Vitamin C

Vitamin C is a natural supplement belonging to the supplement category of the water-soluble vitamins class.

Vitamin C is also called ascorbic acid, L-Ascorbic acid.

Deficiency of Vitamin C may lead to scurvy. Scurvy is a disease whose primary risk factors include socioeconomic status and dietary availability. In those who acquire this condition, signs and symptoms are frequently evident. The three most commonly recognized signs of scurvy are gingival bleeding, perifollicular haemorrhage, and corkscrew hairs.

Vitamin C is produced from collagen, a protein necessary for wound healing. Additionally, vitamin C supports healthy immunological function and increases iron absorption from plant-based meals, protecting the body against disease.

Although humans cannot directly produce vitamin C, it is widely available in many foods. Plants like citrus fruits, red and green peppers, potatoes and animal organs, such as the liver, kidney, and brain, are the best-known sources of vitamin C.

The sodium vitamin C co-transporter 1 (SVCT1) transports vitamin C to the epithelial cells of the small intestine, where dehydroascorbic acid, an oxidized form of ascorbate, is quickly converted to ascorbate, which is then processed by the liver, filtered by the kidneys, and eliminated in the urine. The renal threshold for excretion of vitamin C is 1.4 mg/100 mL.

The biological half-life of vitamin C is 8–40 days.

The common side effects of vitamin C are flushing, flank pain, loose bowels and diarrhoea, faintness, abdominal cramps, headache, dyspepsia, nausea, vomiting and hyperoxaluria (large doses).

Vitamin C is available in various forms like tablets, chewable, extended-release capsules, extended-release tablets, granules, powder effervescent, powder, syrup and injectable solutions.

Biochemical action of Vitamin C

Vitamin C belonging to the water-soluble vitamins acts through an energy-dependent process via simple diffusion and active transport. In this process, hexose and sodium-dependent vitamin C transporters (SVCTs) are involved. The distal small intestine is the absorption location, while the renal is the primary organ for excretion. Up to 100 mg of the average daily food intake is entirely absorbed, and organs like the pituitary gland, the adrenal gland, the brain, leukocytes, and the eyes have the most significant levels of ascorbic acid in the body.

In several reactions and metabolic processes, vitamin C is an enzyme cofactor, co-substrate, complement, and potent antioxidant. Additionally, it improves iron absorption while stabilizing vitamin E and folic acid. It reduces inflammatory reactions, including sepsis syndrome, and neutralizes free radicals and toxins.

Vitamin C is available in tablets, capsules, chewable tablets, powders and injectable solutions.

• Tablets and capsules will be swallowed whole with water/liquid, as applicable.
• Chewable tablets are to be chewed entirely before swallowing, as applicable.
• Powders must be mixed thoroughly with the appropriate amount of liquid or soft food and stirred, as applicable.
• Injectable solutions are to be administered parenterally, as applicable.

To reduce the adverse reactions of intravenous injection, dilution into a high-volume parenteral such as Normal Saline or Glucose is recommended.

Vitamin C is used as a supplement for strengthening one's immune system. It possesses an antioxidant and anti-inflammatory activity and has been shown as a supplement for use in heart disease prevention, iron-deficiency anaemia, dermatological, antiageing, sunburn prevention, photo-damaged skin, wound healing, gout, improve bone density by increasing collagen accumulation, the common cold.

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s)

Vitamin C may be useful as a supplement for the following health benefits:

• Antioxidant: Powerful antioxidant vitamin C eliminates free radicals and protects against the oxidative harm that ROS can cause to cells. It preserves glutathione and regenerates vitamin E, boosting the antioxidant power of the latter compound.
• Connective Tissue: Vital for collagen formation, vitamin C ensures stable tissues in blood vessels, skin, tendons, and more. Its absence leads to unstable collagen, affecting tissue structure.
• Collagen Stability: Vitamin C plays a crucial role in collagen synthesis; it stabilizes collagen molecules through specific hydroxylation reactions, bolstering tissue strength.
• Brain and Nerve: Vitamin C aids neurotransmitter synthesis, influencing dopamine to norepinephrine conversion and serotonin production. It protects nerves and enhances neural maturation.
• Immunostimulant Boosting immune function: vitamin C modulates T-cell gene expression and stimulates interferon production, enhancing immunity against viral attacks.
• Anticancer: At higher concentrations, vitamin C exhibits selective cytotoxicity to cancer cells, inhibiting cell growth, inducing apoptosis, and showing potential as an adjunctive anticancer therapy.
• Gene Expression: Vitamin C redox's influence on transcription factors and signal transduction enzymes modulate gene expression, impacting various cellular processes.

Vitamin C is commonly administered orally before or after meals for all oral solids and oral liquids forms.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional.

Vitamin C may be administered intramuscularly, intravenously (IV), or subcutaneously when malabsorption is suspected.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional.

