Topical Review Article
Vitamin C: Overview and Update
Amanda K. Schlueter, MS1 and Carol S. Johnston, PhD1
Journal of Evidence-Based
Complementary & Alternative Medicine
16(1) 49-57
ª The Author(s) 2011
Reprints and permission:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/1533210110392951
http://cam.sagepub.com
Abstract
Vitamin C functions in enzyme activation, oxidative stress reduction, and immune function. There is considerable evidence that
vitamin C protects against respiratory tract infections and reduces risk for cardiovascular disease and some cancers. Current
trials are examining the efficacy of intravenous vitamin C as cancer therapy. Many experts believe that the recommended intakes
for vitamin C (45 to 90 mg daily) are several orders of magnitude too low to support optimal vitamin C functionality. Also, there is
a misperception that vitamin C deficiency disease (scurvy) is largely historical and rarely observed in developed nations. Physical
symptoms of scurvy include swelling of the lower extremities, bleeding gums, fatigue, and hemorrhaging, as well as psychological
problems, including depression, hysteria, and social introversion. The long-term safety of vitamin C supplementation seems evident as large investigations have noted reduced risk of mortality in vitamin C supplementing populations and in those with elevated
plasma vitamin C concentrations.
Keywords
vitamin C, scurvy, metabolism, disease states, ascorbic acid, dehydroascorbic acid, cancer
Received September 24, 2010. Accepted for publication October 16, 2010.
History
Cases of ascorbic acid (vitamin C) deficiency disease (scurvy),
are well documented throughout history. Although it is probable that many have suffered from the disease for centuries
while on land, scurvy is most commonly associated with the
extended sea travels in the 16th, 17th, and 18th centuries.1
A Dutch fleet sailed to the East Indies in 1595 with 249 men,
returning in 1597 with only 88; presumably, scurvy was a
major cause for this loss.2 In 1620, the Mayflower lost 50 of its
102 men aboard, many because of scurvy. At the time, treatments for the disease were ineffective and ranged from
molasses and cider to sweating and purges.1
Scurvy symptoms include bleeding gums, swollen and painful legs, bruising, skin hemorrhages, weakness, and apathy.
James Lind is widely recognized as the first to identify an
effective treatment for scurvy through the use of a clinical trial.
While aboard the HMS Salisbury in 1747 as a surgeon, he
selected 12 men with similar cases of scurvy. After placing the
men into 6 pairs, he proceeded to carry out 6 different treatments for their maladies: a quart of cider a day, 25 drops of
vitriol a day, 2 spoonfuls of vinegar 3 times a day, half a pint
of sea water a day, or a purgative electuary a day. The final pair
received 2 oranges and 1 lemon a day for 6 days. The final pair
recovered whereas the other pairs did not. Lind recorded his
trial in Treatise of the Scurvy in 1753.3
By 1796, British ships were instructed to include lemon
juice in their crew cargo in order to prevent scurvy.1 As a result,
deaths due to scurvy decreased. By the late 1800s, it was widely
accepted around the world that scurvy was a nutritional disease,
and that fresh fruits and vegetables were the cure. Although a
cure was known for the disease, the agent responsible was not.
In 1912, Casimir Funk working at the Lister Institute in the
United Kingdom recognized scurvy, as well as beriberi and
rickets, as diseases of dietary deficiencies. The lacking ingredients responsible for these diseases he termed vital amines
or vitamins.4 In 1928, while studying the oxidation reduction
reactions in plants and animals, the Hungarian scientist,
Albert Szent-Györgyi isolated a powerful reducing agent he
termed hexuronic acid.5 In 1932, hexuronic acid was revealed
to be the antiscorbutic factor, vitamin C, in independent
reports by Szent-Györgyi and Glen King of the University of
Pittsburgh.6,7
Biochemistry and Function
Vitamin C represents a redox system consisting of 2 L-isomers:
ascorbic acid (vitamin C) in the reduced state and dehydroascorbic acid (DHA) in the oxidized state (Figure 1). Most of
the vitamin’s functionality in the human body is related to the
role of vitamin C as an electron donor; hence, vitamin C is the
active, stable form of vitamin C in tissues. When used as a cofactor or antioxidant, vitamin C is oxidized to the more unstable
1
Arizona State University, Phoenix, AZ, USA
Corresponding Author:
Carol S. Johnston, PhD, 6950 E. Williams Field Road, Mesa, AZ 85212, USA
Email: carol.johnston@asu.edu
50
Journal of Evidence-Based Complementary & Alternative Medicine 16(1)
VEO.
