Does macrocytic anemia cause symptoms? What to know

October 1, 2025 •

4 min read

Macrocytic anemia, a condition defined by abnormally large red blood cells, is surprisingly common, affecting 2–4% of the population. But does macrocytic anemia cause symptoms? Yes, it can, though the severity varies greatly depending on the underlying cause and how long the condition has been present.

Quick Summary

Macrocytic anemia often causes symptoms such as fatigue, weakness, and pale skin, but it can also be asymptomatic in mild cases and progress to more severe neurological or cardiac issues if left untreated. Symptoms often relate to the specific nutritional deficiency or underlying medical condition causing the anemia, including vitamin B12 or folate deficiency, liver disease, or certain medications.

Key Points

Symptom Severity Varies: Macrocytic anemia can cause symptoms ranging from mild fatigue to severe neurological issues, or sometimes no symptoms at all, especially in early stages.
Fatigue is a Key Sign: One of the most common indicators is persistent, unexplained fatigue and weakness due to the impaired oxygen-carrying capacity of large red blood cells.
Neurological Issues are Distinct: If caused by vitamin B12 deficiency, macrocytic anemia can lead to neurological problems like numbness, tingling, memory loss, and balance issues, which can become permanent if untreated.
Causes Determine Symptoms: The specific symptoms experienced often depend on the root cause, which can include deficiencies in vitamin B12 or folate, liver disease, alcohol abuse, or medications.
Diagnosis is Found in Blood Tests: Diagnosis typically involves a complete blood count (CBC) showing an elevated MCV, followed by further tests for vitamin levels or other underlying conditions.
Treatment Targets the Root Cause: Effective treatment focuses on addressing the underlying issue, such as correcting nutritional deficiencies with supplements, managing related medical conditions, or adjusting medications.

Understanding the role of large red blood cells

Your body's red blood cells are responsible for carrying oxygen from your lungs to your tissues and organs. In macrocytic anemia, these cells are larger than normal, which can impair their ability to function effectively. This compromised oxygen delivery is the root cause of many of the condition's symptoms. The mean corpuscular volume (MCV), a value measured in a routine complete blood count (CBC), is used to define macrocytosis, with a reading over 100 fL indicating enlarged red blood cells. While some individuals with a high MCV may not experience any issues, others develop symptoms of anemia as a result.

Common symptoms of macrocytic anemia

Many of the symptoms associated with macrocytic anemia are related to the decreased oxygen-carrying capacity of the blood. They often develop gradually and may go unnoticed at first, but can become more pronounced over time.

Fatigue and Weakness: This is one of the most common signs, as reduced oxygen delivery to tissues leaves the body feeling perpetually tired and drained of energy.
Pale Skin: A noticeable pallor, especially in the lips, gums, and inside the lower eyelids, can occur due to low hemoglobin levels.
Shortness of Breath (Dyspnea): Individuals may experience difficulty breathing, particularly during physical exertion, as the heart works harder to compensate for the oxygen deficit.
Dizziness and Lightheadedness: Insufficient oxygen supply to the brain can lead to feelings of dizziness, lightheadedness, or vertigo.
Heart Palpitations: The heart may beat faster or irregularly (tachycardia) as it tries to circulate more oxygenated blood to the body.

Neurological symptoms: unique to certain causes

When macrocytic anemia stems from a vitamin B12 deficiency (a type known as megaloblastic anemia), it can uniquely affect the nervous system. These neurological symptoms can appear even before the anemia is severe and may become permanent if left untreated.

Peripheral Neuropathy: A feeling of numbness or tingling, often described as “pins and needles,” in the hands and feet.
Difficulty with Balance and Coordination (Ataxia): Poor coordination can lead to an unsteady gait and difficulty walking.
Cognitive Issues: Memory loss, confusion, and poor concentration are common, and severe, long-term deficiency can contribute to dementia.
Psychiatric Disturbances: Mood changes, irritability, and even depression can manifest from B12 deficiency.

Gastrointestinal and other signs

Beyond the more common and neurological symptoms, macrocytic anemia can cause other physical changes depending on the underlying cause.

Glossitis: The tongue may become sore, swollen, and appear red and smooth.
Digestive Issues: Symptoms like diarrhea, loss of appetite, or unexplained weight loss can occur.
Jaundice: A yellowish tint to the skin and whites of the eyes can be a sign of increased red blood cell destruction (hemolysis), which is more common in megaloblastic anemia.