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablets:100mg,250mg, 500mg,1g
• Chewable tablets: 100mg,250mg,500mg
• Extended-release Capsule: 500mg
• Extended-release Tablets:500mg, 1000mg, 1500mg
• Crystals: 120g, 480g
• Granules: 100g/ 500g, 1000g
• Injectable solution: 250mg/mL, 500mg/mL
• Oral solution: 100mg/mL
• Powder effervescent: 150g
• Powder, oral: 113mg, 120mg, 480mg
• Syrup, oral: 100mg/mL

Dosage Adjustment in Adult Patients

• Urinary Acidification

4-12 g/day oral/ intravenous divided three or four times daily

• Ascorbic Acid Deficiency (Scurvy)

Oral prevention: 70 to 150 mg of vitamin C daily is the typical protective adult intake.

When scurvy is present, the dosage should be increased from 300 mg to 1 g daily.

Oral treatment: 250 mg oral QID for 1 week.

• Treatment with IV ascorbic acid

Indicated for the short-term less than 1-week therapy of scurvy in adults and children older than 5 months for whom oral administration is not feasible, inadequate, or contraindicated.

The recommended daily duration of treatment shouldn't last exceed longer than 7 days.

If there is no improvement in them, retreat till scorbutic symptoms seem to disappear

Macular Degeneration (Off-label)

500 mg/day oral with other vitamins and minerals.

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• In the intestines, carbohydrates impair Vitamin C absorption, and Vitamin C competes with glucose for absorption.
• Limit foods and drinks higher in added sugars, saturated fat, and sodium.
• Limit alcoholic beverages.
• Stay within your daily calorie needs.

The dietary restriction should be individualized as per patient requirements.

Recommended Daily Allowance (RDA)

The RDA of vitamin C for adult men is 90 mg /day day,  and for adult women is 75 mg per day.

Upper Tolerable Intake (UTL):

The UTL for adults is set at 2 g/day.

• Vitamin C supplementation is contraindicated in patients who are sensitive to iron overload, vitamin C may exacerbate iron toxicity by mobilizing iron reserves. As such, vitamin C supplementation should be used with caution by people with blood disorders like thalassemia major or sideroblastic anaemia, G6PD deficiency, sickle cell disease, and hemochromatosis.
• Avoid taking Vitamin C immediately before or following angioplasty.
• For people with diabetes, vitamin C supplements should be used with caution as they may raise blood sugar levels.
• As ascorbic acid acidification increases the likelihood of precipitating cysteine, urate, and oxalate stones, vitamin C should be administered with caution in cases of oxalate nephropathy or nephrolithiasis.

The treating healthcare professional must closely keep a watch and monitor for any reactions like nausea, GI disturbances and diarrhea. It is always advised to take the physician-recommended dosage to avoid any potential side effects.

High daily dosages of up to 1000 mg raise milk levels, but not to the point where the newborn is at risk for health problems, and they are not a reason to stop nursing.

Food may decrease the rate but not the extent of absorption. Limit foods and drinks higher in added sugars, saturated fat, and sodium.

Vitamin C is generally well-tolerated.

The adverse reactions related to Vitamin C can be categorized as:

• Common: Diarrhoea, nausea, abdominal cramps and other gastrointestinal disturbances.
• Less common: Migraine headaches with a daily dose of 6 g.
• Rare: High vitamin C consumption can elevate uric acid and oxalate as it acidifies the urine, increasing the risk of kidney stones.

However, the dose at which this occurs varies between individuals and for each individual at different times.

• Aluminium-based antacids: Vitamin C increases the amount of aluminium absorbed—separate doses by at least 2 hours.
• Aspirin: Aspirin may interfere with both absorption and cellular uptake mechanisms for vitamin C; increased vitamin C intake may be required with long-term therapy.
• Chitosan: According to a preliminary study in rats, taking vitamin C in combination with chitosan might provide additional benefits in lowering cholesterol—a potentially beneficial interaction.
• Corticosteroids: Based on in vitro and in vivo findings, corticosteroids may increase the need for vitamin C; therefore, greater vitamin C consumption may be necessary with long-term medication therapy.
• Cyanocobalamin: Vitamin C can reduce the absorption of cyanocobalamin—separate doses by at least 2 hours.
• Anti-cancer drugs: Vitamin C enhanced the antitumour activity in vitro and in vivo of drugs like Cisplatin, Cyclophosphamide, Etoposide, Fluorouracil, Tamoxifen, and Vincristine. Potentially beneficial but difficult to assess.
• Doxorubicin: Vitamin C enhanced the therapeutic drug effect and reduced drug toxicity in vivo. Potentially beneficial but difficult to assess.
• Iron: Iron absorption is improved by vitamin C. interaction which might be beneficial.
• L-Dopa: A case report of co-administration with vitamin C suggests this may reduce drug side effects. Beneficial interaction.
• Proteasome inhibitor PS-341 (bortezomib, Velcade): The medicine's ability to treat patients with relapsed multiple myeloma—vitamin C inactivated drug activity in vitro—is approved by the US FDA. As long as safety cannot be independently proven, avoid it.
• Intravenous vitamin C: A dose-response study involving patients with solid tumours receiving high-dose IV vitamin C found virtually all the side effects that occurred were consistent with the side effects attending the rapid infusion of any high-osmolarity solution. By encouraging patients to consume water both before and during the infusion, the symptoms may have been prevented.
• Laboratory tests: Vitamin C can affect the results of numerous serum and urine biochemical parameter measurements in both in vivo and in vitro studies.

