VITAMIN C

Dian Luthfita Prasetya Muninggar

Metabolisme Gizi Mikro
Matrikulasi Profesi Dietisien
2019
༝ It is water-soluble vitamin, commonly found in fruits and
vegetables.
༝ Vitamin C also known as ascorbic acid or ascorbate.
༝ Most animals are able to synthesize all vitamin C they
need from dietary sugars
༝ Also, animals are able to increase synthesis of vitamin C
during stress but humans’ strictly depend on dietary
sources, increases risk of deficiency during stress time.

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༝ Human being is one of the few mammals unable to
synthesize vitamin C.
༝ Other animals unable to synthesize vitamin C include
primates, fruit bats, guinea pigs, and some birds.

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History of Vitamin C
 ༝

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༝ Vitamin C was isolated in 1928, and its structure &
metabolism was determined in 1933 through uronic acid
pathways.
• although but humans do not have an ability to synthesize
vitamin C eventhough they also have uronic acid pathways
• The inability to synthesize vitamin C results from the lack of
gulonolactone oxidase, the last enzyme in the vitamin C
synthetic pathway.

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 “
Scurvy was common between
sailors, pirattes, and others
who were on ships for
months without eating fresh
fruits and vegetables.

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 Vitamin C Structure
Physiologically active forms for vitamin C
 Chemistry, Stability &
Sensitivity of Vitamin C
 Chemistry & Stability of Vitamin C
༝ It is a weak acid and its salts called ascorbate.
༝ Unstable in alkaline pH, high temperature, and in the
presence of oxygen or metals.
༝ Ascorbic acid is strong reducing agent, serves as an anti-
oxidant and co-factor in hydroxylation reactions.
༝ Ascorbic acid is reversibly oxidized to L- dehydroascorbic
acid and both L-ascorbic and L-dehydroascorbic acids are
physiologically active forms for vitamin C.

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༝ Vitamin C have a number of vitamers that have vitamin C
activity in animals:
༝ Ascorbic acid in biological system (low pH)
༝ Oxidized form deyhroascorbic acid.
༝ Ascorbate in neutral salt solution (pH>5)
༝ Ascorbate and ascorbic acid are both naturally present in the
body, since the forms interconvert according to pH.

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 Sensitivity of Vitamin C
༝ Very significant losses occur as vegetables wilt, or when
they are cut, as a result of the release of ascorbate
oxidase from the plant tissue.
༝ Significant losses of the vitamin also occur in cooking, both
through leaching into the cooking water and also
atmospheric oxidation, which continues when foods are
left to stand before serving.

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Sources of Vitamin C
Natural Source of Vitamin C
Guava Orange Lemon
.

Grapefruit Mango Strawberry

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Natural Source of Vitamin C
Plum Red Pepper Papaya
.

Kiwi Broccoli
.

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 Sources of Vitamin C
༝ Fruits, vegetables and organ meats (liver, kidney).
༝ The best food sources of vitamin C include asparagus,
papaya, oranges, cantaloupe, cauliflower, broccoli, green
peppers, grapefruit, grapefruit, lemons, and strawberries.
༝ Citrus products are most commonly cited as significant
sources of the vitamin.
༝ Supplements supply vitamin C typically as free ascorbic
acid, calcium ascorbate, sodium ascorbate, and ascorbyl
palmitate.

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Digestion, Absorption
& Transport of
Vitamin C
༝ Vitamin C does not require digestion prior to being
absorbed into intestinal cells.
༝ There is active transport of the vitamin at the intestinal
mucosal brush border membrane. Both ascorbate and
dehydroascorbate are absorbed across the buccal
mucosa by carrier-mediated passive processes.
༝ Intestinal absorption of dehydroascorbate is carrier-
mediated, followed by reduction to ascorbate before
transport across the membrane.

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༝ Prior to absorption, ascorbic may be oxidized to
dehydroascorbate, which may be absorbed by facilitated
diffusion.
༝ Although dehydroascorbic acid is absorbed in higher rate
than ascorbate, the amount of dehydroascorbic acid found
in plasma and tissues under normal conditions is low, as
cells rapidly reduce dehyroascorbic acid to ascorbate.

