Anaemia – Vitamin B12 and Folate Deficiency

Vitamin B12 deficiency anaemia and folate deficiency anaemia causing the body to produce abnormally large red blood cells.

Tiredness, fatigue and lethargy can ensue.

Introduction

The main symptoms of vitamin B12 deficiency or folate deficiency anaemia are:

• tiredness
• lethargy (lack of energy)

Anaemia

There are several different types of anaemia, and each one has a different cause. This article focuses on anaemia that is caused by a lack of vitamin B12 or folate in the body.

This article also covers pernicious anaemia (an autoimmune condition where the body’s immune system attacks cells in the stomach), which is the most common cause of vitamin B12 deficiency.

The most common type of anaemia is iron deficiency anaemia, which occurs when the body does not contain enough iron to produce red blood cells.

Vitamin B12 and folate

Vitamin B12 and folate work together to help the body produce red blood cells. They also have several other important functions:

• vitamin B12 helps to keep the nervous system (brain, nerves and spinal cord) healthy
• folate is important for pregnant women because it reduces the risk of birth defects in unborn babies

Vitamin B12 is found in:

• meat
• eggs
• dairy products

The best source of folate is green vegetables such as:

• broccoli
• Brussel sprouts
• peas

How common is vitamin B12 deficiency or folate deficiency?

Both vitamin B12 deficiency and folate deficiency are more common in older people, affecting around 1 in 10 people above the age of 75. Vitamin B12 deficiency is rare in younger people, although those who follow a strict vegan diet (a diet that only contains food from plants) may be more at risk.

Pernicious anaemia, which is the most common cause of vitamin B12 deficiency, affects 1 in 10,000 people in northern Europe.

Outlook

Vitamin B12 deficiency anaemia can be treated with vitamin B12 supplements. Vitamin B12 is usually given by injection every other day for two weeks, followed by tablets, until the deficiency is under control.

Folate deficiency anaemia can be treated with folate supplements. Folic acid tablets are used to restore folate levels, which usually need to be taken for four months.

Depending on the underlying cause of a vitamin B12 or folate deficiency, dietary improvements can prevent the condition returning, or supplements may need to be taken for life.

Blood

Blood contains a clear fluid called plasma which contains three different types of cells:

• white blood cells – are part of the body’s immune system and defend it against infection
• red blood cells – carry oxygen around the body in a substance called haemoglobin
• platelets – help the blood to clot

Haemoglobin

Haemoglobin acts as a transport mechanism for the blood. As blood passes through the lungs, the haemoglobin pulls in oxygen molecules and releases carbon dioxide molecules.

After moving away from the lungs, the haemoglobin delivers the oxygen molecules to the body’s tissue, and it absorbs any excess carbon dioxide molecules to take back to the lungs.

Bone marrow

Red blood cells, which contain haemoglobin, are produced in the bone marrow (a red spongy material that is found inside the larger bones). Vast quantities (millions) of new blood cells are produced every day to replace old cells that break down.

Nutrients from food, such as iron and certain vitamins, ensure that your bone marrow remains healthy and able to produce a constant supply of red blood cells.

Symptoms of vitamin B12 or folate anaemia

The symptoms of each type of anaemia vary depending on the underlying cause of the condition. However, there are some general symptoms associated with all types of anaemia. These include:

• fatigue (extreme tiredness)
• lethargy (lack of energy)
• breathlessness (dyspnoea)
• faintness
• irregular heart beats (palpitations)
• headache
• tinnitus(the perception of a noise in one or both ears, or inside your head, which comes from inside your body for example, a ringing in your ears)
• loss of appetite

Vitamin B12 deficiency

If you have anaemia that is caused by a vitamin B12 deficiency, you may have the symptoms listed above, as well as:

• a yellow tinge to your skin (jaundice)
• a sore and red tongue (glossitis)
• ulcers inside your mouth
• an altered or reduced sense of touch
• a reduced ability to feel pain
• a change in the way that you walk and move around
• disturbed vision
• irritability
• depression: feelings of extreme sadness that last for a long time
• psychosis; a condition that affects your mind and changes the way you think, feel and behave
• dementia: a decline in your mental abilities, such as your memory, understanding and judgement

Folate deficiency

As well as the general symptoms of anaemia, a folate deficiency may also cause:

• loss of sensation, such as a reduced sense of touch or pain
• muscle weakness
• depression

Causes of vitamin B12 or folate deficiency anaemia

Vitamin B12 deficiency and folate deficiency can be caused by a number of different factors. These factors can cause anaemia because they affect the body’s ability to produce fully functioning red blood cells (cells that carry oxygen around the body).

