Vitamin C

Abstract:
• One of the most common & essential vitamin.
• Supplementation of Vitamin-C becomes a must especially during higher pollution & other
oxidative stress levels.
• It’s still cheap & chosen treatment option & part of management that can preserve and protect
human beings from infections, toxicity, autoimmune disorders and tumorous growth development
of any differentiation.
• Vitamin C has a role as anti-aging agent, skin health and texture, other aesthetic benefits too that
can happen over a healthy antioxidant rich & balanced dietary maintained body.
• Do notice & mark it important that; general human population is often un-aware of sources of
vitamin C. Although it is not naturally synthesized in our bodies, by grace of god, our food is
entirely rich of it.

Produced only in non-humans; primate species, guinea pigs, fishes & birds.
• Humans suffer from evolutionarily mutation in DNA-Protein coding of gulono-g-lactone-oxidase
which is the main enzyme responsible for ascorbic acid synthesis. Hence the external
supplement of vitamin C becomes a natural choice to stay fit & nourished.
• Chief source of vitamin C for human beings: fruits and vegetables.
• Citrus fruits and others particularly rich in vitamin C are; cantaloupe, water melon, berries,
pineapple, strawberries, cherries, kiwi fruits, mangoes, & tomatoes. Vegetables include many
variants like, Cabbage, Broccoli, Brussels sprouts, Bean sprouts, Cauliflower, Mustard greens,
Peppers, Peas & Potatoes.

Vitamin C is generic name of L-Ascorbic Acid.
• Other names: Ascorbate & Antiscorbutic vitamin.
• L-Ascorbic structure: Formed of asymmetrical 06-C atoms (C6H8O6) (related to glucose).
• Molecular Weight: 176Da
• Melting Point: 190–192°C (with decomposition)
• Density (approx.): 1.65 g/cm3
• Solubility:
o Water: 300 g/L at 20°C (highly soluble forming clear colourless slightly yellow solution
which is rapidly oxidized)
o Alcohol: 20 g/L at 20°C
o Chloroform, ether and benzene: clear colourless to slightly yellow solution.
o Difficulty in solubility: alcohol, chloroform, ether and benzene
o pKa values (it has two): 4.2 & 11.6
o pH of 5% (w/v) solution in water: 2.2–2.5
• Chemically its’ a weak, water soluble, unstable organic acid which can be easily oxidized by & in;
light, aerobic condition (oxygen), high temperature, alkali, humidity, copper and heavy metals.
• Usually found as white or slightly yellowish crystalline powder. Crystalline form is stable in
dryness.
• Few derivatives of ascorbic acid:
o Sodium L-ascorbate (Sodium Ascorbate)
o Calcium L-ascorbate (Calcium Ascorbate)
o Zinc ascorbate
o 6-Palmityl-L-ascorbic acid (Ascorbyl Palmitate)
o Ascorbyl monophosphate calcium sodium salt (sodium calcium ascorbyl phosphate)

Chemistry & Metabolisms:
• Vitamin C functions mainly as a reducing agent and the results of its oxidation mechanisms are
either reversible or irreversible depending only on the pH changes and not on presence or
absence of air or oxidizing agents.
• Ascorbic acid undergoes a 3-step oxidation process.
o In the beginning, ascorbic acid can reversibly oxidize into dehydroascorbic acid on the
exposure to copper, low alkaline media and heat. Dehydroascorbic acid is a very short halflife
(few minutes) product which can either reversibly or irreversibly oxidize in tissues.
Ascorbic acid and dehydroascorbic acid have the same anti-ascorbutic effect.
o Above pH 4.0, ordinary temperatures & aqueous media: dehydroascorbic acid can be
oxidized irreversibly into 2,3-diketo-l-glutonic acid (diketogulonic acid).
o At pH 4: If dehydroascorbic acid oxidation begins in mild acidic media (pH 4.0), it requires a
neutral or alkaline media to progress more rapidly. The resultant diketogulonic acid is a
stronger reducing agent, not reduced by glutathione or H2S and not an anti-ascorbutic
agent.
o At < pH 4.0: diketogulonic acid losses its reducing property. In acidic media and H2S,
dehydroascorbic acid can also reversibly change into ascorbic acid.
o At pH 7-9: At alkali pH third oxidation product is l-threonic acid & oxalic acid.
o All reversible changes can be done in the presence of H2S & glutathione in neutral or
alkaline media.
• In human beings, ascorbic acid is reversibly oxidized into dehydroascorbic acid, which can be
reduced back to ascorbic acid or hydrolyzed to diketogulonic acid and then oxidized into oxalic
acid, threonic acid, xylose, xylonic acid and lyxonic acid. Further oxidation (decomposition) may
occur by oxidizing agents in food.
• According to the oxidation-reduction reactions, ascorbic acid is the reduced form of vitamin C
while dehydroascorbic acid is the oxidized form of vitamin C.
• The ‘L-isomer’ of ascorbic acid is the only active form.
• Other isomers as d-ascorbic acid, D-isoascorbic acid and L-isoascorbic acid are present. These
stereoisomers have NO effect in the treatment of scurvy / or any nutritional & dietary benefit.
• Absorbed & unabsorbed forms can be excreted in conjugated or non-conjugated pattern.
Ascorbic acid may undergo limited conjugation with sulphate to form ascorbate-2-sulphate, which
is excreted in the urine. Unchanged ascorbic acid and its metabolites are excreted in the urine. In
the presence of intestinal flora, high doses of ascorbic acid (unabsorbed part) can oxidized into
carbon dioxide which is the main excretory mechanism of vitamin C in guinea pigs, rats and
rabbits.
• There exists equilibrium between ascorbic acid & dehydroascorbic acid, dependent on redox
status of every individual cell.

