Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 558

Folate deficiency anaemia has become uncommon in the United States after a 1998 mandate by the Food and Drug Administration to fortify all grain products with folic acid. This was done in an effort to reduce congenital neural tube defects.⁴³ Folate is considered an ‘essential micronutrient’. It is not synthesized by the body and needs to be consumed through diet or supplementation. Also known as vitamin B9, folate plays an essential role in neurotransmitter synthesis as well as cellular DNA synthesis and repair.⁴⁴ It is primarily contained in green, leafy vegetables and also in some animal products. Folic acid is the synthesized form of folate that is present in supplements or fortified foods and has a higher bioavailability than folate. Although rare, folate deficiency can still occur due to inadequate intake, malabsorption, or conditions resulting in increased folate requirements. Several medications such as methotrexate, sulfasalazine, trimethoprim, and phenytoin interfere with folate metabolism and can lead to deficiencies in the absence of supplementation.⁴⁵

Individuals with chronic malnourishment, restrictive diets, or alcoholism are at risk for folate deficiency and resultant anaemia. Impaired absorption can occur in those with a history of gastric or bowel resection or of inflammatory bowel disease since folate is absorbed in the jejunum by passive transport. Vitamin B12 deficiency can lead to relative folate deficiency because vitamin B12 is required for cellular metabolism cycles that convert folate into its most active bioavailable form, tetrahydrofolate.⁴⁶ In such cases, once vitamin B12 levels are corrected, the folate deficiency resolves without supplementation. Unlike vitamin B12, folate is not stored in large quantities, and deficiencies develop much more quickly, over weeks to months. Once deficient, individuals may develop non‐specific symptoms similar to those seen in vitamin B12 deficiency – glossitis, fatigue, depression, and/or cognitive impairment.

Laboratory studies are used to confirm the diagnosis of folate deficiency anaemia. Classically considered a megaloblastic anaemia, a low haemoglobin, elevated MCV, and low serum folate level will be seen. Typically, there is also a low reticulocyte count. Serum folate levels <2 ng/mL are considered deficient, while levels 2–4 ng/mL are borderline and >4 ng/mL are considered normal. When folate levels are borderline, further confirmation of a deficiency can occur with MMA and homocysteine levels. MMA levels are normal, while homocysteine levels are elevated in folate deficiency. This is contrasted in vitamin B12 deficiency, which can be confirmed when both the MMA and homocysteine levels are elevated. Another confirmative test that may be useful is the quantitative level of folate within RBCs (as opposed to the folate level in blood plasma). Because this is relatively fixed for the lifecycle of the RBC, it is indicative of folate status over the preceding 120 days and can help identify when the deficiency began.⁴⁷ The serum folate level varies widely on recent food ingestion and is not indicative of overall bioavailable folate, thus limiting its accuracy. There are no evidence‐based guidelines regarding screening for folate deficiency, and routine screening is not recommended. However, screening should be considered in high‐risk individuals who are anaemic and also in the workup of anaemia of unknown aetiology.

In people with confirmed folate deficiency anaemia, supplementation must be initiated. Most commonly, folate deficiency is treated with oral replacement, although IV preparations are available for those unable to consume oral repletion. No evidence‐based guidelines exist regarding dose or duration of treatment; however, folic acid 1 mg daily is a typical supplementation dose. If the folate deficiency is secondary to malabsorption, supplementation will likely be needed indefinitely. If medication‐induced, supplementation should occur for as long as the individual is receiving the offending medication.

In summary, folate deficiency anaemia is not as common in the US as it once was because of government‐mandated grain‐fortification policies. However, it is still seen in countries that lack these policies and can occur globally in those with malnutrition or restrictive diets, impaired absorption, or high RBC turnover states. There are also several medications that induce folate deficiency. The diagnosis of folate deficiency anaemia typically relies on low haemoglobin and low serum folate levels and can be confirmed by low RBC folate, normal MMA, and elevated homocysteine levels. At the present time, there are no evidence‐based guidelines for screening or treatment, but generally, oral folic acid supplementation daily is sufficient for correction of plasma levels and stores.