Vitamin C Review

Vitamin C Review

Vitamin C first isolated in 1928 (Szent-Gyorgy) and structre determined in 1933 (King). However scurvy had been known for centuries - lime rations began in 1790s in Britain

Forms and Structure

At physiological pH, AH2 loses a hydrogen and is in ionized form, AH- (Ascorbate), ascobate (mono) anion, or monodehydroascrobate.

Oxidation of ascorbate generates the ascobyl radical A- (one electron and one proton less than ascorbate).

The oxidized form (with 2 electrons and 2 protons/hydrogens removed) is called dehydroascorbic acid, and has vitamin activity as it can be converted into ascorbate in cells.

Forms:

• Ascorbic acid (AH2)
• Ascorbate (AH-) - occurs at physiological pH when AH2 loses a H+
• Dehydroascorbate (A-) radical occurs when Ascorbate oxidized.

Isomers exist, but only the L-isomer biologically active in humans.

Humans, primates, fruit bats, guinea pigs and some birds are unable to synthesize vitamin C.
Vitamin C is derived from glucose and requires gulonolactone oxidase.

SOURCES

Food: citrus and vegetables (ascorbic acid)
Fortified foods
Supplements (ascorbic acid, calcium ascorbate, sodium ascorbate)
Fat soluble form: ascorbyl palmitate
Skin creams
Vitamin C destroyed by heat (cooking), light, oxidation, and alkaline soluntions. Stable in acid.

DIGESTION, ABSORPTION, TRANSPORT, STORAGE

Does not require digestion

Ascorbate requires:

Absorption requires NA-DEPENDENT VITAMIN C TRANSPORTERS (SVCT 1 AND 2)

Transporters are regulated downstream by ascorbic acid

Dehydro-ascorbate requires:

Absorption via GLUCOSE TRANSPORTERS (GLUT) followed by reduction to ascorbate with GSH (glutathione)

70-95% absorption rate, decreases with intake

Ingesting 75-90 mg given plasma [ ] 08. mg/dL

Absorption decreases with intake (best with ~500 mg daily).

In intestinal cells:

• A- rapidly converted to AH-
• Enters blood supply by diffusing out of intestinal cells into extracellular fluid via anion pores

In the blood:

• Transported in free form mostly as ascorbic acid 
• Plasma levels = 0.6-2.0 mg/dL - maintained in a narrow range
• 70% in plasma, 30% in WBC

In the tissues:

• uptake of AH occurs by SVCT1 into liver and kidneys
• uptake of A- by GLUT transporters
• SVCT and GLUT facilitate tissue uptake
  - Tissue levels vary
  - High levels maintain in WBC, adrenal, pituitary, eyes, brain
  - 100-200 mg/d maaximizes body pool, higher amounts only raise plasma levels temporarily

Storage:

• WBC, adrenals, pituitary, eyes, brain, organs, muscle

FUNCTIONS AND MECHANISMS OF ACTION

Functions:

• Antioxidant
• Co-substrate for enzyme activity:
• some enzymes contain a mineral (copper or iron) cofactor for which vitamin C functions as a reducing agent to maintain the iron and copper atoms in the reduced state.

Collagen Synthesis

• Vitamin C functions as a co-substrate in a number of hydroxylation reactions
• 3 of these reactions are necessary for synthesis of collagen
• Vitamin C act as a co-substrate in converting ferrous to ferric state:

Carnitine Synthesis

• Vit C functions as a reducing agent reducing the iron atoms from the ferric state back to ferrous form for reactions.

Tyrosine Catabolism

• Tyrosine can be degraded to produce energy
• Vitamin C is a preferred reductant for iron in reactions

Neurotransmitter Synthesis

• Vitamin C reduces mineral cofactors that become oxidized during neurotrasmitter and hormone formation
• Norepinephrine ~ requires Copper atoms for formation
• Occurs by amidation of peptides like pituitary and gastric hormones:

Microsomal Metabolism ~ helps inactivate endogenous (cholesterol, hormones) and exogenous (xenobiotic) substances

Antioxidant Activity

• Regenerating vitamin C ~ niacin, thiols
• Readily given up electrons available in OH and carbonyl groups: 

Pro-Oxidant Activity (minimal)

• HISPERIDAN - in the peel called the pith, so more in whole fruit than juice

Treatment uses:

- Colds

- Cancer

- CV disease

- Eye health

INTERACTIONS

Iron:  Enhances intestinal absorption

METABOLISM AND EXCRETION

Urine predominantly:

• Renal threshold reached at upper end of normal range of plasma [vit c].
• Catabolism to OXALIC ACID may result in kidney stones.

RDA

90 mg men, 75 mg women

Smokers, add 35 mg

DEFICIENCY

Scurvy

• When total body vitamin C < 300 mg and plasma < 0.2 mg
• Less than 10 mg a day for 4-6 months
• 4 Hs
• Hemorrhagic
• Hyperkerotinosis of hair follicles
• Hypochondriasis
• Hematological abnormalities
• RX: 100-500 mg daily for 3 months

At risk: smokers, older, etoh, malabsorption, DM, cancer

TOXICITY

GI upset, diarrhea

TUL 2g

Kidney stones, iron toxicity

ASSESSMENT

Plasma [ ] <  0.2

Leukocyte [ ] <10