Overview

Vitamin B12 or B9 (commonly called folate) deficiency anaemia occurs when a lack of vitamin B12 or folate causes the body to produce abnormally large red blood cells that can't function properly.

Red blood cells carry oxygen around the body using a substance called haemoglobin.

Anaemia is the general term for having either fewer red blood cells than normal or having an abnormally low amount of haemoglobin in each red blood cell.

There are several different types of anaemia, and each one has a different cause. For example, iron deficiency anaemia, which occurs when the body doesn't contain enough iron.

Title
Vitamin B12 or folate deficiency anaemia

Symptoms

Vitamin B12 or folate deficiency anaemia can cause a wide range of symptoms. These usually develop gradually but can worsen if the condition goes untreated.

Anaemia is where you have fewer red blood cells than normal or you have an abnormally low amount of a substance called haemoglobin in each red blood cell. General symptoms of anaemia may include:

Symptoms of vitamin B12 deficiency

If you have anaemia caused by a vitamin B12 deficiency, you may have other symptoms, such as:

  • a pale yellow tinge to your skin
  • a sore and red tongue (glossitis)
  • mouth ulcers
  • pins and needles (paraesthesia)
  • changes in the way that you walk and move around
  • disturbed vision
  • irritability
  • depression
  • changes in the way you think, feel and behave
  • a decline in your mental abilities, such as memory, understanding and judgement (dementia)

Some of these symptoms can also occur in people who have a vitamin B12 deficiency, but have not developed anaemia.

Symptoms of folate deficiency

Additional symptoms in people with anaemia caused by a folate deficiency can include:

  • symptoms related to anaemia
  • reduced sense of taste
  • diarrhoea
  • numbness and tingling in the feet and hands
  • muscle weakness
  • depression
Causes

Vitamin B12 or folate deficiency anaemia occurs when a lack of either of these vitamins affects the body's ability to produce fully functioning red blood cells.

Red blood cells carry oxygen around the body. Most people with vitamin B12 or folate deficiency anaemia have underdeveloped red blood cells that are larger than normal. The medical term for this is "megaloblastic anaemia".

A vitamin B12 or folate deficiency can be the result of a variety of problems, such as:

Causes of vitamin B12 deficiency Pernicious anaemia

Pernicious anaemia is the most common cause of vitamin B12 deficiency in the UK.

Pernicious anaemia is an autoimmune condition that affects your stomach. An autoimmune condition means your immune system (the body's natural defence system that protects against illness and infection) attacks your body's healthy cells.

In your stomach, vitamin B12 is combined with a protein called intrinsic factor. This mix of vitamin B12 and intrinsic factor is then absorbed into the body in part of the gut called the distal ileum.

Pernicious anaemia causes your immune system to attack the cells in your stomach that produce the intrinsic factor, which means your body is unable to absorb vitamin B12.

The exact cause of pernicious anaemia is unknown, but the condition is more common in women around 60 years of age, people with a family history of the condition and those with another autoimmune condition, such as Addison's diseaseor vitiligo.

Diet

Some people can develop a vitamin B12 deficiency as a result of not getting enough vitamin B12 from their diet.

A diet that includes meat, fish and dairy products usually provides enough vitamin B12, but people who don't regularly eat these foods – such as those following a vegan diet or who have a generally very poor diet – can become deficient.

Stores of vitamin B12 in the body can last around two to four years without being replenished, so it can take a long time for any problems to develop after a dietary change.

Conditions affecting the stomach

Some stomach conditions or stomach operations can prevent the absorption of enough vitamin B12.

For example, a gastrectomy (a surgical procedure where part of your stomach is removed) increases your risk of developing a vitamin B12 deficiency.

Conditions affecting the intestines

Some conditions that affect your intestines can also stop you from absorbing the necessary amount of vitamin B12.

For example, Crohn's disease (a long-term condition that causes inflammation of the lining of the digestive system) can sometimes mean your body doesn't get enough vitamin B12.

Medication

Some types of medicine can lead to a reduction in the amount of vitamin B12 in your body.

