Folate Deficiency Anemia

What is folate deficiency anemia?

In folate deficiency anemia, you have a lower than normal number of red blood cells and these cells are abnormally large. These differences lead to a reduced amount of oxygen circulating in your blood. Over time, having less oxygen in your blood can make you feel weak, tired or cold.

Folate deficiency anemia results from not having enough folate (vitamin B9) in your body.

How does folate deficiency anemia occur?

Red blood cells start as stem cells in the spongy area inside of your bones called bone marrow. As red blood cells develop, they enter your bloodstream and carry oxygen to all of the organs and tissues in your body.

Folate is a nutrient that’s essential for the development of healthy red blood cells. When your body doesn’t have enough folate, your bone marrow produces unusually large red blood cells called megaloblasts.

Because megaloblasts are so large, they may not make it out of your bone marrow and into your bloodstream. Those that do enter your bloodstream usually don’t live as long as healthy red blood cells. Together, these factors decrease the number of red blood cells you have, causing anemia.

What are the types of anemia?

Anemia is a common condition that occurs due to a shortage of healthy red blood cells. There are many reasons why people develop anemia, including:

• Abnormally large red blood cells.
• Decreased production of healthy red blood cells.
• Increased destruction of red blood cells by your liver and spleen.
• Low levels of hemoglobin, a protein inside red blood cells that binds to oxygen.
• Poorly functioning hemoglobin that doesn’t bind to oxygen the way it should.
• Rupture of red blood cells circulating in your bloodstream.

Macrocytic anemia is a broad category of anemias that result from abnormally large red blood cells. One type of macrocytic anemia is megaloblastic anemia, which has several subtypes, including:

• Folate deficiency anemia.
• Vitamin B12 deficiency anemia.
• Pernicious anemia.

Other common types of anemia include:

• Iron deficiency anemia.
• Sickle cell anemia.

How common is folate deficiency?

Folate deficiency is rare in developed countries where many foods have added folate. In 1998, the U.S. Food and Drug Administration (FDA) began requiring folate fortification in foods because of the important role it plays in fetal development.

Healthcare providers have linked folate deficiency to congenital conditions (present at birth), especially neural tube defects such as spina bifida. Because of this, you’ll find folate added to many of the foods you eat, including grain and rice products.

Who is most at risk of developing folate deficiency anemia?

Risk factors for folate deficiency anemia include:

• Assigned female at birth (AFAB) and childbearing age.
• Excessive alcohol use.
• Older age (over 60).
• Poverty.
• Pregnancy and breastfeeding (chestfeeding).

What causes folate deficiency anemia?

Folate deficiency anemia can occur if you don’t get enough folate in your diet. Other causes include conditions that prevent your body from absorbing or using folate, such as:

• Alcohol use disorder.
• Dialysis treatment for kidney failure.
• Digestive diseases, including Crohn’s disease and celiac disease.
• Drugs such as some antiseizure, antirheumatic, antibiotic and immunosuppressant medications.
• Hereditary folate malabsorption, an inherited disorder that affects your body’s ability to absorb folate.

What are the symptoms of folate deficiency anemia?

Folate deficiency anemia can occur without any symptoms. Your healthcare provider may find that you’re anemic when doing routine lab testing.

When symptoms occur, they may include:

• Tiredness (fatigue).
• Weakness in muscle strength during your daily activities.
• Lightheadedness or feeling like you might faint.
• Pale skin (pallor).
• Racing, pounding or missed heartbeats (heart palpitations).
• Shortness of breath (dyspnea).

How is folate deficiency anemia diagnosed?

A healthcare provider will perform a physical exam and review your medical history and symptoms. Because the symptoms of folate deficiency anemia look like many other health problems, providers order blood tests to make a clear diagnosis.

