxidized, Vitamin E is not and it can do other things) which results in a reduction in lipid peroxidation; incubations of Vitamin C with Vitamin E synergistically reduces lipid peroxidation


Dietary Minerals

Vitamin C has been found to increase the absorption of both iron not bound by heme (ie. not in meat products)[266][267]) and has been noted to reduce the inhibitory effects of phytic acid[268] but not tannins.[269]

May increase the absorption rates of zinc and iron, which would be of interest to those with anemia



Nitrate is a small molecule found in leafy green vegetables and most popularly in Beetroot, and is able to convert into nitric oxide independent of the NOS enzyme system (the enzyme system that arginine is subject to). Nitrate's reduced form (nitrite) can convert amines in the body into nitrosamines via a process known as nitrosylation (which is donating a nitric oxide group to the structure of the amines, this is usually conducted by N2O3 or N2O4), and some of these nitrosamines are known to be carcinogenic.

Vitamin C interacts with nitrite to block nitrosamine formation as the products that conduct the nitrosylation, usually N2O3 or N2O4, react with vitamin C more readily than they do with many amines; the potency of blocking nitrosamine formation is dependent on the amine.[270][271] It has been noted that while a 2:1 ratio (ascorbate:nitrite) is sufficient to block a majority of some nitrosylation, even 20-fold higher dosages do not fully abolish nitrosamine formation.[271] This inhibition appears to occur at a pH of 3-4,[270] and although vitamin C is most well researched for this role some other antioxidant compounds are also implicated (Vitamin E[272] and both ferulic and caffeic acid[273]).

There are some instances where vitamin C has been implicated in augmenting nitrosamine production, such as coingestion with lipids[273] and at pH values below 2.[274][270]

Nitrates can form nitric oxide via nitrite, and nitric oxide that reacts with amines may cause the production of nitrosamines which are known carcinogens. This is mostly a concern with meat products (due to heme causing an increase in the reaction rate), and not too much of a concern with vegetables or water inherently

A few epidemiological studies note significant interactions between vitamin C intake and nitroso compound dietary intake and their influence on cancer.[275]

Oral ingestion of high doses vitamin C (23g/kg in mice) is able to reduce nitroso compound formation from nitrate by 42-56% as assessed by fecal analysis[276] (with no influence on nitroso increases in feces from hot dog ingestion, as the nitroso compounds were premade in the hotdog).


Safety and Toxicology



Vitamin C is generally thought to be safe, although at higher doses (2,000-6,000mg) may cause diarrhea;[277][278] this is due to Vitamin C being near completely absorbed at low dietary levels (100mg or so) and progressively experiencing less absorption at doses exceeding 500mg.[279]

One meta-analysis of four studies reported a 16% increased risk of dental erosion with vitamin C supplementation from chewable tablets.[280]


Case studies

There appears to be a rare possibility of nephrotoxicity (kidney toxicity) associated with oral Vitamin C supplementation, which has sometimes been reported to be fatal (72 year old man reported to take 'several grams a day'; exact dose not stated[281]). In other instances, clinical usage of intravenous Vitamin C has resulted in renal oxalate nephropathy when very large boluses (45-60g) are given[282][283][284][285][286] which results in development of reversible tubulointerstitial nephritis and possible renal failure.[287][288] This is a fairly treatable condition carrying a good prognosis if readily treated,[289] but again it can be fatal if left untreated or if treatment is refused.[281]

The above observations are thought to be due to the metabolism of Vitamin C into oxalate (known to occur with superloading),[290] which the (admittedly unreliable) production of excess oxalate and then deposition into kidney tissues is a known cause of renal failure.[291][292] It has been noted to be a bit more reliably occurring in calcium-kidney stone forming patients.[292]

At least one case study has linked 'several grams of vitamin C' daily towards oxalate nephrotoxicity (a toxic kidney condition due to excessive oxalate concentrations in the kidneys), and it is reasonable to assume that Vitamin C plays a significant role here since it is well established to be able to cause oxalate nephrotoxicity in clinical settings with injections of Vitamin C

Due to the lack of information in the lone oral case study and the long history of safe usage, it is reasonable to assume that oral supplementation does not carry a significant risk. However, intravenous usage of Vitamin C appears to carry more risk and unless supervised by a medical professional should be avoided