For example, proton pump inhibitors (PPIs) – a medication sometimes used to treat indigestion – can make a vitamin B12 deficiency worse. PPIs inhibit the production of stomach acid, which is needed to release vitamin B12 from the food you eat.

Your GP will be aware of medicines that can affect your vitamin B12 levels and will monitor you if necessary.

Functional vitamin B12 deficiency

Some people can experience problems related to a vitamin B12 deficiency, despite appearing to have normal levels of vitamin B12 in their blood.

This can occur due to a problem known as functional vitamin B12 deficiency – where there's a problem with the proteins that help transport vitamin B12 between cells. This results in neurological complications involving the spinal cord.

Causes of folate deficiency

Folate dissolves in water, which means your body is unable to store it for long periods of time. Your body's store of folate is usually enough to last four months. This means you need folate in your daily diet to ensure your body has sufficient stores of the vitamin.

Like vitamin B12 deficiency anaemia, folate deficiency anaemia can develop for a number of reasons, including:

Diet

Good sources of folate include broccoli, Brussels sprouts, asparagus, peas, chickpeas and brown rice. If you don't regularly eat these types of foods, you may develop a folate deficiency.

Folate deficiency caused by a lack of dietary folate is more common in people who have a generally unbalanced and unhealthy diet, people who regularly misuse alcohol and people following a fad diet that doesn't involve eating good sources of folate.

Malabsorption

Sometimes your body may be unable to absorb folate as effectively as it should. This is usually due to an underlying condition affecting your digestive system, such as coeliac disease.

Excessive urination

You may lose folate from your body if you urinate frequently. This can be caused by an underlying condition that affects one of your organs, such as:

  • congestive heart failure – where the heart is unable to pump enough blood around the body
  • acute liver damage – often caused by drinking excessive amounts of alcohol
  • long-term dialysis – where a machine that replicates the kidney function is used to filter waste products from the blood
Medication

Some types of medicine reduce the amount of folate in your body, or make the folate harder to absorb.

These include some anticonvulsants (medication used to treat epilepsy), colestyramine, sulfasalazine and methotrexate.

Your GP will be aware of medicines that can affect your folate levels and will monitor you if necessary.

Other causes

Your body sometimes requires more folate than normal. This can cause folate deficiency if you can't meet your body's demands for the vitamin.

Your body may need more folate than usual if you:

  • are pregnant
  • have cancer
  • have a blood disorder – such as sickle cell anaemia (an inherited blood disorder which causes red blood cells to develop abnormally)
  • are fighting an infection or health condition that causes inflammation (redness and swelling)

Premature babies (born before the 37th week of pregnancy) are also more likely to develop a folate deficiency, because their developing bodies require higher amounts of folate than normal.

Pregnancy

If you're pregnant or trying to get pregnant, it's recommended that you take a 400 microgram folic acid tablet every day until you're 12 weeks pregnant. This will ensure that both you and your baby have enough folate and help your baby grow and develop.

Folic acid tablets are available with a prescription from your GP, or you can buy them over the counter from pharmacies, large supermarkets and health food stores.

If you're pregnant and have another condition that may increase your body's need for folate, your GP will monitor you closely to prevent you from becoming anaemic.

In some cases, you may need a higher dose of folic acid. For example, if you have diabetes, you should take a 5 milligrams (5mg) supplement of folic acid instead of the standard 400 micrograms.

Diagnosis

A diagnosis of vitamin B12 or folate deficiency anaemia can often be made by your GP based on your symptoms and the results of blood tests.

Blood tests

Different types of blood tests can be carried out to help identify people with a possible vitamin B12 or folate deficiency. These tests check:

  • whether you have a lower level of haemoglobin (a substance that transports oxygen) than normal
  • whether your red blood cells are larger than normal
  • the level of vitamin B12 in your blood
  • the level of folate in your blood

However, some people can have problems with their normal levels of these vitamins or may have low levels despite having no symptoms. This is why it's important for your symptoms to be taken into account when a diagnosis is made.

A particular drawback of testing vitamin B12 levels is that the current widely-used blood test only measures the total amount of vitamin B12 in your blood.