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༝ Simple diffusion (may occur in stomach and small intestine)
provides for vitamin C absorption with ingestion of higher
amounts of the vitamin.
༝ Anion channels in some cells may mediate vitamin C
diffusion faster than the transporters.
༝ From intestinal cells, ascorbate may diffuses through anion
channels into extracellular fluid and enters plasma by way
of capillaries.

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 Within intestinal cells
༝ Dehydroascorbic acid is rapidly reduced back to ascorbic
acid by enzyme dehydroascorbate reductase.
༝ Glutathione (GSH), which is required for the reduction of
dehydroascorbate, is oxidized in process. Glutathione
spares vitamin C and, in general, improves the antioxidant
protection capacity of blood.
༝ Degree of vitamin C absorption decrease with increased
vitamin intake.

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༝ Some 80–95% of dietary ascorbate is absorbed at usual
intakes (up to about 100 mg/day).
༝ The fractional absorption of larger amounts of the vitamin
is lower, and unabsorbed ascorbate from very high doses
is a substrate for intestinal bacterial metabolism, causing
gastrointestinal discomfort and diarrhea.

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༝ Absorption of ascorbate may be diminished in the presence
of high intracellular glucose, which appears to interfere
with ascorbate transporter.
༝ Unabsorbed vitamin C may be metabolized by intestinal
flora.
༝ Ingesting large amounts of iron with vitamin C may result
in oxidative destruction of vitamin C in digestive tract,
yielding other products without vitamin C activity.

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 In plasma
༝ Ascorbic acid is transported in the plasma primarily in free
form as an ascorbate anion.
༝ Normal plasma level of vitamin C 0.4 – 1.7 mg/dL.

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 In cells
༝ Uptake of ascorbate into body cells requires sodium and a
carrier and into some cells such as leukocytes, uptake is
also energy dependent.
༝ Tissue concentrations of vitamin C usually exceed plasma
concentrations.
༝ Ascorbate and dehydroascorbate concentrations are
much greater in some tissues than others. The highest in
adrenal and pituitary glands (~30-50mg/100 g of wet
tissue).

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༝ Intermediate in liver, spleen, heart, kidneys, lungs
pancreas and leukocytes.
༝ Smaller amounts in muscles and red blood cells.
༝ Maximal vitamin C pool is estimated at about 1.500mg.
༝ Intakes of about 100-200mg vitamin C/d have been shown
to produce plasma concentrations of about 1.0mg/dL and
to maximize body pool.

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 Summary of Absorption
༝ Absorbed in the intestine by an energy-requiring, sodium-
dependent, carrier- mediated transport system.

༝ After absorption, ascorbic acid is then transported as a

free acid in plasma into the cells, including leukocytes and
red blood cells.

༝ In the tissues, Vitamin C serves as an electron donor for a

number of enzymes.

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Function & Mechanism
of Action of Vitamin C
༝ Vitamin C has very complex functional roles in the body as
a cofactor in around eight reactions :
• Collagen synthesis
• Carnitine synthesis
• Tyrosine synthesis and catabolism
• Neurotransmitter synthesis.
• Drug and steroid metabolism.
• Maintain the iron and copper atoms in the metalloenzymes in the
reduced state.
• In addition vitamin C acting role as reducing agent in enzymatic
reactions.
• Ascorbate may also act as an antioxidant against oxidative
stress or oxidation by free radicals

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 Collagen Synthesis
༝ Most abundant protein found in the body.
༝ Vitamin C is necessary for collagen synthesis.
༝ Collagen is a structural protein found in tissues in skin,
joints, muscles, bones ligaments, tendons, and cartilage.
• All collagen (n~19) have a triple helical structure.
• For the collagen molecule to aggregate into its triple-helix
configuration selected proline residues must be hydroxylated
forming hydroxyproline.
• Requires di-oxygenase enzymes, reduced iron (Fe2+),
ascorbate.