VEOH
OH .
H2O
enzyme-Fe(III)
enzyme-Fe(II)
enzyme-Cu(II)
enzyme-Cu(I)
REDUCTION ROLE
ASCORBYL
RADICAL
ASCORBIC
ACID
DEHYDROASCORBIC
ACID
REGENERATION
GSSG
2GSH
+
NADP
NADPH
Figure 1. Relationships between the vitamin C redox system and
other compounds
Abbreviations: VEOH, vitamin E; VEO., tocopheroxyl radical;
OH. ¼ hydroxyl radical; GSH, reduced glutathione.
dehydroascorbic acid, which is readily ‘‘recycled’’ back to
vitamin C by several enzyme systems, including glutathionedependent systems or reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent systems.8 One report calculated that these enzyme systems can regenerate the amount
of vitamin C typically in blood (35 mmol/L) every 3 minutes
suggesting a remarkable ability of the human system to
conserve vitamin C.9
Vitamin C functions as an enzyme cofactor in a number of
hydroxylation reactions in vivo; specifically, vitamin C maintains
metal ions within these enzymes in a reduced state which is
required for enzyme activity. Although alternate electron donors
can function in these roles, vitamin C is the most effective cofactor for these enzymes as indicated by the development of disease
states when vitamin C status is poor.10 Three of these enzymes
function in collagen biosynthesis: prolyl 4-hydroxylase, prolyl
3-hydroxylase, and lysyl hydroxylase enzymes. In these enzymes,
vitamin C maintains the iron ion in the reduced ferrous (Fe2þ)
state required for enzyme activity.11
Carnitine, tyrosine, and certain neurotransmitter and hormone
synthesis is aided by vitamin C as well. Trimethyllysine dioxygenase and 4-g-butyrobetaine dioxygenase are both enzymes
used in the production of carnitine. In these enzymes, vitamin C
again serves as a reducing agent, reducing iron to its ferrous
state.12 In tyrosine synthesis, vitamin C is thought to maintain ferrous iron in the homogentisate dioxygenase enzyme and cuprous
copper (Cu1þ) in p-hydroxyphenylpyruvate. Both enzymes are
essential in the conversion of phenylalanine to tyrosine. The production of certain neurotransmitters and hormones require vitamin C to maintain cuprous copper for enzyme activity.
Dopamine b-hydroxylase catalyzes the conversion of dopamine
to norepinephrine, requiring vitamin C for the process.13 In addition, peptidyl-glycine a-amidating monooxygenase catalyzes
many reactions through the amidation of peptides. This enzyme
is responsible for the synthesis of neurotransmitters and hormones, including calcitonin, oxytocin, vasopressin, cholecystokinin, and gastrin-releasing peptide.14
As an effective reducing agent, vitamin C also serves as a
powerful antioxidant, scavenging reactive oxygen and nitrogen
species in the body. Reactive species are generated by normal
cell processes as well as environmental stressors and can cause
oxidative damage to lipids, cell proteins, and nucleic acids in
DNA. Vitamin C supplementation has been shown to reduce
levels of oxidative stress, thereby reducing potential damage
to tissues.15
Although the direct antioxidant protection afforded by
vitamin C is limited to water-soluble environments, vitamin
C does play an antioxidant role in lipids through its regeneration of fat-soluble vitamin E. Vitamin C readily donates an
electron to the vitamin E radical to regenerate the active form
of vitamin E, a-tocopherol. The antioxidant function of a-tocopherol limits lipid peroxidation in the membranes of cells,
mitochondria, and endoplasmic reticulum, and thereby maintains
cell integrity.8
Histamine promotes blood flow and healing in times of
physiological stress. However, excess histamine is noted
during periods of chronic stress, inflammation, or allergy, and
negatively affects immunity and respiration. Vitamin C
destroys the imidole ring of the histamine molecule, and an
inverse relationship has been demonstrated between plasma
vitamin C concentrations and blood histamine.16 This result
could be of importance, as histamine can aggravate the respiratory tract and impair neutrophil chemotaxis, resulting in
allergy-like symptoms and weakened immunity.
