It’s estimated that anemia, low hemoglobin, and/or red blood cell counts, affect approximately one-third of the world’s population. (2) According to the National Heart, Lung, and Blood Institute, anemia is the most common blood disorder in the United States, and it is diagnosed when hemoglobin is less than 13.5 gm/dl in men and less than 12.0 gm/dl in women. (1)
Macrocytic anemia is caused by enlarged red blood cells, which creates a mean corpuscular volume (MCV), the size of red blood cells, of greater than 100 fL. (7) There are two macrocytic anemias: megaloblastic macrocytic anemia and nonmegaloblastic macrocytic anemia.
Macrocytic anemia causes
The biggest difference between nonmegaloblastic macrocytic anemias vs megaloblastic macrocytic anemias is the cause. Typically, nonmegaloblastic macrocytic anemia is caused by alcohol abuse, hypothyroidism, liver disease, medications, or myelodysplastic syndrome. (10) Megaloblastic anemia, on the other hand, is caused by a deficiency or an impaired utilization of vitamin B12 and/or folate. (7)
Macrocytic anemia pregnancy
The rapid increase in fluid within the blood during pregnancy significantly dilutes the red blood cells leading to what appears to be a reduction of red blood cells. (11) Pregnancy-induced anemia can be further complicated by nutrient deficiencies in iron, folic acid, protein, and vitamin B12. (11)
Iron deficiency-induced microcytic anemia is the most common type of anemia occurring during pregnancy with a prevalence of 48%. (11) Contrary to macrocytic anemia, microcytic anemia has small red blood cells. (6) However, approximately 40% of individuals develop macrocytic anemia during their pregnancies. (11)
Macrocytic anemia symptoms
One of the challenges with macrocytic anemia is that it can develop slowly over time with few or no symptoms until the anemia becomes severe. (4) Hallmark signs of any anemia include fatigue, paleness, and weakness. However, with vitamin B12 macrocytic anemia, the nerves can be affected causing tingling, loss of sensation, and muscle weakness. (4) Depending on the degree of anemia, other symptoms can include poor exercise tolerance, shortness of breath, and psychiatric manifestations such as depression, mania, and memory loss. (10)
Diagnosing macrocytic anemia
In addition to a symptom evaluation, blood tests are used to diagnose macrocytic anemia. In most cases, when MCV is greater than 100 fL, serum folate and vitamin B12 levels are measured to determine if there is a deficiency. When B12 levels are <200 pg/mL, vitamin B12 deficiency is very likely. When folate levels are <2 ng/mL, folate deficiency is diagnosed. (7)
Keep in mind that with prolonged anemia, there may also be a reduction in platelets and white blood cells. (4)
Macrocytic anemia diet
Treatment of megaloblastic macrocytic anemia involves correcting vitamin deficiencies and making dietary recommendations. Focusing on a diet rich in sources of deficient nutrients is important. The following are some nutrients and examples of food sources to focus on.
Dietary sources high in folate include:
- Cooked lentils, black beans, pinto beans, and chickpeas
- Cooked spinach, broccoli, Brussels sprouts, and cauliflower (with spinach having the highest content)
- Fortified and cooked cereals
- Orange juice, papaya, and strawberries
- Raw lettuce and asparagus
Dietary sources high in B12 include:
- Canned tuna
- Cooked beef, chicken breast, lamb loin, and salmon
- Fortified cereals
- Milk and cheese
- Roasted turkey (9)
It’s important to note that, oftentimes, strict vegans and vegetarians may be deficient in vitamin B12, a key cause of macrocytic anemia. (8)(10) For individuals who wish to maintain their vegan or vegetarian diet, a Mediterranean diet that focuses on walnuts and vegetable protein is high in iron and can help reduce the risk of anemia and, in some cases, may help to reverse it. (3) Supplementing with B12 may also be a good idea for vegans or vegetarians.
Nutrient absorption issues in the gut that are caused by Crohn’s disease or other inflammatory bowel disorders and some medications, such as chemotherapy agents, metformin, and immunosuppressants, may also contribute to vitamin B12 and folate deficiencies. (10)
The bottom line
When caught early, macrocytic anemia can be easily addressed and has an excellent prognosis. (5) By correcting vitamin deficiencies and focusing on diet, macrocytic anemia responds well to an integrative treatment approach.
If you’d like more guidance on how to address and even reverse macrocytic anemia, consider speaking with your integrative healthcare professional.
- American Society of Hematology. (Accessed 2021, December). Anemia. https://www.hematology.org/education/patients/anemia
- Chaparro, C. M., & Suchdv, P. S. (2019). Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries. Ann NY Acad Sci, 1450(1), 15-31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697587/
- Meir, A., Tsaban, G., Zelicha, H., Rinott, E., Kaplan, A., Youngste, I., Rudich, A., Shelef, I., Tirosh, A., Brikner, D., Pupkin, E., Sarusi, B., Bluher, M., Stumvoll, M., Thiery, J., Ceglarek, U., Stampfer, M., J., & Shai, I. (2019). A green-mediterranean diet, supplemented with Mankai duckweed, preserves iron-homeostasis in humans and is efficient in reversal of anemia in rats. J Nutr, 149(6), 1004-1011. https://pubmed.ncbi.nlm.nih.gov/30915471/
- Merck Manual Consumer Version. (Accessed 2022, December 22). Vitamin deficiency anemia (megaloblastic anemia). https://www.merckmanuals.com/home/blood-disorders/anemia/vitamin-deficiency-anemia
- Moore, C. A., & Adil, A. (2021). Macrocytic anemia. StatPearls, July 15. https://www.ncbi.nlm.nih.gov/books/NBK459295/
- Massey, A. C. (1992). Microcytic anemia. Differential diagnosis and management of iron deficiency anemia. Med Clin North Am, 76(3), 549-66. https://pubmed.ncbi.nlm.nih.gov/1578956/
- Nagao, T., & Hirokawa, M. (2017). Diagnosis and treatment of macrocytic anemias in adults. J Gen Fam Med, 18(5), 200-204. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689413/
- Rawlak, R., Berger, J., & Hines, I. (2018). Iron status of vegetarian adults: a review of the literature. Am J Lifestyle Med, 12(6), 486-498. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367879/
- Santoyo-Sanchez, A., Aponte-Castillo, J. A., Parra-Pena, R. I., & Ramos-Penafiel, C. O. (2015). Dietary recommendations in patients with deficiency anemia. Revista Medica Del Hospital General De Mexico, 78(3), 144-150. https://www.sciencedirect.com/science/article/pii/S0185106315000463
- Socha, D. S., DeSouza, S. I., Flagg, A., Sekeres, M., & Rogers, H. J. (2020). Severe megaloblastic anemia: vitamin deficiency and other causes. Cleveland Clinic Journal of Medicine, 87(3), 153-164. https://www.ccjm.org/content/87/3/15311. Tripathi, R., Tyagi, S., Singh, T., Dixit, A., & Mala, M. (2011). Clinical evaluation of severe anemia in pregnancy with special reference to macrocytic anemia. The Journal of Obstetrics and Gynaecology Research, 38(1), 203-207. https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/j.1447-0756.2011.01679.x