Vitamin B12 Review

Vitamin B12

aka COBALAMIN - the last vitamin to be discovered

Forms associated with group attached to COBALT (Co):

SOURCES

DIGESTION, ABSORPTION, TRANSPORT, STORAGE

Intestinal absorption:

• IF-Carrier mediated: 1.5 to 2.0 ug becomes saturated
• Passive diffusion with 1-3%
• So, for 1,000 ug = 2ug absorbed by IF-mediated absorption and 30ug from passive absorption
• 50% absorbed

Enterohepatic circulation:

• B12 long half life as if released in bile, can bind to free IF and be re-absorbed

In the blood:

• Following absorption, appears in blood in 3-4 hours with peak 8-12 hours
• 60-80% METHYCOBALAMIN, 20% ADENOSYLVCOBALAMIN
• Circulates bound to transport proteins:
• TRANSCOBALMIN (TC)
• HAPTOCORRIN (HC)
• Genetic mutation:
• TCII carrier protein  - diminished ability to bind B12

Into tissues:

• Receptor dependent
• All tissues have receptors for TCII
• Chaperones (intracellular transport proteins) escort B12 in cell
• Metabolism of various forms of B12 occur within cells

Storage:

• Unlike other water soluble vitamins, can be stored for 3-5 years
• Liver 50% has 2-3 mg, Muscle 30%
• Adenosylocobalmin is predominant storage form

FUNCTIONS and MECHANISM OF ACTION

2 enzymatic reactions requiring B12 have been recognized in humans which facilitate nutrient metabolism and energy production:

1. Methionine Synthase
2. L-Methylmalonyl CoA Mutase ~ elevated MMA levels when B12 deficient

METABOLISM AND EXCRETION

No degradation
2ug excreted in bile, however 75% reabsorbed
0.25 ug in urine

RDA

2.3 ug/d

DEFICIENCY

Stages:

1. Serum B12 decreases when storage depleted
2. Cell [B12] diminishes resulting in higher homocysteine and MMA levels
3. Morphological changes occur due to DNA synthesis issues

Neural tube defects

Neurological problems

Associated:

• Aging 15% elderly
• Inadequate intake: vegan, infant
• Altered gastric pH (achlorhydria)
• HCl production
• Atrophic gastritis
• Pernicious anemia
• Partietal cell destruction
• Altered duodenal pH
• Impaired pancreatic exocrine function (insufficient bicarb release)
• Zollinger Ellison Syndrome
• Impaired intestinal integrity
• Crohn's
• Celiac
• Resection of stomach and small intestines
• Competition
• Parasitic infections
• SBO
• Nitrous oxide

RX: 1mg a day for 1 week then lower dose for months

IM: 500-1000 ug

Nasacobal

TOXICITY

No TUL

ASSESSMENT

Serum [B12] <200 pg/mL
MMA >350 nmol.L in serum or >300 mg/d urine
Homocysteine
Breath test ~ CO2
Deoxyurinidine suppression test
Schilling