Bioavailability:
• The bioavailability is a measure of the efficiency of gastrointestinal tract absorption.
• Vitamin C absorption (active transport):
o The hydrophilic nature of ascorbic acid facilitates its absorption through buccal mucosa,
stomach & small intestine.
o Its absorption depends mainly on passive diffusion through the buccal mucosa.

Vitamin C absorption occurs through small intestine (distal intestine) by active transport
mechanism. Sodium electrochemical gradient is the process by which active transport of
ascorbic acid occurs. This process proceeds by ‘Sodium Vitamin C Transporter’ Type-1
(SVCT1). The same transporter is responsible for vitamin C transport in retina. SVCT2 is
responsible for transporting vitamin C into brain, lung, liver, heart and skeletal muscles. The
absorption process is usually inhibited by glucose.
o The majority of ascorbate is transported by SVCT1 in epithelial cells (e.g., intestine, kidney
and liver), and the remaining is transported by SVCT2 in specialized cells (e.g., brain & eye).
• The main concentrations of vitamin C are located in brain and adrenal cells.
• The oxidative products of vitamin C, for example dehydroascorbic acid are transported faster into
cells than pure form.
• While the absorption of low or dietary or nutritional supplement doses (15–30 mg) is very high (up
to 98%), ascorbic acid absorption decreases (50%) with larger doses (1000–1250 mg) which is
commonly administrated in acute illness. There happens an osmosis depended absorption for
‘gradient or genetically defaulter’ SVCT channels.
• In human blood, ascorbic acid is always found in reduced form (ascorbic acid). RBCs are not
permeable for ascorbic acid and glucose. It oxidized very slowly in blood than in plasma (no
oxidation reactions occur). Its normal plasma level ranges 50-100μM according to the diet intake
in healthy non-smoker individuals.
• Increasing plasma and intracellular level is not dose dependent. Its intracellular level is higher
than plasma. The plasma level does not increase above the normal range even by increasing the
intake into 500 mg because of its excellent excretion from kidneys through urine.
Distribution & Excretion:
• Vitamin C is widely distributed in all tissues. Its level is high in adrenal gland, pituitary gland, and
retina. Its level decreases in kidneys and muscles.
• Vitamin C metabolites (oxalate salts) & unmetabolized vitamin C are excreted by kidneys. Few
percentage of vitamin C is excreted through faeces. The urinary excretion of vitamin C is dose
dependent. For <100 mg/day no vitamin C was detected in urine. At 100 mg/day, 25% was
excreted in urine. Later percentage is doubled with 200 mg/day. At high doses, large amount of
unmetabolized vitamin C is excreted.
• The higher doses of vitamin C intake, the higher vitamin C concentration in blood and tissues
occurs. As a response for high doses, vitamin C excretion from kidneys and sweat occur. The
antiviral and anti-bacterial effect of vitamin C protects skin and kidneys from infection. Also in
extra doses, oxidation components were used more for anticancer effect than vitamin C itself.
• It was found that the excretion of ascorbic acid when administrating 400 mg ascorbic acid ranges
between 30 and 50% in healthy individuals. This percent decreases in diseased patients due to
higher consumption.
• Repeated low doses (about 200 mg) are highly recommended in diseased individuals due to
theses low doses saturate the body.
• Extremely low dosages (90 mg/day) could result in inability of immune system to respond to
diseases as degenerative diseases. Therefore, limited renal clearance of ascorbic acid is usually
detected.

