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 (using energy). In the blood, it is v.a. It is transported as dehydroascorbic acid and then reduced back to ascorbic acid in the tissue/cells using glutathione.

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

Absorption rate	Single dose (mg)	Amount absorbed (mg)
90%	100	90
60-75%	1000	600-750
40%	3000	1200
16%	120,000	1920

However, absorption can be improved by

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

The lower dose of 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 doses have a high bioavailability of up to 95% when actively transported. %. Therefore, it is recommended to divide the vitamin C intake into several doses.. At higher doses, bioavailability decreases rapidly. A liposomal preparation should be more effective here (in Davis's study, 4 g of "normal" and 4 g of liposomal vitamin C were compared).

Vitamin C plasma levels:

Source: Pascoe

Vitamin C dose-response relationship:

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

Dosage recommendations:

Effects of Vitamin C:

• 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, and leukocyte mobility and chemotaxy ↑
• Anti-allergic 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 (vitamin 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) through hydroxylation of proline and lysine residues to hydroxy amino 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 -> Norepinephrine)
    • Tryptophan hydroxylase (hydroxylated tryptophan -> 5 HTP)
  • Glucocorticoids and corticosterones --> 11,18,21-Hydroxylase
• Tyrosine degradation to fumarate and acetoacetate --> 4-Hydroxyhenylpyruvate dioxygenase
• Activation of peptide hormones
  • such asCorticotropin-releasing hormone (CRH), TRH, gastrin, ADH, GRH, bombesin, calcitonin, pancreozymin, cholecystokinin, VIP, ACTH, u.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 Fe absorption (u.a. metal ions) by a factor of 4
  • Vitamin C complexes Fe (formation of Fe2+ chelates)
  • Vitamin C reduces Fe3+ to Fe2+
• Improvement of oxygen uptake (z.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 (through oxidation of L-ascorbic acid to biologically inactive dehydroascorbic acid)
  • Breakdown 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 radicals.

Vitamin C with antioxidant 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
• Orthopedic disorders (e.g., lumbosacral radiculopathy, Sudeck's atrophy, 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 lower 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 of radicals during radiation, chemotherapy) ↓)
• Independent cytotoxic effect without systemic toxicity
  • Effect of basic therapy ↑
  • Resistance to basic therapy ↓
• Modulation of inflammation and the immune system
• detoxification function ↑
• Consequences of tumor and therapy ↓ (z.B. Fatigue, cachexia, pain)
• regeneration ↑ (incl.Wound healing)
• metabolism ↑ (z.B. Vitamin C as a cofactor)

--> Shortening of the recovery period
--> Improving quality of life
--> Extended survival time

(Source: Dr. Udo Böhm, 2015)

Examples of increased vitamin C requirements:

• pregnancy
• dialysis
• Smoke
• Infections
• Injuries and operations
• cancer or diabetes
• Medication intake

Possible symptoms of vitamin C deficiency:

• 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 area of ​​the extremities)
• Papules and ecchymoses
• Hemarthrosis
• Subperiosteal hemorrhages
• 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, feeling cold, dizziness, urge to urinate
• Stomach cramps and vomiting (especially when taken on an empty stomach) à use salt (z.B. sodium ascorbate) and should not be taken on an empty stomach.
• Pro-oxidative effect (z.B. (desired in oncology)
• It reduces transition metals such as Fe3+ and Cu2+ and may generate hydroxyl radicals (at high levels of Fe and Cu).
• Complex formation with inorganic selenite
• Risk of hemolysis in genetically determined glucose-6-phosphate dehydrogenase (G6PH) deficiency
• Increased oxalic acid excretion (risk of calcium oxalate stones in patients with a history of kidney stones)
• Reduction in the effect of anticoagulants (at higher doses)