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Vitamin C - Biochemistry and Therapeutic Application

Vitamin C is one of the water-soluble vitamins (and water-soluble antioxidants), just like the B vitamins.

In the organism it occurs in its active, reduced form as ascorbic acid and in its inactive, oxidized form as dehydroascorbic acid.

Bioavailability decreases with oral dose:

Vitamin C taken orally is actively absorbed via sodium-dependent transporters (with energy consumption). In the blood it is v.a transported as dehydroascorbic acid and then reduced back to ascorbic acid in the tissue/cells using glutathione.

The resorption rate, i.e.H The proportion of orally administered vitamin C that actually reaches the cells decreases as the dose increases. With a 100 mg single dose, around 90% of the amount taken reaches the cells, with 3000 mg this value drops to only 40%.

Absorption rate

Single dose (mg)

Amount absorbed (mg)













However, absorption can be improved by

  • Esterification of calcium ascorbate (“ester C”) and
  • in combination with bioflavonoids

The lower dose vitamin C complex in natural plants appears to be particularly well bioavailable (Source: Kober S Bush MJ et al.; Res Comm Chem Pathol and Pharmacol 1987; 137-140; Wright JV et al.; Int Clin Nutrition Rev 1990; 10; 267-270).


Oral vitamin C preparations in low doses up to 500 mg have a high bioavailability of up to 95 % during active transport. It is therefore advisable to distribute the vitamin C administration over several doses. In higher doses, bioavailability decreases quickly. Here, a liposomal preparation should be more effective (in Davis' study, 4 g of “normal” and 4 g of liposomal vitamin C were compared).



Vitamin C plasma level:

Source: Pascoe


Vitamin C dose-response relationship:

Source: Modified after Hahn A et al.; Dtch Apoth Ztg 2004; 144; 43-60


Dosage recommendations:



Vitamin C effects:

  • Electron donor and reducing agent (details: see.u)
  • Antioxidant effect
  • Numerous enzymes are dependent on vitamin C
  • Immune effect (improvement of immune competence)
    • Histamine, bacteria, thromboxane ↓
    • Phagocytosis, interferon, PGE2, PGI2, IgM, IgA, IgG as well as mobility and chemotaxis of leukos ↑
  • Anti-allergic effect as an antihistamine (supports histamine breakdown)
  • Involved in phase I detoxification (pollutant functionalization), e.g.b Hydroxylation of steroids, heavy metals, nitrosamines and bile acids (stimulation of the cytochrome P450 family)
  • Reduction of folic acid to dihydrofolic acid (and to tetrahydrofolic acid)
    -> folic acid reductase (Vit C-dependent)
  • Cofactor in the reduction of folic acid to dihydrofolic acid and in the activation of vitamin D
  • Cofactor in biosynthesis of
    • Collagen (and other connective tissue building blocks) through hydroxylation of proline and lysine residues to hydroxyamino acid residues
      • Prolyl 4-hydroxylase
      • Lysyl-5-hydroxylase
    • Carnitine (from lysine)
      • Trimethyllysine-α-ketoglutarate dioxygenase
      • γ-Butyrobetaine-α-ketoglutarate dioxygenase
    • Serotonin and catecholamines (e.g.b dopamine)
      • Dopamine β-monooxygenase (hydroxylates dopamine -> norepinephrine)
      • Tryptophan hydroxylase (hydroxylated tryptophan -> 5 HTP)
    • Glucocorticoids and corticosterones --> 11,18,21-hydroxylase
  • Tyrosine degradation to fumarate and acetoacetate --> 4-hydroxyhenylpyruvate dioxigenase
  • Activation of peptide hormones
    • such as Corticotropin-releasing hormone (CRH), TRH, gastrin, ADH, GRH, bombesin, calcitonin, pancreozymin, cholecystokinin, VIP, ACTH, etc.a
    • by α-amidation at the C-end
    • Peptidylglycine α-amidation monooxygenase
  • Complex formation (chelation as a ligand for metal ions) à Vitamin C is a ligand for metal ions:
    • Improvement of absorption of Fe (e.g.a metal ions) by 4 times
    • Vitamin C complexes Fe (formation of Fe2+ chelates)
    • Vitamin C reduces Fe3+ to Fe2+
  • Improvement of oxygen absorption (e.g.b in sports)
  • Cholesterol reduction
    • to 7α-hydroxycholesterol (--> 7α-hydroxylase), bile acids, vitamin D