The plasma saturation of ascorbic acid at 70 μM (0.123 mg/dl). This level controls the excretion of
the ascorbic acid through kidneys. At Higher plasma levels (above 70 μM), higher excretion levels
are usually detected.
• The intravenous route exerts 30–70 folds of vitamin C plasma levels than the oral route.
• The rapid excretion due to its water soluble nature limits its harmful effect and makes it totally
safe product in normal doses.
• Upper tolerable limit (UL): 2.0gm.
• Depending on the depletion-repletion study,
o RDA-Women: 75 mg
o RDA-Men: 90 mg
o Final Common & current-RDA by Levine et al. 2001: 90 mg (all sexes)
o The maximum bioavailability and absorption of vitamin C achieved at 500mg.
Body Storage:
• In 1936, Marinesco et al. detected lower levels in others organs as pancreas, spleen and thymus
gland. Plaut and Billow detected the ascorbic acid lowering not only in the organs but also in body
fluids as CSF, blood and urine. They also detected deficiency in neural diseases, alcoholism, old
people, decreased intestinal absorption and dietary deficiency.
• In human blood, ascorbic acid is always found in reduced form (ascorbic acid).
• The ascorbic acid amount found in organs at different ages:
AGE:    1–30 days (g) 11–45 years (g) 46–77 years (g)
Adrenals  0.581              0.393                 0.230
Brain        0.460 — 0.110
Liver            0.149      0.135         0.064
Kidney         0.153          0.098           0.047
Lung            0.126        0.065            0.045
Heart                             0.042               0.021

Functions:
• Immune system and inflammation: [vitamin C in Immuneknight (adults) & LIQ (children)]
o Vitamin C has must role in maintenance of healthy immune system & deficiency causes
immune insufficiency with risk of infections. The ascorbic acid level is lowered in various body
fluids during bacterial infections. Thus, it is commonly used as adjunctive treatment in many
infectious diseases such as hepatitis, HIV, influenza and periodontal diseases.
o Vitamin C administration modifies and enhances both; innate & adaptive immune response.
o It neutralizes bacterial toxins especially endotoxins by blocking essential signal for
lipopolysaccharides (LPS) formation. On the other hand, LPS block the passage of ascorbic
acid through blood brain barrier and inhibits its uptake by various cells.