In the intestinal tract, vitamin C enhances iron bioavailability by maintaining non-heme iron in the ferrous state. Vitamin
C also promotes duodenal ferric reductase activity further contributing to the absorption potential of dietary iron.17 Hallberg
et al18 showed that iron absorption increased in a dose–
response manner when vitamin C was ingested with a meal.
These investigators recommended a dose of 50 mg vitamin C
per meal to maximize non-heme iron absorption; natural or
synthetic sources of ascorbic acid both have the ability to perform this function. In tissues, vitamin C upregulates ferritin
messenger ribonucleic acid (messenger RNA) translation
thereby increasing intracellular iron storage and preventing
iron-induced oxidative damage within cells.19,20 These data
provide strong evidence that vitamin C has a potent regulatory
influence on iron metabolism.
Metabolism and Deficiency
Vitamin C is ingested in both its reduced and oxidized forms
throughout the length of the human small intestine, albeit
through different mechanisms.21 Vitamin C is absorbed via the
sodium-dependent active transporter, SVCT1, largely in the
Schlueter and Johnston
ileum and jejunum; whereas, dehydroascorbic acid is
absorbed, with lesser frequency, by facilitated diffusion with
higher concentration in the more proximal portions of the
intestines, the duodenum, and jejunum.22 When glucose is
added to in vitro systems, dehydroascorbic acid, but not vitamin C, uptake by brush border cells is inhibited, implying
that dehydroascorbic acid, is mainly absorbed with the aid
of glucose transporters.23
The absorption efficiency of vitamin C is highly dependent
on the amount ingested, and can vary widely. At low doses
(20 mg), absorption can reach nearly 100%, whereas at higher
doses (12 g), only 16% is absorbed.24 The bioavailability of
vitamin C can be represented by a curve with a steep incline
between 30 mg and 100 mg daily intake. At a single 100 mg/d
dose, tissue saturation is achieved; however, higher intakes
(>500 mg/d) are required to achieve plasma saturation and to
maximize antioxidant protection.25 Single doses >1000 mg/d
can cause gastrointestinal distress, nausea, and osmotic diarrhea, as the body attempts to rid itself of the high intraluminal
concentration of vitamin C. The tolerable upper intake level
(UL) for vitamin C, 2000 mg daily, is based on likely observance of osmotic diarrhea and related gastrointestinal
disturbances.
Vitamin C circulates mainly as unbound vitamin C and is
available as a reductant in blood and interstitial fluids. Vitamin
C oxidation forms the transient ascorbyl radical, monodehydroL-ascorbic acid, which is either quickly recycled to vitamin C
or, when oxidative stress is high, oxidized to form dehydroascorbic acid. Dehydroascorbic acid is rapidly transported into
bystander cells (eg, erythrocytes, leukocytes, and many
insulin-sensitive tissues) on glucose transporters;26 once inside
cells, dehydroascorbic acid is rapidly recycled to vitamin C, an
important source of intracellular vitamin C. Because these
transporters are also responsible for glucose absorption, glucose is a competitive inhibitor of dehydroascorbic acid transport. In fact, hyperglycemia, which can be caused by
diabetes, sepsis, or stress, results in decreased uptake of dehydroascorbic acid, and therefore, lower concentrations of intracellular vitamin C.27 dehydroascorbic acid has a short halflife (<2 minutes) and if not taken up by cells, it is metabolized
to excretory products, mainly oxalic acid.
Vitamin C is directly transported into tissues via the sodiumdependent transporter, SVCT2.28 SVCT2 can in part account
for gender differences in vitamin C status with lower plasma
vitamin C concentrations consistently demonstrated for males
versus females. In female mice, SVCT2 in the spleen had
decreased uptake of vitamin C in comparison with male mice,
decreasing the amount of vitamin C that was cleared from
plasma.28 In addition, female mice showed a decrease in urinary vitamin C excretion, resulting in higher plasma vitamin C
concentrations in female mice in comparison to male mice.
