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Manifestations of Low Vitamin B12 Levels

Although some clinical expressions remain mysterious, especially the neurological dysfunction, our view of cobalamin deficiency has expanded beyond the question of megaloblastic anemia.” Carmel, 2000

Today, in the United States, megaloblastic anemia is most likely due to a vitamin B12 deficiency until proven otherwise.

No single symptom, or cluster of symptoms, has been uniquely associated with inadequate levels of vitamin B12. Among older adults, the most frequently reported symptoms of vitamin B12 deficiency are hematologic or neurologic in nature, but gastrointestinal and possibly vascular symptoms are also common. The typically nonspecific manifestations of a vitamin B12 deficiency underscore the importance of encouraging all older adults to consume the synthetic form of the vitamin each day. Recent concerns have also been raised about potential adverse effects on infant growth and development in exclusively breastfed babies of mothers who adhere to a strict vegan diet.11,16 While this situation is rare in the United States, sequelae are often severe and irreversible in these children.

Hematologic Manifestations

Common symptoms associated with hematologic pathology include skin pallor, weakness, fatigue, syncope, shortness of breath, and palpitations.2,10 A classic hematologic sign of severe vitamin B12 deficiency is megaloblastic anemia.2 Hematologic manifestations might also be due to folate deficiency. However, since 1998, the U.S. Food and Drug Administration has required fortification of all enriched grain and cereal products with 140 µg of folic acid per 100 grams of cereal grain product,37 and that fortification of the U.S. food supply has essentially eliminated the prevalence of folate deficiency.21 Today, in the United States, a case of megaloblastic anemia is most likely due to vitamin B12 deficiency until proven otherwise.

Many B12 - deficient patients do have anemia or macrocytosis.

Although vitamin B12 deficiency is not always accompanied by hematologic changes, the majority of patients with clinical deficiency will have signs of megaloblastic anemia. In various studies conducted among patients with overt vitamin B12–deficiency, 56% to 77% of people had signs of macrocytosis or anemia.5,38-41 Furthermore, some researchers have found that the presence of neurologic manifestations of a vitamin B12 deficiency might even be correlated inversely with evidence of hematologic effects.10,39,42

Neurologic Manifestations

Common neurologic complaints include paresthesias (with or without objective signs of neuropathy), weakness, motor disturbances (including gait abnormalities), vision loss, and a wide range of cognitive and behavioral changes (e.g., dementia, hallucinations, psychosis, paranoia, depression, violent behavior, and personality changes). Tingling of the hands and feet is perhaps the most common neurologic complaint.2,41,42

The pathology of vitamin B12 deficiency on the nervous system is unknown.7

All patients newly diagnosed with unexplained cognitive decline or dementia should be assessed for a possible vitamin B12 deficiency.

All patients with unexplained cognitive decline or dementia should be assessed for a possible vitamin B12 deficiency.41,43-45 Several current case reports and studies support the common practice of assessing vitamin B12 levels during dementia workups.41,46-48 Although only a minority (1.5%) of all dementia cases are fully reversible following treatment49, many dementias from other etiologies (e.g. Parkinson or Alzheimer disease) are exacerbated when patients have a concomitant low vitamin B12 level. The American Academy of Neurology (AAN) has concluded that because vitamin B12 deficiency is a likely comorbidity in the elderly, and among patients with suspected dementia in particular, it should be recognized and treated. The AAN practice guideline state that B12 levels should be included in routine assessments of dementia among the elderly.44

Gastrointestinal Manifestations

Vitamin B12 deficiency might also manifest with gastrointestinal complaints. Some frequently mentioned symptoms include anorexia, flatulence, diarrhea, and constipation.7,10,36,50 These symptoms can develop among patients with a vitamin B12 deficiency without accompanying anemia, macrocytosis, or overt neurologic deficits. Glossitis, which is commonly thought to be a cardinal sign of some anemias, is actually a relatively rare manifestation of clinical vitamin B12 deficiency and is completely absent in subclinical vitamin B12 deficiency according to Carmel.(Carmel RA. New York Methodist Hospital [personal communication] 2006-2007).

Vascular Manifestations

Both low vitamin B12 levels and low folate levels are associated with elevated levels of homocysteine (Hcy). Hyperhomocysteinemia increases the chance of developing a vascular occlusion,51 thus potentially increasing the risk of coronary heart disease and ischemic stroke. Although the association of coronary heart disease or ischemic stroke with vitamin B12 or folate deficiency has not been proven, the SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine) study in the United Kingdom is seeking to obtain evidence about the impact of reducing homocysteine on cardiovascular risk while treating patients with 2 milligrams of folic acid plus 1 milligram of vitamin B12 daily. In addition, the SEARCH study is looking at the efficacy and safety of two different dosages of simvastatin in regard to risk reduction for major cardiovascular events.52 This randomized study is scheduled to end in 2008 and should provide evidence about the causal relationship of homocysteine to cardiovascular disease and about the value of folic acid and vitamin B12 supplementation in addition to answering questions about simvastatin therapy.

Effects on Infant Growth and Development

Nursing infants of mothers who adhere to a strict vegetarian or vegan diet throughout their pregnancy and while breastfeeding might also experience serious B12 - related deficiency effects.

Although the previously cited hematologic, neurologic, gastrointestinal, and cardiovascular consequences are typically observed among older patients, several cases of significant vitamin B12 deficiencies among infants and young children have been reported.53-56 Low or marginal vitamin B12 status in pregnant women increases the risk for neural tube birth defects.57 Exclusively breastfed infants of mothers who adhere to a strict vegetarian or vegan diet that excludes all animal proteins might also experience serious effects related to vitamin B12 deficiency.50,53,54,56 Clinical manifestations among infants and young children are widely varied, encompassing hematologic, neurologic, and gastrointestinal symptoms. Some potential effects include the following:

  • Failure to thrive
  • Hypotonia
  • Ataxia
  • Developmental delays
  • Macrocytosis or anemia
  • General weakness

Many of these consequences will improve with prompt vitamin B12 administration, but, sometimes, irreversible neurologic damage occurs before the diagnosis is made and treatment is begun.50,53-56 Nursing infants of vegan mothers can develop significant problems even when the mother is not anemic or symptomatic in any way.50,53,55 It is important for you to ask pregnant women and new mothers who breastfeed about their diets.


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  • Page last updated: June 29, 2009 The U.S. Government's Official Web PortalDepartment of Health and Human Services
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