1.^Svirbely JL, Szent-Györgyi AThe chemical nature of vitamin CBiochem J.(1932)
2.^Zilva SSThe isolation and identification of vitamin CArch Dis Child.(1935 Aug)
3.^Kyle RA, Shampo MAWalter Haworth--synthesis of vitamin CMayo Clin Proc.(2002 Feb)
5.^Deni LDr. Linus Pauling and vitamin CJ Nurs Care.(1979 Feb)
8.^Karlowski TR, Chalmers TC, Frenkel LD, Kapikian AZ, Lewis TL, Lynch JMAscorbic acid for the common cold. A prophylactic and therapeutic trialJAMA.(1975 Mar 10)
9.^Cameron E, Pauling L, Leibovitz BAscorbic acid and cancer: a reviewCancer Res.(1979 Mar)
10.^Maughan RJ, Depiesse F, Geyer H; International Association of Athletics FederationsThe use of dietary supplements by athletesJ Sports Sci.(2007)
12.^García-Closas R, Berenguer A, José Tormo M, José Sánchez M, Quirós JR, Navarro C, Arnaud R, Dorronsoro M, Dolores Chirlaque M, Barricarte A, Ardanaz E, Amiano P, Martinez C, Agudo A, González CADietary sources of vitamin C, vitamin E and specific carotenoids in SpainBr J Nutr.(2004 Jun)
13.^Nishiyama I, Yamashita Y, Yamanaka M, Shimohashi A, Fukuda T, Oota TVarietal difference in vitamin C content in the fruit of kiwifruit and other actinidia speciesJ Agric Food Chem.(2004 Aug 25)
14.^Agudo A, Amiano P, Barcos A, Barricarte A, Beguiristain JM, Chirlaque MD, Dorronsoro M, González CA, Lasheras C, Martínez C, Navarro C, Pera G, Quirós JR, Rodríguez M, Tormo MJDietary intake of vegetables and fruits among adults in five regions of Spain. EPIC Group of Spain. European Prospective Investigation into Cancer and NutritionEur J Clin Nutr.(1999 Mar)
15.^Subar AF, Krebs-Smith SM, Cook A, Kahle LLDietary sources of nutrients among US adults, 1989 to 1991J Am Diet Assoc.(1998 May)
16.^Cotton PA, Subar AF, Friday JE, Cook ADietary sources of nutrients among US adults, 1994 to 1996J Am Diet Assoc.(2004 Jun)
17.^Furusawa H, Sato Y, Tanaka Y, Inai Y, Amano A, Iwama M, Kondo Y, Handa S, Murata A, Nishikimi M, Goto S, Maruyama N, Takahashi R, Ishigami AVitamin C is not essential for carnitine biosynthesis in vivo: verification in vitamin C-depleted senescence marker protein-30/gluconolactonase knockout miceBiol Pharm Bull.(2008 Sep)
18.^HELLMAN L, BURNS JJMetabolism of L-ascorbic acid-1-C14 in manJ Biol Chem.(1958 Feb)
19.^Seib PA, Tolbert BMAscorbic Acid: Chemistry, Metabolism, and UsesAdv Chem.(1982 Jun)
20.^Dhariwal KR, Hartzell WO, Levine MAscorbic acid and dehydroascorbic acid measurements in human plasma and serumAm J Clin Nutr.(1991 Oct)
23.^Rush RA, Geffen LBDopamine beta-hydroxylase in health and diseaseCrit Rev Clin Lab Sci.(1980)
26.^Kasa RMVitamin C: from scurvy to the common coldAm J Med Technol.(1983 Jan)
27.^Touyz LZVitamin C, oral scurvy and periodontal diseaseS Afr Med J.(1984 May 26)
28.^Wilson LGThe clinical definition of scurvy and the discovery of vitamin CJ Hist Med Allied Sci.(1975 Jan)
29.^Ayaori M, Hisada T, Suzukawa M, Yoshida H, Nishiwaki M, Ito T, Nakajima K, Higashi K, Yonemura A, Ohsuzu F, Ishikawa T, Nakamura HPlasma levels and redox status of ascorbic acid and levels of lipid peroxidation products in active and passive smokersEnviron Health Perspect.(2000 Feb)
30.^Schectman GEstimating ascorbic acid requirements for cigarette smokersAnn N Y Acad Sci.(1993 May 28)
32.^Stankova L, Riddle M, Larned J, Burry K, Menashe D, Hart J, Bigley RPlasma ascorbate concentrations and blood cell dehydroascorbate transport in patients with diabetes mellitusMetabolism.(1984 Apr)
33.^Sinclair AJ, Taylor PB, Lunec J, Girling AJ, Barnett AHLow plasma ascorbate levels in patients with type 2 diabetes mellitus consuming adequate dietary vitamin CDiabet Med.(1994 Nov)
34.^Hume R, Weyers E, Rowan T, Reid DS, Hillis WSLeucocyte ascorbic acid levels after acute myocardial infarctionBr Heart J.(1972 Mar)
35.^Riemersma RA, Carruthers KF, Elton RA, Fox KAAVitamin C and the risk of acute myocardial infarctionAm J Clin Nutr.(2000 May)
36.^Scott P, Bruce C, Schofield D, Shiel N, Braganza JM, McCloy RFVitamin C status in patients with acute pancreatitisBr J Surg.(1993 Jun)
37.^Bonham MJ, Abu-Zidan FM, Simovic MO, Sluis KB, Wilkinson A, Winterbourn CC, Windsor JAEarly ascorbic acid depletion is related to the severity of acute pancreatitisBr J Surg.(1999 Oct)
38.^Padayatty SJ1, Katz A, Wang Y, Eck P, Kwon O, Lee JH, Chen S, Corpe C, Dutta A, Dutta SK, Levine MVitamin C as an antioxidant: evaluation of its role in disease preventionJ Am Coll Nutr.(2003 Feb)
39.^Dallongeville J, Marécaux N, Fruchart JC, Amouyel PCigarette smoking is associated with unhealthy patterns of nutrient intake: a meta-analysisJ Nutr.(1998 Sep)