Lab tests may include:

• Complete blood count (CBC): Evaluates the number of red blood cells, white blood cells and platelets, and the amount of hemoglobin in your blood.
• Peripheral blood smear (PBS):Shows the size and shape of your blood cells under a microscope.
• Reticulocyte count: Measures the immature red blood cells (reticulocytes) in your bone marrow to determine if you’re producing enough red blood cells.

Your provider will also check your blood folate levels and evaluate the levels using this scale:

• Deficient: Less than 2 nanograms per milliliter (ng/mL).
• Borderline: Between 2 ng/mL and 4 ng/mL.
• Sufficient: Greater than 4 ng/mL.

Because vitamin B12 deficiency and folate deficiency can occur together, providers will also usually do a vitamin B12 blood test.

How is folate deficiency anemia treated?

Vitamin B9 supplements are the main treatment. You usually take them by mouth. If you can’t swallow pills, you may receive vitamin B9 through a shot or an intravenous (IV) line. You’ll need to take supplements for at least several months.

Your provider may also recommend changes to your diet. If you have an underlying condition that’s causing the deficiency, you’ll receive treatment for that condition.

Can I prevent folate deficiency anemia?

There are several ways to prevent folate deficiency anemia:

• Make sure you get enough folate through your diet or by taking a dietary supplement containing vitamin B9 (folic acid).
• Reduce the amount of alcohol you consume. Excessive alcohol use may prevent your body from absorbing the nutrients you need, including folate.
• Talk to your healthcare provider if you have a condition that prevents your body from absorbing or using folate.

How much folate (vitamin B9) do I need?

Folate is the form of vitamin B9 found in foods, while folic acid is the form in enriched foods and supplements. The daily recommended values for folate vary by:

• Age: You need more folate as you get older.
• Dietary source: Your body absorbs folic acid better than folate.

The recommended daily allowances (RDAs) are in micrograms (mcg) of dietary folate equivalents (DFEs) where:

• 1 mcg folate from a food source = 1 mcg DFE.
• 1 mcg folic acid from fortified foods or dietary supplements consumed with foods = 1.67 mcg DFE.
• 1 mcg folic acid from dietary supplements taken on an empty stomach = 2 mcg DFE.

For example, if you take a multivitamin with 200 mcg folic acid on an empty stomach, you can count that as 400 mcg DFE (200 mcg x 2 = 400 mcg).

According to the Food and Nutrition Board at the National Academies of Sciences, Engineering and Medicine, the RDAs for folate are:

Which foods should I eat to get enough folate in my diet?

Foods rich in folate include:

• Meat: Beef liver.
• Green vegetables: Spinach and other leafy greens, asparagus, Brussels sprouts, avocado and broccoli.
• Fortified foods: Cereal, rice, bread, pasta, flour and cornmeal.
• Beans: Black-eyed peas and kidney beans.
• Nuts: Peanuts and walnuts.
• Fruits: Citrus fruits and juices.

What is the outlook for folate deficiency anemia?

Treatment for folate deficiency anemia is usually successful. Within several months of taking or receiving vitamin B9 supplements, most people start producing healthy red blood cells again and their symptoms improve.

When should I talk to a healthcare provider about folate deficiency anemia?

Talk to your healthcare provider if you:

• Aren’t sure how much folate you need or how to make sure you’re getting enough each day.
• Experience any anemia symptoms, such as fatigue, weakness or shortness of breath.
• Have a condition that could cause folate deficiency.
• Received treatment for folate deficiency anemia and notice your symptoms returning.
• Plan to become pregnant or are pregnant.

A note from Cleveland Clinic

Discovering an issue with your blood cells can be startling. Symptoms are your body’s way of letting you know something is off. They could reflect a need for a more balanced diet or an underlying condition. Your healthcare provider will work with you to figure out what’s causing your condition. They’ll recommend a vitamin B9 supplement and other treatment options if you have a condition that’s causing folate deficiency anemia. With effective treatment and regular follow-up care, your symptoms will most likely resolve.