Folic acid deficiency can arise from several causes. Recent data indicates that blood folate concentrations in the US population overall and in women have not decreased recently, and folate insufficiency rates are ∼20%.
Studies show that folic acid deficiency can occur after vitamin B-12 deficiency due to an impairment caused by methionine synthase, which results in the trapping of folate as methyltetrahydrofolate. Whereas, methylene THFA accumulates in serum leading to the folate trap phenomenon and increased urinary excretion of folate.
It is observed that folate is absorbed in the intestinal walls through the active and passive transport mechanisms. Therefore, diseases such as celiac disease, tropical sprue, short bowel syndrome, gastric bypass, or mesenteric vascular insufficiency can affect the intestinal walls which inhibits folate absorption resulting in a deficiency.
Folic acid and vitamin B9 refer to the same essential nutrient, but they are not identical in their forms or sources. Folic acid is the Synthetic form of vitamin B9, which is present in fortified foods and supplements and has a higher bioavailability than the naturally occurring form of vitamin B9, known as folate. The potent form of folic acid is tetrahydrofolate.
There are many other uses of folate, such as in the United States, it is added to grains to prevent congenital disabilities like neural tube defects. In addition to this, it is necessary for the formation of multiple coenzymes in many metabolic systems and maintenance in erythropoiesis.
What is Folic Acid?
Folic acid is also known as pteroylglutamic acid which is a water-soluble B-vitamin (B9). Folic acid is involved in the synthesis of genetic material DNA, cell division, and growth. It supports many important bodily functions and is essential for the human body.
Folic acid plays a significant role in one-carbon metabolism, where it acts as a donor and acceptor of single-carbon units in various biochemical reactions. Most importantly, folic acid plays a crucial role in the development of the embryos by protecting the neural tune in the postnatal period. It was published in the Journal of Nutrition that adequate folic acid intake before and during pregnancy can significantly reduce the risk of congenital anomalies.
Folic acid supports the function of other B vitamins, such as B12 and B6, and works alongside the conversion of homocysteine to methionine, which is vital for various metabolic processes. In the deficiency of folic acid, there is a disruption in the conversion of homocysteine, which can increase the risk of cardiovascular diseases.
It is observed that folic acid also plays a role in the production of red blood cells and the formation of S-adenosylmethionine (SAMe). SAMe is a compound involved in methylation reactions that regulate gene expression and neurotransmitter synthesis, hence folic acid also supports the proper functioning of the brain.
Mechanism of Action of Folic Acid
As mentioned above the scientific name of folic acid is pteroylmonoglutamic acid (C19H19N7O6), which plays a crucial role in neurotransmitter synthesis and overall brain function. In the body, the dihydrofolate reductase enzyme converts the folic acid into its active form tetrahydrofolate (THF). THF (C20H23N7O6) acts as a cofactor in various metabolic reactions, particularly in the synthesis of nucleotides and amino acids.
Folic acid influences neurotransmitter synthesis through its role in the one-carbon cycle. THF participates in the transfer of one-carbon units necessary for the methylation reactions, which is crucial for the synthesis of neurotransmitters such as serotonin, dopamine, and norepinephrine.
Then 5-methyltetrahydrofolate (5-MTHF) (a derivative of THF) donates a methyl group to homocysteine, which converts to methionine. At last, Methionine gets converted into S-adenosylmethionine (SAMe), which is a universal methyl donor and promotes methylation of neurotransmitters and their precursors.
Neurotransmitters like serotonin, dopamine, and norepinephrine are mood regulators and support the proper functioning of the brain. Folic acid increases the production of these neurotransmitters and therefore plays an important role in mood regulation. Due to folic acid deficiency, the production of neurotransmitters gets affected which results in depressive symptoms. Clinical studies have indicated that folic acid supplementation can enhance the efficacy of antidepressants, suggesting its role in the modulation of neurotransmitter pathways and neuroplasticity.
Natural Sources of Folic Acid
It is important to maintain adequate levels of folate (folic acid) in the body as it supports various important functions in the body such as healthy cell division and proper fetal growth. Folate or Vitamin B9 is naturally found in many foods, as well as in the form of folic acid in fortified foods. Researchers have suggested adults consume at least 400 mcg of folate per day to prevent folic acid deficiency.
Consuming folate from natural sources ensures better bioavailability and reduces the risk of deficiencies compared to synthetic supplements. A study published in The American Journal of Clinical Nutrition found that adequate folate intake from natural food sources is associated with a lower risk of neural tube defects and improved overall health outcomes.