41.^Pereda J, Sabater L, Aparisi L, Escobar J, Sandoval J, Viña J, López-Rodas G, Sastre JInteraction between cytokines and oxidative stress in acute pancreatitisCurr Med Chem.(2006)
42.^Stadler KOxidative stress in diabetesAdv Exp Med Biol.(2012)
45.^Gruenwald J, Graubaum HJ, Busch R, Bentley CSafety and tolerance of ester-C compared with regular ascorbic acidAdv Ther.(2006 Jan-Feb)
47.^Moyad MA, Combs MA, Crowley DC, Baisley JE, Sharma P, Vrablic AS, Evans MVitamin C with metabolites reduce oxalate levels compared to ascorbic acid: a preliminary and novel clinical urologic findingUrol Nurs.(2009 Mar-Apr)
48.^Moyad MA, Combs MA, Baisley JE, Evans MVitamin C with metabolites: additional analysis suggests favorable changes in oxalateUrol Nurs.(2009 Sep-Oct)
50.^Koshiishi I, Mamura Y, Liu J, Imanari TDegradation of dehydroascorbate to 2,3-diketogulonate in blood circulationBiochim Biophys Acta.(1998 Sep 16)
51.^Hickey DS, Roberts HJ, Cathcart RFDynamic Flow: A New Model for AscorbateJ Orthomol Med.(2005)
52.^Wang Y, Mackenzie B, Tsukaguchi H, Weremowicz S, Morton CC, Hediger MAHuman vitamin C (L-ascorbic acid) transporter SVCT1Biochem Biophys Res Commun.(2000 Jan 19)
53.^Hickey S, Roberts HMisleading information on the properties of vitamin CPLoS Med.(2005 Sep)
54.^Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, Wesley RA, Levine MVitamin C pharmacokinetics: implications for oral and intravenous useAnn Intern Med.(2004 Apr 6)
57.^Panda K, Chattopadhyay R, Chattopadhyay DJ, Chatterjee IBVitamin C prevents cigarette smoke-induced oxidative damage in vivoFree Radic Biol Med.(2000 Jul 15)
58.^Harrison FE1, May JMVitamin C function in the brain: vital role of the ascorbate transporter SVCT2Free Radic Biol Med.(2009 Mar 15)
59.^Sotiriou S, Gispert S, Cheng J, Wang Y, Chen A, Hoogstraten-Miller S, Miller GF, Kwon O, Levine M, Guttentag SH, Nussbaum RLAscorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survivalNat Med.(2002 May)
60.^Lam DK, Daniel PMThe influx of ascorbic acid into the rat's brainQ J Exp Physiol.(1986 Jul)
61.^Agus DB, Gambhir SS, Pardridge WM, Spielholz C, Baselga J, Vera JC, Golde DWVitamin C crosses the blood-brain barrier in the oxidized form through the glucose transportersJ Clin Invest.(1997 Dec 1)
62.^García Mde L, Salazar K, Millán C, Rodríguez F, Montecinos H, Caprile T, Silva C, Cortes C, Reinicke K, Vera JC, Aguayo LG, Olate J, Molina B, Nualart FSodium vitamin C cotransporter SVCT2 is expressed in hypothalamic glial cellsGlia.(2005 Apr 1)
64.^Hakvoort A, Haselbach M, Galla HJActive transport properties of porcine choroid plexus cells in cultureBrain Res.(1998 Jun 8)
65.^Spector RVitamin homeostasis in the central nervous systemN Engl J Med.(1977 Jun 16)
66.^Spector R, Lorenzo AVAscorbic acid homeostasis in the central nervous systemAm J Physiol.(1973 Oct)
67.^Miele M, Fillenz MIn vivo determination of extracellular brain ascorbateJ Neurosci Methods.(1996 Dec)
68.^Schenk JO, Miller E, Gaddis R, Adams RNHomeostatic control of ascorbate concentration in CNS extracellular fluidBrain Res.(1982 Dec 16)
69.^Lönnrot K, Metsä-Ketelä T, Molnár G, Ahonen JP, Latvala M, Peltola J, Pietilä T, Alho HThe effect of ascorbate and ubiquinone supplementation on plasma and CSF total antioxidant capacityFree Radic Biol Med.(1996)
71.^Harrison FE, Green RJ, Dawes SM, May JMVitamin C distribution and retention in the mouse brainBrain Res.(2010 Aug 12)
72.^Milby K, Oke A, Adams RNDetailed mapping of ascorbate distribution in rat brainNeurosci Lett.(1982 Feb 12)
73.^Mefford IN, Oke AF, Adams RNRegional distribution of ascorbate in human brainBrain Res.(1981 May 11)
75.^Tsukaguchi H, Tokui T, Mackenzie B, Berger UV, Chen XZ, Wang Y, Brubaker RF, Hediger MAA family of mammalian Na+-dependent L-ascorbic acid transportersNature.(1999 May 6)
76.^Mun GH, Kim MJ, Lee JH, Kim HJ, Chung YH, Chung YB, Kang JS, Hwang YI, Oh SH, Kim JG, Hwang DH, Shin DH, Lee WJImmunohistochemical study of the distribution of sodium-dependent vitamin C transporters in adult rat brainJ Neurosci Res.(2006 Apr)
79.^Chatterjee IB, Majumder AK, Nandi BK, Subramanian NSynthesis and some major functions of vitamin C in animalsAnn N Y Acad Sci.(1975 Sep 30)
84.^Atlante A, Gagliardi S, Minervini GM, Ciotti MT, Marra E, Calissano PGlutamate neurotoxicity in rat cerebellar granule cells: a major role for xanthine oxidase in oxygen radical formationJ Neurochem.(1997 May)
85.^Majewska MD, Bell JA, London EDRegulation of the NMDA receptor by redox phenomena: inhibitory role of ascorbateBrain Res.(1990 Dec 24)
