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)
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 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

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: 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)