Vitamin C

Vitamin C, also known as ascorbic acid (or its ionised form, ascorbate), is a vital water-soluble vitamin that plays a central role in human health. Because humans (and some other animals) cannot synthesise it, vitamin C must be obtained from dietary sources or supplements. It acts as an antioxidant, a cofactor in key enzymatic reactions, and is essential for connective tissue, immune competence, iron metabolism, and many other physiological processes.

Chemistry, Structure and Biosynthesis

Vitamin C has the chemical formula C₆H₈O₆ and structurally is a lactone (a cyclic ester) derived from a hexose (a six-carbon sugar). Its active form is the L-ascorbic acid enantiomer. Upon oxidation, it is converted to dehydroascorbate, which is reversibly reduced back to ascorbate in the body. This redox cycling is essential to its antioxidant function.
In most plants and many animals, vitamin C is produced via multistep metabolic pathways converting glucose (or other sugars) into ascorbic acid. However, in primates (including humans), guinea pigs, many bats, and certain other species, the gene encoding the enzyme L-gulonolactone oxidase (the final enzyme in the pathway) is nonfunctional. As a result, these species cannot synthesise vitamin C internally and depend entirely on exogenous sources.
Industrial synthesis of vitamin C is commonly done via processes that convert glucose → sorbitol → sorbose → 2-keto-L-gulonic acid → ascorbic acid, combining fermentation and chemical steps. Over time, more efficient fermentation and biotechnological routes have evolved to increase yield and reduce cost.

Absorption, Transport and Metabolism

Because vitamin C is water-soluble, it is absorbed in the small intestine (especially the jejunum) via active transporters (e.g. sodium-dependent vitamin C transporters, SVCTs) when intake is moderate. At higher dietary intakes, absorption efficiency falls (i.e. saturation kinetics). Excess vitamin C that is absorbed tends to be excreted in urine, thus preventing substantial accumulation beyond physiological needs.
Within the body, vitamin C is distributed into tissues, with higher concentrations maintained especially in cells and organs with high metabolic demand or antioxidant need (e.g. adrenal glands, leukocytes, retina, brain). It is involved in redox reactions in plasma, cytosol, and organelles, and helps recycle other antioxidants (e.g. regenerating oxidised vitamin E).
Metabolism of vitamin C occurs partly by oxidative pathways, converting it to oxalate and other metabolites, which are excreted. In states of deficiency, renal excretion is minimised; with abundant intake, excess is rapidly excreted.

Physiological Functions

Vitamin C contributes to many critical biological roles, often via its capacity as a reducing (electron-donating) agent or as a cofactor for enzymes that require reduced metal ions (e.g. iron, copper):
1. Collagen synthesis and connective tissue healthVitamin C is essential in the hydroxylation of proline and lysine residues in procollagen, catalysed by prolyl hydroxylase and lysyl hydroxylase. These hydroxylations stabilise the triple helix structure of collagen. Deficiency leads to fragile connective tissues, poor wound healing, bleeding gums, and capillary fragility.
2. Synthesis of other biomolecules

• Carnitine biosynthesis: Enzymes in the carnitine pathway require vitamin C to maintain metal cofactors in reduced form, facilitating fatty acid transport into mitochondria.
• Neurotransmitter synthesis: Vitamin C is required for the enzyme dopamine β-hydroxylase, converting dopamine to norepinephrine.
• In addition, it is implicated in the synthesis of certain peptide hormones and in microsomal and phase I metabolic reactions.