86.^Majewska MD, Bell JAAscorbic acid protects neurons from injury induced by glutamate and NMDANeuroreport.(1990 Nov-Dec)
87.^Radak Z, Taylor AW, Ohno H, Goto SAdaptation to exercise-induced oxidative stress: from muscle to brainExerc Immunol Rev.(2001)
88.^Kovacheva-Ivanova S, Bakalova R, Ribavov SRImmobilization stress enhances lipid peroxidation in the rat lungs. Materials and methodsGen Physiol Biophys.(1994 Dec)
89.^Oishi K, Yokoi M, Maekawa S, Sodeyama C, Shiraishi T, Kondo R, Kuriyama T, Machida KOxidative stress and haematological changes in immobilized ratsActa Physiol Scand.(1999 Jan)
90.^Moretti M, Budni J, Dos Santos DB, Antunes A, Daufenbach JF, Manosso LM, Farina M, Rodrigues ALProtective effects of ascorbic acid on behavior and oxidative status of restraint-stressed miceJ Mol Neurosci.(2013 Jan)
92.^Galeotti N, Ghelardini C, Caldari B, Bartolini AEffect of potassium channel modulators in mouse forced swimming testBr J Pharmacol.(1999 Apr)
93.^Bortolatto CF, Jesse CR, Wilhelm EA, Nogueira CWInvolvement of potassium channels in the antidepressant-like effect of venlafaxine in miceLife Sci.(2010 Feb 27)
94.^Binfaré RW, Rosa AO, Lobato KR, Santos AR, Rodrigues ALAscorbic acid administration produces an antidepressant-like effect: evidence for the involvement of monoaminergic neurotransmissionProg Neuropsychopharmacol Biol Psychiatry.(2009 Apr 30)
95.^Moretti M, Colla A, de Oliveira Balen G, dos Santos DB, Budni J, de Freitas AE, Farina M, Severo Rodrigues ALAscorbic acid treatment, similarly to fluoxetine, reverses depressive-like behavior and brain oxidative damage induced by chronic unpredictable stressJ Psychiatr Res.(2012 Mar)
96.^Cocchi P, Silenzi M, Calabri G, Salvi GAntidepressant Effect of Vitamin CPediatrics.(1980 Apr)
98.^von Arnim CAF, Herbolsheimer F, Nikolaus F, Peter R, Biesalski HK, Ludolph AC, Riepe M, Nagel GDietary Antioxidants and Dementia in a Population-Based Case-Control Study among Older People in South GermanyJ Alzheimers Dis.(2012)
99.^Christen YOxidative stress and Alzheimer diseaseAm J Clin Nutr.(2000 Feb)
100.^Pappolla MA, Omar RA, Kim KS, Robakis NKImmunohistochemical evidence of oxidative (corrected) stress in Alzheimer's diseaseAm J Pathol.(1992 Mar)
101.^Schipper HM, Cissé S, Stopa EGExpression of heme oxygenase-1 in the senescent and Alzheimer-diseased brainAnn Neurol.(1995 Jun)
102.^Smith MA, Harris PLR, Sayre LM, Beckman JS, Perry GWidespread Peroxynitrite-Mediated Damage in Alzheimer’s DiseaseJ Neurosci.(1997 Apr)
103.^Rivière S, Birlouez-Aragon I, Nourhashémi F, Vellas BLow plasma vitamin C in Alzheimer patients despite an adequate dietInt J Geriatr Psychiatry.(1998 Nov)
104.^Quinn J, Suh J, Moore MM, Kaye J, Frei BAntioxidants in Alzheimer's disease-vitamin C delivery to a demanding brainJ Alzheimers Dis.(2003 Aug)
105.^Heo JH, Hyon-Lee, Lee KMThe possible role of antioxidant vitamin C in Alzheimer's disease treatment and preventionAm J Alzheimers Dis Other Demen.(2013 Mar)
106.^Rosales-Corral S, Tan DX, Reiter RJ, Valdivia-Velázquez M, Martínez-Barboza G, Acosta-Martínez JP, Ortiz GGOrally administered melatonin reduces oxidative stress and proinflammatory cytokines induced by amyloid-beta peptide in rat brain: a comparative, in vivo study versus vitamin C and EJ Pineal Res.(2003 Sep)
107.^Harrison FE, Hosseini AH, McDonald MP, May JMVitamin C reduces spatial learning deficits in middle-aged and very old APP/PSEN1 transgenic and wild-type micePharmacol Biochem Behav.(2009 Oct)
108.^May JM, Harrison FERole of Vitamin C in the Function of the Vascular EndotheliumAntioxid Redox Signal.(2013 Apr 15)
111.^Heller R, Münscher-Paulig F, Gräbner R, Till UL-Ascorbic acid potentiates nitric oxide synthesis in endothelial cellsJ Biol Chem.(1999 Mar 19)
112.^Heller R, Unbehaun A, Schellenberg B, Mayer B, Werner-Felmayer G, Werner ERL-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterinJ Biol Chem.(2001 Jan 5)
115.^Sönmez MF, Narin F, Akkuş D, Ozdamar SEffect of melatonin and vitamin C on expression of endothelial NOS in heart of chronic alcoholic ratsToxicol Ind Health.(2009 Jul)
116.^Bendich A, Machlin LJ, Scandurra OThe antioxidant role of vitamin CAdv Free Radical Biol Med.(1986)
120.^Ginter EVitamin-C deficiency and gallstone formationLancet.(1971 Nov 27)
121.^[No authors listedAscorbic acid and the catabolism of cholesterolNutr Rev.(1973 May)
124.^Steffner RJ, Wu L, Powers AC, May JMAscorbic acid recycling by cultured beta cells: effects of increased glucose metabolismFree Radic Biol Med.(2004 Nov 15)
