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:

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

The absorption rate, i.e. the 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)	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).

Oral vitamin C preparations in low doses up to 500 mg have a high bioavailability of up to 95 %. It is therefore recommended to divide the vitamin C dose into several doses. At higher doses, bioavailability decreases rapidly. In this case, a liposomal preparation should be more effective (in the study by Davis, 4 g of “normal” and 4 g of liposomal vitamin C were compared).

Vitamin C plasma levels:

Source: Pascoe

Vitamin C dose-effect relationship:

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

Dosage recommendations:

Vitamin C effects:

• electron donor and reducing agent (details: see below)
• 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 chemotaxis of leukocytes ↑
• Antiallergic effect as an antihistamine (supports histamine degradation)
• Involved in Phase I detoxification (pollutant functionalization), e.g.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) 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 (e.g. 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, among others
  • by α-amidation at the C-end
  • peptidylglycine α-amidation monooxygenase
• Complex formation (chelation as ligand for metal ions) à Vitamin C is a ligand for metal ions:
  • improvement of resorption of Fe (including metal ions) by 4 times
  • Vitamin C complexes Fe (formation of Fe2+ chelates)
  • Vitamin C reduces Fe3+ to Fe2+
• Improvement of oxygen uptake (e.g. 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: see below)
• susceptibility to infection
• Infections (e.g. herpes, Candida albicans, Helicobacter pylori)
• Allergies (histamine), autoimmune diseases, asthma
• Orthopedic disorders (e.g. lumboischialgia, M. Sudeck, bone formation disorders)
• metabolic diseases (e.g. diabetes mellitus, gout)
• Cardiovascular diseases
• Mental disorders (e.g. stress, depression)
• Neurological and eye diseases
• Surgery, Burns and Wound Healing
• Diseases of the gastrointestinal tract (e.g.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 ↓ (e.g. fatigue, cachexia, pain)
• regeneration ↑ (including wound healing)
• metabolism ↑ (e.g. vitamin C as a cofactor)

--> shortening of 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
• medication intake

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
• hemarthrosis
• Subperiosteal bleeding
• joint inflammation
• myalgia
• muscle atrophy
• cardiomyopathy
• Microcytic anemia (with iron absorption disorder)

Possible side effects of vitamin C:

Basically, 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 (e.g. sodium ascorbate) and do not take on an empty stomach
• Pro-oxidative effect (e.g. 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 case of kidney stone history)
• Reduction of the effect of anticoagulants (in higher doses)