How does folate mask vitamin b12 deficiency

More surveillance of possible B deficiency and additional studies are needed, said Dr. Irwin Rosenberg, dean of the Gerald J. Green recommends that elderly people be tested for vitamin B deficiency on a yearly basis.

Improved diagnostic tests for B deficiency could make such screening feasible. Short of routine B testing, Green suggests that people age 60 and older avoid excessive folic acid. The vitamin is also found in dark green, leafy vegetables; citrus fruits; and beans. A typical folic acid supplement contains 0. All Sections. About Us. B2B Publishing. Business Visionaries. In one study, 1 15 percent of adults older than 65 years had laboratory evidence of vitamin B 12 deficiency.

The nearly ubiquitous use of gastric acid—blocking agents, which can lead to decreased vitamin B 12 levels, 2 may have an underappreciated role in the development of vitamin B 12 deficiency. Taking the widespread use of these agents and the aging of the U. Despite these facts, the need for universal screening in older adults remains a matter of controversy. Vitamin B 12 deficiency is associated with hematologic, neurologic, and psychiatric manifestations Table 1.

It is a common cause of macrocytic megaloblastic anemia and, in advanced cases, pancytopenia. Neurologic sequelae from vitamin B 12 deficiency include paresthesias, peripheral neuropathy, and demyelination of the corticospinal tract and dorsal columns subacute combined systems disease. Vitamin B 12 deficiency also has been linked to psychiatric disorders, including impaired memory, irritability, depression, dementia and, rarely, psychosis.

Combined systems disease demyelination of dorsal columns and corticospinal tract. In addition to hematologic and neuropsychiatric manifestations, vitamin B 12 deficiency may exert indirect cardiovascular effects. Similar to folic acid deficiency, vitamin B 12 deficiency produces hyperhomocys-teinemia, which is an independent risk factor for atherosclerotic disease.

This possibility becomes especially important when considering vitamin replacement therapy. Folic acid supplementation may mask an occult vitamin B 12 deficiency and further exacerbate or initiate neurologic disease. Therefore, clinicians should consider ruling out vitamin B 12 deficiency before initiating folic acid therapy. In humans, only two enzymatic reactions are known to be dependent on vitamin B In the first reaction, methylmalonic acid is converted to succinyl-CoA using vitamin B 12 as a cofactor Figure 1.

Vitamin B 12 deficiency, therefore, can lead to increased levels of serum methylmalonic acid. In the second reaction, homocysteine is converted to methionine by using vitamin B 12 and folic acid as cofactors.

In this reaction, a deficiency of vitamin B 12 or folic acid may lead to increased homocysteine levels. Vitamin B 12 deficiency leads to a serum build-up of methylmalonic acid. Deficiency of vitamin B 12 or folic acid can lead to increased homocysteine levels.

Information from Stabler SP. Screening the older population for cobalamin vitamin B 12 deficiency. J Am Geriatr Soc ; An understanding of the vitamin B 12 absorption cycle helps illuminate the potential causes of deficiency.

The acidic environment of the stomach facilitates the breakdown of vitamin B 12 that is bound to food. Intrinsic factor, which is released by parietal cells in the stomach, binds to vitamin B 12 in the duodenum.

This vitamin B 12 —intrinsic factor complex subsequently aids in the absorption of vitamin B 12 in the terminal ileum. In addition to this method of absorption, evidence supports the existence of an alternate system that is independent of intrinsic factor or even an intact terminal ileum. Approximately 1 percent of a large oral dose of vitamin B 12 is absorbed by this second mechanism. Once absorbed, vitamin B 12 binds to transcobalamin II and is transported throughout the body. The interruption of one or any combination of these steps places a person at risk of developing deficiency Figure 2.

The diagnosis of vitamin B 12 deficiency has traditionally been based on low serum vitamin B 12 levels, usually less than pg per mL pmol per L , along with clinical evidence of disease. However, studies indicate that older patients tend to present with neuropsychiatric disease in the absence of hematologic findings.

In a large study 10 of patients with known vitamin B 12 deficiency, Only one patient out of had normal levels of both metabolites, resulting in a sensitivity of Interestingly, 28 percent of the patients in this study had normal hematocrit levels, and 17 percent had normal mean corpuscular volumes. In another study 13 of patients with known pernicious anemia who had not received maintenance vitamin B 12 injections for months to years, the rise of methylmalonic acid and homocysteine levels was found to precede the decrease in serum vitamin B 12 and the decline in hematocrit.

This finding suggests that methylmalonic acid and homocysteine levels can be early markers for tissue vitamin B 12 deficiency, even before hematologic manifestations occur. Use of methylmalonic acid and homocysteine levels in the diagnosis of vitamin B 12 deficiency has led to some surprising findings.

If increased homocysteine or methylmalonic acid levels and a normalization of these metabolites in response to replacement therapy are used as diagnostic criteria for vitamin B 12 deficiency, approximately 50 percent of these patients have serum vitamin B 12 levels above pg per mL. Other studies have shown similar findings, with the rate of missed diagnosis ranging from 10 to 26 percent when diagnosis is based on low serum vitamin B 12 levels alone.

There are, however, a few caveats to keep in mind. Looking at the reactions that use vitamin B 12 Figure 1 , 3 an elevated methylmalonic acid level is clearly more specific for vitamin B 12 deficiency than an elevated homocysteine level.

Vitamin B 12 or folic acid deficiency can cause the homocysteine level to rise, so folic acid levels also should be checked in patients with isolated hyperhomocysteinemia. In addition, folic acid deficiency can cause falsely low serum vitamin B 12 levels. One study 14 revealed that approximately one third of patients with folic acid deficiency had low serum vitamin B 12 levels—less than pg per mL 74 pmol per L in some patients. Also, methylmalonic acid levels can be elevated in patients with renal disease the result of decreased urinary excretion ; thus, elevated levels must be interpreted with caution.

An algorithm for the diagnosis of vitamin B 12 deficiency is provided in Figure 3. Suggested approach to the patient with suspected vitamin B 12 deficiency. Laboratory diagnosis of vitamin B 12 and folate deficiency. Arch Intern Med ; Once vitamin B 12 deficiency is confirmed, a search for the etiology should be initiated.

Causes of vitamin B 12 deficiency can be divided into three classes: nutritional deficiency, malabsorption syndromes, and other gastrointestinal causes Table 2.

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Dietary sources of vitamin B 12 are primarily meats and dairy products. In a typical Western diet, a person obtains approximately 5 to 15 mcg of vitamin B 12 daily, much more than the recommended daily allowance of 2 mcg. Normally, humans maintain a large vitamin B 12 reserve, which can last two to five years even in the presence of severe malab-sorption. The dietary limitations of strict vegans make them another, less common at-risk population.

The classic disorder of malabsorption is pernicious anemia, an autoimmune disease that affects the gastric parietal cells. Destruction of these cells curtails the production of intrinsic factor and subsequently limits vitamin B 12 absorption.

Laboratory evidence of parietal cell antibodies is approximately 85 to 90 percent sensitive for the diagnosis of pernicious anemia. However, the presence of parietal cell antibodies is nonspecific and occurs in other autoimmune states. However, in successfully delivering additional folic acid to pregnant women fortification also increases the consumption of folic acid of everyone who consumes products containing flour, including the elderly.

It is argued that consuming additional folic acid as 'synthetic' pteroylglutamic acid from fortified foods increases the risk of 'masking' megaloblastic anaemia caused by vitamin B12 deficiency. Thus, a number of issues arise for discussion.