126.^Malaisse WJ, Malaisse-Lagae F, Sener A, Pipeleers DGDeterminants of the selective toxicity of alloxan to the pancreatic B cellProc Natl Acad Sci U S A.(1982 Feb)
127.^Wells WW, Dou CZ, Dybas LN, Jung CH, Kalbach HL, Xu DPAscorbic acid is essential for the release of insulin from scorbutic guinea pig pancreatic isletsProc Natl Acad Sci U S A.(1995 Dec 5)
128.^Zhou A, Thorn NAHigh ascorbic acid content in the rat endocrine pancreasDiabetologia.(1991 Nov)
135.^Rafighi Z, Shiva A, Arab S, Mohd Yousof RAssociation of dietary vitamin C and e intake and antioxidant enzymes in type 2 diabetes mellitus patientsGlob J Health Sci.(2013 Mar 20)
136.^Nieman DC, Henson DA, McAnulty SR, McAnulty L, Swick NS, Utter AC, Vinci DM, Opiela SJ, Morrow JDInfluence of vitamin C supplementation on oxidative and immune changes after an ultramarathonJ Appl Physiol (1985).(2002 May)
137.^Ghaffari P, Nadiri M, Gharib A, Rahimi FThe effects of vitamin C on diabetic patientsPharm Lett.(2015)
141.^Davison GW, Ashton T, George L, Young IS, McEneny J, Davies B, Jackson SK, Peters JR, Bailey DMMolecular detection of exercise-induced free radicals following ascorbate prophylaxis in type 1 diabetes mellitus: a randomised controlled trialDiabetologia.(2008 Nov)
142.^Tousoulis D, Antoniades C, Vasiliadou C, Kourtellaris P, Koniari K, Marinou K, Charakida M, Ntarladimas I, Siasos G, Stefanadis CEffects of atorvastatin and vitamin C on forearm hyperaemic blood flow, asymmentrical dimethylarginine levels and the inflammatory process in patients with type 2 diabetes mellitusHeart.(2007 Feb)
143.^Chen H, Karne RJ, Hall G, Campia U, Panza JA, Cannon RO 3rd, Wang Y, Katz A, Levine M, Quon MJHigh-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistanceAm J Physiol Heart Circ Physiol.(2006 Jan)
145.^Gokce N, Keaney JF Jr, Frei B, Holbrook M, Olesiak M, Zachariah BJ, Leeuwenburgh C, Heinecke JW, Vita JALong-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery diseaseCirculation.(1999 Jun 29)
146.^Pirbudak L, Balat O, Cekmen M, Ugur MG, Aygün S, Oner UEffect of ascorbic acid on surgical stress response in gynecologic surgeryInt J Clin Pract.(2004 Oct)
148.^Pleiner J, Schaller G, Mittermayer F, Bayerle-Eder M, Roden M, Wolzt MFFA-induced endothelial dysfunction can be corrected by vitamin CJ Clin Endocrinol Metab.(2002 Jun)
149.^Bo S, Ciccone G, Durazzo M, Gambino R, Massarenti P, Baldi I, Lezo A, Tiozzo E, Pauletto D, Cassader M, Pagano GEfficacy of antioxidant treatment in reducing resistin serum levels: a randomized studyPLoS Clin Trials.(2007 May 4)
150.^Mahmoudabadi MM, Djalali M, Djazayery SA, Keshavarz SA, Eshraghian MR, Yaraghi AA, Askari G, Ghiasvand R, Zarei MEffects of eicosapentaenoic acid and vitamin C on glycemic indices, blood pressure, and serum lipids in type 2 diabetic Iranian malesJ Res Med Sci.(2011 Mar)
151.^Ashor AW, Werner AD, Lara J, Willis ND, Mathers JC, Siervo MEffects of vitamin C supplementation on glycaemic control: a systematic review and meta-analysis of randomised controlled trialsEur J Clin Nutr.(2017 Dec)
152.^ Creagan ET, Moertel CG, O'Fallon JR, Schutt AJ, O'Connell MJ, Rubin J, Frytak SFailure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial N Engl J Med.(1979 Sep 27)
153.^Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A, Rivera K, Roper J, Chio II, Giannopoulou EG, Rago C, Muley A, Asara JM, Paik J, Elemento O, Chen Z, Pappin DJ, Dow LE, Papadopoulos N, Gross SS, Cantley LCVitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDHScience.(2015 Dec 11)
157.^Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, Khosh DB, Drisko J, Levine MPharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in miceProc Natl Acad Sci U S A.(2008 Aug 12)
158.^Cairns RADrivers of the Warburg phenotypeCancer J.(2015 Mar-Apr)
160.^Carr AC, Bozonet SM, Pullar JM, Simcock JW, Vissers MCHuman skeletal muscle ascorbate is highly responsive to changes in vitamin C intake and plasma concentrationsAm J Clin Nutr.(2013 Apr)
161.^Savini I, Rossi A, Pierro C, Avigliano L, Catani MVSVCT1 and SVCT2: key proteins for vitamin C uptakeAmino Acids.(2008 Apr)
163.^Cupps TR, Fauci ASCorticosteroid-mediated immunoregulation in manImmunol Rev.(1982)
165.^Palmer FM, Nieman DC, Henson DA, McAnulty SR, McAnulty L, Swick NS, Utter AC, Vinci DM, Morrow JDInfluence of vitamin C supplementation on oxidative and salivary IgA changes following an ultramarathonEur J Appl Physiol.(2003 Mar)
166.^Carrillo AE, Murphy RJ, Cheung SSVitamin C supplementation and salivary immune function following exercise-heat stressInt J Sports Physiol Perform.(2008 Dec)
