Folic acid is a synthetic variant of vitamin B9 that is frequently incorporated into fortified foods and dietary supplements. This nutrient offers a variety of health benefits, although it may also carry some risks. As a water-soluble vitamin, folic acid is a manufactured form of folate, one of the essential B vitamins. Since your body is incapable of synthesizing folate independently, it is crucial to obtain it through your diet. Folate can naturally be found in various foods, while folic acid is typically added to others. Additionally, you can acquire folic acid through dietary supplements.

What distinguishes folate from folic acid?

While “folate” and “folic acid” are often used interchangeably, they represent different forms of the same vitamin: vitamin B9. Folic acid possesses a unique structure compared to folate and exhibits slightly varying effects within your body. Folate serves as the umbrella term for all vitamin B9 varieties, encompassing both folic acid and 5-MTHF, whereas folic acid specifically refers to the synthetic form of this vitamin.

Folate can be sourced from various plant and animal foods, including:

• spinach (palak)
• kale (kela)
• broccoli (hari gobhi)
• avocado (makhanphal)
• citrus fruits (citron)
• eggs (anda)
• beef liver (beef ka jigar)

Folic acid is commonly added to products such as flour, ready-to-eat cereals, and breads. Additionally, it is found in dietary supplements, including multivitamins.

What role does folate play in the body?

Your body utilizes folate for several critical functions:

• to create and repair DNA
• to support cell growth, division, and proper functioning
• to synthesize specific proteins
• to aid in the maturation of red blood cells

A deficiency in folate can lead to numerous health issues, such as:

• anemia
• an elevated risk of heart disease and certain cancers
• developmental abnormalities in infants if pregnant individuals do not consume adequate folate

Many nations, including India, Canada, and Australia, mandate that specific grain products be fortified with folic acid. Such fortification significantly aids in preventing neural tube defects in newborns.

Recommended Intake Levels

The Recommended Dietary Allowance (RDA) for folate is expressed in Dietary Folate Equivalents (DFEs), a measurement that reflects the varying degrees to which the body absorbs folate from natural foods as opposed to folic acid found in fortified products and dietary supplements. Notably, your system typically absorbs natural folate at roughly half the efficiency compared to folic acid sourced from supplements.

For adults, a daily intake of approximately 400 mcg DFE of folate is essential. This requirement can increase significantly during pregnancy and lactation, where the RDA rises to 600 mcg DFE. It's crucial for expectant and nursing mothers to meet these elevated folate needs for the health of both themselves and their infants.

The body can store between 15 to 30 mg of folate, predominantly in the liver, with additional amounts circulating in the blood and residing in tissues.

The RDA for folate varies across different life stages, particularly for infants, children, and adolescents:

• Birth to 6 months: 65 mcg DFE
• Ages 7–12 months: 80 mcg DFE
• Ages 1–3: 150 mcg DFE
• Ages 4–8: 200 mcg DFE
• Ages 9–13: 300 mcg DFE
• Ages 14–18: 400 mcg DFE

Advantages and Applications

Both folic acid and folate serve essential roles in dietary supplements. While these two nutrients address similar health concerns, they are metabolized distinctly within the body, leading to varying health impacts.

Below are several notable applications and advantages of folic acid supplements.

Treating Folate Deficiency

Folate deficiency can arise from numerous factors. Some common causes include:

• insufficient folate intake in your diet
• medical conditions or surgical procedures that interfere with folate absorption, such as celiac disease, short bowel syndrome, and gastric bypass
• absence of stomach acid (achlorhydria) or low stomach acid (hypochlorhydria)
• medications that hinder folate absorption, including methotrexate and sulfasalazine (Azulfadine)
• alcohol dependency
• pregnancy
• hemolytic anemia
• dialysis treatment

Inadequate folate consumption can lead to health issues such as anemia, complications in fetal development, cognitive decline, weakened immune response, and depression. Supplementing with folic acid or folate can help elevate your levels and avert these potential complications.

Preventing Birth Defects and Complications During Pregnancy

Folic acid supplements are instrumental in preventing neural tube defects, including spina bifida and anencephaly. Adequate intake of folic acid during pregnancy is vital in reducing the risk of your baby being born with these conditions. Moreover, folic acid not only aids in preventing fetal development issues but also helps mitigate the risk of complications during pregnancy, such as preeclampsia.

