From the Guidelines

Macrocytosis without anemia is most commonly caused by vitamin B12 or folate deficiency.

Vitamin B12 deficiency: can be caused by insufficient uptake or inadequate absorption through lack of intrinsic factor, and can lead to megaloblastic anemia 1
Folate deficiency: can be caused by insufficient intake, malabsorption, or certain medications such as anticonvulsants, sulfasalazine, and methotrexate 1
Other causes: include thiopurine treatment (azathioprine or 6-mercaptopurine), other medications, alcohol abuse, hypothyroidism, or reticulocytosis 1

Diagnosis: involves measuring vitamin B12 and folate levels, as well as complete blood count (CBC) with mean corpuscular volume (MCV) and reticulocyte count 1
Treatment: vitamin B12 deficiency should be treated immediately with hydroxocobalamin, and folate deficiency should be treated with oral folic acid after excluding vitamin B12 deficiency 1 It is essential to note that folate supplementation may mask severe vitamin B12 depletion, and therefore, vitamin B12 deficiency should be treated first 1. Additionally, the assessment of vitamin B9 status should include an estimation of vitamin B12 status, as vitamin B12 deficiency can lead to a functional vitamin B9 deficiency 1.

From the Research

Macrocytosis without anemia can be caused by various factors, including vitamin B12 deficiency 2, as 9 cases (20.9%) of Vitamin B12 deficiency presented with isolated macrocytosis without anemia.
Other causes of macrocytosis without anemia may include drug-related factors, as some medications can cause macrocytosis without leading to anemia 3.
Hypothyroidism, liver disease, and primary bone marrow dysplasias (including myelodysplasia and myeloproliferative disorders) are also possible causes of macrocytosis without anemia 3.
In some cases, the cause of macrocytosis without anemia may not be immediately apparent, and close follow-up with blood cell counting every 6 months may be necessary to monitor the condition 4.

A complete medical history, red cell parameters, and peripheral blood smear can be helpful in identifying the underlying cause of macrocytosis without anemia 2.
Vitamin B12 level, reticulocyte count, and a peripheral smear can also be useful in evaluating the cause of macrocytosis without anemia 3.
In cases where the peripheral smear indicates megaloblastic anemia, vitamin B12 or folate deficiency is the most likely cause, even if anemia is not present 3.

Macrocytosis without anemia can be an early indicator of an underlying pathology, and it is essential to evaluate the condition even in the absence of anemia 2.
Close follow-up and monitoring of patients with macrocytosis without anemia can help identify any potential underlying conditions and allow for early intervention 4.