How do large red blood cells make you feel?

October 1, 2025 •

5 min read

According to a study cited by StatPearls, macrocytosis is estimated to affect 2% to 4% of the population, often leading to symptoms that can significantly impact daily life. The specific answer to how do large red blood cells make you feel? depends largely on whether the condition is accompanied by anemia and the underlying cause, ranging from mild fatigue to severe neurological issues.

Quick Summary

Large red blood cells, a condition called macrocytosis, may cause symptoms like fatigue, weakness, and paleness if it leads to anemia. Depending on the underlying cause, such as a vitamin deficiency, neurological issues like tingling and balance problems can also occur.

Key Points

Fatigue and Weakness: The most common symptom associated with large red blood cells, especially when it leads to anemia, is a persistent feeling of tiredness due to reduced oxygen transport.
Neurological Problems: A chronic vitamin B12 deficiency can cause severe neurological symptoms, including numbness or tingling, balance issues, and cognitive difficulties like memory loss.
Cause-Specific Symptoms: The specific symptoms, such as jaundice in liver disease or a sore tongue in B12 deficiency, are tied to the underlying condition and not just the cell size.
Diagnostic Testing: Macrocytosis is detected through a routine complete blood count (CBC) test, which measures the mean corpuscular volume (MCV), and is followed by further bloodwork to identify the cause.
Symptom-Free Macrocytosis: It is possible to have large red blood cells without experiencing any noticeable symptoms, especially if there is no anemia present.
Reversibility: In many cases, especially those caused by nutritional deficiencies or alcohol, treating the underlying cause can resolve the macrocytosis and alleviate symptoms.

What are large red blood cells (macrocytosis)?

Large red blood cells, a condition known as macrocytosis, are identified during a routine complete blood count (CBC) test. The test measures the mean corpuscular volume (MCV), and a result above 100 femtoliters (fL) in adults indicates macrocytosis. Macrocytosis is not a disease itself but rather a sign of an underlying medical condition. While some people with large red blood cells may not experience any symptoms, especially in cases without anemia, others can have noticeable effects on their well-being.

The most common cause of macrocytosis is a deficiency in vitamin B12 or folate (vitamin B9). These two nutrients are essential for the production of healthy, mature red blood cells. Without them, the red blood cells cannot divide properly and become abnormally large and oval-shaped. In addition to nutritional deficiencies, other potential causes include liver disease, alcohol use disorder, certain medications, and myelodysplastic syndrome.

Symptoms of macrocytic anemia

When large red blood cells are also accompanied by a low red blood cell count (anemia), symptoms are much more likely to appear due to the reduced ability to transport oxygen throughout the body. The severity of symptoms can vary, and they often progress gradually.

Fatigue and Weakness: This is one of the most common and noticeable symptoms. A lack of oxygen circulating in the body's tissues can leave you feeling extremely tired and weak, even after resting.
Pale Skin: A reduced number of red blood cells carrying hemoglobin can lead to a paler complexion than usual, which is often visible on the skin and inner eyelids.
Shortness of Breath: With less oxygen being delivered to the tissues, the heart and lungs may have to work harder, causing breathlessness, especially during physical activity.
Heart Palpitations: The heart may beat faster or irregularly to compensate for the lower oxygen levels, leading to a noticeable sensation of a pounding heart.
Headaches and Dizziness: Insufficient oxygen reaching the brain can cause headaches and a lightheaded or dizzy feeling.

Specific symptoms by underlying cause

The specific set of symptoms you experience can offer clues about the root cause of your macrocytosis.

Vitamin B12 deficiency symptoms

A long-term deficiency of vitamin B12 can damage nerve cells, leading to a range of neurological symptoms. These may not be present in a folate deficiency, which is a key differentiator.

Numbness and Tingling: A characteristic sensation of pins and needles, particularly in the hands and feet.
Balance Problems: Damage to nerves can lead to difficulty with balance and coordination, sometimes resulting in a shaky gait.
Cognitive Issues: These can include memory loss, confusion, and problems concentrating. In severe, untreated cases, it can progress to dementia.
Mood Disturbances: Irritability, depression, and other psychological problems can occur.
Sore, Red Tongue (Glossitis): The tongue may appear smooth and inflamed.

Folate deficiency symptoms

While folate deficiency can cause many of the general anemia symptoms, its neurological effects are generally not as pronounced as those seen with a B12 deficiency.

Diarrhea or Constipation: Digestive problems are a common sign.
Reduced Appetite: A lack of interest in eating, sometimes leading to weight loss.
Irritability: Changes in mood are often reported.
Oral Symptoms: Besides a sore tongue, mouth ulcers may also develop.