167.^Nakhostin-Roohi B, Babaei P, Rahmani-Nia F, Bohlooli SEffect of vitamin C supplementation on lipid peroxidation, muscle damage and inflammation after 30-min exercise at 75% VO2maxJ Sports Med Phys Fitness.(2008 Jun)
168.^Nieman DC, Henson DA, McAnulty SR, McAnulty L, Swick NS, Utter AC, Vinci DM, Opiela SJ, Morrow JDInfluence of vitamin C supplementation on oxidative and immune changes after an ultramarathonJ Appl Physiol.(2002 May)
169.^Fischer CP, Hiscock NJ, Penkowa M, Basu S, Vessby B, Kallner A, Sjöberg LB, Pedersen BKSupplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscleJ Physiol.(2004 Jul 15)
170.^Fischer CP, Hiscock NJ, Penkowa M, Basu S, Vessby B, Kallner A, Sjöberg LB, Pedersen BKSupplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscleJ Physiol.(2004 Jul 15)
171.^Keller C, Steensberg A, Pilegaard H, Osada T, Saltin B, Pedersen BK, Neufer PDTranscriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen contentFASEB J.(2001 Dec)
172.^Steensberg A, Febbraio MA, Osada T, Schjerling P, van Hall G, Saltin B, Pedersen BKInterleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen contentJ Physiol.(2001 Dec 1)
173.^Petersen EW, Carey AL, Sacchetti M, Steinberg GR, Macaulay SL, Febbraio MA, Pedersen BKAcute IL-6 treatment increases fatty acid turnover in elderly humans in vivo and in tissue culture in vitroAm J Physiol Endocrinol Metab.(2005 Jan)
174.^Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG, Ramm G, Prelovsek O, Hohnen-Behrens C, Watt MJ, James DE, Kemp BE, Pedersen BK, Febbraio MAInterleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinaseDiabetes.(2006 Oct)
176.^van Hall G, Steensberg A, Sacchetti M, Fischer C, Keller C, Schjerling P, Hiscock N, Møller K, Saltin B, Febbraio MA, Pedersen BKInterleukin-6 stimulates lipolysis and fat oxidation in humansJ Clin Endocrinol Metab.(2003 Jul)
177.^Douglas RM, Hemilä H, Chalker E, Treacy BVitamin C for preventing and treating the common coldCochrane Database Syst Rev.(2007 Jul 18)
178.^Hemilä H, Chalker EVitamin C for preventing and treating the common coldCochrane Database Syst Rev.(2013 Jan 31)
182.^Morrison D, Hughes J, Della Gatta PA, Mason S, Lamon S, Russell AP, Wadley GDVitamin C and E supplementation prevents some of the cellular adaptations to endurance-training in humansFree Radic Biol Med.(2015 Dec)
183.^Marshall RJ, Scott KC, Hill RC, Lewis DD, Sundstrom D, Jones GL, Harper JSupplemental vitamin C appears to slow racing greyhoundsJ Nutr.(2002 Jun)
184.^Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, Sastre J, Viña JOral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performanceAm J Clin Nutr.(2008 Jan)
185.^Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Blüher MAntioxidants prevent health-promoting effects of physical exercise in humansProc Natl Acad Sci U S A.(2009 May 26)
186.^Zhu LL, Cao J, Sun M, Yuen T, Zhou R, Li J, Peng Y, Moonga SS, Guo L, Mechanick JI, Iqbal J, Peng L, Blair HC, Bian Z, Zaidi MVitamin C prevents hypogonadal bone lossPLoS One.(2012)
187.^Anderson TW, Suranyi G, Beaton GHThe effect on winter illness of large doses of vitamin CCan Med Assoc J.(1974 Jul 6)
192.^Schulze HR, Gallenkamp H, Staudinger HMicrosomal NADH-dependent electron transportHoppe Seylers Z Physiol Chem.(1970 Jul)
193.^Lumper L, Schneider W, Staudinger HStudies on the kinetics of microsomal NADH:semidehydroascorbate oxidoreductaseHoppe Seylers Z Physiol Chem.(1967 Mar)
195.^Bielski BHJ, Allen AO, Schwarz HAMechanism of the disproportionation of ascorbate radicalsJ Am Chem Soc.(1981 Jun)
196.^Wells WW, Xu DPDehydroascorbate reductionJ Bioenerg Biomembr.(1994 Aug)
198.^Landino LM, Koumas MT, Mason CE, Alston JAAscorbic acid reduction of microtubule protein disulfides and its relevance to protein S-nitrosylation assaysBiochem Biophys Res Commun.(2006 Feb 10)
200.^Buettner GR, Jurkiewicz BACatalytic metals, ascorbate and free radicals: combinations to avoidRadiat Res.(1996 May)
205.^Heitkamp HC, Wegler S, Brehme U, Heinle HEffect of an 8-week endurance training program on markers of antioxidant capacity in womenJ Sports Med Phys Fitness.(2008 Mar)
206.^Higuchi M, Cartier LJ, Chen M, Holloszy JOSuperoxide Dismutase and Catalase in Skeletal Muscle: Adaptive Response to ExerciseJ Gerontol.(1985)
207.^Oh-ishi S, Kizaki T, Nagasawa J, Izawa T, Komabayashi T, Nagata N, Suzuki K, Taniguchi N, Ohno HEffects of endurance training on superoxide dismutase activity, content and mRNA expression in rat muscleClin Exp Pharmacol Physiol.(1997 May)