Vitamin C excretory products include vitamin C, dehydroascorbic acid, and oxalic acid. At high intakes (>500 mg), 50% of
the absorbed dosage is excreted unmetabolized as vitamin C
after several hours. With typical intakes, approximately 1.5%
of ingested vitamin C is converted to oxalate for urinary
51
excretion. Massey et al29 demonstrated that 40% of subjects
supplemented with high-dose vitamin C (2000 mg/day as
divided doses) exhibited a 10% or greater increase in oxalate
excretion, whereas the remaining 60% of supplemented subjects showed no change in urinary oxalate. In addition, these
same 40% showed an increased risk of developing oxalate kidney stones, because of increased endogenous oxalate synthesis
and absorption. Thus, it would be prudent for those individuals
susceptible to oxalate stones to limit vitamin C supplementation to 500 mg daily.30
Plasma vitamin C concentration <11 mmol/L (0.2 mg/dL),
is indicative of scurvy.31 Common physical symptoms
of scurvy include swelling of the lower extremities, bleeding gums, malaise or fatigue, bruising, petechiae, corkscrew
hairs, dry skin, and hemorrhaging.32,33 Although less appreciated, psychological symptoms accompany scurvy, including depression, hysteria, and social introversion.34-37 These
personality changes occur at higher body pools of vitamin
C (761 to 561 mg) than do psychomotor alterations (190
to 63 mg); furthermore, after the initiation of vitamin C
therapy in deficient individuals, depression was alleviated
more rapidly than was the physical pain of swollen legs.34
Hence, mental affect appears to be very sensitive to vitamin
C status.
Although scurvy is easily detected through detailed diet
recalls and blood tests, symptoms of the disease are often
nonspecific or masquerade as other diseases such as cellulitis,36 vasculitis, or arthritis.38 The misperception that scurvy
is largely a historical disease and rarely observed in developed nations where fruits and vegetables are abundant further complicates diagnoses. This is evident in the recent
medical literature, as many scurvy cases were first misdiagnosed and mistreated before the root of the problem is discovered and treated. In affluent societies, those at risk of
developing vitamin C deficiency typically have diets lacking in fresh fruits and vegetables (often associated with poor
diet choices or imposed restrictive diet plans). Also, cigarette smokers exhibit decreased plasma vitamin C concentrations despite adequate dietary intakes39 as do individuals
with chronic hyperglycemia due to diabetes, sepsis, or
stress.27 Additionally, adult males consistently exhibit lower
plasma vitamin C concentrations across the life cycle than
do their female counterparts.
Vitamin C and Disease States
Vitamin C supplementation has a protective influence on several disease states, most notably the common cold, cardiovascular disease, and some cancers (Figure 2). Many other
disease states have been studied in relationship to vitamin C,
including age-related macular degeneration, cataract, diabetes,
and rheumatoid arthritis; however, the link between vitamin C
and these conditions has not been clearly established.40 More
research is warranted to determine if vitamin C can play a protective or therapeutic role in these conditions.
52
The Common Cold
Vitamin C is thought to reduce the duration and severity of
common cold symptoms by enhancing immune responses and
by functioning as an antihistamine. In vitro, vitamin C destroys
histamine by breaking the imizadole ring structure of the molecule,41 and, in vivo, plasma histamine concentrations are
reduced 40% in healthy adults after 2 weeks of vitamin C supplementation (2 g/d).42 Since histamine is a mediator for the
common symptoms of colds and allergy, this antihistamine
property of vitamin C could function to reduce cold severity.