This means it measures forms of vitamin B12 that are "active" and can be used by your body, as well as the "inactive" forms, which can't. If a significant amount of the vitamin B12 in your blood is "inactive", a blood test may show that you have normal B12 levels, even though your body can't use much of it.

There are some types of blood test that may help determine if the vitamin B12 in your blood can be used by your body, but these aren't yet widely available.

Identifying the cause

If your symptoms and blood test results suggest a vitamin B12 or folate deficiency, your GP may arrange further tests. If the cause can be identified, it will help to determine the most appropriate treatment.

For example, you may have additional blood tests to check for a condition called pernicious anaemia. This is an autoimmune condition (where your immune system produces antibodies to attack healthy cells), which means you're unable to absorb vitamin B12 from the food you eat.

Tests for pernicious anaemia aren't always conclusive, but they can often give your GP a good idea of whether you have the condition.

Referral to a specialist

You may be referred to a specialist for further tests or treatment. This may include:

  • a haematologist (specialist in treating blood conditions) – if you have vitamin B12 or folate deficiency anaemia and your GP is uncertain of the cause, you're pregnant or symptoms suggest your nervous system has been affected
  • a gastroenterologist (specialist in conditions that affect the digestive system) – if your GP suspects you don't have enough vitamin B12 or folate because your digestive system isn't absorbing it properly
  • a dietitian (specialist in nutrition) – if your GP suspects you have a vitamin B12 or folate deficiency caused by a poor diet  
  • A dietitian can devise a personalised eating plan for you to increase the amount of vitamin B12 or folate in your diet.
Treatment

The treatment for vitamin B12 or folate deficiency anaemia depends on what's causing the condition. Most people can be easily treated with injections or tablets to replace the missing vitamins.

Treating vitamin B12 deficiency anaemia

Vitamin B12 deficiency anaemia is usually treated with injections of vitamin B12, in a form called hydroxocobalamin.

At first, you'll have these injections every other day for two weeks, or until your symptoms have started improving. Your GP or nurse will give the injections.

After this initial period, your treatment will depend on whether the cause of your vitamin B12 deficiency is related to your diet. The most common cause of vitamin B12 deficiency in the UK is pernicious anaemia, which isn't related to your diet.

Diet-related

If your vitamin B12 deficiency is caused by a lack of the vitamin in your diet, you may be prescribed vitamin B12 tablets to take every day between meals. Alternatively, you may need to have an injection of hydroxocobalamin twice a year.

People who find it difficult to get enough vitamin B12 in their diets, such as those following a vegan diet, may need vitamin B12 tablets for life.

Although it's less common, people with vitamin B12 deficiency caused by a prolonged poor diet may be advised to stop taking the tablets once their vitamin B12 levels have returned to normal and their diet has improved.

Good sources of vitamin B12 include:

  • meat
  • salmon and cod
  • milk and other dairy products
  • eggs

If you're a vegetarian or vegan, or are looking for alternatives to meat and dairy products, there are other foods that contain vitamin B12, such as yeast extract (including Marmite), as well as some fortified breakfast cereals and soy products.

Check the nutrition labels while food shopping to see how much vitamin B12 different foods contain.

Not diet-related

If your vitamin B12 deficiency isn't caused by a lack of vitamin B12 in your diet, you'll usually need to have an injection of hydroxocobalamin every three months for the rest of your life.

If you've had neurological symptoms (symptoms that affect your nervous system, such as numbness or tingling in your hands and feet) caused by a vitamin B12 deficiency, you'll be referred to a haematologist, and you may need to have injections every two months. Your haematologist will advise on how long you need to keep taking the injections.

For injections of vitamin B12 given in the UK, hydroxocobalamin is preferred to an alternative called cyanocobalamin. This is because hydroxocobalamin stays in the body for longer.

If you need regular injections of vitamin B12, cyanocobalamin would need to be given once a month, whereas hydroxocobalamin can be given every three months.

Cyanocobalamin injections aren't routinely available on the NHS. However, if you need replacement tablets of vitamin B12, these will be cyanocobalamin.