Common side effects of vitamin C include diarrhoea, faintness, abdominal cramps, headache, dyspepsia, nausea, vomiting, and hyperoxaluria (large doses).

• Pregnancy:

It is recommended not to exceed the therapeutic dose nor abruptly cease supplementation.

No adverse developmental outcomes are reported.

There is no sufficient scientific evidence traceable regarding the use and safety of Vitamin C for use in special populations

• Paediatrics:

Children's health and development depend significantly on vitamin C. The body requires it to synthesize and maintain bones, tissues, and red blood cells. Along with preventing bruising from falls and scrapes, it helps the child's gums stay healthy and strengthens the blood vessels.

40 mg daily dose of vitamin C is recommended with infants aged 6 months or less.

Dosage Adjustment for Paediatric Patients

• Urinary Acidification

500 mg/day divided oral/ intravenous TID/QID

• Ascorbic Acid Deficiency (Scurvy)

Oral prevention: Oral treatment, infants or children: 100 mg oral TID for 1 week, then 100 mg oral qDay until the issue is resolved (typically for 1-3 months)

• Treatment with IV ascorbic acid

Indicated for short term less than1 week treatment of scurvy in children and adolescents more than 5 months for whom oral administration is not feasible, insufficient or contraindicated

<5 months: Safety and effectiveness are unknown.

5 to less than 12 months: 50 mg IV qDay

1 year to more than 11 years: 100 mg IV qDay

11 years or older: 200 mg IV qDay; the recommended daily duration of treatment should not exceed 7 days

Scorbutic symptoms is observed and if no improvement is seen, retreat until the issue is resolved.

It is not recommended to repeat dosing in children and adolescents older than 11 years

• Geriatrics:

Excellent at fighting free radical damage, vitamin C has long been considered to possess some level of protection against the general cognitive loss associated with ageing and the pathology of Alzheimer's disease.

• Lactating mothers:

Human milk naturally contains vitamin C, which is an important milk antioxidant.

There is no sufficient scientific evidence traceable regarding the use and safety of Vitamin C for use in special populations.

Dosage Adjustment in Kidney Impairment

60-100 mg/day supplement recommended for CKD patients (dialysis and non-dialysis).

During renal replacement therapy (RRT), 2 g/day of intravenous vitamin C may be required to maintain average plasma concentrations.

Current recommendations for the maintenance of haemodialysis patients is to take the supplement with ascorbic acid 75–90 mg daily during dialysis.

The use of Vitamin C should be cautiously administered in patients with renal impairment as it has been reported to cause haemolysis.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

High dosages of vitamin C are linked with low toxicity, and no known adverse responses are known to occur.

In the event of an overdose, there is no particular therapy available. If an overdose occurs, the intake of vitamin C should be stopped immediately, the patient should be treated symptomatically, or any appropriate supporting measures should be put in action.

Biochemistry profile of vitamin C

The biochemical functions of Vitamin C are mainly dependent on the oxido-reduction properties of l-AA, which is a cofactor for hydroxylation and activity of mono-oxygenase enzymes in the synthesis of collagen, carnitine and neurotransmitters; it also plays a role in the conversion of folic acid to folinic acid.

Kinetic profile of vitamin C

• Absorption: In vivo, the two main forms of vitamin C are found in vivo are ASC (reduced form) and DHA (oxidised form). Ascorbate (ASC) is transported across the intestinal epithelium by sodium-coupled active transport via the SVCT1 transporter, while dehydroascorbic acid (DHA) is transported across the intestinal epithelium by facilitated diffusion via GLUT1 or GLUT3 transporters. DHA is effectively converted to ASC or transferred to circulation once within the cell through GLUT1 and GLUT2 in the basolateral membrane, maintaining a low intracellular concentration and promoting more DHA absorption.
• Distribution: Intense compartmentalization characterizes the vitamin C distribution. To maintain high levels of vitamin C during periods of insufficient availability, specific organs contain concentration-dependent systems that compete with other organs for the vitamin. The brain is specially shielded, and concentration-dependent absorption and re-absorption processes also aid the body's homeostatic regulation of vitamin C.
• Metabolism: The metabolism of Vitamin C is intimately linked to its antioxidant function. As mentioned earlier, DHA is efficiently reduced intracellularly to ASC and is metabolized in the liver.
• Excretion: Vitamin C is efficiently filtered by the glomerulus to the renal tubule lumen in the kidney. Reabsorption under vitamin C deficiency is primarily achieved by SVCT1 transporters in the apical membrane, although diffusion from the luminal surface may also contribute to the overall uptake. Under saturated conditions, vitamin C is quantitatively excreted.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727637/
2. https://ods.od.nih.gov/factsheets/VitaminC-Consumer/#h13
3. https://www.ncbi.nlm.nih.gov/books/NBK225480/
4. https://ods.od.nih.gov/
5. Braun L, Cohen M. October 1, 2014.Herbs and Natural Supplements; 4^th Edition Vol-2. Australia. Elsevier.