Here are some of the natural sources of Folic acid:
Leafy Green Vegetables: Spinach, kale, and other leafy greens are rich in folate. Just one cup of raw spinach provides about 15% of the daily recommended intake of folate.
Citrus Fruits: Oranges, lemons, and grapefruits are excellent sources of folate. One medium-sized orange contains approximately 10% of the daily recommended value of folate.
Beans and Legumes: Lentils, chickpeas, and black beans are high in folate. A single cup of cooked lentils provides nearly 90% of the daily folate requirement.
Avocados: Avocados are not only delicious but also packed with folate. One whole avocado contains around 20% of the daily folate needs.
Nuts and Seeds: Nuts like almonds and seeds like sunflower seeds are good sources of folate. A quarter cup of sunflower seeds provides about 17% of the daily folate requirement.
Beets: Beets are known for their high folate content. One cup of raw beets can provide about 37% of the daily recommended intake of folate.
Brussels Sprouts: Brussels sprouts are another great source of folate. Half a cup of cooked Brussels sprouts offers about 12% of the daily folate requirement.
Asparagus: Asparagus is rich in folate, with one cup of cooked asparagus providing nearly 67% of the daily recommended value.
What is Folic Acid Deficiency?
Folic acid deficiency can also be referred to as folate deficiency, it occurs when there is an insufficient amount of folic acid in the body. Folic acid is involved in the production of red blood cells, and its deficiency can result in megaloblastic anemia, where the bone marrow produces abnormally large, immature red blood cells that cannot function properly. Due to this many important functions of the body are disrupted which leads to deficiency symptoms, such as fatigue, weakness, pallor, and shortness of breath.
Folic acid is important during pregnancy because it supports the developing embryo by protecting the neural tube. Therefore, the Journal of Obstetrics and Gynecology emphasizes the importance of folic acid supplementation for women of childbearing age to prevent these serious problems. Low levels of folate have been linked to cognitive impairments, mood disorders, and even dementia. Therefore, it is suggested by healthcare providers to take an adequate amount of folic acid to prevent deficiency and other serious health problems.
Does Folic Acid Deficiency Cause Depression?
Folic acid deficiency has been increasingly linked to the development of depression because folic acid is essential for proper brain function and neurotransmitter production. When folic acid levels are insufficient, it disrupts the production of neurotransmitters leading to deficiency of serotonin, dopamine, and norepinephrine, which are important for regulating mood.
According to a study published in the Journal of Affective Disorders found that individuals with folate deficiency were significantly more likely to exhibit symptoms of depression. It mentioned that SAMe is a major methyl donor in the brain and is involved in the synthesis of neurotransmitters. Its production is impaired by folate deficiency which increases the risk of depression. Therefore, adequate folic acid intake is not only vital for physical health but also for maintaining mental well-being.
Folic Acid Deficiency Causes
Folate is a water-soluble vitamin, which means it can easily dissolve in water and does not get stored in the fat cells. Therefore, it is important to keep taking folate through diet or supplements as the body can not develop a reserve. It is important to understand the causes of folic acid deficiency to prevent and manage the condition effectively.
Recommended Daily Intake of Folic Acid
The recommended daily intake (RDI) of Folic Acid varies by age, gender, and life stage:
- Infants (0-6 months): 65 mcg
- Infants (7-12 months): 80 mcg
- Children (1-3 years): 150 mcg
- Children (4-8 years): 200 mcg
- Children (9-13 years): 300 mcg
- Teens (14-18 years): 400 mcg
- Adults (19+ years): 400 mcg
- Pregnant Women: 600 mcg
- Breastfeeding Women: 500 mcg
Some of the causes of folic acid deficiency are mentioned below:
- Inadequate Dietary Intake: It is important to consume folic acid-rich foods, such as leafy greens, legumes, and fortified grains. Individuals with poor diets or limited access to nutritious food are particularly at risk.
- Malabsorption Disorders: Certain medical conditions hinder the absorption of folic acid through the digestive tract. Such as celiac disease, Crohn’s disease, and other gastrointestinal disorders. These disorders damage the inner lining of the intestine, which affects its absorption ability.
- Increased Requirements: Certain conditions require a higher amount of folic acid such as pregnancy, breastfeeding, and periods of rapid growth. These conditions require appropriate supplements along with a folic acid-rich diet.
- Alcoholism: Excessive alcohol consumption interferes with the absorption and metabolism of folic acid. It is important to avoid alcohol as it can cause other health problems as well.
