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The Importance of Vitamin C

By: Sarah Brand


Imagine boarding a ship in the 18th century that will set sail for months at a time. Everything is
going well until a couple months in, the symptoms of fatigue, bone pain so bad it hurts to walk, bleeding
gums, and teeth falling out begin to occur. Everyone on the ship begins to have the same problems, but
it is a mystery of why this is happening. Luckily, an interested passenger on the ship is curious as to why
these symptoms are occurring, and his name is Dr. James Lind, or better known as the person who
discovered that Vitamin C could prevent the disease that has left many sailors suffering over the years:
scurvy.1 While scurvy has been known since Hippocrates, Dr. Lind was the first to conduct a trial to
discover that citrus fruits prevent scurvy.1 It wasnt until about 80 years ago that a chemist named
Albert Szent-Gyorgyi won the Nobel Prize for the isolation and identification of vitamin C and the
discovery of the metabolic mechanism that enables its use within cells.2 Thanks to the many discoveries
of talented scientists, we now understand the importance of vitamin C, or ascorbic acid. In this paper,
the metabolism, disease process, sources of, recommendations, toxicity, and deficiencies of vitamin C
will be discussed.

The recommended dietary allowance of vitamin C for adult men is 90mg/day, and 75mg/day for
adult women, and the Daily Value on food and supplement labels is 60mg.3 These RDAs are based on its
known physiological and antioxidant functions in white blood cells.4 While majority of the U.S. exceeds
these amounts, about 40% of adults consume less than the EAR for vitamin C, 22% of adults have serum
vitamin C levels below normal, and about 6% have vitamin C serum concentrations indicating a
deficiency.3 Fruits and vegetables are the best sources of vitamin C, but some fruits and vegetables are
better sources than others. For Americans, the leading fruits and vegetables consumed are iceberg
lettuce, tomatoes, french fries, bananas, and orange juice; out of all these, orange juice is the only rich
source. Citrus fruits, tomatoes and tomato juice, and potatoes are the main contributors in the U.S., but
other good food sources are red and green peppers, kiwi, broccoli, strawberries, brussel sprouts, and
cantaloupe.4 Typically, consuming five varied servings of fruits and vegetables can provide the RDA of
vitamin C, but content of the vitamin in certain foods could be reduced by prolonged storage, or cooking
due to its unstable properties.

The absorption of vitamin C occurs in the small intestine by active transport for ascorbic acid,
and by facilitated diffusion for dehydroascorbic acid.3 As intake of vitamin C increases, the efficiency of
the absorptive mechanism decreases. To be specific, 70-90% of vitamin C is absorbed at a daily intake
between 30 and 200mg, and the rate of absorption declines substantially as the intake of vitamin C
increases over 200mg.3 This absorption is regulated by at least one specific dose-dependent, active
transporter, and cells accumulate vitamin C via a second specific transport protein.4 Some in vitro
studies have shown that dehydroascorbic acid enters cells via facilitated glucose transporters, and is
then reduced to ascorbic acid.4 Once vitamin C is digested, it is dispersed throughout the body and
accumulates in varying concentrations in various cells and organs. Highest concentrations are found in
the pituitary and adrenal glands, eyes, leukocytes, and brain, while saliva and plasma are among the
lowest concentrations.5 Just like other water-soluble vitamins, excess vitamin C is passed out of the
body through excretion. When ascorbic acid in plasma increases, the ability of renal tubules to reabsorb
the compound decreases, and when levels are low, the tubules reabsorb larger amounts.5 This means
that excess vitamin C is excreted easily through the urine, and when times of low vitamin C intakes, the
body conserves vitamin C, delaying the symptoms of scurvy.

Vitamin C is also known as ascorbic acid, and the oxidized form is known as dehydroascorbic
acid. Dehydroascorbic acid occurs when ascorbic acid undergoes a reversible oxidation and reduction by
the loss of two hydrogens and two electrons.3 As an electron donor, vitamin C has a cofactor role for
several metalloenzymes, which contain metals as a part of their structures, and has antioxidant
functions. This metal ion becomes oxidized when a metalloenzyme catalyzes a reaction, and allows
enzymatic action to continue.3 Research has shown that vitamin C acts as an antioxidant in vitro, but it
is unaware how much it acts as an antioxidant in the body. However, research has also shown that
vitamin C present in the eye possibly protects against free radicals produced by UV-light, and it may be
used for the protection against the free radicals produced during immune functions.3 In addition,
vitamin C has shown protective and therapeutic efficiency against oxidative energy, creating a new
therapeutic mechanism for Alzheimers Disease.6 This vitamin also plays a role in redox balance, which is
the balance between oxidants and antioxidants in the body that helps maintain redox homeostasis.7
Since redox balance is altered in diseases such as obesity, cancer, neurodegenerative diseases,
hypertension, and autoimmune diseases, future research of this vitamin could help with the cure of
these diseases.