Reduced leukocyte motility, for example, chemotaxis, is also
associated with severity of cold symptoms,43 and several studies demonstrated that vitamin C supplementation enhances leukocyte chemotaxis.44,45 Furthermore, acute vitamin C
supplementation (1 g) is associated with a rapid, but transient,
rise in vitamin C concentrations in respiratory tract lining
fluids, which could provide immediate antioxidant protection
to lung tissues and temporarily attenuate oxidative stress in
airways.46
In elderly patients hospitalized with acute respiratory infections, patients randomized to receive 200 mg of vitamin C daily
recovered more rapidly than patients receiving placebo, and the
vitamin C supplemented patients experienced lower death rates
compared with the placebo group (4% vs 17%).47 In a Japanese
population (439 patients with atrophic gastritis), chronic vitamin C supplementation (500 mg/d) reduced the number of
common colds by 20% over a 3-year period compared with placebo ingestion.48 In a randomized clinical trial conducted in the
United Kingdom (168 healthy adults), vitamin C supplementation
(1 g/d for 60 days) was associated with shorter cold durations (1.8 vs 3.1 days) and fewer reported colds (0.4 vs 0.6
colds/person).49 Recent meta-analyses show modest beneficial
effects of vitamin C supplementation for reducing common
cold duration (8% to 14%) and severity (as indicated by days
confined to home and off work or school).50,51
The most pronounced benefit of vitamin C supplementation
for reducing cold incidence and severity has been demonstrated
in populations experiencing extreme physical stress. Vitamin C
supplementation (600 mg/d) markedly reduced the incidence of
upper respiratory tract infections in ultramarathon runners for
the 14-day period following a competitive 42-km race when
compared with placebo treatment (33% vs 68%, respectively).52 In military recruits, vitamin C supplementation
(range 300 to 3000 mg/d) was associated with significant
reductions in cold severity in 4 of 5 controlled trials; but a significant reduction in cold episodes associated with vitamin C
supplementation was noted in only 1 of these trials.53
Journal of Evidence-Based Complementary & Alternative Medicine 16(1)
50% for individuals in the top quartile for plasma vitamin C
levels as compared with that observed for those in the lowest
quartile.54 A later analysis from EPIC-Norfolk study indicated
that risk for incident stroke was reduced 42% for individuals in
the top quartile for plasma vitamin C as compared with that
observed for those in the lowest quartile.55 National survey data
collected in the United States from 1976 to 1980 (the NHANES
data set) showed similar results: For every 0.5 mg/dL rise in
serum vitamin C, there was an 11% decrease in the prevalence
of cardiovascular disease and stroke incidence.56 However,
analysis of a later NHANES data set (1989-1994) by these same
investigators showed an inverse relationship between serum
vitamin C concentrations and risk for cardiovascular disease
only for participants who consumed alcohol.57 The authors
speculated that the lack of an inverse relationship between vitamin C status and cardiovascular disease risk in the general population could be explained by survivor bias; that is, those who
survived a cardiovascular event could have made dietary
changes resulting in an increased plasma vitamin C status, or
those with low serum vitamin C could have perished by a stroke
or heart attack.
A pooled analysis of 9 cohorts (293 172 total participants;
4647 major incident coronary heart disease events) revealed
that dietary vitamin C was not related to incident coronary
heart disease when supplement users were excluded from the
analyses.58 However, in this pooled analysis, supplemental
vitamin C (400 mg/d) was associated with a 25% reduction
in incident coronary heart disease in comparison with that noted
for nonusers of vitamin C supplements (P < .001). Adjustments
for ‘‘healthy’’ lifestyle and potential dietary confounders did not
weaken this association. Hence, the heart-protective effects of
vitamin C appear to be most pronounced with supplemental
intakes >400 mg/d.
Clinical trial results are mixed regarding a role for supplemental vitamin C in reducing cardiovascular disease risk.
A large-scale randomized trial in more than 14 000 men did not
show a beneficial effect of supplemental vitamin C (500 mg/d
for 8 years) for any cardiovascular end point, including myocardial infarction, total stroke, or cardiovascular mortality.59
Yet in smaller randomized clinical trials, vitamin C supplementation (500 to 1000 mg/d for up to 8 weeks) was associated
with reduced systolic and diastolic blood pressure, reduced
systemic arterial stiffness, and reduced elevated C-reactive protein.60-62 Moreover, both oral and intravenous injection of vitamin C enhanced flow-mediated endothelium-dependent
dilation 40% to 180%.63,64 These latter investigations provide
theoretical mechanisms for the reported beneficial effects of
supplemental vitamin C for reducing cardiovascular disease risk.