3. Antioxidant and redox protectionVitamin C neutralises reactive oxygen species (ROS) and free radicals by donating electrons, thus protecting lipids, proteins, DNA, and other biomolecules from oxidative damage. It also regenerates other antioxidants (e.g. helps reduce oxidised vitamin E back to its active form).
4. Immune supportVitamin C is involved in various immune functions: enhancing chemotaxis and phagocytosis of leucocytes, supporting epithelial barrier integrity, and modulating cytokine production. During infections or oxidative stress, tissue levels of vitamin C may be depleted, indicating its consumption in defensive roles.
5. Iron absorption and metabolismBy reducing ferric iron (Fe³⁺) to the more soluble ferrous (Fe²⁺) state in the gut, vitamin C enhances absorption of non-heme iron (plant-based iron). It also forms soluble complexes with iron, preventing precipitation at intestinal pH. This role helps prevent iron deficiency anaemia especially in diets rich in plant foods.
6. Miscellaneous rolesVitamin C may influence cholesterol metabolism, bile acid synthesis, nitric oxide production, and gene regulation (through involvement in dioxygenases that regulate epigenetic modifications). Some of these roles remain under active investigation.

Dietary Sources and Recommended Intake

Rich dietary sources of vitamin C include citrus fruits (oranges, lemons, grapefruits), berries, kiwifruit, guava, papaya, bell peppers (red, green), broccoli, Brussels sprouts, tomatoes, leafy greens (spinach, kale), and various tropical fruits (e.g. acerola, camu camu). Because vitamin C is sensitive to heat, light and oxygen, significant losses can occur during cooking, storage, and processing.
Dietary recommendations vary by country and age group. As a rough guideline, many authorities suggest 60–100 mg per day for adults (women slightly lower, men slightly higher). During pregnancy, lactation, smoking, illness or periods of oxidative stress, requirements may be higher.
Because vitamin C is water-soluble and excreted when in excess, toxicity is rare. However, many countries set an upper tolerable intake (e.g. ~2,000 mg/day for adults) above which risks of side effects (e.g. gastrointestinal upset, kidney stone formation) may increase.

Deficiency and Excess

Deficiency (Scurvy and subclinical deficiency)Prolonged inadequate intake of vitamin C causes scurvy, characterised by:

• Weakness, fatigue, lethargy
• Gingival swelling, bleeding gums, loose teeth
• Poor wound healing and skin changes (petechiae, ecchymoses, hyperkeratosis)
• Joint pain and swelling
• Anemia (often due to impaired iron metabolism)
• Capillary fragility and spontaneous bleeding

Milder deficiency (hypovitaminosis C) may present with fatigue, irritability, reduced immunity, increased susceptibility to infections, and delayed tissue repair.
Excess / toxicityLarge supplemental doses (above several grams daily) can lead to:

• Gastrointestinal distress: diarrhoea, nausea, abdominal cramps
• Kidney stones (particularly in predisposed individuals), owing to increased urinary oxalate
• Iron overload risk in persons with hemochromatosis, since vitamin C enhances iron absorption
• Possible interference in certain diagnostic laboratory tests
• Rare pro-oxidant effects under special circumstances (e.g. in presence of free transition metals), though this is not typical physiological behaviour

Because absorption efficiency declines with high doses and excess is excreted, risk of true toxicity is limited in healthy individuals, though prudence is warranted.

Clinical and Therapeutic Applications

Supplementation and pharmacological useVitamin C is widely available as dietary supplements (ascorbic acid, sodium ascorbate, calcium ascorbate, liposomal ascorbate, etc.). In deficiency states or certain clinical conditions, supplementation helps restore normal levels and correct symptoms.
High-dose vitamin C (e.g. intravenous) has been studied (and sometimes used experimentally) in contexts such as cancer support, sepsis, and critical illness, on the premise of antioxidant, immunomodulatory and cytotoxic potential. However, evidence is mixed and definitive clinical benefits remain under investigation.
Adjunct in infection or immune supportSome clinical trials and meta-analyses suggest that regular vitamin C supplementation may modestly reduce the duration and severity of common colds, particularly under physical stress or in individuals with low baseline levels. Its role in broader infection prevention remains debated.
Other proposed usesVitamin C has been explored in cardiovascular disease prevention, blood pressure control, diabetes management, neuroprotection, and skin health (as a topical agent). Some observational studies suggest correlations between higher vitamin C status and lower risk of various chronic diseases, but proving causation or benefit from supplementation beyond baseline adequacy is challenging.