Vitamin B12 - Cobalamin

Question 1

List dietary sources of vitamin B12

Answer 1

Only dietary sources are animal products

• meat, poultry
• fish, shellfish (especially clams & oysters)
• eggs (especially yolks)
• milk and dairy products

Question 2

Discuss the digestion of vitamin B12

Answer 2

Two phases:

Stomach

• vitamin B12 is released from protein (to which it is bound in the diet) by pepsin and HCL
• free vitamin B12 binds to a R protein
• • cobalophilins or heptocorrins
• • found in saliva and gastric juices
• • prevent bacterial use of B12

Duodenum

• R protein hydrolyzes to release B12
• free B12 binds to intrinsic factor (IF), a mucopolysaccharide secreted by the gastric parietal cells

Question 3

Discuss the absorption of vitamin B12

Answer 3

In the ilium (primary distal 1/3) IF-bound B12 is absorbed by binding with receptors called cubilins (receptor mediated endocytosis)

1-3% can also be absorbed via passive diffusion when present in high amounts

Dietary absorption ranges between 11-65% with efficiency decreasing with increasing intake

Question 4

Discuss transport of vitamin B12

Answer 4

In the enterocyte
- vitamin B12 is released from IF and binds to transcobalamin (TC) II for transport in portal circulation

Systemic circulation

• TCII main protein that carries newly absorbed vitamin B12 to tissues
• TCIII takes B12 from periphery back to liver, for storage
• TCI circulating storage of B12

Uptake of B12 into tissues (via endocytosis) is receptor dependent

• all tissues have receptors for TCII
• lysosomes degrade TCII and release free B12

In blood 60-80% of B12 is in the form of methylcobalamin

Question 5

Discuss the storage of vitamin B12

Answer 5

B12 can be stored and retained in body for long periods of time
- enough to sustain for 3-5 years of a deficient diet

50% is stored in the liver, and of that 70% of that is in the form of adEnosylcobalamin

Question 6

Describe the function and mechanism of action of B12

Answer 6

Coenzyme forms of B12:

Methylcobalamin

• Requires 5-methyl THF for formation
• Required for the conversion of homocysteine to methionine

Adenosylcobalamin
- required for the conversation of L-methylmalonyl CoA to succinyl CoA (reaction also require Mg and biotin)

Question 7

List interactions with other nutrients

Answer 7

Folic acid can mask vitamin B12 deficiency by normalizing CBC
Folic acid can increase B12 requirements
Folic acid can aggravate neurological symptoms associated with B12 deficiency

B12 may increase Folic acid requirements and aggravate folate deficeciency

Question 8

Describe the metabolism and excretion

Answer 8

B12 has a long biological half life
1.4 mcg/d (>0.1%) excreted in bile
- bound to R protein 
- It can then bind to IF and be reabsorbed
Very little is excreted in urine

Question 9

Describe consequences and symptoms of deficiency

Answer 9

Megoblastic macrocytic anemia

Hematologic
- skin pallor, fatigue, SOB, palpitations and orthostatic hypotension
- can be corrected with large doses of folate
Neurologic
- peripheral peresthesia, abnormal gait, insomnia, loss of concentration, memory loss, disorientation, confusion, paranoia and swelling of myelinated fibers
-does not respond to folate supplementation
- possibly due to decreased SAM production caused by B12 deficiency
- may be permanent if not treated in time
Glosittishyperhomocysteinemia
- risk factor for coronary heart disease
-can be lowered with B12, folate, B6, and betaine supplements

Question 10

Describe consequences and symptoms of toxicity

Answer 10

No upper limits established

With tobacco smokers - cyanocobalamin is contraindicated because it antagonizes cyanide (could go blind). Hydroxylcobalamin is therapeutic

In rare cases, when taken orally, acneiform rash occurs

In rare cases, when given IM/IV, can cause anaphylaxis

IM/IV should be given early in the day - may cause increased energy

Question 11

Describe the assessment of nutrient status

Answer 11

For anemia/macrocytosis - CBC

Serum B12 - normal is 100-220, but NDs like it above 500
- may be falsely elevated in renal failure or hepatitis patients

Serum methylmalonyl CoA and homocysteine
- deficiency of B6, B12 or folate result in elevated homocysteine levels

Doxyuridine suppression test

Shilling test
- determines absorption problems relating to IF

Question 12

Discuss some of the therapeutic uses (clinical indications)

Answer 12

Megaloblastic macrocytic anemia
Fatigue
Neuropathies
Some psychiatric disorders have been linked to low cerebrospinal levels of B12
Insomnia

Question 13

Who is at most risk of a vitamin B12 deficiency?

Answer 13

Those that lack IF

• pernicious anemia
• atrophic gastritis
• gastrectomy or gastric bypass

Those that lack HCL - hypochlorhydria/achlohydria

• decreased gastric HCL –> decreased B12 released from food
• intestinal bacteria overgrowth –> increased bacterial use of B12

Decreased absorptive surface in the ilium brush border
- ileal resection, celiac disease, chrone’s disease

Pancreatic insufficiency
- interferes with B12 release from R protein