Comparison of causes and their associated symptoms

Understanding the type of macrocytic anemia is crucial because the symptoms and treatment depend on the cause. The two main types are megaloblastic (due to vitamin B12 or folate deficiency) and non-megaloblastic.


Feature	Megaloblastic Anemia (B12/Folate Deficiency)	Non-Megaloblastic Anemia (Other Causes)
Red Blood Cell Shape	Macro-ovalocytes (large and oval-shaped) with hypersegmented neutrophils.	Round macrocytes.
Neurological Symptoms	Common, including peripheral neuropathy, memory loss, and ataxia.	Rare or absent, unless related to another underlying condition.
Gastrointestinal Symptoms	Diarrhea, glossitis, anorexia are common.	May occur, especially with liver disease or alcohol abuse.
Other Associated Conditions	Autoimmune gastritis (pernicious anemia), malabsorption issues like Crohn's disease.	Liver disease, hypothyroidism, myelodysplastic syndrome, and chronic alcohol use.
Key Laboratory Findings	High methylmalonic acid (MMA) and homocysteine levels (B12); high homocysteine (folate).	Variable; may show abnormal liver function or thyroid tests depending on cause.

When to seek medical attention

While mild symptoms might be tolerable, it's essential to seek prompt medical care, especially if you notice neurological signs. Early diagnosis and treatment are key to preventing permanent damage. Serious warning signs that require immediate attention include severe shortness of breath, chest pain, confusion, or a rapid heart rate. For more information on general blood health, the National Heart, Lung, and Blood Institute website is a reputable resource.

Diagnosis and treatment

Macrocytic anemia is diagnosed through a series of tests, starting with a routine CBC. A mean corpuscular volume (MCV) over 100 fL is the initial indicator. Additional tests may include a peripheral blood smear to examine the shape of the red blood cells, as well as blood tests to check vitamin B12 and folate levels. For more complex cases, such as suspected myelodysplastic syndrome, a bone marrow biopsy may be necessary. Treatment focuses on addressing the underlying cause. For nutritional deficiencies, treatment typically involves supplements or injections of the missing vitamin. If another medical condition or medication is the cause, treating that issue or adjusting medication will be the primary course of action.

Conclusion

Macrocytic anemia can definitely cause symptoms, and while they can be mild and subtle initially, they have the potential to become serious if left unaddressed. Recognizing early signs like persistent fatigue, weakness, and pallor is crucial. Promptly seeking medical evaluation, especially when neurological symptoms arise, is vital for a good prognosis. The good news is that with an accurate diagnosis and targeted treatment, the symptoms are often reversible, and complications can be prevented. Living with macrocytic anemia requires careful management and consistent follow-up with a healthcare provider to ensure optimal health.

Frequently Asked Questions

Yes, it is possible to have macrocytic anemia and be asymptomatic, especially in the early stages or in mild cases. The condition is often discovered incidentally during routine blood work, such as a complete blood count (CBC).

Megaloblastic anemia is a subtype caused by vitamin B12 or folate deficiency, leading to oval-shaped red blood cells. Non-megaloblastic anemia is caused by other factors like liver disease, alcohol use, or certain medications, and the red blood cells are typically round.

Both vitamin B12 and folate are essential for proper DNA synthesis during red blood cell production. A deficiency in either impairs this process, resulting in larger, underdeveloped red blood cells that cannot function normally.

The most serious symptoms include neurological complications like severe confusion, memory loss, gait instability, and peripheral neuropathy, which can become permanent if a severe vitamin B12 deficiency is not treated promptly.

Diagnosis starts with a complete blood count (CBC) showing an elevated mean corpuscular volume (MCV > 100 fL). A healthcare provider will then perform further blood tests to check vitamin B12 and folate levels and look for other underlying causes.

Yes, in many cases, treating the underlying cause can resolve the condition. For example, supplementing with vitamin B12 or folate often reverses the anemia, while addressing issues like alcohol abuse or liver disease can also lead to improvement.

For macrocytic anemia caused by nutritional deficiencies, dietary modifications are key. This includes eating foods rich in vitamin B12 (like red meat, fish, and dairy) and folate (like leafy greens and fortified cereals).