The mean corpuscular volume (MCV) reflects the size or volume of the red blood cell, so an increase indicates the average size of the RBC is increasing. This can happen with various types of anemias, alcoholism, liver disease, myelodysplasia, and increased numbers of immature RBCs called reticulocytes. Some medications can increase MCV including phenytoin, azathioprine, and zidovudine.
Cappellini, M Domenica, and Irene Motta. “Anemia in Clinical Practice-Definition and Classification: Does Hemoglobin Change With Aging?.” Seminars in hematology vol. 52,4 (2015): 261-9. doi:10.1053/j.seminhematol.2015.07.006.
Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference. Elsevier Health Sciences. 2019.
Macrocytic megaloblastic anemia may be caused by a deficiency of folate or B12. It is possible that the synthetic form of folic acid or cyano-form of B12 may not be well utilized by some individuals so check the type of folate and B12 in their supplement if the MCV has risen and you believe the patient is taking supplemental B complex. Often times the forms of B12 and folate in a B complex might not be the best for absorption. The bioactive forms of those vitamins may be tolerated and utilized better. Consider adding in a separate B12/folate formula.
Pernicious anemia is associated with increased MCV and is caused by malabsorption of vitamin B12 so some individuals require intramuscular or sometimes sublingual forms to correct the deficiency and bring the MCV back down to an optimal level.
Macrocytic anemia may also be caused by hepatic insufficiency, chronic alcohol abuse, or Diamond-Black fan anemia which is congenital.
Maner, Brittany S. and Leila Moosavi. “Mean Corpuscular Volume.” StatPearls, StatPearls Publishing, 10 July 2021.
Increased MCV may also be associated with peripheral artery disease and elevated homocysteine and GGT.
Mueller, T et al. “Association between erythrocyte mean corpuscular volume and peripheral arterial disease in male subjects: a case control study.” Angiology vol. 52,9 (2001): 605-13. doi:10.1177/000331970105200904