Supporting Cognitive Health

Low levels of folate in the bloodstream are associated with diminished cognitive function and a heightened risk of dementia. Even folate levels that fall within the normal range but are on the lower side may elevate the risk of cognitive decline in older adults.

Ensuring sufficient folate intake may also serve as a protective measure against Alzheimer’s disease. In a 2019 study involving 180 adults with mild cognitive impairment, daily consumption of 400 mcg of folic acid over two years resulted in improved cognitive measures and a decrease in blood levels of proteins linked to Alzheimer’s disease.

Another study focused on 121 individuals newly diagnosed with Alzheimer’s who were undergoing treatment with the medication donepezil (Aricept). Those who also supplemented with 1,250 mcg of folic acid daily for six months experienced enhancements in cognitive ability and reduced inflammation compared to those solely on Aricept.

Addressing Mental Health Conditions

Folate plays a crucial role in the synthesis of brain chemicals known as neurotransmitters. Insufficient folate levels have been correlated with conditions such as depression, schizophrenia, and other mental health disorders.

For instance, individuals suffering from depression often exhibit lower blood folate levels than those without depression. A 2022 review of various studies suggests that folic acid and folate supplements might alleviate symptoms associated with mental health issues, including postpartum depression, schizophrenia, and bipolar disorder. Supplementing with folate alongside antidepressants may enhance the effectiveness of depression treatment compared to antidepressants alone.

A review encompassing seven studies indicated that combining folate supplements with antipsychotic medications may yield greater symptom improvement in individuals with schizophrenia than treatment with antipsychotics alone. However, further extensive research is warranted to substantiate these findings.

Lowering Heart Disease Risk Factors

Folate-based supplements, including folic acid, may contribute positively to cardiovascular health and diminish heart disease risk. Elevated homocysteine levels are believed to pose an increased risk for heart disease. Since folate assists in breaking down homocysteine, low folate levels can lead to elevated homocysteine levels, known as hyperhomocysteinemia. Folic acid supplements can help reduce homocysteine levels, potentially lowering heart disease risk.

For example, a comprehensive review that analyzed 30 studies with over 80,000 participants found that supplementation with folic acid resulted in a 4% reduction in overall heart disease risk and a 10% decrease in stroke risk. Additionally, combining folic acid supplements with antihypertensive medications may lead to a more significant reduction in high blood pressure compared to antihypertensives alone. Folic acid supplements might also enhance vascular function in individuals with heart disease.

Other Potential Benefits

Folic acid supplements may also be beneficial for the following health conditions:

• Diabetes: Folate supplementation may enhance blood sugar management and lower insulin resistance in individuals with diabetes. Since the diabetes medication metformin can diminish folate levels, supplementation may be necessary for those experiencing low levels.
• Fertility Challenges: Folate can enhance egg quality and promote egg growth and implantation in the uterus. Increased folate intake may improve the chances of conception and successful pregnancy. Individuals utilizing assisted reproductive technology may have a higher likelihood of conception with elevated supplemental folate intake.
• Reducing Inflammation: Inflammation is implicated in numerous health conditions. Folic acid and folate supplementation have been shown to lower inflammation markers such as C-reactive protein.
• Kidney Disease: Healthy kidneys typically filter waste from the bloodstream; however, when damaged, homocysteine can accumulate. About 85% of individuals with chronic kidney disease exhibit elevated homocysteine levels. Folic acid supplements may help lower homocysteine levels and reduce heart disease risk in this population.

Further large-scale studies are necessary to validate the advantages of folate supplementation. This list is not exhaustive, as there are many additional reasons individuals may choose to utilize folate-based supplements.

Consult with a Healthcare Professional

Prior to initiating folic acid supplementation, it is essential to consult with a healthcare professional. They can ensure that the supplements will not interact adversely with any other medications you may be taking. Folic acid supplements are widely recommended to prevent fetal development problems in pregnant individuals. Low folate levels pose health risks, and deficiencies in this vital nutrient may stem from various medical conditions.

Folic Acid and Its Importance During Pregnancy

Folate is crucial for a baby’s growth and development, playing vital roles throughout pregnancy.

This essential nutrient is significantly involved in cell division and tissue growth, especially in the formation of the neural tube, which encompasses the baby’s brain and spine. Consuming folic acid before conception and during pregnancy can greatly help in preventing neural tube defects such as anencephaly and spina bifida.

The U.S. Preventive Services Task Force, a group of renowned experts dedicated to national disease prevention, strongly advises that individuals planning to conceive should begin taking a daily folic acid supplement containing 400–800 mcg at least one month prior to pregnancy and continue through the initial 2–3 months of gestation.

