Absorption mechanism of Vitamin B12
Bound to ingested animal proteins - proteins denatures by acids and pepsin in stomach to release B12 -> B12 binds to haptocorrin to protect from B12 degradation - haptocorrin degraded by pancreatic enzymes in duodenum and B12 free again - binds to intrinsic factor travels to terminal ileum - B12/IF complext binds to IF receptor -> once absorbed binds to haptocorrin in blood (70-80%, inactive) and transcobalamin II (<30%, active)
Function of vitamin b12
Important role in DNA synthesis and neurological function byt acting as a COFACTOR for 2 reactions:
- MMA -> succinyl-CoA
- homocysteine -> methionine (along with folic acid)
Dietary sources of Vitamin B12
Animal products
- meat
- poultry
- fish!! (crab, clams, mussels esp. high levels)
- eggs
- dairy products (low levels)
Fortified foods including:
- soy milks
- vegetarian “meats”
- yeast spreads e.g. vegemite
- breakfast cereals
Recommended daily intake of Vitamin B12
2.4mcg/day
85g of salmon
Risk factors for B12 deficiency (8)
Vegetarian/vegan diet Age >65y Institutionalised/RACF residents Newborns of vegetarian or malnourished mothers Gastric surgery patients Atrophic gastritis patients H. Pylori infection Patient with GI disorders (e.g. Crohn's, coeliac disease)
Causes of Vit B12 deficiency
Nutritional:
- Low dairy/meat intake >65y
- alcoholism
- strict veganism
Increased requirements:
- pregnancy/lactation
Impaired absorption
- anti-intrinsic factor antibodies (i.e. Pernicious anaemia)
- autoantibodies to gastric parietal cells (atrophic body gastritis)
- gastrectomy
- prolonged use of PPI, metformin or H2RAs
Other GI causes:
- chronic GI symptoms
- coeliac disease
- Crohn’s
- intestinal surgery, gastric resection, sleeve or banding
- intestinal parasites
- ileocystoplasty
Main medications known to lower Vit B12 levels
Histamine 2 receptor antagonists
Metformin (>4 months use)
PPIs (>12 months use)
Clinical manifestations of Vit B12 deficiency
Haem:
- megaloblastic anaemia
- pancytopaenia
- pernicious anaemia
Neuro:
- paraesthesia
- peripheral neuropathy
- Combined systems disease
Psych:
- irritability, personality change
- mild memory impairment
- depression
- psychosis
- Alzheimer’s disease
CVS:
- ?increased risk of MI/Stroke
Conditions causing falsely low serum vitamin B12 levels
Pregnancy Primary folate deficiency Iron deficiency Inherited disorders of B12 metabolism Oral contraception
Management of B12 deficiency
To correct deficiency:
- hydroxocobalamin 1mg IM alternate days for 2 weeks (less intensive tx required if no anaemia or neuro symptoms)
Maintenance:
- if absorption not impaired: cyanocobalamin 50-200 microg/day orally, between meals
- if absorption impaired: hydroxocobalamin 1mg IM every 2-3 months
*iron supplementation may be required for patients with severe anaemia as iron stores will start to fall 1-2 days post first injection
Recovery of symptoms after treatment of B12 deficiency
Hb will increase approx 10g/L per week, some symptoms will start to improve within 48h
Neuropathy improves more slowly, patients with long history of neurological symptoms may have residual effects