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 Vitamin C Roles in Collagen Synthesis
༝ During hydroxylation, iron cofactor in the enzymes is
oxidized, (ferrous(2+) state ---- ferric (3+) state).
༝ Ascorbate is needed to function as a reductant thereby
reducing iron back to its ferrous (2+) in prolyl and lysyl
hydroxylases
༝ Vitamin C may also influence mRNA levels needed for
collagen synthesis.
༝ Although these reactions may seen simple, normal
development and maintenance of skin, tendons, cartilage,
bone and dentine depend on an adequate supply of vitamin C.
༝ Also, important in wound healing and bleeding prevention
from capillaries.
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༝ Ascorbate function in the hydroxlation of peptine-bound
proline and lysine in procollagen.
༝ One atom of oxygen (*) appears in the hydroxyl group of the
product and the other in succinate

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 Carnitine Synthesis
༝ Carnitine is a methylated from nitrogen containing
compound made from lysine.
༝ Sufficient carnitine is critical in fat metabolism, because it
is essential to transport long- chain fatty acids from cell
cytoplasm into mitochondrial matrix where β-oxidation
occurs.

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 Vitamin C Role Carnitine Synthesis
༝ Vitamin C required for 2 hydroxylation reaction in
synthesis carnitine, which functions as preferred reducing
agent, specifically reducing Fe from ferric (Fe3+ ) back to
ferrous state (Fe2+ )

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 Vitamin C Role in Tyrosine Synthesis
༝ Vitamin C along with niacin and vitamin B6 required in
breakdown of fats for energy
༝ Hydroxylation of phenylalanine
༝ Requires phenylalanine mono-oxygenase (hydroxylase),
Fe+2,O2, tetrahydrobiopterin, NADPH, vitamin C
༝ Vitamin C regenerating tetrahydro-biopterin from
dihydrobiopterin.
༝ Occurs in liver and kidney.

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 Vitamin C Role in Tyrosine Catabolism
༝ Tyrosine catabolism require ascorbate as reductant for
hydroxylases
༝ Cu-dependent enzyme p-hydroxyphyenylpyruvate
(dioxygenase)
༝ Fe-dependent enzyme homogentisate dioxygenase.

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Vitamin C Role in Neurotransmitter Synthesis
༝ Vitamin C maintains mineral cofactors for some of the
enzymes involved in synthesis of neurotransmitters in its
reduced state.
Norepinephrine
༝ It is generated from hydroxylation of dopamine side chain.
༝ This reaction catalyzed by dopamine monoxygenase
(contain 8 Cu atoms)-vitamin C- dependent reaction.
༝ Found in nervous tissue and adrenal medull.

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Dopamine Hydroxylase

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Vitamin C Role in Neurotransmitter Synthesis
Serotonin
༝ Hydroxylation of tryptophan (in brain)
༝ Requires tryptophan mono-oxygenase (hydroxylase), O2
tetrahydrobiopterin, vitamin C → first step in serotonin
synthesis.

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Vitamin C Role in Neurotransmitter Synthesis
Other Neurotransmitters and Hormones
༝ Keeping Cu in reduced for peptidylgycine α-amidating
mono-oxygenase
༝ Many of amidated peptides are active as hormones, such
as calcitonin, cholecystokinin (CCK) and gastrin
༝ The enzyme found in pituitary, adrenal, thyroid glands and
brain

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Vitamin C Role in Detoxification &
Excretion of Drugs
༝ Vitamin C maintains the enzyme systems in liver that
detoxify and excrete drugs and toxic pollutants

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Vitamin C Importants for Healthy Immune
Function
༝ Vitamin C is essential for optimum activity of WBCs and
production of chemical mediators which direct the immune
response.
༝ Vitamin C seems to increase T-lymphocyte activity,
phagocyte function, leukocyte mobility, and possibly
antibody and interferon production.

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Protective Effects of Vitamin C
༝ Vitamin C helps to protect folate and vitamin E from
oxidation.

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Antioxidants activity
༝ The reduction potential of ascorbate is such that it readily
donates electrons/hydrogen ions to regenerate other
antioxidants, such as vitamin E, glutathione, and uric acid,
and to reduce numerous reactive oxygen (ROS) and
nitrogen species (RNS).
༝ Ascorbic acid interact with oxidants in the aqueous phase
(blood or intracellular) before they initiate damage in
nucleus, cell lipids.