Another main function of vitamin C is collagen synthesis. Collagen is a necessary structure in the
body that makes up connective tissue, which holds together tendons, ligaments, bone, blood vessels,
eyes, and skin.3 Without ascorbic acid, the triple helix structure of collagen would not form. In addition,
they are essential in wound healing. Vitamin C works with the metalloezyme prolyl and lysyl
hydroxylase to convert proline and lysine in collagen to hydroxyproline and hydroxylysine.3 These
stabilize the collagen structure, and without vitamin C, hydroxyproline and hydroxylysine couldnt be
synthesized, resulting in collagen that is weak and fragile.3 In absence of this essential part of the body,
the most visible and primary symptoms of scurvy occur. In addition, clinical studies have shown that
topical use of vitamin C can be used in dermatology. With the excellent safety profile it has, it has been
used increasingly in photo ageing, hyperpigmentation, tissue inflammation, and promotion of tissue
healing.8

There is some evidence that suggests higher intake of vitamin C is associated with lower risks of
cancer; specifically, lung, breast, colon or rectum, stomach, oral cavity, larynx or pharynx, and
esophagus.4 A review by Carr and Frei concluded that in the majority of prospective cohort studies not
reporting a significantly lower cancer risk, most participants had relatively high vitamin C intakes, with
intakes higher than 86 mg/day in the lowest quintiles.9 Studies reporting significantly lower cancer risk
found these associations in individuals with vitamin C intakes of at least 80110 mg/day, a range
associated with close to vitamin C tissue saturation.9 In addition, there have been some trials to observe
if vitamin C is beneficial to cancer treatment. Further research needs to be done on the analysis of
vitamin C treating cancer, but many trials have showed survival curves in cancer patients progressing
when given mega-doses of vitamin C supplement.9

Some other functions of vitamin C are synthesis of vital compounds, iron absorption, and
immune function. Some of the important biological compounds are the amino acid tyrosine, the
hormone thyroxine, the fatty acid transport compound carnitine, and the neurotransmitters
norepinephrine, epinephrine, and serotonin.3 Additionally, vitamin C is involved in the conversion of
cholesterol to bile acids and biosynthesis of two important hormones, corticosteroids, and aldosterone.3
Vitamin C also facilitates the intestinal absorption of nonheme iron due to the conversion of iron to
ferrous iron in the GI tract, and also counters the action of certain food components that inhibit iron
absorption.3 Immune function is one of the main functions of vitamin C that everyone observes. White
blood cells contain the highest vitamin C concentration in the body, which may protect against the
oxidative damage associated with cellular respiration. When free radicals generated during
phagocytosis and neutrophil activation damage the bodys own immune cells, the antioxidant effects of
vitamin C can reduce this self-destruction.3

On top of all the other functions of vitamin C, this vitamin has shown improvements in physical
activity levels and a decrease in the common cold. In a randomized controlled trial performed by Carol
S. Johnston, Gillean M. Borkyoumb, and Sara S. Schumacher in 2014 called Vitamin C Supplementation
Slightly Improves Physical Activity Levels and Reduces Cold Incidence in Men with Marginal Vitamin C
Status: A Randomized Controlled Trial, they found that vitamin C has even more beneficial effects. They
took 43 healthy, non-smoking men who did not engage in exercise training for competitive sports or use
prescription medications. They excluded those who regularly took supplements or consumed foods
over 60mg Vitamin C per serving, and those who took a postprandial venous blood sample and had
plasma vitamin C concentrations less than 45umol/L were eligible to participate in the study, which was
30 men. These men were then paired by age, BMI, and plasma concentration, and assigned to the
vitamin C group or placebo group by a coin toss. For eight weeks, participants were instructed to restrict
all juice or fruit-flavored drinks, and were told to ingest two capsules daily. The vitamin C group
capsules contained 500mg vitamin C per capsule, and the placebo group contained white flour.10