In practice, it is often recommended that anyone of childbearing age—particularly those who are sexually active and could become pregnant—should take a folic acid supplement, as many pregnancies occur unexpectedly. Since the 1990s, various food products, including flour, have been fortified with folic acid. Incorporating both fortified foods and folic acid supplements into the diet before and during pregnancy can effectively diminish the risk of neural tube defects. Apart from its role in preventing developmental issues in the fetus, folic acid supplementation during pregnancy may enhance a child’s cognitive abilities and potentially lower the risk of autism spectrum disorder (ASD).

However, it’s important to note that excessive intake of folic acid could negatively impact brain development in children and may increase their likelihood of developing autism, a topic that will be addressed in the following section.

Folate additionally promotes the health of the pregnant individual. Research has indicated that adequate folic acid intake can minimize the risk of pregnancy-related complications, including preeclampsia, while higher folate levels in pregnant individuals can potentially decrease the chances of preterm birth.

Genetic Variations Impacting Folate Levels

When you consume folic acid, your liver is tasked with converting it into its active form, 5-methyltetrahydrofolate (5-MTHF). If this conversion process is sluggish, excess folic acid may accumulate in your bloodstream. To mitigate this issue, incorporating foods rich in 5-MTHF rather than relying solely on folic acid is advisable.

Foods abundant in 5-MTHF include a variety of options such as:

• leafy greens (palak, methi)
• beans and lentils (dal)
• asparagus (shatavari)
• avocado (makhanphal)

Genetic variations can influence how effectively your body metabolizes folate. The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in the breakdown of homocysteine. Mutations in the MTHFR gene can significantly impact your health by altering folate levels within your body.

One prevalent mutation is known as C677T. Individuals carrying this variant often experience reduced activity of the enzyme responsible for decomposing homocysteine, potentially leading to elevated homocysteine levels, which in turn heightens the risk of heart disease.

For pregnant individuals, this genetic variant may also elevate the risk of neural tube defects in the developing fetus, making it a significant health consideration. While genetic testing for MTHFR variants is available, it is not commonly necessary for most individuals.

It is important to note that having an MTHFR mutation does not automatically indicate a risk for health complications or imply that treatment is required. However, if a healthcare professional observes elevated homocysteine levels, they might suggest a supplement as a precaution.

Side Effects and Precautions

Incorporating foods rich in folate and utilizing natural forms of folate, like 5-MTHF, are widely regarded as safe practices. However, consuming excessive amounts of folic acid through supplements may lead to an accumulation of unmetabolized folic acid in the bloodstream.

The term “unmetabolized” indicates that the body has not processed the folic acid or transformed it into other folate forms. While no established health risks associated with unmetabolized folic acid have been identified, there remains a possibility of undiscovered risks . It is essential to recognize that the majority of children and adults in countries like India and Canada obtain sufficient folate from their diet, rendering folic acid supplementation unnecessary.

Autism

Supplementing with folic acid during pregnancy is instrumental in preventing neural tube defects. However, elevated levels of unmetabolized folic acid in the bloodstream might heighten the likelihood of Autism Spectrum Disorder (ASD) in offspring. Individuals consuming less than 400 mcg of folic acid daily are generally unlikely to experience elevated levels of unmetabolized folic acid in their blood. Moreover, high concentrations of unmetabolized folic acid during pregnancy could potentially influence the cognitive development of children.

A study involving 1,682 mother-child pairs revealed that children whose mothers ingested over 1,000 mcg of folic acid daily during pregnancy exhibited lower scores on cognitive ability tests compared to those whose mothers consumed between 400 and 999 mcg per day. While these findings raise concerns about high doses of folic acid during pregnancy, further investigations are essential to validate these observations.

Other Possible Risks of High Folic Acid Intake

Excessive consumption of folic acid may be linked to various health issues, including the following.

Cancer

Folic acid may reduce the risk of certain cancers, particularly those affecting the head and neck, pancreas, esophagus, and bladder; however, it may also elevate the risk of prostate cancer. Current research has not provided definitive conclusions, necessitating further studies. Interestingly, while folate may inhibit certain cancer types in their initial stages, high doses of folic acid consumed post-development of precancerous cells could potentially promote cancer growth and progression.

