Vitamin B12 deficiency

Vitamin B12 deficiency
Specialty	Endocrinology

B12 deficiency is a reduction in vitamin B12 from inadequate dietary intake or impaired absorption. The condition is commonly asymptomatic, but can also present as anemia characterized by enlarged blood corpuscles, so-called megaloblastic anemia. However in serious cases deficiency can potentially cause severe and irreversible damage to the nervous system.

The anemia is thought to be due to problems in DNA synthesis, specifically in the synthesis of thymine, which is dependent on products of the MTR reaction. Other cell lines such as white blood cells and platelets are often also low. Bone marrow examination may show megaloblastic hemopoiesis. The anemia is easy to cure with vitamin B12.

Presentation

Early and even fairly pronounced deficiency does not always cause distinct or specific symptoms. Common early symptoms are tiredness or a decreased mental work capacity, decreased concentration and decreased memory, irritability and depression.

Sleep disturbances may occur, because B12 may be involved in the regulation of the sleep wake cycle by the pineal gland (through melatonin).

Neurological signs of B₁₂ deficiency, which can occur without anemia, include sensory disturbances due to damage to peripheral nerves caused by demyelination and irreversible nerve cell death. Symptoms include numbness, tingling of the extremities, disturbed coordination and, if not treated in time, an ataxic gait, a syndrome known as subacute combined degeneration of spinal cord.

B12 deficiency can also cause symptoms of mania and psychosis.

Recent studies have devalued a possible connection between B12 deficiency and Alzheimer's dementia, and such a correlation is unlikely as of June 2007.

Studies showing a relationship between clinical depression levels and deficient B₁₂ blood levels in elderly people are documented in the clinical literature. and 2002

Bipolar disorder appears to genetically co-segregate with the hereditary B12-deficiency disorder pernicious anemia .

Causes

• Inadequate dietary intake of vitamin B₁₂. As the vitamin B₁₂ occurs naturally only in animal products (eggs, meat, milk), and a particular strain of nutritional yeast; a vegan diet can produce a deficiency unless one uses supplements or eats enriched food.

• Selective impaired absorption of vitamin B₁₂ due to intrinsic factor deficiency. This may depend on loss of gastric parietal cells in chronic atrophic gastritis (in which case, the resulting megaloblastic anaemia takes the name of "pernicious anaemia"), or on wide surgical resection of stomach (such as in bariatric surgery), or on rare hereditary causes of impaired synthesis of intrinsic factor.

• Impaired absorption of vitamin B₁₂ in the setting of a more generalised malabsorption or maldigestion syndrome. This includes any form of structural damage or wide surgical resection of the terminal ileum (the principal site of vitamin B₁₂ absorption), forms of achlorhydria (including that artificially induced by drugs such as proton pump inhibitors), as well as bacterial overgrowth (such as in blind loop syndrome).

• Chronic intestinal infestation by the fish tapeworm Diphyllobothrium, that competes for vitamin B₁₂, seizing it for its own use and therefore leaving insufficient amount for the host organism. This is mostly confined to Scandinavia and parts of Eastern Europe (for example, in preparers of gefilte fish, who would acquire the tapeworm by sneaking bits of fish before it was cooked while making the Eastern European delicacy).

• The diabetes medication, metformin may interfere with B12 dietary absorption.

• Hereditary causes such as severe MTHFR deficiency, homocystinuria, and transcobalamin deficiency.

• Some studies have shown that giardiasis, or similar parasite should be considered as a cause of Vitamin B12 deficiency, this a result of the problems caused within the intestinal absorption system.

Incidence/prevalence

Recent research indicates that B12 deficiency is far more widespread than formerly believed. A large study in the US found that 39 percent had low values. This study at Tufts University used the B12 concentration 258 pmol/l (= 350 pg/liter) as a criterion of "low level". However, recent research has found that B12 deficiency may occur at a much higher B12 concentration (500-600 pg/l). On this basis Mitsuyama and Kogoh . proposed 550 pg/l, and Tiggelen et al proposed 600 pg/l. Against this background, there are reasons to believe that B12 deficiency is present in a far greater proportion of the population than 39% as reported by Tufts University.

In the developing world the deficiency is very widespread, with significant levels of deficiency in Africa, India, and South and Central America. This is due to low intakes of animal products, particular among the poor. Increased intake of animal products or supplements have been suggested.

B12 deficiency is even more common in the elderly . This is because B₁₂ absorption decreases greatly in the presence of atrophic gastritis, which is common in elderly.