Ascorbic acid improves phagocytic properties & activity of immune cells including neutrophils,
natural killer cells, macrophages and lymphocytes.
o Vitamin C increases lymphocytes proliferation and antibody production.
• Anti-oxidant property: [Vitamin C 1000mg/500mg]
o Oxidative stress / Reactive Oxygen Species have a main role in inflammatory diseases.
o The ROS are classified into 3 classes;
1. Reactive free radicals as oxygen related radicals (superoxide, hydroxyl radical or
peroxyl radicals)
2. Reactive species but not free radicals as hypochlorous acid.
3. Radicals resulted from the reaction with ascorbic acid.
o Antioxidants are also classified into enzymatic & non-enzymatic. Enzymatic antioxidants
include catalase enzyme, thiol-containing agents (cysteine, methionine, taurine), glutathione &
lipoic acid.
o Vitamin C is one of the nutrient non-enzymatic anti-oxidants. Its antioxidant effect is by
electron donation process where vitamin C easily donates two electrons (reduction reaction) to
other compounds in order to prevent its oxidation. When ascorbic acid donates the first
electron, it is transformed into a free radical called ascorbyl radical (semi-dehydroascorbic
acid). It is a relatively stable, unreactive free radical with unbound electron in its outer shell but
it has a short life time (10–15 s). The unreactivity of this radical makes it non-harmful to the
surrounding cells. This process is called free radical scavenging or quenching. When it
donates the second electron, it transformed into dehydroascorbic acid. Its stability may only
last for few minutes.
o As a general rule, it was detected that vitamin C acts as a pro-oxidant at low doses and acts
as an antioxidant in high doses. It was also detected that the level of vitamin C in the skin
usually exposed to ultraviolet radiation is lower than that exposed. The antioxidant activity of
vitamin C enhances the epidermal turn over, and the movement of young cells to the surface
of the skin where they replace old cells. The study conducted by Frank in showed that RNA
improved the ability of the skin cells to utilize oxygen.
o Ascorbyl radical & dehydroascorbic acid are reversible agents which can easily rebound into
ascorbic acid. These reversible agents can irreversibly transformed into 2,3-diketogulonic acid
which is further metabolized into xylose, xylonate, lyxonate and oxalate.
o Vitamin C is considered as a strong anti-inflammatory agent as it inhibits many types of
inflammatory mediators as TNF-α (tumour necrosis factor-alpha). This property is commonly
used in the treatment of postoperative erythema formed after CO2 laser in skin resurfacing.
o In 1987, it was found that there’s significant reduction of plasma levels of ascorbic acid in
association with elevated histamine in inflammatory diseases as ulcerative colitis and
rheumatoid arthritis. This was explained by the discovery of the anti-histaminic effect of vitamin
C. It was also found that the higher ascorbic acid content in joints, the higher protection levels
against damage which directed many physicians to use ascorbic acid in combination therapy
with drugs aiming to joint protection as glucosamine.
o It was discovered that vitamin C has an efficient chemotherapeutic effect. The cytotoxic effect
of vitamin C is dose and route dependent. The tumour cells are more sensitive to high
intravenous (cytotoxic) levels of vitamin C than the normal ones. At administration of 10gm of
IV-vitamin C, a marked elevation of the extracellular concentration (1000 μmol/L) is detected
which have a toxic effect on cancer cells due to action of the ascorbyl radicals (free radical
species). On the contrary to the cancer cells, normal cells can compensate the damage
occurred by these oxidative species. It was also found that these mega doses of vitamin C are essential in other diseases as diabetes, cataracts, glaucoma, macular degeneration,
atherosclerosis, stroke and heart diseases.
o Vitamin C improves immune system and its deficiency causes immune insufficiency and
multiple infections. Vitamin C modifies behaviour & activity of immune cells; it also improves
phagocytic properties of neutrophils and macrophages, increases antibody production,
concentration of antibodies and activity(s) of lymphocytes.
o It was detected that the level of vitamin C in leukocytes is higher than its level in plasma
because they have the ability to store it. It has an important role in antibacterial reactions
performed in our body by neutralization of the bacterial toxins especially endotoxins. It was
found that 100μM/L ascorbic acid can lower bacterial replication (bacteriostatic effect).
o Sufficient amount of vitamin C causes blockage of signalling, essential for lipopolysaccharides
(LPS) formation. It also stops the production of ROS especially reactive nitrogen species
which is mainly produced during infection. In bacterial infections, the level of ascorbic acid in
various body fluids is lower than usual which perform further depression due to the action of
LPS in blocking the passage of ascorbic acid through blood brain barrier. LPS also inhibits the
uptake of various cells to ascorbic acid.
o The anti-aging effect of vitamin C is regarding to its potent antioxidant effect, its stimulatory
effect of enhancing collagen formation, protection of persistent collagen (especially elastin)
against damage and finally, inhibits the cross-linking effect formed in wrinkles.
o It was found that the amount of ascorbic acid changes with age. The younger the age, the
higher the ascorbic acid level present.
• Depigmenting effect : [Facial Flare]
o Higher the ROS, deeper the pigmentation produced.
o Anti-oxidants act a great role in lowering melanin formation.
o Vitamin C is considered a potent depigmenting agent which is used in treatment of various
cases of skin hyperpigmentation. It can be used as an adjunctive treatment in melasma &
severe cases of hyperpigmentation and as a treatment in mild and moderate cases.
o Vitamin C inhibits melano-genesis via more than one mechanism:
1. Being an anti-oxidant, ascorbic acid prevents production of free radicals which
triggers melanogenesis,
2. It reduces o-dopaquinone back to dopa, preventing dopachrome of 5,6-DHICA,
3. Reduces oxidized melanin changing pigmentation from jet black to light tan,
4. Direct suppression of tyrosinase enzyme exhibits a great property.
5. The higher the ROS is, the deeper the pigmentation produced. Antioxidants act a
great role in lowering the melanin formation.
6. Other mechanisms of blocking melanogenesis include inhibition of tyrosinase activity
by interacting with copper ions at active sites of the enzyme, inhibits melanocyte
proliferating agents (IL-1, MSH, and PGE2) and block peroxidase reactions on
melanocytes.
o The cytotoxic effect of vitamin C is due to ascorbyl free radical & it is dose as well as route
dependent. The tumour cells are more sensitive to high intravenous (cytotoxic) levels of
vitamin C than the normal ones. A synergistic effect is detected between IV-vitamin C
accompanying the tumour cytotoxic agent in patients suffering from advanced cancer.
o Melanoma is most commonly treated malignant tumour using vitamin C due to high
susceptibility and sensitivity of its cells to vitamin C. It induces sodium ascorbate induced
apoptosis of melisma. The lethal effect of ascorbic acid is attributed to inhibiting the production
of IL-18 (essential for melanoma proliferation).