Impaired Immune Function

High-dose folic acid supplements could potentially suppress the immune system by diminishing the functionality of protective immune cells, including natural killer (NK) cells. The implications of these immune alterations on infection susceptibility remain uncertain. Overall, studies indicate that high folic acid intake may correlate with a range of health concerns, such as cancer, autism, and immune system suppression.

How to Take

Folate and its synthetic counterpart, folic acid, are available in a variety of forms. These nutrients are commonly incorporated into multivitamin and B-complex supplements. Typically, adult supplements provide 680–1,360 mcg DFE, equating to approximately 400–800 mcg of folic acid.

The Tolerable Upper Intake Level (UL) denotes the maximum daily dose of folic acid that can be ingested without leading to harmful side effects. This UL pertains exclusively to folate obtained from fortified foods and dietary supplements. Notably, excessive consumption of naturally occurring folate from food sources has not been associated with negative effects ().

The established UL for folate derived from supplements and fortified foods is as follows:

In countries like India and Australia, most children receive adequate folate through their diets. Nonetheless, data from the U.S. indicates that 30–66% of children aged 1–13 who consume folic acid supplements exceed the UL for their respective age groups. It is advisable to consult a pediatrician before administering a folic acid supplement to ensure safety. Folic acid can be taken at any time, with or without meals.

Before Taking Folic Acid

Consultation with a healthcare provider regarding folic acid supplements is recommended if you have a deficiency, are pregnant, or are planning to conceive. Inform your healthcare provider about all prescription and over-the-counter medications you are currently using, as folic acid may interact with certain drugs.

Storage and Handling

Store folic acid supplements in a cool, dry environment, avoiding exposure to humid areas like bathrooms.

Overdose

There is no defined upper limit for folate intake from food sources since folate is water-soluble, and the body naturally excretes any excess. However, adverse effects may occur if you consume folic acid supplements beyond the established UL. A healthcare professional may prescribe higher dosages if a folate deficiency is diagnosed. It is important to adhere to the UL unless specifically directed otherwise by a healthcare expert.

The maximum safe intake of folic acid and folate for adults from supplements and fortified foods is 1,000 mcg. Generally, children obtain sufficient folate through their dietary intake alone.

Interactions

It's important to be aware that folic acid supplements can interact with a variety of commonly prescribed medications. Some notable interactions include:

• Methotrexate, a medication often utilized in the treatment of certain cancers and autoimmune disorders.
• Epilepsy medications such as phenytoin (known as Dilantin), carbamazepine (marketed as Carbatrol, Tegretol, among others), and valproate (also referred to as Depacon).
• Sulfasalazine (branded as Azulfadine), which is typically prescribed for managing ulcerative colitis.

If you are currently using any of these medications, it is essential to consult your healthcare provider prior to starting folic acid supplements. Remember, folic acid supplements can indeed interact with certain medications.

Targeted Groups for Folate Supplementation

Folate supplements play a crucial role for specific groups of individuals, including those who:

• are pregnant or of childbearing age
• experience conditions that hinder folate absorption, like celiac disease or inflammatory bowel disease
• have genetic variations that influence their ability to metabolize and utilize folate
• are elderly individuals residing in care facilities
• are at an increased risk of folate deficiency due to dietary restrictions
• struggle with alcohol use disorder

It is important to refrain from administering folate supplements to infants under the age of one, unless specifically directed by a healthcare professional. For infants, breastmilk, formula, and food should serve as the sole sources of folate in their nutrition.

Individuals who are pregnant, of childbearing age, or diagnosed with folate deficiencies frequently turn to folic acid supplements for their nutritional needs.

Folate Options

Numerous forms of folate exist, with the most commonly utilized in dietary supplements being folinic acid, folic acid, and 5-methyltetrahydrofolate (5-MTHF). Each of these variants plays a significant role in nutritional health. Folinic acid, known as leucovorin in medical circles, is a natural folate found in various foods. Its primary purpose is to mitigate the toxic side effects associated with methotrexate, a medication often prescribed for certain cancer types. Interestingly, research indicates that folinic acid is more effective than folic acid in elevating blood folate concentrations.

Moreover, some studies have suggested that 5-MTHF has superior absorption rates compared to other synthetic folate forms, coupled with a lower likelihood of drug interactions. This points to the potential benefits of opting for 5-MTHF supplements over traditional folic acid. Nevertheless, other research has found no notable differences between these folate forms.

In summary, the primary types of folate frequently found in dietary supplements include folinic acid, folic acid, and 5-methyltetrahydrofolate (5-MTHF).