Participants were to complete the Wisconsin Upper Respiratory Symptom Survey-21 daily, and
the Godin Leisure-Time Exercise Questionnaire and a short food frequency measure weekly. In addition,
at week 4 and 8 participants fasting venous blood samples were collected for vitamin C and histamine
analyses. Due to one participant being non-compliant and one reporting a severe cold, they were left
with 13 in the trial group and 15 in the placebo group. After the eight weeks, looking at the vitamin C
group, they found that fasting vitamin C concentrations raised significantly, physical activity increased
slightly, and 7 of the participants in the vitamin C group reported cold episodes vs. 11 of the placebo
group. Overall, this study reported a measurable benefit of vitamin C supplementation for reducing cold
episodes, and a modest benefit for enhancing weekly activity levels.10 This study was a small sample
size, the physical activity levels varied between participants, and the diet was not controlled, so more
studies need to be done to assess the validity of these results. Although it proved that increase of
vitamin C correlated to a decrease in cold incidences and increase in physical activity, the small sample
size almost proves this test to be invalid.

In addition, vitamin C has shown to help with vision, due to the collagen found in the cornea of
the eye. A study done in 2017 by Young-Sool Hah et al called Ascorbic acid concentrations in aqueous
humor after systemic vitamin C supplementation in patients with cataract: pilot study showed the
importance of vitamin C for the eye. Ascorbate concentration is about 15 times greater in the aqueous
humor than in the plasma, suggesting that vitamin C protects the eye from harmful effects.11 To prove
this, they took forty-two eyes of 42 patients with cataracts who underwent cataract surgery. The mean
age at surgery was 62.5 years. They split them into 3 groups of patients who were administered oral
vitamin C, intravenous vitamin C, or no vitamin C at all on the day before surgery on their eye. During
surgery, they obtained 0.1cm3 of aqueous humor, and measured the ascorbic acid concentration
through high-pressure liquid chromatography. Results showed that intravenous vitamin C increased the
vitamin C concentration in the aqueous humor, which may protect the lens against cataractogenic
effects of UV radiation and may play a role in cataract formation.11 This study was a small sample size,
and serum concentrations of vitamin C were not measured. In addition, the subjects were not randomly
divided into the three groups, so there could have been some bias. More studies need to be done to
test the cataract formation related to vitamin C.

Found in the Evidence Analysis Library, the relationship between vitamin C intake and blood
pressure in healthy and hypertensive adults was observed. They observed twelve different studies.
Four studies using supplemental doses of at least 500mg of vitamin C per day reported a decrease in
systolic blood pressure and two studies reported a 4mmHg decrease of diastolic blood pressure.12 In
addition, one study found that a high fruit and vegetable intake was associated with lower systolic blood
pressure, and one study demonstrated that tissue stores of vitamin C from dietary intake were inversely
correlated with diastolic blood pressure.12 Most of the studies found that controlling vitamin C intake
had no effect on blood pressure. In addition, most of the studies lasted only a few weeks, which is a
small amount a time to get valid results. This was given a grade of three, and they concluded that due
to the small study sizes and excess limitations, the effect of vitamin C on blood pressure reported
inconclusive findings.

Like stated before, the upper limit of vitamin C is 2,000mg/day. Much like other water-soluble
vitamins, excess vitamin C is excreted through the urine and toxicity is extremely rare. Although toxicity
is rare, megadoses of vitamin C supplements may cause diarrhea, nausea, vomiting, heartburn,
abdominal bloating and cramps, headaches, and insomnia.13 In addition, kidney stone formation and
excess iron absorption can occur with high doses of vitamin C, but only to those who have preexisting
iron absorption disorders and who are predisposed to form kidney stones.3 High doses of vitamin C can
also cause blood clotting, death (heart-related), pro-oxidant effects, red blood cell destruction, and
appears to interfere with blood-thinning effects of anticoagulants such as warfarin.14 One study put on
by the Iowa Womens Health Study observed postmenopausal women with diabetes intaking at least
300mg/day by supplement was associated with an increased risk of cardiovascular disease mortality.4
The significance of this study was uncertain, so it is still believed that high intakes of vitamin C does not
cause serious adverse effects.

