I'd like to know why B12 deficiency enlarge red blood cells

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    $\begingroup$ Welcome to Biology.SE, Adriana. @SPr has shared a reference with you that may answer your question. If not, it may help to know more about what you understand and what you don't. See the help center article on how to ask a good question $\endgroup$
    – De Novo
    Feb 28, 2019 at 13:18

2 Answers 2


@SPr has given you a good reference in his answer. I thought I'd add some context to it.

The basic problem here is that red blood cells need B12 in order to synthesize DNA. Red blood cells live for about 4 months, and have to constantly be replaced, so when you have a problem with B12, this is one of the cell populations that will be affected. The problem here is actually the anemia. It's not that the cells are too big, but that there aren't enough of them (see the linked reference, as well as Robbins and Cotran Pathologic Basis of Disease, Ch 13, subsection "Anemias of Diminished Erythropoiesis"). The size itself helps identify why there aren't enough of them, distinguishing this anemia from other anemias that cause cells that are smaller than normal.

The mechanism in lay terms (which hasn't entirely been worked out, again, see both the article and Robbins), is that a problem with DNA synthesis causes the cells get larger before they divide. So you have fewer, larger cells. Because it's a universal problem with DNA synthesis, red blood cells aren't the only cells affected.

  • $\begingroup$ @user1136 that is a good question. Perhaps you could ask it? I'd be happy to answer. $\endgroup$
    – De Novo
    Feb 28, 2019 at 14:29
  • $\begingroup$ @user1136 I'm not sure what the purpose of your comment is, but perhaps we can chat about it $\endgroup$
    – De Novo
    Feb 28, 2019 at 15:14

The technical term for enlarged blood cells is macrocytosis (macro means large, -cyto- means cell).

Macrocytosis due to vitamin B12 or folate deficiency is a direct result of ineffective or dysplastic erythropoiesis. These important vitamins and cofactors are required for normal maturation of all cells. Marrow erythroblasts are no exception. When either of these two factors is deficient, RBC proliferation and maturation result in large erythroblasts with nuclear/cytoplasmic asynchrony. These abnormalities are caused by a defect in DNA synthesis that interferes with cellular proliferation and maturation. RNA synthesis and cytoplasmic components remain relatively unaffected. The marrow is hypercellular with all forms of the myeloid cell line being increased and erythroid elements being dominant on the marrow aspirate smear preparations. The erythroblasts become large, oval shaped and contain a characteristic immature, lacy nucleus. These bone marrow features are called “megaloblastic” and are highly suspicious of a vitamin B12 or folate deficiency. Megaloblastoid (megaloblastic-like) abnormalities of the marrow are frequently seen in other hematologic disorders not associated with vitamin B12 or folate deficiency, (e.g., myelodysplasia and leukemia) and a careful examination of the bone marrow is necessary to make this distinction.

Source: Megaloblastic Anemia and Other Causes of Macrocytosis

Erythropoiesis simply means the process of red blood cell production.

Erythroblasts are immature red blood cells that still have a nucleus. Mature red blood cells lose their nucleus before they enter the bloodstream to become active oxygen carriers.

  • $\begingroup$ I'm not the down voter, but I suspect this may have been because your answer is mostly a reference with a small glossary. Your answer is correct, and I think better than an explanation with no reference. $\endgroup$
    – De Novo
    Feb 28, 2019 at 13:50
  • $\begingroup$ Indeed, why paraphrase when another has said it more accurately and concisely? I'll happily add that B12 is additionally known to affect epigenetic mechanisms as a coenzyme of methyltransferase that methylates, demethylates and remethylates various biological molecules including DNA. B12, and DNA methylation status, is important for structural stability of regions of chromosomes such as centromeres and subtelomeres. Medically it may explain why B12 deficiency affects pregnancy, and from a molecular point of view, why DNA synthesis is affected globally across the entire body! $\endgroup$
    – S Pr
    Feb 28, 2019 at 14:14
  • $\begingroup$ that was perhaps an indirect way of saying I personally think your answer could be better (as a response to this basic question) with more than just a reference and a glossary. But I didn't think it was worthy of a downvote, specifically because it was correct and referenced. $\endgroup$
    – De Novo
    Feb 28, 2019 at 14:40
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    $\begingroup$ Other things that compromise DNA synthesis also produce macrocytosis - nucleoside analog chemotherapy / antiviral therapy are good examples. $\endgroup$
    – Willk
    Feb 28, 2019 at 17:13

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