Cardiovascular Disease
Cancer
Data from a prospective population study encompassing more
than 25 000 men and women (40 to 79 years old) living in the
United Kingdom (the European Prospective Investigation into
Cancer [EPIC]-Norfolk study) indicated that risk of dying from
cardiovascular disease or ischemic heart disease was reduced
High intakes of vitamin C have been associated with decreased
risk of certain cancers, particularly cancers of the pharynx, oral
cavity, esophagus, lung, and stomach.65 Although the anticancer actions of vitamin C are not well defined, it is thought that
the antioxidant properties of vitamin C protect against
Schlueter and Johnston
53
Vitamin C and Health
Cardiovascular
Health
Common Cold
Anhistamine acon
Chemotaxis promoon
Respiratory tract anoxidant
Hypotensive acon
Endothelial compliance
CRP reducon
GI tract Cancers
Gastric juice anoxidant
Luminal anoxidant
Reduced reacve oxygen species
Figure 2. Protective influence of vitamin C supplementation on disease states
molecular damage that is associated with carcinogenesis and/or
that vitamin C may modulate signal transduction and gene
expression.66
In the stomach, vitamin C is present in high concentrations
in gastric juice (10-fold higher concentrations than in plasma)
and protects the gastric mucosa from reactive oxygen
species and N-nitroso compounds. Patients with gastritis and
Helicobacter pylori infections have decreased amounts of
vitamin C in gastric juice, a factor that could contribute to risk
for gastric cancer.67 Vitamin C supplementation in these
patients increased vitamin C concentrations in gastric juice and
decreased cancer biomarkers.65 Using a case–control study
design nested within a large, 10-country prospective investigation, gastric cancer risk was reduced 45% for individuals in the
highest versus the lowest quartile of plasma vitamin C levels.68
Risk for gastric cancer was particularly strong in subjects
consuming high amounts of red and processed meats, which
elevate endogenous levels of N-nitroso compounds. These data
suggest that this specific population (those with high intakes of
red and processed meats) would particularly benefit from
vitamin C supplementation.
Meta-analyses indicate that individuals with high intakes of
vitamin C are at reduced risk for esophageal cancer,69 lung cancer,70 and breast cancer.71 However, these analyses examined
only relationships between diet and cancer risk and cannot
distinguish if the relationship is specific to dietary vitamin C
or related to other components in vitamin C–rich fruits and
vegetables.
Randomized clinical trials have not demonstrated a benefit
for supplemental vitamin C in cancer prevention72-74 leading
many to conclude that high oral dosages of vitamin C should
not be promoted as an anticancer therapy. Importantly, some
evidence suggests that vitamin C can reduce the effectiveness
of anticancer therapies by preserving tumor cell integrity during chemotherapy.75 Yet a recent meta-analysis was unable
to demonstrate a reduction in chemotherapy efficacy associated
with the use of vitamin C supplements; in fact, the analysis
suggested a possible benefit of antioxidant supplementation
during chemotherapy on survival times and tumor responses.76
Although controversial, interest in intravenous vitamin C
injection to treat cancer patients has resurfaced in recent years.
Plasma vitamin C is tightly controlled and concentrations do
not generally exceed about 100 mM even with oral dosages
as high as 2500 mg because of saturation of the mucosal
vitamin C transporter, SVCT1, and increased renal losses.24
However, pharmacologic concentrations (0.3 to 20 mmol/L)
are achieved in blood with intravenous infusions of vitamin
C, and there is much research in vitro suggesting that, at pharmacologic concentrations, vitamin C is highly effective at
selectively destroying a wide variety of cancer cells.77-79
Recently, several small uncontrolled trials have examined the
efficacy of intravenous vitamin C as cancer therapy with mixed
results.80-82 However, the observation that patient well-being
and quality of life assessments were improved with vitamin C
infusions is encouraging.83
Intravenous vitamin C is widely used by complementary and
alternative medicine practitioners for a variety of conditions
including infection and fatigue.84 Apart from the known
adverse effects of vitamin C (the potential for renal stone
formation and for hemolysis in glucose-6-phosphate
dehydrogenase deficiency), intravenous administration of
vitamin C by these practitioners, which averaged 28 g every
4 days for 22 treatments, was evidently safe and well tolerated.
Well-designed trials are needed to assess the role vitamin C
infusions have in cancer treatment.
