What Is Folate Deficiency

Overview

Folate, also known as vitamin B9, is an essential water-soluble micronutrient.¹ This means that we do not store it in our body’s cells, and instead, excrete any excess in our urine. Folate is naturally found in many foods such as green, leafy vegetables, fruits, legumes, and liver.However, , we can also take folate supplements, which contain a manufactured version of it , called folic acid. A key difference between folate and folic acid is that the latter is significantly more bioavailable than folate, a word that  refers  to the degree and rate at which a substance (folic acid in our case) is absorbed into the body or is made available at the site of physiological activity. 

Folate plays a key role in DNA synthesis, gene expression, protein synthesis, and red blood cell synthesis,¹  which are all cornerstones in how our bodies are run and how our characteristics affect offsprings. Without the ability to store folate in our bodies, and if we do not consume enough, we are susceptible to developing a deficiency. This can develop within a few weeks,² and with the important role folate plays in our bodies, can have more serious consequences, if we do not restore our levels of folate. This article aims to cover causes, symptoms, treatments, diagnosis, potential risk factors, and consequences  of folate deficiency. 

Causes of folate deficiency

 Folate deficiency can develop within a few weeks,² for  a number of reasons, including: 

• Inadequate dietary intake: Folate is found in vegetables, especially green, leafy vegetables, fruits, legumes, and liver.¹ It is important to note that food processing can alter the amount of folate present in our food. Cooking and heating foods can destroy folate. In vegetables, this heat can destroy up to 40% of the folate present³
• Malabsorption: Folate is absorbed in our small intestines via active and passive transport mechanisms.² If, for any reason, absorption is defective, and despite how much folate you may have in your diet, you could develop a deficiency. This can occur due to excessive alcohol intake, or malabsorption syndromes including, among others, celiac disease or inflammatory bowel disease
• Increased folate demand: Folate plays a key role in foetal   development.³ Because of this, during pregnancy the  body requires an increased amount/intake to meet this demand. As a result, folate deficiency is common during pregnancy
• Medications: Certain medications can interfere with folate absorption and processing in the body, meaning that the amount of folate available in our diets is reduced, which can lead to  deficiency.² Such medications include aminopterin, methotrexate, pyrimethamine, trimethoprim, triamterene, anticonvulsants, and antituberculosis drugs⁴
• Genetics: Hereditary folate malabsorption results from  genetic mutations in the genes responsible for coding the proteins involved in the transport of folate into the body at the interface of  the small intestine, thus facilitating its absorption.⁵ Individuals with these mutations are unable to effectively transport dietary folate into their bodies, resulting in the  deficiency

Signs and symptoms of folate deficiency

If you have  folate deficiency, you might not experience any signs or symptoms for up to 8-16 weeks.² You also might not notice the signs and symptoms immediately because they can be very subtle. The main ones to look out for are: 

• Fatigue or feelings of extreme tiredness 
• Grey hair 
• Mouth sores and ulcers
• Tongue swelling and inflammation

Folate deficiency often leads to the development of anaemia . This leads to other symptoms including: 

• Persistent fatigue 
• Pale skin 
• Shortness of breath 
• Irritability 
• Muscle weakness

Some of these signs and symptoms can also occur because of  vitamin B12 deficiency, so it is important, if you think you have anaemia, to  see a doctor and receive the  accurate diagnosis in order to be treated effectively. 

Management of folate deficiency

Depending on the cause of deficiency, treatment can be short-term or long-term. So, if you are suffering from folate deficiency due to a genetic condition, such as hereditary folate malabsorption, you will require long-term/life-long treatment. If the deficiency is simply caused by an inadequate dietary intake, then taking folate supplements for approximately four months is usually sufficient to treat the condition. 

The first line of  treatment of folate deficiency is usually supplementing folic acid,² which is a synthetic version of folate. This form of  vitamin is more bioavailable than folate, meaning our bodies can absorb and process it more easily, and subsequently, deficiency can be  more effectively treated.¹ 

Folate supplements are often taken orally. However, if this is not possible, they  can be given intravenously, subcutaneously, or intramuscularly. A supplement containing 1-5 mgs of folic acid is usually enough to treat folate deficiency.  

The recommended daily intake of folate is 200 ug for an adult. Folate is naturally found in many fruits and vegetables, but many grains and cereals can also be fortified with folate or folic acid to help you reach your recommended daily intake. 

