B12 Deficiency

Manifestations

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, neurologic, or psychiatric in nature, but gastrointestinal and indirect cardiovascular and bone health symptoms are also common.

Hematologic
Common symptoms associated with hematologic pathology include skin pallor, weakness, fatigue, syncope, shortness of breath, and palpitations.[16] A classic hematologic sign of severe vitamin B12 deficiency is pernicious anemia, a megaloblastic anemia caused specifically by impaired B12 absorption due to atrophic gastritis and a lack of parietal cells (which produce intrinsic factor) in the stomach.[17] Hematologic manifestations might also be due to folate deficiency. Although vitamin B12 deficiency is not always accompanied by hematologic changes, the majority of patients with clinical deficiency will have signs of megaloblastic anemia.[16]

Neurologic and Psychiatric
Common neurologic and psychiatric 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.[16]

Gastrointestinal
Vitamin B12 deficiency might also manifest with gastrointestinal complaints. Some frequently mentioned symptoms include anorexia, flatulence, diarrhea, and constipation. These symptoms can develop among patients with a vitamin B12 deficiency without accompanying anemia, macrocytosis, or overt neurologic deficits.[16]

Cardiovascular
Both low vitamin B12 levels and low folate levels are associated with elevated levels of homocysteine, leading to hyperhomocysteinemia, a medical condition characterized by an abnormally high level of homocysteine in the blood.

Elevated homocysteine is a known risk factor for cardiovascular disease and thrombosis. It has also been shown to be associated with microalbuminuria, which is a strong indicator of the risk of future cardiovascular disease and renal dysfunction. Although the role of folic acid supplementation in reducing homocysteine levels as a method for preventing coronary artery disease and stroke continues to be a subject of great interest, there has been little emphasis on the potential role of vitamin B12 deficiency as a contributing factor in the development of cardiovascular disease. Folic acid supplementation may mask an occult vitamin B12 deficiency and further exacerbate or initiate neurologic disease.[8]

Bone
Elevated levels of homocysteine have also been strongly associated with the increased risk of fractures in older men and women (van Meurs & al, 2004).[18],[19] The mechanism underlying the association between the homocysteine level and the risk of fracture may involve interference by homocysteine in collagen cross-linking. Homocysteine has been shown to interfere specifically with the formation of collagen cross-links and fibrils in solution. Interference with collagen cross-links results in an altered bone matrix, which then results in fragile bone.[19]