Treating folate deficiency anaemia

To treat folate deficiency anaemia, your GP will usually prescribe daily folic acid tablets to build up your folate levels. They may also give you dietary advice so you can increase your folate intake.

Good sources of folate include:

  • broccoli
  • Brussels sprouts
  • asparagus
  • peas
  • chickpeas
  • brown rice

Most people need to take folic acid tablets for about four months. However, if the underlying cause of your folate deficiency anaemia continues, you may have to take folic acid tablets for longer – possibly for life.

Before you start taking folic acid, your GP will check your vitamin B12 levels to make sure they're normal. This is because folic acid treatment can sometimes improve your symptoms so much that it masks an underlying vitamin B12 deficiency.

If a vitamin B12 deficiency isn't detected and treated, it could affect your nervous system.

Monitoring your condition

To ensure your treatment is working, you may need to have further blood tests.

A blood test is often carried out around 10-14 days after starting treatment to assess whether treatment is working. This is to check your haemoglobin level and the number of the immature red blood cells (reticulocytes) in your blood.

Another blood test may also be carried out after approximately eight weeks to confirm your treatment has been successful.

If you've been taking folic acid tablets, you may be tested again once the treatment has finished (usually after four months).

Most people who have had a vitamin B12 or folate deficiency won't need further monitoring unless their symptoms return, or their treatment is ineffective. If your GP feels it's necessary, you may have to return for an annual blood test to see whether your condition has returned.

Complications

As most cases of vitamin B12 deficiency or folate deficiency can be easily and effectively treated, complications are rare.

However, complications can occasionally develop, particularly if you've been deficient in either vitamin for some time.

Anaemia complications

All types of anaemia, regardless of the cause, can lead to heart and lung complications as the heart struggles to pump oxygen to the vital organs.

Adults with severe anaemia are at risk of developing:

  • an abnormally fast heart beat (tachycardia)
  • heart failure – where the heart fails to pump enough blood around the body at the right pressure
Complications of vitamin B12 deficiency

A lack of vitamin B12 (with or without anaemia) can cause the following complications:

Neurological changes

A lack of vitamin B12 can cause neurological problems (issues affecting your nervous system), such as:

If neurological problems do develop, they may be irreversible.

Infertility

Vitamin B12 deficiency can sometimes lead to temporary infertility (an inability to conceive). This usually improves with appropriate vitamin B12 treatment.

Stomach cancer

If you have a vitamin B12 deficiency caused by pernicious anaemia (a condition where your immune system attacks healthy cells in your stomach), your risk of developing stomach cancer is increased.

Neural tube defects

If you're pregnant, not having enough vitamin B12 can increase the risk of your baby developing a serious birth defect known as a neural tube defect. The neural tube is a narrow channel that eventually forms the brain and spinal cord.

Examples of neural tube defects include:

  • spina bifida – where the baby's spine doesn't develop properly
  • anencephaly – where a baby is born without parts of the brain and skull
  • encephalocele – where a membrane or skin-covered sac containing part of the brain pushes out of a hole in the skull
Complications of folate deficiency

A lack of folate (with or without anaemia) can also cause complications, such as:

Infertility

As with a lack of vitamin B12, a folate deficiency can also affect your fertility. However, this is only temporary and can usually be reversed with folate supplements.

Cardiovascular disease

Research has shown a lack of folate in your body may increase your risk of cardiovascular disease (CVD).

CVD is a general term that describes a disease of the heart or blood vessels, such as coronary heart disease (CHD).

Cancer

Research has shown that folate deficiency can increase your risk of some cancers, such as colon cancer.

Problems in childbirth

A lack of folate during pregnancy may increase the risk of the baby being born prematurely (before the 37th week of pregnancy) or having a low birthweight.

The risk of placental abruption may also be increased. This is a serious condition where the placenta starts to come away from the inside of the womb wall, causing tummy (abdominal) pain and bleeding from the vagina.

Neural tube defects

As with a vitamin B12 deficiency, a lack of folate can also affect an unborn baby's growth and development in the womb (uterus). This increases the risk of neural tube defects such as spina bifida developing in the unborn baby.