Some possible causes of vitamin B12 deficiency and folate deficiency are described below.

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 (part of your digestive system that helps to digest food by mixing it with acids). An autoimmune condition is when the immune system (the body’s natural defence system that protects against illness and infection) starts to attack your body’s healthy cells.

Vitamin B12 is absorbed into your body through your stomach. The vitamin combines with a protein substance called intrinsic factor, which is produced in the stomach, so that it can be absorbed from the food that you eat.

Pernicious anaemia causes your immune system to attack the cells in your stomach that produce the intrinsic factor. This means that your body does not produce enough intrinsic factor and cannot absorb vitamin B12. This causes a deficiency in vitamin B12.

It is not known what triggers the immune system to attack the cells in this way, but there are some risk factors.

Risk factors

Pernicious anaemia may be more likely if:

• you are around 60 years of age – pernicious anaemia is most common at this age
• you are female – pernicious anaemia affects slightly more women than men
• you have a family history of the condition – nearly a third of people with pernicious anaemia also have a family member with the condition
• you have another autoimmune condition, such as Addison’s disease (a disorder that affects the adrenal glands) or vitiligo (a condition that causes pale patches of skin to develop) – there is an association between pernicious anaemia and other autoimmune conditions

Vitamin B12 deficiency

Vitamin B12 deficiency can also be caused by a number of other factors, although these are rare. Some possible causes are described below.

Diet

The body usually stores enough vitamin B12 to last for approximately two to four years. However, it is important to have vitamin B12 in your diet to ensure that the store is kept at a healthy level.

Most people will eat enough vitamin B12 by having a diet that includes meat, fish or dairy products. People who may not have enough vitamin B12 in their diet include vegans (people whose diet only contains food from plants) or those who have a very poor diet for a prolonged period of time.

Conditions affecting the stomach

Some stomach conditions, or procedures that are carried out on the stomach, can prevent it absorbing enough vitamin B12. For example, a gastrectomy (a surgical procedure where part of your stomach is removed) increases your risk of developing vitamin B12 deficiency anaemia.

Conditions affecting the intestines

Some conditions that affect your intestines (part of the digestive system) stop you from absorbing as much vitamin B12 as normal. For example, Crohn’s disease (a long-term condition that causes inflammation of the lining of the digestive system) can sometimes result in your body not having enough vitamin B12.

Medication

Some types of medicine can reduce the amount of vitamin B12 in your body. For example, proton pump inhibitors (PPIs) (a medication that treats 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 any medicines that can affect your vitamin B12 levels, and will monitor you if they think it is necessary.

Folate deficiency anaemia

Folate is a water-soluble vitamin (it dissolves in water), which means that your body is unable to store it for long periods of time. Your body’s stores of folate are usually enough to last for four months. This means you need to have folate in your daily diet to ensure that your body has sufficient stores of the vitamin.

Like vitamin B12 deficiency anaemia, folate deficiency anaemia can develop for a number of reasons. Some of these reasons are described below.

Diet

Some people do not have enough folate in their daily diet. This may be because:

• they have recently changed their diet – for example, to lose weight
• their diet is not healthy and balanced

Malabsorption

Sometimes your body may be unable to absorb folate as effectively as it should. This is usually the result of an underlying condition affecting your digestive system, such as irritable bowel syndrome (IBS) (a long-term disorder that causes abdominal pain, diarrhoea and constipation).

Excessive urination

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

• kidneys (two bean-shaped organs that filter the blood)
• liver (the largest organ in the body, performing many vital functions)

The following can all make you urinate frequently:

• congestive heart failure – where the heart is unable to pump enough blood around the body
• acute liver damage – which often occurs as a result of drinking excessive amounts of alcohol
• long-term dialysis – where a dialysis machine filters waste products from the blood

Medication

Some types of medicine can reduce the amount of folate in your body, or make the folate harder to absorb. Your GP will be aware of any medicines that can affect your folate levels and will monitor you if they feel that it is necessary.