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Pro-oxidants activity
༝ Vitamin C (ascorbate) can reduce transition metals, while
itself becoming oxidized to semidehydroascorbate:
(AH2) +Fe3+ or Cu2- (AH−) + Fe2+ or Cu1+

༝ These reduced metal ions can cause cell damage by

generating ROS and free radicals.
Fe2+ or Cu1+ + H2O2 Fe3+ or Cu2- + H2O2 + OH
Fe2+ or Cu1+ + O2 Fe3+ or Cu2- + O2-

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Summary of Role of Vitamin C
༝ Vitamin C acts as an electron donor for 8 different
enzymes:
§ Three enzymes participate in collagen hydroxylation.
§ Two enzymes are necessary for synthesis of carnitine.
§ Three remaining enzymes have the following functions in
common, but have other functions as well:
• Dopamine β-hydroxylase participates in biosynthesis of
norepinephrine from dopamine.
• Enzyme adds amide groups to peptide hormones.
• One modulates tyrosine metabolism.

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Vitamin C and Colds
༝ Vitamin C is thought to moderate colds by enhancing many
immune cell (such as some leukocyte) functions while also
destroying histamine, which causes many of a cold’s
symptoms.

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Vitamin C and Cancer
༝ It is controversial issue due to:
§ Epidemiological studies suggest inverse relationship between
vitamin C and cancers of oral cavity, esophagus and stomach.
§ Clinical studies:
• Some shown that survival time in cancer time patients may be
prolonged, possible protective mechanisms
• Ability to act as a reducing agent
• Detoxify carcinogens.

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Vitamin C and Cardio Vascular Disease
༝ Many (but not all) epidemiological and prospective studies
report that increased fruit and vegetable intake, vitamin C
intake, and plasma vitamin C concentration are associated
with decreased risk of heart disease.
༝ Low vitamin C status also is related to increased blood
total cholesterol concentrations, whereas high plasma
vitamin C concentrations have been associated with lower
blood pressure and with higher plasma high-density
lipoprotein cholesterol concentrations, both of which are
protective against heart disease.
༝ Studies with supplements of vitamin C and other
antioxidants have not reported beneficial effects.
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Other Function of Vitamin C
Bone Density
Positive relation with vitamin C, supplements of Vitamin C have
recently been recognized as having an important role in the
prevention and treatment of osteoporosis because of its ability
to increase bone density

Wound healing and connective tissue metabolism

Control of histamine levels

When vitamin C status is poor → High levels of histamine →
aggravate allergies, asthma, stomach ulcers, and certain
psychiatric disorders
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 Interaction of
Vitamin C with Other
Nutrients
Vitamin C & Iron
༝ Increase intestinal absorption of non-heme iron
༝ Reduce Fe3+ to Fe2- forms a soluble complex with iron in
alkaline pH of SI.
༝ Effects on iron distribution in the body.
༝ Vitamin C aids incorporation of iron into ferritin
༝ Excessive iron in presence of vitamin C can accelerate
oxidative catabolism of vitamin C.

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Vitamin C & Copper
༝ May increase absorption and excretion of heavy metals
༝ Vitamin C intakes above 600 mg/d may interfere with
copper metabolism.

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Vitamin C & Folate
༝ Vitamin C helps keep folate in its reduced and active form.

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Excretion of
Vitamin C
༝ Excretion through urinary excretion
༝ Excretion of vitamin C reduced when intake of vitamin C is
low
༝ Body pool <1.500mg leads to only metabolites in urine
༝ Body pool > 1500mg leads to proportionately more
ascorbate in urine
༝ Vitamin C may be excreted intact or oxidized by L-ascorbate
oxidase to oxalic acid, primarily in liver and some in kidney.

