Introduction

Vitamin B12 deficiency can lead to macrocytic anaemia. However, in many cases, other symptoms and complaints occur before anaemia occurs, such as: general weakness, increased fatigue, atypical neuropsychiatric symptoms, muscle weakness, reduced appetite, diarrhoea, neurological disorders: irritations/sensitivity of feet and hands, coordination problems and gait disorders. Furthermore, there is an increased risk of cardiovascular disease and microangiopathy in Raynaud's disease (white stiff fingers in the cold) and occurrence of glossitis and gastritis (which further reduces the production of intrinsic factor).

Function in the body

Vitamin B12 and folic acid are important cofactors for enzymes in methyl transfer metabolism. Methyl groups are used for the synthesis of DNA, essential for cell division and thus for the production of new cells. Deficiency of these vitamins leads to reduced blood cell production (anaemia), reduced nerve cell production (neuropathy; tingling or numbness in hands and feet), reduced bone production (osteoporosis), reduced endothelial cell production (risk of cardiovascular disease) and microangiopathy in Raynaud's disease (white stiff fingers in the cold), reduced cell production from tongue to intestine (glossitis, gastritis, duodenitis). In addition, folic acid deficiency at the beginning of pregnancy can lead to the birth of a baby with spina bifida.

Both vitamin B6, vitamin B12 and folic acid are involved as cofactors in the transmission of methyl groups. The methyl groups are transferred from homocysteine to methionine. Methionine is recycled back to homocysteine. In case of a deficiency of one of these factors, an accumulation of homocysteine occurs. This is therefore a marker for subnormal vitamin levels.

Pathophysiology

Because vitamin B12 is present in the body in large quantities, it often takes years before a deficiency occurs and people get complaints. Vitamin B12 is absorbed in the body in the last part of the small intestine (ileum). It is only absorbed there if it is linked to intrinsic factor, a component of the gastric juice produced by the stomach mucosa. If the gastric mucosa is damaged or part of the stomach is removed, no/less intrinsic factor is produced, so that the body can no longer absorb vitamin B12 and a deficiency occurs. The development of a vitamin B12 deficiency can have several causes:

• lack of hydrochloric acid in gastric juice due to gastritis, gastric resection, use of antacids
• bacterial overgrowth of the small intestine, parasitic infections.
• furthermore, deficiency can occur in case of suspicion of malnutrition (often due to alcoholism) and in case of intestinal problems such as Crohn's disease or celiac disease (hypersensitivity to gluten) or atrophic gastritis (common in the elderly).

Vitamin B12 is mainly present in animal products such as (red) meat, fish, poultry, milk and eggs. Vitamin B12 and folic acid are nowadays added to some cereal products; this is stated on the packaging. This is particularly important for vegetarians and vegans. Folic acid is also abundant in leafy vegetables, citrus fruits and legumes.

Target Values

In healthy people, the level of active vitamin B12 in the blood varies between 30 and 120 pmol/l. Probably a level lower than 60 pmol/l already indicates a deficiency. There are indications that at a level above 80 pmol/l there is no accumulation of homocysteine in the blood and no increase of methyl malonic acid in the urine. We therefore consider this to be the most optimal level (and target value) for active B12.