However, treating folate-deficiency should include a diet rich in folate-containing foods to ensure meeting the body needs/demands. So to  help treat and manage folate deficiency, and  prevent it at the same time,  from recurring, you should look to include some of the following foods into your diet: 

• Green, leafy vegetables (e.g., broccoli, spinach)
• Peas
• Brussels sprouts
• Asparagus
• Mushrooms
• Citrus fruits
• Bananas
• Melons
• Beans
• Legumes
• Eggs
• Fortified cereals
• Wheat Bran
• Liver meat

Prognosis of  dietary folate deficiency is usually very positive.² However, it can contribute to the onset of other more serious and potentially irreversible conditions, so early diagnosis and treatment are  vital. These other conditions include:²

• Macrocytic anaemia  
• Atherosclerotic disease
• Issues during pregnancy: Neural tube defects, spontaneous abortion, placental abruption, and language deficits in the offspring

Diagnosis

If you experience any symptoms related to a folate deficiency it is important you see your doctor to gain an accurate diagnosis for the most effective treatment. A diagnosis is usually made based on the symptoms you are experiencing as well as a blood test.² Because folate is important for the synthesis of red blood cells, folate deficiency often leads to anaemia  and changes in your blood cell counts. Your blood can also show your serum levels of folate. Normal levels of serum folate are greater than 4 ng/mL,  and you  are considered clinically folate deficient if your serum folate levels are below 2 ng/mL.² A complete blood count and peripheral blood smear test are  used to determine this. 

Risk factors

There are several factors that can increase your risk of developing  folate deficiency. Research has shown that the elderly, women in the childbearing  age, and non-black Hispanic women are at the greatest risk of developing this vitamin deficiency from an inadequate intake.²

Several conditions can also increase your risk of developing a folate deficiency, including:²

• Bariatric surgery 
• Malnutrition 
• Chronic Alcohol use 
• Chronic Haemolytic anaemia 
• Celiac disease
• Tropical Sprue 
• Short Bowel Syndrome 
• Amyloidosis
• Gastric Bypass
• Mesenteric Vascular Insufficiency 
• Achlorhydria 
• Congenital deficiencies that affect folate metabolism 
• Pregnancy
• Dialysis 

Medications used to treat other conditions can also increase your risk of developing a folate deficiency if they also impact folate absorption and metabolism in the body. Examples of these medications are:⁴

• Methotrexate
• Phenytoin
• Sulfasalazine
• Trimethoprim 
• Aminopterin
• Pyrimethamine
• Triamterene
• Anticonvulsants
• Antituberculosis drugs 

If you have a greater risk of developing  folate deficiency, it is important to talk to your doctor about preventative measures. A diet rich in folate-containing foods  can help to reduce your risk of developing a deficiency. Your doctor might also recommend you take a folic acid supplement to help reach your daily recommended intake of folate. An excess of folate can also cause negative effects, ⁶ so, doing so it is important to discuss whether you need to take a supplement with your doctor. 

Consequences 

While it is uncommon for a folate deficiency to lead to more serious conditions, it can happen, especially if you have been deficient for some time. These conditions include: 

• Megaloblastic anaemia² 
• Peripheral Neuropathy
• Temporary infertility 
• Heart Disease¹
• Pregnancy complications and Birth defects (called neural tube defects)
  • Spina bifida: A condition that affects the development of the baby’s central nervous system, including both the spinal cord and the brain
  • Anencephaly: A condition where the baby’s skull and brain development  is impaired in the womb, often leading to a stillbirth

• Cancer: A meta-analysis has shown that  folate deficiency in some populations is associated with a greater risk of developing cancers of the head, neck, oral cavity, pharynx, pancreas, oesophagus , bladder, and cervix.⁶ Importantly, genetics also play a role in this, although research is still needed to fully understand this relationship. 

FAQs

How can I prevent folate deficiency

To help lower your risk of developing folate deficiency, you should consume a diet rich in folate-containing  foods (these mostly consist of green, leafy vegetables, fruits, fortified cereals, and liver). If you are pregnant, it is recommended that you take a folate supplement. 

How common is folate deficiency

​​Folate deficiency affects approximately 1 in 20 individuals aged 65-74 and 1 in 10 individuals aged 75 and older. 

When should I see a doctor

You should see a doctor if you think you are experiencing any symptoms of  folate deficiency. 

Summary

Folate is an essential vitamin found in many fruits and vegetables. It plays an important role in our bodies, so while uncommon, folate deficiency can cause serious health issues. While the prognosis for a folate deficiency is usually very positive, and the treatment often involves taking an oral supplement, it is important to see a doctor as soon as possible if you experience any symptoms.