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RDA of Vitamin C
Adult male : 90mg
Adult female : 75 mg
Pregnancy : 100my
Lactating : 120mg
Smokers : extra 35 mg
UL : adult 2000mg.
Deficiency of
Vitamin C
Symptoms of Vitamin C Deficiency
༝ Scurvy, impaired connective tissue synthesis and fragility of
blood vessels causes abnormal bleeding: easy bruising,
subcutaneous hemorrhagic spots, inflamed and bleeding
gums, joint stiffness and pain (due to bleeding into joints)
༝ Impaired wound healing
༝ Build-up of keratin in hair follicles producing rough
“sandpaper skin”
༝ Weakness, exhaustion, fatigue (due to impaired carnitine
synthesis).
༝ Impaired immunity with increased risk of infection.
༝ Diminished antioxidant defenses: increase risk of cancer,
heart disease, stroke, cataract.
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People at High Risk of Vitamin C Deficiency
༝ Increased physical stress (e.g. infection, fever, burns,
surgery, trauma to soft tissues or bones, and chronic
illnesses such as hyperthyroidism, diabetes, rheumatoid
arthritis, alcoholism, and kidney failure).
༝ Chronic use of drugs such as aspirin and oral
contraceptives impair vitamin C status.
༝ Older people, particularly those with chronic illness, and
aging.
༝ Periods of rapid growth–childhood, adolescence, pregnancy,
and lactation.
༝ Regular cigarette smoking sharply increases breakdown
and excretion of vitamin C.

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Toxicity of Vitamin C
༝ Toxicity is rare, because vitamin C is generally regarded as
safe in usual doses (up to 1000 mg)
༝ Tolerable upper intake level of 2g vitamin C/day
༝ The most common side effect with ingestion of large
amounts (2 g) of the vitamin is gastrointestinal problems
characterized by abdominal pain and osmotic diarrhea.
༝ Other side effects include increased risk of kidney stones
for those with renal disease and iron toxicity for those with
iron metabolism disorders

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༝ Large doses may precipitate hemolysis in patients with
glucose 6-phosphate dehydrogenase deficiency.
༝ Vitamin C is metabolized to oxalic acid. Increased
consumption increases the urinary concentration of oxalic
acid and increases the risk of oxalate stone formation.

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Uses of Vitamin C in
Prevention and
Therapy
༝ Enhance ability to fight infection, Vitamin C stimulates the
activity and ability of WBCs to destroy bacteria and viruses.
༝ Treatment of cold and flu: At doses of 1-2 g, it slightly
increases body temperature → ↑ functions of WBCs and
↓blood histamine → ↑ immune response and ↓ nasal &
bronchial congestion → ↓ duration and symptoms of cold
and flu.
༝ Helps reduce risk of cancer: particularly cancers of GIT,
bladder, breast, pancreas, and uterus (antioxidant +
enhancer for immune defenses against cancer and + helps
detoxify carcinogenic food additives e.g. nitrates, pesticides,
and other chemicals and heavy metals).

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༝ Large doses ↓ platelet aggregation → reduce risk of blood
clots. In addition, vitamin C ↑ the strength of blood vessel
walls. By these mechanisms, vitamin C can protect from
coronary heart disease, thrombotic stroke, and peripheral
vascular disease.
༝ Protection from heavy metals: It will ↓ absorption and
↑detoxification and ↑ excretion of heavy metals.
༝ Improves healing of wounds and fractures in burns, trauma,
and surgery.
༝ Iron deficiency (by iron absorption from meals).
༝ Preventing and curing Scurvy.

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Recommended Therapeutic Doses
༝ For scurvy, 100-250 mg once or twice daily.
༝ For treating the common cold, 1-3 g daily.
༝ During acute stress, 1 g (3 times daily)
༝ For preventing sunburn, 2 g of vitamin C and 1000 IU
vitamin E has been used.

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Vitamin C and Drug
Interaction
༝ Vitamin C → ↑ chromium and aluminium absorption.
Patients with renal failure who take (Al) compounds should
avoid vitamin C in doses above the RDA.
༝ Vitamin C can destroy dietary vitamin B12 (so, it must be
taken at least 2 hours after meals).
༝ Acidification of the urine by vitamin C could increase
reabsorption of salicylates by the renal tubules, and
increase plasma salicylate levels .

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༝ High doses of vitamin C can ↓ the response to warfarin,
possibly by causing diarrhea and reducing warfarin
absorption
༝ Aspirin increases elimination of vitamin C. It reduces tissue
and leukocyte uptake of vitamin C, leaving more in the
plasma to be excreted into the urine.
༝ Estrogens can ↓ vitamin C absorption or ↓ its breakdown.

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 Thanks!
Further question?

dianluthfita@yahoo.com

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