In contrary to toxicity of vitamin C, the deficiency of vitamin C is scurvy. This prevents the
normal synthesis of collagen, which causes widespread changes in the body to connective tissue. The
signs and symptoms of this disease appear about 20-40 days on a Vitamin C-free diet, and are fatigue,
pinpoint hemorrhages around the hair follicles, gums and joints bleeding, bone pain, fractures, and
diarrhea.3 In addition, some physiological problems can occur, such as depression in advanced scurvy.
Scurvy is most common in poverty, alcoholics, and smokers. This is because smokers require a higher
intake of vitamin C, and alcoholics and the poverty have poor diets that do not contain an adequate
amount of this vitamin. In addition, since vitamin C is found in expensive food items, fruits and
vegetables, this could be why the poverty suffer with scurvy greatest. Infants who are fed boiled milk
are especially at risk because all forms of milk are poor sources of vitamin C, and some parents do not
realize that and dont provide their child with a good source of vitamin C or supplement.3 Scurvy is rare
in the United States, but deficiency is common.

In conclusion, we discussed the metabolism, disease process, sources of, recommendations,


toxicity, and deficiencies of vitamin C. All of these aspects of vitamin C are what make it so unique and
so important to the body. Without the scientific works of Dr. James Lind and Albert Szent-Gyorgyi,
millions of sailors around the world would have suffered from scurvy longer than they did. This vitamin
is very interesting to me, and I think the most interesting thing about it is that it is found in connective
tissues, which consumes so much of our body. Next time I sit down and enjoy a kiwi, red pepper, or
orange juice, I will think of the many beneficial functions that vitamin C is doing to my body.
References
1. Milne I. Who was James Lind, and what exactly did he achieve. Journal of the Royal Society of
Medicine. 2012;105(12):503-508. doi:10.1258/jrsm.2012.12k090.
2. Albert Szent-Gyorgyi Vitamin C - Landmark. American Chemical Society.
https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/szentgyorgyi.html.
Accessed October 15, 2017.
3. Wardlaws Perspectives in Nutrition. 10th ed. New York, NY: Mcgraw-Hill Education; 2016.
4. Vitamin C: Fact Sheet for Health Professionals. NIH Office of Dietary Supplements.
https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/. Accessed October 15, 2017.
5. Scurvy and Vitamin C. LEDA at Harvard Law School. https://dash.harvard.edu/bitstream/handle
/1/8852139/Mayberry.html?sequence=2. Accessed October 14, 2017.
6. Heo J-H, Lee H, Lee K-M. The Possible Role of Antioxidant Vitamin C in Alzheimers Disease
Treatment and Prevention. American Journal of Alzheimers Disease & Other Dementiasr.
2013;28(2):120-125. doi:10.1177/1533317512473193.
7. Figueroa-Mndez R, Rivas-Arancibia S. Vitamin C in Health and Disease: Its Role in the
Metabolism of Cells and Redox State in the Brain. Frontiers in Physiology. 2015;6:397.
doi:10.3389/fphys.2015.00397.
8. Telang P. Vitamin C in dermatology. Indian Dermatology Online Journal. 2013;4(2):143-146.
doi:10.4103/2229-5178.110593.
9. Goodman A. Vitamin C and Cancer. AIMS Medical Science. 2015;3(1):41-51.
doi:10.3934/medsci.2016.1.41.
10. Johnston CS, Barkyoumb GM, Schumacher SS. Vitamin C Supplementation Slightly Improves
Physical Activity Levels and Reduces Cold Incidence in Men with Marginal Vitamin C Status: A
Randomized Controlled Trial. Nutrients. 2014;6(7):2572-2583. doi:10.3390/nu6072572.
11. Hah Y-S, Chung HJ, Sontakke SB, et al. Ascorbic acid concentrations in aqueous humor after
systemic vitamin C supplementation in patients with cataract: pilot study. BMC Ophthalmology.
2017;17(1):121. doi:10.1186/s12886-017-0515-2.
12. Hypertension. Evidence Analysis Library.
https://www.andeal.org/topic.cfm?cat=2788&evidence_summary_id=250183&highlight=vitami
n c&home=1. Published 2007. Accessed October 15, 2017.
13. Zeratsky K. Is it possible to take too much vitamin C? Mayo Clinic.
https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/expert-
answers/vitamin-c/faq-20058030. Published February 5, 2015. Accessed October 15, 2017.
14. Vitamin C (ascorbic acid) Safety. Mayo Clinic. https://www.mayoclinic.org/drugs-
supplements/vitamin-c/safety/hrb-20060322. Published November 1, 2013. Accessed October
15, 2017.

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