- Medications: Some medications can interfere with folic acid metabolism or absorption. It is important to get a proper prescription from a healthcare provider because long-term use of these medications may necessitate supplementation to prevent deficiency.
- Genetic Variants: Sometimes genetic mutations cause changes in some genes that can impair the body’s ability to process folic acid effectively. Individuals with these mutations may require higher folic acid intake to maintain adequate levels.
- Medical Conditions: Some severe conditions like kidney disease and liver disease can affect the body’s ability to utilize folic acid properly. These conditions may necessitate medical intervention to manage folic acid levels.
- Hemolytic Anemia: This condition increases the destruction of red blood cells, which affects many important bodily functions. It also depletes the storage of folic acid, leading to folic acid deficiency.
Alcohol and Folic Acid Deficiency
Alcoholism is a significant cause of folate deficiency. Chronic alcohol intake interferes with the absorption, storage, metabolism, and excretion of folate. Alcohol mainly impairs the function of folate transporters in the intestine, which disrupts the absorption of folate through intestinal walls, leading to folic acid deficiency.
A study published in the American Journal of Clinical Nutrition highlighted that individuals with high alcohol consumption were diagnosed with lower levels of folate compared to non-drinkers, even when their dietary intake of folate was similar. This data indicates that alcohol and folic acid deficiency are linked to each other.
In addition to this, alcohol also affects the conversion of folic acid into its active form by impairing the liver’s ability. The liver is a primary site for folate storage and metabolism which becomes less effective in its function due to the hepatotoxic effects of alcohol. This can lead to a depletion of folate reserves and an overall reduction in folate availability for essential physiological functions, including DNA synthesis and repair.
How to test for Folic Acid Deficiency?
A folic acid test measures the levels of folic acid, or folate, in the blood. Individuals with chronic conditions need to keep a regular check on folic acid levels as its deficiency can affect many important functions.
Healthcare professionals also measure levels of other B vitamins, including vitamin B12 or vitamin B6, as these may affect folate absorption. Understanding folic acid and other B vitamin levels can help in better diagnosis and appropriate treatment. Early detection and intervention are key to managing and preventing the complications associated with folic acid deficiency.
The key steps to test for folic acid deficiency are mentioned below:
- Consultation with a Healthcare Provider: The first step in testing for folic acid deficiency is to discuss the deficiency symptoms and medical history with a healthcare provider. Symptoms such as fatigue, mouth sores, or feeling of sadness.
- Complete Blood Count (CBC): A CBC test is done to evaluate overall health to detect a variety of disorders, including anemia. A low hemoglobin level or abnormal red blood cell size can suggest a folic acid deficiency.
- Serum Folate Test: This blood test measures the level of folate in your blood. Low serum folate levels indicate the deficiency.
- Red Blood Cell Folate Test: This test is done to measure folate levels in red blood cells which provide a more accurate long-term indicator of folate levels in comparison to the serum folate test.
- Homocysteine Levels: Elevated homocysteine levels can be an indirect marker of folic acid deficiency because folate is involved in homocysteine metabolization. It is important to check homocysteine levels as it can also increase the risk of cardiovascular diseases.
- Vitamin B12 Test: It is observed that folic acid and vitamin B12 deficiencies can present with similar symptoms, so it is important to test for both to confirm concurrent deficiencies as it can help in getting an appropriate prescription.
- Dietary Assessment: It is important to consult with a nutritionist or healthcare provider to get a proper diet plan. It can help in overcoming deficiency and will help in alleviating the depressive symptoms.
- Medical Imaging: In certain cases, bone marrow biopsies might be performed if a severe deficiency or other underlying conditions are suspected. It is done only in complex cases, where initial tests are inconclusive.
Physical Symptoms of Folic Acid Deficiency
- Fatigue
- Weakness
- Pale skin
- Shortness of breath
- Mouth sores
- Swollen tongue
- Gastrointestinal issues
- Weight loss
Psychiatric Symptoms Folic Acid Deficiency
- Depression
- Irritability
- Cognitive decline
- Memory problems
- Difficulty concentrating
- Apathy
- Anxiety
- Sleep disturbances
Psychiatric Illness exacerbated by Folic Acid Deficiency
- Major depressive disorder
- Bipolar disorder
- Schizophrenia
- Anxiety disorders
- Obsessive-compulsive disorder
- Dementia
- Attention-deficit hyperactivity disorder (ADHD)
- Panic disorder
Medical Illness exacerbated by Folic Acid Deficiency
- Cardiovascular disease
- Anemia
- Neural tube defects in pregnancy
- Stroke
- Peripheral neuropathy
- Gastrointestinal disorders
- Chronic fatigue syndrome
- Osteoporosis
Consequences of Folic Acid Deficiency
Folic acid deficiency has many consequences, such as megaloblastic anemia, which affects many important functions of the body. Therefore, it is important to understand these consequences for prevention and early intervention.
