The awareness of vitamin B12/folate deficiency among practitioners has broadened from an exclusive haematological disease, pernicious anemia, via the neurological speciality, neuropathy, to the neurogeriatric field, dementia. The metabolism of vitamin B12 and folate is intimately connected and deficiency occurs in 10-15 % of the elderly population(1). The classical pernicious anemia is nowadays unusual, implying the importance of recognizing the complex and non-haematological symptomatology of B12/folate deficiency. It is of utmost importance to correctly treat the conditions, which is simple, cheap, with a minimum of side effects, and might be irreversible if untreated. In addition, there is a documented increased risk of neural tube defects in new born babies of mothers with folate deficiency(2), vast evidence of correlation with cardiovascular diseases(3,4), and probable correlation with certain malignancies(5). Despite this documentation the question of folate enrichment of flour is complex as the current experiences of enrichment are not entirely positive with risks of unmasking latent B12 deficiency(6), increasing twin births(7) and defects of the MTHFR enzyme in the folate metabolism(8).

Symptoms(9)

• Macrocytic anemia.
• Neurological symptoms with peripheral neuropathy, decreased sense of vibration, restless legs.
• Mental symptoms from mild cognitive impairment and dementia to depression and psychosis.
• Tiredness, fumlingness, alopecia, blurred vision, headache, infertility.
• Correlation with cardiovascular disease.

The clinical picture of B12/folate deficiency is often complex especially in elderly persons(10). Owing to the large supplies of B12/folate in the body, deficiency conditions often develop insidiously. The patient is easily attenuated to slowly developing deficiency states and interprets the symptomatology as the normal aging process. In addition, the deficiency conditions are often troubled by neuronal damages and atherosclerosis.

 Causes and risk conditions(11, 12)

• Impaired diet (vegans, alcoholics, anorectics)
• Gastrointestinal (GI) diseases (atrophic gastritis, coeliaci, inflammatory bowel diseases, status post GI operation)
• Medication (warfarin, cytotoxics, anti-epileptics, trimethoprim, N20, anti-acid drugs, levodopa)
• Enzyme defects of folate meatbolism
• Altered absorption, transport, or metabolism of B12/folate

 Investigation

The diagnostic possibilities have increased through new methods in clinical practice but new insights and more rigorous laboratory tests have not always simplified clinical practice. However, it is not reasonable to investigate all persons with one or some of the florid symptoms accompanying B12/folate deficiency. An investigation must be reserved for patients with macrocytic anemia or patients with clinical findings stated above. It must yield good and broad information about the patient´s nutritional habits, medication, life style, and metabolic balance.

Screening blood samples of B12, folate, and/or tissue markers of their deficiency, p-homocysteine (Hcy) and s-methylmalonic acid (MMA), where Hcy appears as the earliest, most sensitive but non-specific marker of B12/folate deficiency(13, 14)

Complement with haemoglobin, MCV, MCHC, sedimentation rate, creatinine, iron, glucose, thyroid markers, and sometimes, but above all when there is a suspicion of deranged absorption - pepsinogene, gastrine, and coeliaci serology(10). Gastroscopy may sometimes be necessary in order to verify/falsify atrophic gastritis or coeliaci(15). In elderly persons with elevated Hcy levels, a pragmatic attitude is to primarily exclude nutritional factors, renal affection, and to focus the investigation towards coeliaci or atrophic gastritis. They should be the most common causes of deficiency in otherwise healthy persons. The elderly patient with impaired memory and atherosclerotic cardiovascular changes should otherwise be a typical person for controlling Hcy levels, as there among them is a covariation with unclear causality(16,17)

 Treatment

 A clinical correlate of deficiency together with elevated Hcy levels and/or low B12/folate levels motivate treatment, which may vary widely not only between hospitals and departments but also between doctors. Haematological, neurological, and neuropsychiatric symptoms respond differently to treatment from complete remission of anemia to no effect at all in severe dementia(18). Duration as well as severity of the neurological and neuropsychiatric symptoms are of importance for improvement of treatment(19). This, in turn, must be individualized and given in combination because of the intimate connection between B12 and folate.

Treatment for remission can be given with 1 mg cobalamin intramuscularly/subcutaneously every/every second day for 1-2 weeks followed by 1 mg monthly as maintenance treatment. Alternatively, oral treatment with 2 mg cobalamin twice daily for 4-6 weeks followed by 1 mg daily as continous treatment can be tried. It is also reasonable to sometimes furnish the patient with additional vitamins and trace elements in order to optimize treatment effect(20,21). It is imperative with evaluation and follow-up of clinical state and laboratory parameters in order to have a well-tailored strategy of future treatment.

References