• Ascorbic acid also acts as An Electron-Donor for eight (08) enzymatic metabolic tracts:
o Three of these enzymes are involved in collagen formation
o Other two enzymes are responsible for carnitine formation
o One enzyme is responsible for epinephrine production from dopamine
o One for addition of the amide groups into peptide hormones.
o Finally, it is essential for tyrosine metabolism and melanin production. The anti-tyrosinase
enzyme occurs at 0.05–0.50mM intracellularly.
• Collagen production & anti-aging effects: [SkinNailHair Care; Hyaluronic-Bamboo Plus]
o Vitamin C is an essential factor for hydroxylation of proline, cofactor during collagen
processing, activation of pro-collagen messenger RNA, inhibition of matrix metalloproteinases
(MMPs) that are responsible for collagen fibers degradation & fibroblast activation intended for
new & proper collagen formation.
o Effecting periodontal ligament, it enhances the periodontal ligament maturation and renewal by
induction of the collagen formation especially collagen III (young collagen) and keeps the
balance between collagen I (mature collagen) and III for tissue maturation.
o Thicker periodontal ligament were detected near CEJ and narrower ones were detected in
middle 1/3rd of root due to vitamin C keeping collagen bundles as well organized and more
resistant to tension. It also activates fibroblast’ proliferation, production & differentiation.
o As a cofactor in hydroxyproline synthesis and improve endothelial cell vitality, angiogenesis.
o Collagen is the main component of bone matrix. Vitamin C is a potent factor in the extracellular
bone matrix proteins formation as collagen type I, osteonectin and osteocalcin. Its combination
with vitamin E has an essential role in the proliferation and differentiation of the osteoblasts.
o In postmenopausal women, higher levels of vitamin C, must to reduce osteoporosis-incidence.
o When vitamin C is used with scaffolds in tissue engineering, the sustained release of vitamin C
stimulates the formation of type I collagen and alkaline phosphatase enzyme.
o The anti-oxidant property is also involved in the anti-aging effect; protecting cellular integrity as
it scavenges ROS, prevents oxidation of cellular proteins, lipids as well as DNA and protects
cellular junctions. It also improves the tissue vasculature.
• Others functions: [multi-vitamin-herbal formulations® of targeted organ-systems]
o Vitamin C and metal absorption: Vitamin C increases the absorption of heavy metals from
intestine, as iron. Vitamin C has an important role in the carnitine synthesis which is an
enzyme co-factor that increases the absorption of non-haem iron in GIT. It also enhances
production of reduced iron which is preferred form for intestinal absorption.
o Vitamin C & drug absorption: Combination of vitamin C supplements with aspirin and opiates
has a strong synergistic effect on these drugs. On the other hand, oral contraceptive pills
increases ascorbic acid turnover and reduce level of ascorbic acid. Many vitamins including
vitamin E (α-tocopherol), vitamin B15 (carnitine), tryptophan and folic acid require vitamin C for
their absorption. eb™FFT blocks its’ (& most of non-corrosive ingested particles’) absorption.
o The combination of vitamin C and E enhance the efficiency and life span of vitamin E by
providing sustained release effect and regeneration of the oxidized vitamin E. Thus, vitamin C
deficiency is considered a cause of other vitamins’ deficiencies, e.g. folic acid deficiency.
o Marked increase of ascorbic acid turnover was reported on consumption of oestrogen
containing medications. As a result of oxidation reaction, production of hydrogen peroxide is enhanced by cations as iron and copper. EDTA is the only permissible preservative that could
be used with injectable vitamin C products.
o Limited evidence suggests that ascorbic acid may influence the intensity and duration of action
of bis-hydroxy-coumarin.
• Vitamin C and Lipid Metabolism: [NWL: Nutritious Weight Loss; Tri-Systemic Signature Formula]
Although vitamin C is water soluble, it has great effects on lipids either intracellularly or
extracellularly. Vitamin C is an essential factor protecting the lipids of cell membrane from
oxidation. It also protects the lipid bilayer of skin. Significant control of hypertension & high
cholesterol levels:
o It improves lipid metabolism by inhibiting oxidation of unsaturated lipids & lipoproteins.
o ROS can easily oxidize cellular lipoproteins & circulatory LDL, leading to results in lipid
peroxidation.
o By a process called radical propagation, the formed lipid peroxides can easily reacts with
oxygen to finally form lipid hydro-peroxides.
o Ascorbic acid can easily inhibit this process by reducing the ROS.
o Vitamin C decreases oxidation of lipids & lower low density lipoprotein (LDL) cholesterol.
• Vitamin C & Bone Formation:
o Increases production of collagen type I & X needed for matrix formation
o Activation of osteoblast growth & differentiation
o To maintain adequate bone density
o Stimulation & higher expression of osteocalcin-osteonectin on osteoblasts
o In postmenopausal women, higher levels of vitamin C are needed for bone abnormalities as it
is one of the ‘delaying osteoporosis’ factors
o In scurvy, lower bone density with marked bone abnormalities occur, due to deficiency in
young individuals & their respective bone-fragility, cartilage bone-resorption and fracture of
growth plates. Abnormalities were attributed to reduced activity of osteo-&-chondro cytes. It
also maintains and preserves the balance between osteoblasts and osteoclasts. In order to
achieve optimum proliferation of the osteoblasts and fibroblasts, IV 200 μg/ml is the maximum
dose needed. Apoptosis occurs when exceeding such dose.
o In 2004, an in vitro study used vitamin C with scaffolds in tissue engineering in order to
regenerate bone. The sustained released vitamin C stimulates the formation of type I collagen
and alkaline phosphatase.
• Vitamin C & Stress (cortisone): In stress, overproduction of cortisone affects defence
mechanisms, explained by reduction of glucose level.
• Renal Stones:
o There WAS a hypothesis that Vitamin C metabolism results in calcium oxalate salts, hence
formation of renal stones & oxaluria may occur in overdoses of vitamin C. After few researches
later, it was detected that oxaluria is usually due to laboratory bias, occurs in urine collection
tube (ex vivo).
o Vitamin C counteracts the formation of calcium oxalate crystals because of its ability to bind to
calcium found in urine, & increases solubility of calcium oxalate due to mild acidity.
o It also triggers normal urination process & prevents urine retention.
o All the previous actions decrease the incidence of kidney stones formation.