Some of the consequences of folic acid deficiency are mentioned below:
- Megaloblastic Anemia: Studies show that folic acid deficiency leads to a condition characterized by the production of abnormally large and immature red blood cells known as megaloblastic anemia. Changes in shape affect the ability of red blood cells to carry oxygen, which can cause further problems in the body.
- Birth Defects: As mentioned above folic acid supports the growth of an embryo, therefore pregnant women with insufficient folic acid levels are at a higher risk of giving birth to babies with neural tube defects (NTDs). This affects the brain as well as the spinal cord, leading to severe physical and neurological impairments.
- Cardiovascular Issues: Folic acid deficiency interrupts the metabolization of homocysteine. Due to this homocysteine level increases in blood which increases the risk of cardiovascular problems. For example, it can damage, the inner lining of arteries, which promotes the formation of blood clots and atherosclerosis leading to heart attacks.
- Cognitive Impairment: Folic acid deficiency can also lead to cognitive impairments, including memory loss, difficulty concentrating, and an increased risk of dementia and Alzheimer’s disease, particularly in older adults.
- Depression and Mood Disorders: Folic acid has been linked to depression and other mood disorders. Due to its deficiency, the synthesis of neurotransmitters gets disrupted which further causes depressive symptoms and other mental health issues.
- Impaired Immune Function: Folic acid is important for the proper functioning of the immune system. It helps in the production and repair of DNA in white blood cells, which are essential for a functioning immune system. Folic acid deficiency can weaken the immune response, which can increase the risk of infections and illnesses.
- Growth and Development Issues in Children: It was observed that children with inadequate folic acid levels may experience poor growth and development. Folic acid is important for physical growth, cognitive development, and overall health.
- Digestive Problems: Folic acid deficiency can also cause digestive problems such as glossitis (inflammation of the tongue) and gastrointestinal disturbances. These impair the absorption of nutrients, leading to deficiency symptoms.
Folic Acid Deficiency Treatment
Folic acid deficiency treatment involves several steps to restore adequate levels and prevent associated complications. There are certain steps, by following which individuals can effectively treat folic acid deficiency and mitigate its adverse health effects.
Some of the steps for folic acid deficiency treatment are mentioned below:
- Dietary Changes: Incorporating folic acid-rich foods into your diet is a primary step in treating deficiency. For example, leafy green vegetables, legumes, nuts, seeds, and fortified grains. Ensuring these foods in the diet will help in increasing folic acid naturally in the blood.
- Folic Acid Supplements: In severe deficiency cases dietary changes alone may not be sufficient, in such conditions healthcare providers recommend folic acid supplements.
- Treating Underlying Conditions: Certain conditions that contribute to poor folic acid absorption are crucial. For example, celiac disease, Crohn’s disease, and other gastrointestinal disorders can hinder nutrient absorption. It is important to manage these conditions for the proper treatment.
- Monitoring and Follow-Up: It is important to monitor folic acid levels regularly, it helps to ensure that treatment is effective. Healthcare providers prescribe supplementation dosages according to the severity of the deficiency.
- Avoiding Alcohol: Reducing or eliminating alcohol consumption is important as chronic alcohol use can interfere with folic acid absorption and metabolism. Avoiding alcohol can help in folic acid absorption and will restore the folic acid levels in the body.
- Addressing Medication Interactions: Some medications can interfere with folic acid absorption or metabolism. It is important to consult with healthcare providers If you are taking these medications, your healthcare provider may need to counteract these effects.
- Prenatal Care: During pregnancy, it is important to take adequate levels of folic acid for the development of the embryo. Healthcare providers recommend prenatal vitamins containing folic acid to ensure sufficient intake during pregnancy and breastfeeding.
- Education and Counseling: It is important to educate patients about the importance of folic acid and how to incorporate it into their daily lives can help in maintaining long-term health.
Supplements for Folic Acid Deficiency
Treating folic acid deficiency through supplements is an effective way to improve health and prevent related complications. There are different routes through which supplements could be taken, such as tablets, multivitamins, prenatal vitamins, or B-complex vitamins. It is important to ensure adequate intake of this essential nutrient.
