Deficiency symptoms

The functions of vitamin B12 are red blood cell formation, DNA synthesis and nervous system function; in deficiency, symptoms cluster in these same three areas.

Which symptoms occur in B12 deficiency?

Blood and general symptoms

The classic finding is megaloblastic anemia, with large, immature red blood cells. Besides anemia, NIH lists findings such as low white blood cell and platelet counts, tongue inflammation (glossitis), fatigue, palpitations, pallor, weight loss and infertility. The Turkish Hematology Association guideline reports pallor, mild jaundice, rapid breathing and an increased heart rate as signs of anemia, and loss of papillae on the tongue, giving a smooth, shiny red appearance, as the typical tongue finding. ^{[1] [2]}

Nervous system symptoms

Unexplained paresthesia (tingling), numbness in the arms and legs, and unsteady gait are the notable findings. When the posterior and lateral columns of the spinal cord are involved, vibration and position sense in the lower limbs can be lost. NIH emphasizes that these nerve symptoms can occur without anemia; the guideline emphasizes that neurological and psychiatric findings can also appear before hematological findings. ^{[1] [2]}

Mood and cognitive symptoms

In older adults, unexplained mood disorders or dementia-like presentations are considered a reason to investigate for deficiency. Some studies have found an association between B12 deficiency and depression; this association does not mean “B12 causes depression” or “supplements treat depression.” ^{[1] [2]}

In infants and children

Infants can show growth delay, loss of acquired motor skills, tremor, poor appetite and apathy. NIH reports that infants whose deficiency is not detected and treated can develop nerve damage, developmental delay and anemia. ^{[1] [2]}

Why do symptoms appear years later?

The body’s B12 store is about 1–5 mg, which is roughly 1,000–2,000 times the daily intake. For this reason, when intake or absorption is impaired, symptoms can appear after several years. Having no symptoms does not show that the level is adequate; similarly, symptoms are not expected in everyone with a mildly low value. ^[1]

Does B12 deficiency cause permanent damage?

Nerve symptoms can become permanent if untreated; NIH therefore states that early diagnosis and intervention are important to prevent permanent damage. The Turkish Hematology Association guideline, listing response times to treatment, says that signs of anemia resolve within weeks, while recovery of nerve signs is “variable.” ^{[1] [2]}

According to the British Society for Haematology (BSH) guideline, there is no “gold standard” test that defines deficiency; the clinical picture is the most important factor. If there is a discrepancy between the test result and strong clinical findings, treatment should not be delayed, in order to prevent nerve damage. ^[3]

In addition, it should not be assumed that every low result explains a symptom and will be corrected by treatment. In a placebo-controlled double-blind study in the United Kingdom of 201 people aged 75 and over with moderately low serum B12 (107–210 pmol/L) and without anemia or marked cognitive impairment, 1 mg of oral B12 daily for 12 months raised blood levels markedly but made no significant difference compared with placebo in nerve conduction or cognitive function. This result does not apply to deficiency that causes symptoms or occurs with anemia. ^[8]

Does a normal blood count rule out deficiency?

No. According to the guideline, macrocytosis (large red cells) accompanying anemia suggests B12 deficiency, but a complete blood count is not considered diagnostic on its own. If iron deficiency anemia, thalassemia trait or inflammatory disease is also present, cell size can be normal or even small; in severe deficiency, white blood cell and platelet counts can also fall. So “my blood count is clean” does not rule out B12 deficiency. ^[2]

Does folic acid mask B12 deficiency?

Folic acid (folate) can correct megaloblastic anemia but does not correct nerve damage caused by B12 deficiency. NIH states that the concern that high folate intake could cover up B12 deficiency until nerve consequences become permanent was raised in the past, that questions on this remain, and that the concern now focuses more on high amounts of folate triggering or worsening the anemia and cognitive symptoms caused by B12 deficiency. The Turkish Hematology Association guideline also reports that giving folic acid alone to a person with B12 deficiency can worsen nerve findings. ^{[2] [4]}

For this reason, in a person suspected of anemia, measuring B12 status as well is safer than starting self-treatment with folic acid alone or with “blood-building” mixtures. This is not a dose or product recommendation.

What causes B12 deficiency?

Deficiency is mostly due to absorption problems rather than diet. The main causes listed by the guideline and NIH are as follows: ^{[1] [2]}

In the metformin study (Diabetes Prevention Program), low B12 was found in 4.3% at year 5 versus 2.3% in the placebo group; each additional year of metformin use increased the risk of deficiency, and neuropathy was more common in metformin users with low B12. Among people who used PPIs and H2 blockers for at least two years, a deficiency diagnosis was associated with ORs of 1.65 and 1.25; this association is not evidence of cause and effect. ^{[6] [7]}

Who is considered for testing?

According to the guideline, investigating B12 status, with or without symptoms, is considered in these groups: older adults with poor nutrition and nerve-mood symptoms, people on a long-term vegetarian diet, those who have had stomach or small intestine surgery, people with inflammatory bowel disease, and people on long-term H2 blockers or PPIs. A review of 40 studies in vegetarians also reports that deficiency is common in this group (more common in vegans) and recommends screening vegetarians for B12 deficiency. ^{[2] [5]}

The basic test is serum B12; when the result is in the gray zone, additional tests such as MMA and homocysteine are used. These tests and the interpretation of values are covered on a separate page.

When should a health professional be consulted?

Evaluation should not be postponed if there is persistent numbness and tingling in the hands and feet, impaired balance, forgetfulness or mood change, pallor and easy fatigue, or a feeding and growth problem in pregnancy or in an infant. In the evaluation, it helps to mention risk factors such as metformin, medications that suppress stomach acid, or a diet containing no animal foods. Because severe potassium drops have been reported in the first 48 hours of treatment in severe deficiency, treatment is started under physician monitoring. ^[2]

This page does not make a diagnosis and does not give a personal dose or treatment regimen. The related pages cover food sources and the evidence on supplements.