Read ‘Side-Effects’, under contraindications for uricosuric effects, urinary oxalate stones
issues & case of renal insufficiency.

Dosage:
• Dosage calculations differ as per medical status, aim of administration, prophylactic or curative,
route of administration & patient age.
• About ascorbic acid average dosage, we have to differentiate between four terms:
o Estimated Average Requirement (EAR)
o Adequate Intake Level,
o Tolerable Upper Intake Level (ULs)
o Recommended Dietary Allowance (RDA)
• The EAR is used to calculate the RDA and the adequate intake levels. While the UL is the level
below which toxic effects have not been seen.
• Because of poor oral bioavailability of vitamin C, toxic signs & symptoms may appear with large
doses exceeding 1000mg or utilizing more than 2gm as single dose (depending on route of
administration).
• Dosage for healthy individuals:
o Average normal content of ascorbic acid in human body is about 1.5gm;
o Daily, our body usually consumes 3–4% (40–60 mg) of this pool;
o In order to keep this pool balanced, the daily oral intake should be 200–300mg of vitamin C;
more for balancing the extra-needs for any of the reasons detailed under functions.
o Daily intake of 10s of ‘rich’ fruits or vegetables will provide a 2000 mg of vitamin C which will
result in overall 700μM plasma level (approx.). Health food supplements may help in achieving
better levels easily, with options for prolonged release for day-long maintenance.
Recommended dosage of vitamin C can maintain its plasma level constant up to 5–6hr only.
o It was also found that the uptake of vitamin C differs from one tissue to another.
o As an average, RDA of vitamin C for adult healthy men: 90mg and for healthy women: 75mg.
o The ULs dosage was calculated at a level of 2gm per day for healthy fit balanced individuals.
o Based on gender, the RDA of both males and females should not be less than 90mg which secure the neutrophil saturation and urinary excretion.
o The maximum bioavailability could be reached at 500mg dose; or better would be to say; Vitamin C is well absorbed up to 500 mg/day
o Oral route could produce a maximum 220μmol/L of vitamin C plasma concentration even with
high dosage administration while the intravenous route produces higher levels which could reach to 1760μmol/L.
o The recommended dosage also differs according to country or health institute that recommended this dosage.
o The bowel tolerance dose is the dose around which an ingested dosage can produce
diarrhoea. The bowel tolerance usually differs from one to another according to the medical
status. It can be determined only by trail. High dosage ranging between 3-6gm is
recommended till diarrhoea occurred. The dosage then has to be decreased till bowel balance
achieved again. Such side effect (diarrhoea) is useful in treatment in patients with constipation.