Some of the supplements for folic acid deficiency are mentioned below:
- Folic Acid Tablets: Tablets are a type of oral supplement that comes in various dosages, typically ranging from 400 mcg to 1 mg. They are widely available over-the-counter and are often prescribed by healthcare providers for those with a confirmed deficiency. Studies show that folic acid tablets significantly improve folate status and can help prevent neural tube defects during pregnancy.
- Multivitamins: Multivitamin supplements contain a variety of essential vitamins and minerals, including folic acid. These are recommended for those individuals with multiple nutrient deficiencies.
- Prenatal Vitamins: It is specially designed for pregnant women because prenatal vitamins contain higher amounts of folic acid to support fetal development. Adequate folic acid significantly reduces the risk of neural tube defects and supports the overall health of both mother and baby.
- B-Complex Vitamins: These supplements include all the B vitamins, such as folic acid (B9). It is highly effective for those who might have deficiencies in multiple B vitamins. They support energy production, brain function, and cellular metabolism.
Key Steps for Supplementing Folic Acid
Effective supplementation can prevent the complications associated with folic acid deficiency, such as anemia and birth defects.
Some of the key steps and considerations for using supplements to address folic acid deficiency are mentioned below:
- Choosing the Right Supplement: The first step is selecting the appropriate folic acid supplement. It’s important to choose a supplement according to the body’s needs and preferences.
- Dosage and Administration: Determining the correct dosage is critical for effective treatment. As mentioned above standard adult dosages typically range from 400 to 800 micrograms daily, but higher doses may be prescribed for individuals with severe deficiencies or specific health conditions.
- Combination with Other Nutrients: Some folic acid supplements include additional vitamins and minerals, such as vitamin B12 and iron to cure. These are beneficial in cases where folic acid and vitamin B12 deficiencies coexist.
- Monitoring and Adjustments: Regular monitoring of folic acid levels through blood tests is important to track the effectiveness of supplementation.
- Bioavailability: It was observed that some individuals may benefit from methyl folate supplements, which are the active form of folic acid, especially those with genetic variations that affect folic acid metabolism.
- Lifestyle and Dietary Adjustments: Supplements are crucial for treatment but combining them with dietary changes can enhance overall nutrient intake.
- Special Populations: There are specific supplement doses that are recommended for certain types of populations, such as pregnant women, people with gastrointestinal disorders, and those on specific medications.
- Addressing Underlying Causes: Understanding and addressing the root causes of folic acid deficiency is essential for long-term management. This is an effective way of treating folic acid deficiency. There are some habits like excessive consumption of alcohol, that should be avoided, and if required help should be taken from a healthcare provider.
Toxicity from Folic Acid Supplementation
Folic acid supplements are safe when taken within recommended limits, high doses can mask vitamin B12 deficiency, promote tumor growth, and cause other adverse effects. According to research published in the American Journal of Clinical Nutrition, chronic high intake of folic acid supplements, particularly doses exceeding 1,000 micrograms per day, can lead to several health complications.
It is important to understand the potential risks associated with high-dose folic acid supplementation and it is important to consult a healthcare provider before starting any new supplement regimen.
Some of the key causes of folic acid toxicity and their impacts are mentioned below:
- Masking Vitamin B12 Deficiency: High levels of folic acid can mask the hematological symptoms of vitamin B12 deficiency, such as megaloblastic anemia. This can delay the diagnosis and treatment of B12 deficiency which leads to severe neurological damage, as the neurological effects of B12 deficiency progress even in the presence of folate.
- Promoting Cancer Growth: Studies show that excessive folic acid intake can increase the growth of pre-existing cancerous cells. Folate is involved in DNA synthesis and repair, potentially aiding the rapid division of cancer cells.
- Immune System Disruption: High doses of folic acid can disrupt normal immune function because it can interfere with the activity of natural killer cells, which are crucial for the body’s defense against tumors and virally infected cells, this increases the risk of infections and malignancies.
- Negative Effects on Cognitive Function: Excessive folate levels can affect cognitive health. High folic acid levels might exacerbate cognitive decline in older adults, particularly those with low levels of vitamin B12, highlighting the delicate balance required in folate supplementation.
- Potential Cardiovascular Risks: Excessive supplementation might have adverse cardiovascular effects. Some studies reported in the Journal of the American College of Cardiology, suggest that high doses of folic acid could lead to an increased risk of heart disease.
- Gastrointestinal Disturbances: High folic acid intake can cause gastrointestinal issues such as nausea, bloating, and cramps. These symptoms are often mild but can become severe with long-term excessive consumption, which impacts the overall digestive health.
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