B12 deficiency is common among vegetarians and vegans who do not take B12 supplements. In vegans the risk is very high because none of their natural food sources contain B12. One American study found blood levels below normal in 92 % of vegans, 64 % of lactovegetarians, 47 % of lacto-ovovegetarians who did not supplement their diet with B12. . The study applied the old normal values, so in reality a considerably greater proportion may have been deficient.

Diagnosis

Serum B₁₂ levels are often low in B₁₂ deficiency, but if other features of B₁₂ deficiency are present with normal B₁₂ then the diagnosis must not be discounted. One possible explanation for normal B₁₂ levels in B₁₂ deficiency is antibody interference in people with high titres of intrinsic factor antibody. Some researchers propose that the current standard norms of vitamin B12 levels are too low. In Japan, the lowest acceptable level for vitamin B12 in blood has been raised from about 200 picograms/litre (pg/l) = 145 picomol/litre (pm/l) to 550 pg/l = 400 pm/l.

Serum Homocysteine and Methylmalonic acid levels are considered more reliable indicators of B12 deficiency than the concentration of B12 in blood, see for example research at the St. Louis University. The levels of these substances are high in B₁₂ deficiency and can be helpful if the diagnosis is unclear. Approximately 10% of patients with vitamin B12 levels between 200-400pg/l will have a vitamin B12 deficiency on the basis of elevated levels of homocysteine and methylmalonic acid.

Routine monitoring of methylmalonic acid levels in urine is an option for people who may not be getting enough dietary B₁₂, as a rise in methylmalonic acid levels may be an early indication of deficiency.

If nervous system damage is suspected, B12 analysis in cerebrospinal fluid can also be helpful, though such an invasive test would be applicable only after unrevealing blood testing.

Treatment

B₁₂ can be supplemented in healthy subjects by oral pill; sublingual pill, liquid, or strip; or by injection. B₁₂ is available singly or in combination with other supplements. B₁₂ supplements are available in forms including cyanocobalamin, hydroxocobalamin, methylcobalamin, and adenosylcobalamin (sometimes called "cobamamide" or "dibencozide").

Vitamin B₁₂ can be given as intramuscular injections of hydroxycobalamin, methylcobalamin, or cyanocobalamin. Body stores (in the liver) are refilled with half a dozen injections in the first couple of weeks and then maintenance with monthly to quarterly injections throughout the life of the patient.

B₁₂ has traditionally been given parenterally to ensure absorption. However, oral replacement is now an accepted route, as it has become increasingly appreciated that sufficient quantities of B₁₂ are absorbed when large doses are given. This absorption does not rely on the presence of intrinsic factor or an intact ileum. Generally 1 to 2 mg daily is required as a large dose [1]. By contrast, the typical Western diet contains 5–7 µg of B₁₂ (Food and Drug Administration (FDA) Daily Value ).

Hypokalemia, an excessive low potassium level in the blood, is anecdotally reported as a complication of vitamin B₁₂ repletion after deficiency. Excessive quantities of potassium are used by newly growing and dividing hematopoeitic cells, depleting circulating stores of the mineral.

It has been appreciated since the 1960s that deficiency can sometimes be treated with oral B₁₂ supplements when given in sufficient doses. When given in oral doses ranging from 0.1–2 mg daily, B₁₂ can be absorbed in a pathway that does not require an intact ileum or intrinsic factor. However, with the advent of sublingual and intranasal administration, tablet usage is becoming outdated. Oral absorption is limited so regular intramuscular injections or sublingual/intranasal administration of a cobalamin (preferably methyl- or hydroxycobalamin) is necessary to restore systemic stores to physiological levels. Recent research indicates that sublingual administration eliminates a deficiency as well as injections (reference will be added) with the advantage of evading the allergy risk.

Natural Food Sources of B-12

Vitamin B12 is found in foods that come from animals, including fish, meat, poultry, eggs, milk, and milk products and fortified breakfast cereals. One half chicken breast, provides some .3 mc grams per serving or 6% of your daily value, (DV) 3 ounces of beef, 2.4 mc grams, or 40% of your DV, one slice liver 47.9 mc grams or 780% of your DV, and 3 ounces of mollacks 84.1 mc grams, or 1,400 % of your DV while one egg provides .6 mc grams or 10% of your DV. Vegetarians have a challenge to ensure that they meet their daily allowance for B-12.