• Dosage for Smokers: A higher dose of vitamin C is strongly recommended in order to
compensate for smoking hazards & neutralize the resulted oxidative stress. A 110mg is the
recommended daily dosage for smokers due to their antioxidant level at below normal. The lower
plasma level of antioxidants regards to their lower consumption of healthy food, higher levels of
toxic products which produce oxidative stress.
• Dosage in Surgery & Illness: Vitamin C is an important partner in par-enteral nutrition (PAN or
TPAN) especially in acute conditions (shocked surgical, trauma, burn or septic). In surgery &
illness; redistribution & reabsorption of vitamin C occurs leading to increased demand in tissues
resulting a fall in plasma concentration. It was discovered that patients can tolerate much more
doses of vitamin C than healthy individuals. A 3 mg orally or 100 mg parentally is recommended
in acute conditions to compensate diseased conditions and maintain physiologic functions.
• Dosage in Old Patients: In old age (65+), vitamin C deficiency is a common feature. It is mainly
attributed to improper intake within diet which is usually lower than the average recommended
dietary allowance (RDA) by 25.9–38.3%; due to various lifestyle reasons of every individual
including but not limited to, poor diet, wrong habits, circadian-sleep-cholesterol dys-synchronicity,
ill intestines & gut-brain axis, hunger-satiety variations.
• Dosage in Pregnant(s) / Pregnancy: In females, hormonal changes result in increased oxidative
stress. Lower vitamin C levels are usually detected in pregnant women due to several factors;
lack of mobility, sleepiness, obesity, low iron intake, low dietary intakes in later trimesters, all of
which could result in low birth weight, antenatal & postnatal complications, many other disorders
explainable well by Obstetrician or Gynaecologists; Do consult before consuming / stopping /
changing any dosage.
• Dosage in Cancer Patients: The tumour cells are more sensitive to high intravenous (cytotoxic)
levels of vitamin C than the normal ones. Consult Chemotherapist / Cancer Specialist /
Oncologist for more information over Vitamin C dosage in such case.
• It was also found that these mega doses of vitamin C are essential in other diseases as diabetes,
cataracts, glaucoma, macular degeneration, atherosclerosis, stroke and heart diseases.

Routes of Administration:
• Ascorbic acid is a water soluble vitamin which facilitates its absorption from buccal mucosa,
gingival tissues, stomach and small intestine. The literature reported several routes of vitamin C
administration.
• In order to explain how we can reach the optimal route of administration and dosage, accurate
analysis of the treated tissue condition and its nature in healthy and different pathological
conditions is highly recommended.
• By all routes of administration, the plasma level of vitamin C returns to its normal range within
24hr.
o Oral: Most common; eb™ Capsules tablets, powder or solution. It is an essential element in
many of eb™ multivitamins / multiherbal supplements.

Parental: The intravenous route is used in advanced cancer therapy and severe illness, as a
complementary treatment. The intravenous vitamin C administration is usually used to treat
hyperpigmentation especially in patients under chronic renal haemodialysis.
o Topical: Usage of local application promotes surgical healing & better tissue reconstruction
o Vitamin C is easily absorbed by passive diffusion through buccal mucosa. It was found that the
absorption of the ascorbic acid through the buccal mucosa and small intestine is nearly equal.
o Transdermal: The micro-vibrations produced by using ultrasound waves are responsible to
increase the kinetic energy of drug and deliver it deeper through skin layers. E.g.
Sonophoresis & Nanoparticle; that enhance absorption and penetration of topically delivered
hydrophilic drugs. These routes are used for insulin, morphine, caffeine, glucose, lidocaine
and ascorbic acid; as prescribed by qualified professional only.
o Injection: Used by clinicians & qualified persons only. Read Parenteral again.
o Dosage calculation or different routes of administration: Marked absorption (98%) is reported
in lower doses (15–30 mg). On the other hand, vitamin C absorption could be reduced to 50%
in large doses that exceeds 1000 mg. These manifestations are dose related. It can be
controlled by either, reducing total daily dose, dividing the total dose into multiple small doses,
administrating the vitamin with food to decrease its absorption or to take the buffered form of
vitamin C as sodium ascorbate or calcium ascorbate. Consult your GP / dietitian.