Other causes

Sometimes, your body requires more folate than normal. This can cause folate deficiency because you cannot meet your body’s demands for the vitamin. Your body may need more folate than usual when you:

• are pregnant
• have cancer
• have a blood disorder, such as sickle cell anaemia (an inherited disorder that causes your blood cells to change shape)
• are fighting an infection or health condition that causes inflammation (redness and swelling)

Premature babies (babies born before week 37 of the pregnancy) are also more prone to developing folate deficiency anaemia because their developing bodies cannot meet the demand for the folate vitamin.

Pregnancy

If you are pregnant or planning to get pregnant, take a daily supplement of 0.4mg of folic acid until you are 12 weeks pregnant. This will ensure that both you and your baby have enough folate, and it will help your baby to 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
• health food stores

If you are pregnant and you also have another condition that may increase your body’s need for folate, such as those mentioned above, your GP will monitor you closely in order to prevent you from becoming anaemic.

In some cases, you may need to take a higher dose of folic acid. For example, if you have diabetes (a long-term condition that is caused by too much glucose in the blood) you should take a 5mg supplement of folic acid instead of the standard 0.4mg.

Diagnosing vitamin B12 or folate deficiency anaemia

In order to diagnose a vitamin B12 or folate deficiency, your GP will ask you to describe your symptoms and they will look carefully at your medical history. They may also carry out a physical examination.

Blood tests

If your GP suspects that you have vitamin B12 or folate deficiency anaemia, they will carry out a blood test to confirm the diagnosis. A blood sample will be taken from a vein in your arm, and a full blood count will be made. This means that all the different types of blood cells in the sample will be measured.

In particular, your GP will check:

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

If your test results indicate that you are deficient in either vitamin B12 or folate, it will help your GP to determine which type of anaemia you have.

Once your GP has determined that you have vitamin B12 or folate deficiency anaemia, they may have to carry out further tests to establish the underlying cause of your deficiency.

For example, vitamin B12 deficiency is most commonly caused by pernicious anaemia (see Vitamin B12 or folate deficiency anaemia – causes). This is a condition that causes your immune system (the body’s defence system) to attack cells in your stomach, which prevents your body absorbing vitamin B12.

If you have pernicious anaemia, your blood will contain the antibodies (proteins produced by the immune system to fight infections) that attack the stomach cells.

Once your GP has determined the underlying cause of your anaemia, they can give you with the most appropriate treatment (see Vitamin B12 or folate deficiency anaemia – treatment).

Referral

In some circumstances, you may be referred for further testing or treatment with a specialist. Some of the specialists you may be referred to are described below.

Haematologist

A haematologist is a doctor who specialises in treating blood conditions. If you are pregnant and have been diagnosed with vitamin B12 or folate deficiency anaemia, you will be referred to a haematologist. This is because a vitamin B12 or folate deficiency can sometimes affect the development of your baby.

You will also be referred to a haematologist if you have symptoms that suggest that your nervous system (the brain, nerves and spinal cord) has been affected by vitamin B12 or folate deficiency anaemia. These symptoms may include:

• a reduced or altered sense of touch and pain
• a change in your vision
• an inability to control your muscles

If the cause of your vitamin B12 or folate deficiency is unknown, or if a more serious underlying cause is suspected, you may also be referred to a haematologist so that they can carry out further investigations.

Gastroenterologist

A gastroenterologist is a doctor who specialises in conditions that affect the digestive system. You may be referred to a gastroenterologist if your GP suspects that you do not have enough vitamin B12 or folate because your digestive system is not absorbing it properly.

You may also be referred to a gastroenterologist if your GP suspects that you may have stomach cancer. For example, because you also have other symptoms such as:

• iron deficiency anaemia a lack of red blood cells that is caused by bleeding from the wall of your stomach)
• nausea (feeling sick)
• vomiting (being sick)

Dietitian

A dietitian is a healthcare professional who specialises in nutrition. They can give you advice about your diet and ways to change it in order to treat your condition.

You may be referred to a dietitian if you have vitamin B12 or folate deficiency that is thought to be caused by a poor diet. The dietitian can devise a personalised eating plan for you in order to increase the amount of vitamin B12 or folate in your diet

Treating vitamin B12 or folate deficiency anaemia

The treatment for vitamin B12 or folate deficiency anaemia will depend on what is causing the condition. The different treatments are outlined below.

Vitamin B12 deficiency anaemia

Vitamin B12 deficiency anaemia is usually treated with injections of vitamin B12. The vitamin is in the form of a substance known as hydroxocobalamin.