Liver disease symptoms

Macrocytosis is often a sign of underlying liver disease, and the enlarged red blood cells can also have a different shape (round, not oval). The symptoms are related to the liver's declining function.

Jaundice: A yellowing of the skin and whites of the eyes.
Fatigue and Weakness: Similar to anemia, but caused by the liver's inability to function properly.
Swelling (Edema and Ascites): Fluid accumulation in the legs (edema) and abdomen (ascites).
Itchy Skin: A result of bile leakage into the bloodstream.
Easy Bruising or Bleeding: The liver produces clotting factors, and a decline in function can cause bleeding issues.

Distinguishing megaloblastic from non-megaloblastic macrocytosis

Healthcare providers use laboratory tests and a peripheral blood smear to differentiate between the types of macrocytosis, which guides the treatment plan.


Feature	Megaloblastic Macrocytosis	Non-Megaloblastic Macrocytosis
Common Causes	Vitamin B12 and folate deficiency	Alcohol use, liver disease, certain medications
Red Blood Cell Shape	Macro-ovalocytes (large, oval-shaped)	Round macrocytes
Neutrophil Morphology	Hypersegmented (more than 5 lobes)	Normal or abnormal, but not hypersegmented
Underlying Defect	Impaired DNA synthesis during cell division	Various mechanisms, including membrane changes
Associated Symptoms	Anemia, specific neurological and GI symptoms	Anemia, symptoms related to underlying condition

What to do if you feel these symptoms

If you are experiencing persistent fatigue, weakness, or any of the other symptoms associated with macrocytosis, it is crucial to consult a healthcare provider for a proper diagnosis. A simple blood test can measure your MCV and help identify the issue. Depending on the results, further tests may be needed.

How diagnosis is confirmed

Complete Blood Count (CBC): This initial blood test measures your MCV and identifies if anemia is present.
Peripheral Blood Smear: A technician examines a blood sample under a microscope to confirm the large cell size and evaluate the shape and other features, such as hypersegmented neutrophils, which can pinpoint the cause.
Vitamin Levels: Your doctor will order specific tests to check your vitamin B12 and folate levels in the blood.
Methylmalonic Acid (MMA) and Homocysteine: These are more specific metabolic tests that can help confirm a B12 or folate deficiency, especially when initial vitamin levels are borderline.
Liver Function Tests: A panel of blood tests to evaluate the health of your liver.
Bone Marrow Biopsy: In more complex cases, or when a myelodysplastic syndrome is suspected, a bone marrow biopsy may be performed to examine the blood cell production process.

Conclusion

Large red blood cells, or macrocytosis, can manifest in a variety of ways, from being completely asymptomatic to causing significant fatigue, weakness, and neurological problems. The specific feelings and symptoms are directly linked to the underlying cause, whether it's a nutritional deficiency, excessive alcohol consumption, liver disease, or another condition. Because the symptoms are so varied and can overlap with other health issues, proper diagnosis through a blood test is essential. Fortunately, for many common causes like vitamin deficiencies, treatment is straightforward and effective, and resolving the root issue typically leads to a full recovery and improvement of symptoms. Paying attention to your body and seeking medical advice for persistent symptoms is the most important step toward regaining your health.

Visit MedlinePlus for more information on the Mean Corpuscular Volume (MCV) blood test.

Frequently Asked Questions

The primary symptom of macrocytic anemia is fatigue and weakness, resulting from the inefficient transport of oxygen due to an insufficient number of large, dysfunctional red blood cells.

Yes, especially if the cause is a long-term vitamin B12 deficiency. The lack of this vitamin can lead to nerve damage, which manifests as numbness, tingling, and balance problems.

Yes, macrocytosis without anemia often produces no noticeable symptoms. The condition may only be discovered during routine blood tests that measure the red blood cell size.

Large red blood cells are typically detected during a complete blood count (CBC) when the mean corpuscular volume (MCV) is found to be elevated. Further tests, like checking vitamin B12 and folate levels, are then used to determine the cause.

Excessive alcohol consumption is a common cause of large red blood cells. It can interfere with nutrient absorption, including B12 and folate, and can also directly affect red blood cell production.

Megaloblastic macrocytosis is caused by impaired DNA synthesis, usually from a vitamin B12 or folate deficiency, and features specific blood cell shapes. Non-megaloblastic macrocytosis is caused by other conditions like liver disease or alcohol use and lacks these distinct cell characteristics.

In many cases, yes. For nutritional deficiencies, supplementation can correct the problem. If it is caused by alcohol use, abstaining can reverse the condition. Treating other underlying issues like liver disease can also lead to improvement.