208.^Yfanti C, Fischer CP, Nielsen S, Akerström T, Nielsen AR, Veskoukis AS, Kouretas D, Lykkesfeldt J, Pilegaard H, Pedersen BKRole of vitamin C and E supplementation on IL-6 in response to trainingJ Appl Physiol.(2012 Mar)
217.^Harikrishnan R, Abhilash PA, Das SS, Prathibha P, Rejitha S, John F, Kavitha S, Indira MProtective effect of ascorbic acid against ethanol-induced reproductive toxicity in male guinea pigsBr J Nutr.(2013 Jan 21:1-10)
218.^Jewo PI, Duru FI, Fadeyibi IO, Saalu LC, Noronha CCThe protective role of ascorbic acid in burn-induced testicular damage in ratsBurns.(2012 Feb)
219.^Saki G, Jasemi M, Sarkaki AR, Fathollahi AEffect of administration of vitamins C and E on fertilization capacity of rats exposed to noise stressNoise Health.(2013 May-Jun)
220.^Takhshid MA, Tavasuli AR, Heidary Y, Keshavarz M, Kargar HProtective effect of vitamins e and C on endosulfan-induced reproductive toxicity in male ratsIran J Med Sci.(2012 Sep)
221.^Vani K, Kurakula M, Syed R, Alharbi KClinical relevance of vitamin C among lead-exposed infertile menGenet Test Mol Biomarkers.(2012 Sep)
222.^Thomas LD, Elinder CG, Tiselius HG, Wolk A, Akesson AAscorbic acid supplements and kidney stone incidence among men: a prospective studyJAMA Intern Med.(2013 Mar 11)
224.^Njus D, Knoth J, Cook C, Kelly PMElectron transfer across the chromaffin granule membraneJ Biol Chem.(1983 Jan 10)
225.^Levine M, Asher A, Pollard H, Zinder OAscorbic acid and catecholamine secretion from cultured chromaffin cellsJ Biol Chem.(1983 Nov 10)
226.^Padayatty SJ, Doppman JL, Chang R, Wang Y, Gill J, Papanicolaou DA, Levine MHuman adrenal glands secrete vitamin C in response to adrenocorticotrophic hormoneAm J Clin Nutr.(2007 Jul)
227.^Stone KJ, Townsley BHThe effect of L-ascorbate on catecholamine biosynthesisBiochem J.(1973 Mar)
228.^Kurtzman D, Dupont J, Lian F, Curiel-Lewandrowski CFatigue and lower-extremity ecchymosis in a 36-year-old woman. ScurvyArch Dermatol.(2012 Sep 1)
229.^Olmedo JM, Yiannias JA, Windgassen EB, Gornet MKScurvy: a disease almost forgottenInt J Dermatol.(2006 Aug)
230.^Hirschmann JV, Raugi GJAdult scurvyJ Am Acad Dermatol.(1999 Dec)
231.^Amano A, Tsunoda M, Aigaki T, Maruyama N, Ishigami AEffect of ascorbic acid deficiency on catecholamine synthesis in adrenal glands of SMP30/GNL knockout miceEur J Nutr.(2013 Mar 19)
233.^Richards ML, Sadee WHuman neuroblastoma cell lines as models of catechol uptakeBrain Res.(1986 Oct 1)
234.^May JM, Qu ZC, Nazarewicz R, Dikalov SAscorbic acid efficiently enhances neuronal synthesis of norepinephrine from dopamineBrain Res Bull.(2013 Jan)
235.^Bedwal RS, Bahuguna AZinc, copper and selenium in reproductionExperientia.(1994 Jul 15)
236.^Tuncer I, Sunar F, Toy H, Baltaci AK, Mogulkoc RHistological effects of zinc and melatonin on rat testesBratisl Lek Listy.(2011)
237.^Kratzing CC, Kelly JD, Kratzing JEAscorbic acid in fetal rat brainJ Neurochem.(1985 May)
238.^Kratzing CC, Kelly JDTissue levels of ascorbic acid during rat gestationInt J Vitam Nutr Res.(1982)
241.^Harrison FE, Meredith ME, Dawes SM, Saskowski JL, May JMLow ascorbic acid and increased oxidative stress in gulo(-/-) mice during developmentBrain Res.(2010 Aug 19)
242.^Harrison FE, Dawes SM, Meredith ME, Babaev VR, Li L, May JMLow vitamin C and increased oxidative stress and cell death in mice that lack the sodium-dependent vitamin C transporter SVCT2Free Radic Biol Med.(2010 Sep 1)
243.^Tveden-Nyborg P, Johansen LK, Raida Z, Villumsen CK, Larsen JO, Lykkesfeldt JVitamin C deficiency in early postnatal life impairs spatial memory and reduces the number of hippocampal neurons in guinea pigsAm J Clin Nutr.(2009 Sep)
244.^Tveden-Nyborg P, Vogt L, Schjoldager JG, Jeannet N, Hasselholt S, Paidi MD, Christen S, Lykkesfeldt JMaternal vitamin C deficiency during pregnancy persistently impairs hippocampal neurogenesis in offspring of guinea pigsPLoS One.(2012)
245.^Richardson ME, Fox MR, Fry BE JrPathological changes produced in Japanese quail by ingestion of cadmiumJ Nutr.(1974 Mar)
248.^Fox MR, Fry BE Jr, Harland BF, Schertel ME, Weeks CEEffect of ascorbic acid on cadmium toxicity in the young coturnixJ Nutr.(1971 Oct)
250.^Hill CHInteractions of vitamin C with lead and mercuryAnn N Y Acad Sci.(1980)
251.^Blackstone S, Hurley RJ, Hughes RESome inter-relationships between vitamin C (L-ascorbic acid) and mercury in the guinea-pigFood Cosmet Toxicol.(1974 Aug)
254.^Goyer RA, Cherian MGAscorbic acid and EDTA treatment of lead toxicity in ratsLife Sci.(1979 Jan 29)
255.^Calabrese EJ, Stoddard A, Leonard DA, Dinardi SRThe effects of vitamin C supplementation on blood and hair levels of cadmium, lead, and mercuryAnn N Y Acad Sci.(1987)