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

After the initial treatment, your dosage will depend on whether the cause of your vitamin B12 deficiency is:

• related to your diet
• not 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 vegans (people whose diet only contains food from plants), may need to take vitamin B12 tablets for life. For other people, your GP can stop your tablets once your vitamin B12 levels have returned to normal and your diet has improved.

Not diet related

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

If you have had neurological symptoms (symptoms that affect your nervous system, such as an altered sense of touch) because of vitamin B12 deficiency, you will be referred to a haematologist (a doctor who specialises in blood conditions). You may need to have injections every two months. Your haematologist will advise on how long you need to keep taking the injections.

Folate deficiency anaemia

To treat folate deficiency anaemia, your GP will usually prescribe daily folic acid tablets in order to build up your folate levels. They may also give you some dietary advice so that you can increase your folate intake (see box to the left).

Most people will need to take folic acid tablets for about four months. However, if the underlying cause of your folate deficiency anaemia is persistent, you may have to take folic acid tablets for a longer period, and maybe for life.

Before you start taking folic acid, your GP will check your vitamin B12 levels to make sure that they are normal. This is because folic acid treatment can sometimes improve your symptoms so much that is masks an underlying vitamin B12 deficiency. If a vitamin B12 deficiency is not detected and treated, it could affect your nervous system (brain, nerves and spinal cord).

Monitoring your condition

To ensure that your treatment is working, your vitamin B12 or folate levels will need to be closely monitored.

Around 10 days after starting treatment, you will need to have a blood test to check that your vitamin B12 or folate levels are starting to rise. You will need to have another blood test after approximately eight weeks to confirm that your treatment has been successful.

If you have 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 will not need further monitoring unless their symptoms return, or their treatment is ineffective. If your GP feels that it is necessary, you may have to return for an annual blood test to see whether your condition has returned.

Complications of vitamin B12 or folate deficiency anaemia

As most cases of vitamin B12 deficiency or folate deficiency can be easily and effectively treated, complications are relatively rare. However, in some cases, a deficiency of these vitamins can lead to complications, particularly if you have been deficient in vitamin B12 or folate for some time.

Anaemia complications

Anaemia, regardless of what it is caused by, can lead to some complications.

Tiredness

Anaemia can leave you feeling tired and lethargic (lacking in energy), so you may find that you are less productive and active at work. You may be less able to stay awake and focus, and you may not feel able to exercise regularly.

Heart and lung complications

Adults with severe anaemia are at risk of developing complications that affect their heart or lungs. For example, you may develop:

• tachycardia – an abnormally fast heart beat
• heart failure – where your heart does not pump blood around your body very efficiently

If your anaemia is severe, you may have to be admitted to hospital so that your heart and lungs can be carefully monitored.

Vitamin B12 deficiency complications

A lack of vitamin B12 can cause complications, some of which are outlined below.

Nervous system

A lack of vitamin B12 can affect your nervous system (the brain, nerves and spinal cord). For example, you may experience:

• vision problems
• memory loss
• paraesthesia(pins and needles) a prickling or tingling feeling in the arms, legs, hands or feet
• ataxia: the loss of physical coordination, which can affect your whole body and cause difficulty speaking or walking

Fertility

Vitamin B12 deficiency can sometimes affect your fertility and cause temporary sterility (an inability to conceive). However, this will only be temporary because vitamin supplements can reverse your sterility.

Neural tube defects

If you are pregnant, not having enough vitamin B12 can increase the risk of your baby developing a neural tube defect. Neural tube defects affect your baby’s growth and development. Examples of neural tube defects include:

• spina bifida – where the baby’s spine does not develop properly
• anencephaly – where the baby’s brain and skull bones do not develop properly

Folate deficiency complications

A lack of folate can cause complications, some of which are outlined below.

Fertility

As with a lack of vitamin B12, a folate deficiency can also affect your fertility. However, the effects are only temporary and can be reversed by using vitamin supplements.

Cardiovascular disease

Research has shown that a lack of folate in your body may increase your risk of cardiovascular disease. Cardiovascular disease is a term that describes a number of health conditions that affect:

• your heart
• your blood vessels
• the way blood circulates (flows) around your body

Cancer

Research has shown that folate deficiency can be linked to some cancers. A lack of folate is never the sole cause of a cancer developing, but it may be a contributory factor.

Neural tube defects

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

Premature birth

As well as affecting your baby’s growth, a lack of folate during your pregnancy may also increase the risk of your baby being born prematurely (before week 37 of the pregnancy).