Maintaining Adequate Vitamin C Status
Vitamin C is found in a variety of fruits, juices, and vegetables
(Table 1). Natural and synthetic sources of vitamin C appear to
be equally bioavailable and provide similar antioxidant protection after ingestion.85,86 However, the stability of vitamin C in
foods is precarious and readily influenced by oxygen, heat, pH,
and metallic ions, resulting in the oxidation of vitamin C.87
Vitamin C is well preserved in frozen foods; hence, orange
juice reconstituted from frozen concentrate is a better
source of vitamin C as compared with ready-to-drink orange
juice (86 mg/serving vs 39-46 mg/serving).88 Cooking reduces
the vitamin C content of vegetables by 40% to 60%,89 and prolonged warming of foods (150 F for 4 hours) reduces vitamin
C content >75%.90 Vitamin C losses during vegetable storage
are as high as 70%; hence, if vegetables are not purchased
54
Journal of Evidence-Based Complementary & Alternative Medicine 16(1)
Table 1. Dietary Sources of Vitamin C
Food, Standard Amount
Guava, raw, 1=2 cup
Red sweet pepper, raw, 1=2 cup
Red sweet pepper, cooked, 1=2 cup
Kiwi fruit, 1 medium
Orange, raw, 1 medium
Orange juice, 3=4 cup
Grapefruit juice, 3=4 cup
Vegetable juice cocktail, 3=4 cup
Strawberries, raw, 1=2 cup
Brussels sprouts, cooked, 1=2 cup
Cantaloupe, 1=4 medium
Papaya, raw, 1=4 medium
Kohlrabi, cooked, 1=2 cup
Broccoli, raw, 1=2 cup
Edible pod peas, cooked, 1=2 cup
Broccoli, cooked, 1=2 cup
Sweet potato, canned, 1=2 cup
Tomato juice, 3=4 cup
Cauliflower, cooked, 1=2 cup
Pineapple, raw, 1=2 cup
Kale, cooked, 1=2 cup
Mango,1=2 cup
Vitamin C Content (mg)
188
142
116
70
70
61-93
50-70
50
49
48
47
47
45
39
38
37
34
33
28
28
27
23
frozen, storage time should be minimized, and items should
be served fresh or steamed with minimal exposure to heat
and air.91 Orange juice that was refrigerated after reconstitution from frozen concentrate had significantly less bioavailable vitamin C at day 8 compared with baseline, and the
antioxidant protection to plasma was lost at day 8 compared
with baseline.92 The lability of vitamin C in foods is an important consideration since many populations world-wide consume
produce that is transported, stored, and processed prior to
purchase.
Recommended intakes for vitamin C range from 45 mg/d
(World Health Organization) to 90 mg/d (National Academy
of Sciences).93 Since vitamin C is not prevalent in all fruits and
vegetables, foods should be carefully selected to ensure the
inclusion of several vitamin C–rich foods daily, and care
should be taken regarding the storage and handling of these
food items. Although 45 to 90 mg vitamin C daily will protect
against vitamin C deficiency, higher intakes are needed to saturate tissues (100 mg/d) or plasma (e500 mg/d).24 Many experts
believe that the current recommended intakes for vitamin C are
several orders of magnitude too low to support optimal vitamin
C functionality in vivo.94-96
Given the important roles vitamin C plays in enzyme
activation, oxidative stress reduction, immune function, and
carcinogen abatement, daily supplementation of the vitamin
can be considered prudent for maintaining optimal vitamin
C concentrations in plasma and tissues since food sources can
be unreliable. Vitamin C bioavailability is nearly 100% for
vitamin C dosages up to 200 mg and drops to 75% and to
49% for dosages of 500 mg and 1250 mg, respectively.24
There are few toxicity concerns with vitamin C supplementation, and the tolerable upper limit set by the National
Academy of Sciences is quite high, 2000 mg/d. Osmotic diarrhea was the main concern cited by the National Academy of
Sciences; however, risk for kidney stones does increase in
individuals supplementing vitamin C, and renal experts suggest that 500 mg vitamin C per day is the maximum dose that
can be considered safe.30 Many forms of vitamin C are marketed to consumers across a broad price range; yet research
suggests that the forms commonly available (vitamin C with
rose hips, Ester-C, and generic vitamin C) have similar
bioavailability.97
Individuals who supplement vitamin C regularly maintain
higher plasma concentrations of the vitamin,98 and the longterm safety of vitamin C supplementation seems evident as several large investigations have noted reduced risk of mortality in
vitamin C supplementing populations99,100 and in populations
with elevated plasma vitamin C concentrations.54,101
Author Contributions
Both the authors have contributed in this article.
Declaration of Conflicting Interests
The authors declared no conflicts of interest with respect to the authorship
and/or publication of this article.
Funding
The authors received no financial support for the research and/or
authorship of this article.
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