Vitamin C

Overview

• Vitamin C (ascorbic acid) is a water-soluble micronutrient.
• It functions primarily as a potent antioxidant and a vital co-factor for several enzymatic reactions.
• In humans, it is essential for collagen synthesis, neurotransmitter production, and the regeneration of other antioxidants.
• Vitamin C supports tissue integrity and oxidative balance.

Benefits

• Adequate vitamin C status is linked to several health outcomes, as shown by clinical and epidemiological research.
• It enhances immune defense by supporting:
  • Leukocyte chemotaxis
  • Phagocytosis
  • Proliferation of T-lymphocytes
• Vitamin C reduces the duration of common colds in high-stress or physically active individuals.
• As a co-factor for prolyl and lysyl hydroxylases, it is indispensable for collagen formation, thus maintaining skin, vascular, and connective-tissue health.
• Vitamin C reduces the risk of hemorrhagic complications.
• Its antioxidant capacity protects endothelial cells and low-density lipoproteins (LDL) from oxidative damage, contributing to cardiovascular health.
• In the nervous system, vitamin C participates in dopamine and norepinephrine synthesis, supporting cognition and mood regulation.
• It enhances non-heme iron absorption.
• Vitamin C may modestly lower blood pressure through nitric-oxide–mediated vasodilation.
• These effects have been demonstrated in randomized trials, meta-analyses, and large cohort studies.

How It Works

• Vitamin C functions primarily as a reducing agent, donating electrons to neutralize reactive oxygen and nitrogen species.
• It recycles the oxidized forms of vitamin E and glutathione, sustaining the cellular antioxidant network.
• As a co-factor for iron-dependent dioxygenases, it enables hydroxylation of proline and lysine residues in collagen, stabilizing the triple-helix structure.
• Vitamin C also serves as a co-factor for:
  • Dopamine β-hydroxylase, converting dopamine to norepinephrine
  • Peptidyl-glycine α-amidating monooxygenase (PAM) in peptide hormone maturation
• Vitamin C is required for the activity of the enzyme 2-oxoglutarate–dependent dioxygenases that regulate hypoxia-inducible factor (HIF) stability, linking it to cellular oxygen sensing.
• By facilitating the conversion of Fe³⁺ to Fe²⁺, it promotes the activity of ribonucleotide reductase, essential for DNA synthesis and repair.

Dosage

• The Recommended Dietary Allowance (RDA) for vitamin C is:
  • 90 mg/day for adult men
  • 75 mg/day for adult women
• Smokers require an additional 35 mg/day due to increased oxidative turnover.
• Supplemental regimes commonly range from:
  • 200 mg to 1 g daily for general health
  • 500–1,500 mg/day used in short-term cold-prevention trials
• For athletes or individuals under high oxidative stress, 1–2 g/day divided into two doses (morning and early afternoon) is common to maintain plasma concentrations above 70 µmol/L, the threshold for maximal antioxidant capacity.
• Vitamin C is best absorbed on an empty stomach.
• Large doses (>2 g) may cause gastrointestinal upset and are better taken with food to mitigate irritation.
• Intravenous administration (up to 10–20 g) is reserved for clinical settings (e.g., sepsis, severe oxidative stress) under medical supervision.

Safety & Side Effects

• Vitamin C is generally safe; the tolerable upper intake level (UL) for adults is 2 g/day.
• Above this threshold, adverse effects such as:
  • Abdominal cramping
  • Nausea
  • Osmotic diarrhea may occur due to unabsorbed ascorbate in the colon.
• High doses can increase oxalate excretion, potentially exacerbating kidney stone formation in susceptible individuals (e.g., those with hyperoxaluria or a history of calcium oxalate stones).
• Vitamin C may enhance iron absorption, which could worsen iron overload in conditions such as hemochromatosis.
• Drug interactions include:
  • Increased metabolism of certain antihistamines
  • Potential reduction in the efficacy of some chemotherapeutic agents that rely on oxidative mechanisms (e.g., bortezomib)
• Pregnant and lactating women should not exceed 2 g/day.
• Patients on anticoagulants should monitor for possible alterations in clotting parameters due to vitamin C’s impact on platelet aggregation.

Chemistry

• Vitamin C is chemically known as L-ascorbic acid, with the IUPAC name (5R)-[(1S)-1,2-dihydroxy-3-(4-hydroxy-5-oxo-2-hydroxy-4-pyrrolidyl)-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl]-2-oxy-1-[2-hydroxy-2-oxo-1-(hydroxymethyl)-ethyl]-2-pyrrolidine-1-carboxylic acid.
• Its molecular formula is C₆H₈O₆, with a molar mass of 176.12 g mol⁻¹.
• The molecule features a six-membered lactone ring (a γ-lactone) bearing a 2-keto-L-guloside skeleton with an enediol (C2–C3) double bond that confers its strong reducing capacity.
• The molecule is highly water-soluble (≈330 g/L at 25 °C) and displays a pKa of ~4.2, making it predominantly ionized (ascorbate) at physiological pH.
• The stereochemistry (L-configuration) is essential for enzymatic recognition; the D-isomer (D-ascorbic acid) is biologically inactive.

Sources & Quality

• Commercial vitamin C is principally obtained from two sources:
  • Natural extraction from citrus fruits, kiwi, and berries
  • Industrial synthesis via the Reichstein or modern biotechnological fermentation pathways
• The Reichstein process converts glucose to 2-keto-L-gulonic acid, then to ascorbic acid through a series of oxidation, lactonization, and stereospecific steps, yielding a highly pure (>99 %) product.
• Fermentative production uses genetically engineered Gluconobacter or Pseudomonas strains to directly produce L-ascorbic acid from glucose, offering a “natural-origin” label.
• Quality considerations for supplements include:
  • Verifying the absence of heavy metals, pesticide residues
  • Confirming the presence of the L-isomer via chiral HPLC
• Certifications such as GMP, USP–NF, or ISO 9001, and third-party testing for purity and potency, are essential for ensuring safety and efficacy.