Contraindications:
There are no contra-indications of vitamin C administration. Diabetics, patients prone to recurrent
renal calculi, those undergoing stool occult blood tests, and those on sodium restricted diets or
anticoagulant therapy should not take excessive doses of ascorbic acid over an extended period of
time.
Diabetics taking >500 mg of ascorbic acid daily may obtain false readings of their urinary glucose test
(GTT).
No exogenous ascorbic acid should be ingested for 48–72hr before amine dependent stool occult
blood tests, possible false-negative results.

Side Effects:
• Oral route side effects: Side effects of vitamin C could be only detected with large doses
exceeding the ULs for each individual especially on a single intake. Most of the vitamin C
drawbacks were reported during oral uptake. They include diarrhoea, abdominal pain, renal
stones, and enamel erosion during chewing. Overcome few of them by proper hydration while on
Vitamin C Supplements & preferring capsules over tablets or chewable.
• GIT disturbance: Because of poor oral bioavailability of vitamin C, toxic signs & symptoms may
appear with large single doses. Diarrhoea can occur. To avoid occurrence, 2gm is maximum
permissible single dose. Diarrhoea and abdominal pain may occur due to excretion of large
amount of un-metabolized vitamin C. Such manifestations are dose related. It can be controlled
by either, reducing the total daily dose, dividing the total dose into multiple small doses,
administrating the vitamin with food to decrease its absorption or to take the buffered form of
vitamin C as sodium ascorbate or calcium ascorbate. Even the usage of encapsulated vitamin C (as in our Vit-C & Zincorbic) could not protect against the gastric upset. The gastrointestinal
symptoms usually disappear within 1–2 weeks.
• Renal Stones: Some researches favour that Vitamin C increases urinary execration of uric acid &
decrease the plasma level of uric acid. But others demand the uricosuric effects of vitamin C as a
rapid migration of uric acid from tissues. It was found that 1-2gm / day increases urinary oxalate
stones. Some studies detect lowering of urine pH after vitamin C intake. Renal stones incidence
of accumulation occurs in an average concentration of 60gm (IV) & more than 5gm (oral) intakes
over few couple of months to years. In case of renal insufficiency / established renal disease /
ESRD, 1 gm/day for 3 months (or even for weeks) is enough to produce renal stones.
• Metabolic Side Effects: Accelerates absorption of heavy metals as lead & mercury which
increases its toxicity, if consumed together for any reason / mistake. In patients with high iron
stores (genetic or therapeutic or idiopathic or nutritional), vitamin C worsens their state. It also
increases the iron-induced oxidative damage, if already there’s a presence of iron overload &
damage. In healthy individuals, whether on iron supplements or not, regulated & well dosed
vitamin C do not cause such side effects; except little & bearable gastric irritation of higher iron
gastric-absorption, if consumed iron supplement with vitamin C.
• Dental side effects: Enamel erosions were detected on chewing of vitamin C tablets. It was found
that usage of unbuffered form of ascorbic acid could result in enamel erosion. Capsule variants or
special buffered-formulations of vitamin C supplements could be chosen to overcome this.
• Parenteral route side effects: During injection, transited mild soreness occurs during
intramuscular, subcutaneous routes. Faintness or dizziness might get reported on rapid
intravenous administration. The renal stones incidence of accumulation occurs in an average
concentration of 60gm (IV) & over 5gm (oral) dosage for months to years. In case of renal
insufficiency, 1gm/day x3Months is enough to produce renal stones (Alkhunaizi & Chan, 1996).

Vitamin C Deficiency:
• In scurvy, absence of wound healing and failure of fractured bones to heal; such has been
explained by the deficiency of collagen formation due to the vitamin C deficiency.
• Scurvy could be produced if reduction of body reservoir of vitamin C has shifted into its fifth
standard deviation for the age, sex, height, immunity-nutritional status of an individual.
• The required body reservoir & needed dosage are determined according to body weight, BMI,
nutritional status & signs-symptoms for parallel damages occurred in deficiency.
• Scurvy:
o Body weakness, legs & arms oedema, nose, skin & gums haemorrhage, frequency of
infections, bone-cartilage damage (osteoporosis), vasculitis and cardiomegaly.
o Various bleeding incidences as petechiae, subperiosteal hemorrhage, ecchymoses, purpura,
bleeding gums, hemarthrosis.
o Seek Medical-Doctor’ / Consultant’ / Nutritionist’ advice, than local-gossips or non-medic
websites. Consider yourself human & then act accordingly.