256.^Sohler A, Kruesi M, Pfeiffer CCBlood Lead Levels in Psychiatric Outpatients Reduced by Zinc and Vitamin CJ Orthomol Psychiatry.(1977)
257.^Naha N, Manna BMechanism of lead induced effects on human spermatozoa after occupational exposureKathmandu Univ Med J (KUMJ).(2007 Jan-Mar)
259.^Stamp LK, O'Donnell JL, Frampton C, Drake J, Zhang M, Chapman PTClinically insignificant effect of supplemental vitamin C on serum urate in patients with gout; A pilot randomised controlled trialArthritis Rheum.(2013 May 16)
261.^Niki E, Noguchi N, Tsuchihashi H, Gotoh NInteraction among vitamin C, vitamin E, and beta-caroteneAm J Clin Nutr.(1995 Dec)
262.^Seregi A, Schaefer A, Komlós MProtective role of brain ascorbic acid content against lipid peroxidationExperientia.(1978 Aug 15)
264.^Sato K, Saito H, Katsuki HSynergism of tocopherol and ascorbate on the survival of cultured brain neuronesNeuroreport.(1993 Sep 3)
267.^Kalgaonkar S, Lönnerdal BEffects of dietary factors on iron uptake from ferritin by Caco-2 cellsJ Nutr Biochem.(2008 Jan)
268.^Han O, Failla ML, Hill AD, Morris ER, Smith JC JrAscorbate offsets the inhibitory effect of inositol phosphates on iron uptake and transport by Caco-2 cellsProc Soc Exp Biol Med.(1995 Oct)
269.^Engle-Stone R, Yeung A, Welch R, Glahn RMeat and ascorbic acid can promote Fe availability from Fe-phytate but not from Fe-tannic acid complexesJ Agric Food Chem.(2005 Dec 28)
271.^Tannenbaum SR, Wishnok JS, Leaf CDInhibition of nitrosamine formation by ascorbic acidAm J Clin Nutr.(1991 Jan)
273.^Combet E, El Mesmari A, Preston T, Crozier A, McColl KEDietary phenolic acids and ascorbic acid: Influence on acid-catalyzed nitrosative chemistry in the presence and absence of lipidsFree Radic Biol Med.(2010 Mar 15)
274.^Chang SK, Harrington GW, Rothstein M, Shergalis WA, Swern D, Vohra SKAccelerating effect of ascorbic acid on N-nitrosamine formation and nitrosation by oxyhyponitriteCancer Res.(1979 Oct)
275.^Loh YH, Jakszyn P, Luben RN, Mulligan AA, Mitrou PN, Khaw KTN-Nitroso compounds and cancer incidence: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk StudyAm J Clin Nutr.(2011 May)
278.^Hoyt CJDiarrhea from vitamin CJAMA.(1980 Oct 10)
279.^Sauberlich HEBioavailability of vitaminsProg Food Nutr Sci.(1985)
281.^McHugh GJ, Graber ML, Freebairn RCFatal vitamin C-associated acute renal failureAnaesth Intensive Care.(2008 Jul)
283.^Lawton JM, Conway LT, Crosson JT, Smith CL, Abraham PAAcute oxalate nephropathy after massive ascorbic acid administrationArch Intern Med.(1985 May)
285.^Wong K, Thomson C, Bailey RR, McDiarmid S, Gardner JAcute oxalate nephropathy after a massive intravenous dose of vitamin CAust N Z J Med.(1994 Aug)
290.^Hatch M, Mulgrew S, Bourke E, Keogh B, Costello JEffect of megadoses of ascorbic acid on serum and urinary oxalateEur Urol.(1980)
291.^Gabardi S, Munz K, Ulbricht CA review of dietary supplement-induced renal dysfunctionClin J Am Soc Nephrol.(2007 Jul)
292.^Baxmann AC, De O G Mendonça C, Heilberg IPEffect of vitamin C supplements on urinary oxalate and pH in calcium stone-forming patientsKidney Int.(2003 Mar)
293.^Anitra C Carr, Gladys Block, Jens LykkesfeldtEstimation of Vitamin C Intake Requirements Based on Body Weight: Implications for ObesityNutrients.(2022 Mar 31)
294.^BOINES GJ, HOROSCHAK SHesperidine and ascorbic acid in the prevention of upper respiratory infectionsInt Rec Med Gen Pract Clin.(1956 Feb)
295.^Chavance M, Herbeth B, Lemoine A, Zhu BPDoes multivitamin supplementation prevent infections in healthy elderly subjects? A controlled trialInt J Vitam Nutr Res.(1993)
297.^Cook NR, Albert CM, Gaziano JM, Zaharris E, MacFadyen J, Danielson E, Buring JE, Manson JEA randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular StudyArch Intern Med.(2007 Aug 13-27)
299.^Mahalanabis D, Jana S, Shaikh S, Gupta S, Chakrabarti ML, Moitra P, Wahed MA, Khaled MAVitamin E and vitamin C supplementation does not improve the clinical course of measles with pneumonia in children: a controlled trialJ Trop Pediatr.(2006 Aug)
300.^Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Glynn RJ, Gaziano JMVitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trialJAMA.(2008 Nov 12)
301.^Bancalari A, Seguel C, Neira F, Ruíz I, Calvo CProphylactic value of vitamin C in acute respiratory tract infections in schoolchildrenRev Med Chil.(1984 Sep)
302.^Liljefors IVitamin C and the common coldLakartidningen.(1972 Jul 5)
304.^Mochalkin NIAscorbic acid in the complex therapy of acute pneumoniaVoen Med Zh.(1970 Sep)