Vitamin C as an electron donor and reducing agent:

  • Antioxidant effect (with oxidation of L-ascorbic acid to the biologically inactive dehydro-ascorbic acid)
    • Degradation of superoxide radical to H2O2 and hydroxyl radical to H2O
    • Reduction of oxidized antioxidants (such as GSH, Vit E)
    • Protection of healthy cells


  • Pro-oxidative effect on damaged cells and bacteria: Reduces transition metals such as Fe3+ (to Fe2+) and Cu2+ (to Cu+) and generates hydroxyl radical


    Vitamin C with anti- and pro-oxidative effects:


    Indications for vitamin C supplementation:

    • Scurvy (vitamin C as the only possible therapy)
    • Oncology (details: seeu)
    • Susceptibility to infection
    • Infections (e.g.b Herpes, Candida albicans, Helicobacter pylori)
    • Allergies (histamine), autoimmune diseases, asthma
    • Orthopedic disorders (e.g. b Lumbar sciatica, M. Sudeck, bone formation disorders)
    • Metabolic diseases (e.g.b Diabetes mellitus, gout)
    • Cardiovascular diseases
    • Psychological disorders (e.g.b Stress, depression)
    • Neurological and eye diseases
    • Surgery, burns and wound healing
    • Diseases of the gastrointestinal tract (e.g.b Gallstones, pancreatitis)
    • Gastrointestinal side effects of ASA and NSAIDs
    • Sea sickness (to reduce histamine)


    Vitamin C in oncology:

    • Protection of healthy cells (antioxidant effect)
      • in prevention (DNA damage caused by radicals , repair mechanisms and apoptosis )
      • in therapy (NW through radicals in radiation, chemotherapy )
    • Independent cytotoxic effect without systemic toxicity
      • Effect of basic therapy
      • Resistance to basic therapy
    • Modulation of the inflammatory and immune systems
    • Detoxification function
    • Consequences of tumor and therapy (e.g.b Fatigue, cachexia, pain)
    • Regeneration (incl. wound healing)
    • Metabolism (e.g.b Vitamin C as a cofactor)

    --> Shortening of convalescence
    --> Improvement in quality of life
    -- > Extension of survival time

    (Source: Dr. Udo Böhm, 2015)


    Examples of increased vitamin C requirements:

    • Pregnancy
    • Dialysis
    • Smoking
    • Infections
    • Injuries and operations
    • Cancer or diabetes
    • Take medication


    Possible vitamin C deficiency symptoms:

    • Higher risk of infection and cancer
    • Exhaustion, tiredness
    • Depression
    • Hair loss, poor hair structure
    • Poor wound healing
    • Gingivitis and tooth loss
    • Perifollicular petechiae (in the extremities)
    • Papules and ecchymoses
    • Hemarthroses
    • Subperiosteal hemorrhages
    • Joint inflammation
    • Myalgias
    • Muscle atrophies
    • Cardiomyopathy
    • Microcytic anemia (with impaired iron absorption)



    Possible side effects of vitamin C:

    Basically, vitamin C has a very low toxicity and a wide dosage range without relevant side effects. At very high (pharmacological) doses the following side effects may occur:

    • Diarrhea
    • Thirst, cold, dizziness, urge to urinate
    • Stomach cramps and vomiting (especially when taken on an empty stomach) à use salt (e.g.b Na ascorbate) and do not take it on an empty stomach
    • Pro-oxidative effect (e.g.b desired in oncology)
    • Reduces transition metals such as Fe3+ and Cu2+ and possibly generates (at high levels of Fe and Cu). Hydroxyl radicals
    • Complex formation with inorganic selenite
    • Risk of hemolysis with genetic deficiency of glucose-6-phosphate dehydrogenase (G6PH)
    • Increased oxalic acid excretion (risk of Ca-oxalate stones if there is a history of kidney stones)
    • Reduction of the effect of anticoagulants (in higher doses)

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