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

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:

Orally ingested vitamin C 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 with the consumption of glutathione.

The absorption rate, d.hThe proportion of orally administered vitamin C that actually reaches the cells decreases with increasing dose. With a single dose of 100 mg, around 90% of the ingested amount reaches the cells; with 3000 mg, this value drops to only 40%.

Absorption rate	Single dose (mg)	Absorbed amount (mg)
90%	100	90
60-75%	1000	600-750
40%	3000	1200
16%	120000	1920

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 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).

Low-dose oral vitamin C supplements up to 500 mg have a high bioavailability of up to 95 %. Therefore, it is recommended to distribute the vitamin C dose over several dosesAt higher doses, bioavailability decreases rapidly. A liposomal preparation should be more effective in this case (Davis's study compared 4 g of "regular" and 4 g of liposomal vitamin C).

Vitamin C plasma levels:

Source: Pascoe

Vitamin C dose-response relationship:

Source: Modified from Hahn A et al.; German Pharmacology Ztg 2004; 144; 43-60

Dosage recommendations:

Vitamin C effects:

• Electron donor and reducing agent (details: s.u.)
• Antioxidant effect
• Numerous enzymes are vitamin C dependent
• Immune effect (improvement of immune competence)
  • Histamine, bacteria, thromboxane ↓
  • Phagocytosis, interferon, PGE2, PGI2, IgM, IgA, IgG as well as mobility and chemotherapy of leukocytes ↑
• Antiallergic effect as an antihistamine (supports histamine breakdown)
• Involved in Phase I detoxification (pollutant functionalization), z.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 the biosynthesis of
  • Collagen (and other connective tissue building blocks) by 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 (z.B. Dopamine)
    • Dopamine β-monooxygenase (hydroxylates dopamine -> noradrenaline)
    • Tryptophan hydroxylase (hydroxylated tryptophan -> 5 HTP)
  • Glucocorticoids and corticosterones --> 11,18,21-hydroxylase
• Tyrosine degradation to fumarate and acetoacetate --> 4-hydroxyphenylpyruvate dioxygenase
• Activation of peptide hormones
  • such as corticotropin-releasing hormone (CRH), TRH, gastrin, ADH, GRH, bombesin, calcitonin, pancreozymin, cholecystokinin, VIP, ACTH, u.a.
  • by α-amidation at the C-terminus
  • 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 (u.a. metal ions) by 4 times
  • Vitamin C complexes Fe (formation of Fe2+ chelates)
  • Vitamin C reduces Fe3+ to Fe2+
• Improvement of oxygen uptake (z.B. in sports)
• Cholesterol breakdown
  • to 7α-hydroxycholesterol (--> 7α-hydroxylase), bile acids, vitamin D

Vitamin C as an electron donor and reducing agent:

• Antioxidant effect (by oxidation of L-ascorbic acid to 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

But:

• 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: s.u.)
• Susceptibility to infection
• Infections (z.B. Herpes, Candida albicans, Helicobacter pylori)
• Allergies (histamine), autoimmune diseases, asthma
• Orthopaedic disorders (e.g. lumboischialgia, Sudeck's disease, bone formation disorders)
• Metabolic diseases (z.B. Diabetes mellitus, gout)
• Cardiovascular diseases
• Mental disorders (z.B. Stress, depression)
• Neurological and eye diseases
• Surgery, burns and wound healing
• Diseases of the gastrointestinal tract (z.B.Gallstones, pancreatitis)
• Gastrointestinal side effects of ASA and NSAIDs
• Seasickness (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 (side effects from radicals during radiation, chemotherapy ↓)
• Independent cytotoxic effect without systemic toxicity
  • Effect of basic therapy ↑
  • Resistance to basic therapy ↓
• Modulation of inflammatory and immune systems
• Detoxification function ↑
• Consequences of tumor and therapy ↓ (z.B. Fatigue, cachexia, pain)
• regeneration ↑ (including wound healing)
• metabolism ↑ (z.B. Vitamin C as a cofactor)

--> Shortened convalescence
--> Improvement of quality of life
--> Extension of survival time

(Source: Dr. Udo Böhm, 2015)

Examples of increased vitamin C requirements:

• pregnancy
• dialysis
• Smoke
• Infections
• Injuries and operations
• Cancer or diabetes
• Taking medication

Possible vitamin C deficiency symptoms:

• Higher risk of infection and cancer
• Exhaustion, fatigue
• depression
• Hair loss, poor hair structure
• Poor wound healing
• Gingivitis and tooth loss
• Perifollicular petechiae (in the extremities)
• Papules and ecchymoses
• Hemarthrosis
• Subperiosteal bleeding
• Joint inflammation
• Myalgia
• Muscle atrophy
• Cardiomyopathy
• Microcytic anemia (with iron absorption disorder)

Possible side effects of vitamin C:

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

• Diarrhea
• Thirst, chills, dizziness, urinary urgency
• Stomach cramps and vomiting (especially when taken on an empty stomach) à Use salt (z.B. Na-ascorbate) and do not take on an empty stomach
• Pro-oxidative effect (z.B. desired in oncology)
• Reduces transition metals such as Fe3+ and Cu2+ and may generate (at high levels of Fe and Cu).Hydroxyl radicals
• Complex formation with inorganic selenite
• Risk of hemolysis in genetically caused deficiency of glucose-6-phosphate dehydrogenase (G6PH)
• Increased oxalic acid excretion (Ca oxalate stone risk in kidney stone history)
• Reduction of the effect of anticoagulants (in higher doses)