FOLIC ACID: A NUTRIENT FOR ALL, SUPPORTING WELL-BEING FROM PREGNANCY TO BEYOND

Medically Reviewed by Dr. Rosmy Barrios - October 14, 2024

Folic acid is an essential component that is needed for many body functions. Folic acid is the synthetic form of vitamin B9 and Folate is the naturally-occurring form found in foods. Folic acid helps make and repair DNA, produce red blood cells, support cell growth and metabolism, and prevent certain birth defects. Most people know that folic acid is important for women who are pregnant or planning to become pregnant. What some may not realize is that folic acid remains a vital nutritional requirement beyond fetal development, and it poses benefits for both men and women, irrespective of pregnancy or fertility. 

 

In this blog post, we will look into some of the benefits of taking a folic acid supplement for men and women, as well as the symptoms of folic acid deficiency, the possible side effects of taking too much, how much folic acid one needs, and what forms are optimal.

Folic Acid Benefits

The benefits of folic acid far exceed avoiding neural tube defects during pregnancy. Vitamin B9 is required for DNA and RNA synthesis alongside vitamin B12. The main benefit of dietary folate or a folic acid supplement would be to prevent folic acid deficiency and, in so doing, lower homocysteine levels.

Homocysteine is a sulfur-containing amino acid that is an intermediate byproduct in the metabolism of the essential amino acid methionine.^[1] High homocysteine levels are present in many disease states, and some evidence suggests that keeping homocysteine in check can help to prevent their onset. These include high cholesterol levels, cardiovascular conditions like atherosclerosis, stroke, and cerebrovascular conditions. The main reason is the association of homocysteine with vascular damage, although it is not clear how homocysteine causes this or if homocysteine levels are just a reflection of B vitamin deficiency. Treating patients with folate, vitamin B12 and B6 is known to lower homocysteine.^[2]

Folic acid is also good for the following:

• Enhances mental well-being, mood, and cognitive function. Folic acid is associated with the production of neurotransmitters, such as serotonin, dopamine, and norepinephrine, which regulate mood, memory, and learning. Folic acid deficiency can cause depression, irritability, confusion, and cognitive decline. Folic acid supplementation can help improve mood and cognitive function^[3] and has been implicated as an important supplement for those with mood disorders and the elderly.
• Reduces the risk of anemia. Folic acid, together with cobalamin (vitamin B12), is necessary for the synthesis of red blood cells responsible for distributing oxygen throughout the body. Megaloblastic anemia is a form of anemia in which there are larger and fewer than normal red blood cells. This may result in symptoms like weakness, exhaustion, pale complexion, dyspnea, and palpitations in the heart. If folic acid is given in conjunction with vitamin B12, it can help prevent or treat this problem. Otherwise, folic acid can mask a B12 deficiency.
• Cancer prevention. Folate deficiency has been associated with carcinogenesis^[4], while supplementation of folate alongside other B vitamins can help to lower the risk of acquiring cancer and promote balanced cell growth.
• Improving insulin sensitivity. Low blood folate levels appear to be associated with a higher risk for insulin resistance, whereas higher levels may enhance insulin sensitivity.^[5]
• Supports healthy hair, skin, and nails. DNA and RNA synthesis depends on folic acid, making it essential for the growth and repair of tissues, including hair, skin, and nails. Not surprisingly, hair loss has been associated with folate deficiency, yet there is not enough evidence to recommend its use for treating or preventing serious alopecia (balding)^[6]. Folic acid can also help prevent premature graying of hair and improve the appearance of skin.

Can I Take Prenatal Vitamins if I Am Not Pregnant?

All prenatal vitamins are essential vitamins that we need to get from our diets for optimal health. Pregnancy is not essential to benefit from an essential vitamin supplement. It is safe for men and women of all ages to supplement with folate, provided it is taken in the correct form and amount.

Benefits of Folic Acid for Women

Folic acid has many benefits for women, whether they are pregnant or not. Vitamin B9 seems to work closely with female reproductive hormones to regulate tissue growth and regeneration. In recent years, health authorities have been asserting that all women should take a folic acid supplement due to being prone to deficiency, especially in less developed countries.^[7]

Some of the benefits of folic acid for women are:

• Reproductive health and hormones. Folate appears to regulate both estrogen and progesterone levels as well as their downstream effects in women of reproductive ages.^[8] Women on a folic acid supplement had higher progesterone levels during the luteal phase when it was supposed to peak, and this contributed towards menstrual stability and a lower risk for anovulation and associated fertility problems^[9].
• Menopause. Supplementing folic acid in menopause can help to alleviate some of the problematic symptoms in some women, such as hot flashes^[10], mood swings, lower libido, and painful intercourse^[11].
• Prevents cervical dysplasia. Cervical dysplasia is a condition where the cells of the cervix (the lower part of the uterus) become abnormal and potentially precancerous. Folic acid may help prevent cervical dysplasia by preventing DNA damage and promoting normal cell division in the cervix.^[12]
• Lowers the risk for cervical cancer. Low folate levels have been associated in multiple studies with an increased risk of cervical cancer.^[13]

Naturally, a folic acid supplement helps pregnant women accommodate the rapid growth that accompanies pregnancy, as well as helps prevent pre-eclampsia, preterm birth, neural tube defects, and other congenital problems.

Benefits of Folic Acid for Men

Folic acid is good not only for women. While the recommended daily intake is equal between men and women, some studies suggest that men may benefit from a higher intake of folate than women and that they may be more deficient^[14].

Some of the benefits of folic acid for men are:

• Boosts sperm quality and fertility. Folic acid is important for the production and maturation of sperm cells. Low sperm count, poor sperm motility, and increased sperm DNA damage^[15] are all consequences of deficiency that can impact fertility and raise the possibility of birth abnormalities in the offspring. It has been seen that folic acid supplementation increases sperm quality and quantity and increases the likelihood of successful in vitro fertilization for infertile men.
• Prevents prostate cancer. Prostate cancer is the most common cancer among men and one of the leading causes of cancer death. Folic acid may help prevent prostate cancer by preventing DNA damage and abnormal cell growth in the prostate gland.
• Supports muscle growth and performance. Folic acid can help increase the synthesis of proteins and the availability of amino acids for muscle tissue. It can also help reduce muscle fatigue and soreness after exercise.
• Protects against erectile dysfunction. Erectile dysfunction (ED) is a condition where a man has difficulty achieving or maintaining an erection. ED can have various causes, such as psychological, hormonal, vascular, or neurological factors. Folic acid can lower ED risk^[16], possibly by improving blood flow to the area, enhancing nitric oxide production, and reducing oxidative stress and inflammation.

Symptoms of Folate Deficiency

Symptoms of folate deficiency^[17] look almost identical to those of vitamin B12 deficiency, minus the neurological symptoms.

The main folic acid deficiency symptoms in adults include:

• Anemia. Both vitamin B-12 and folic acid deficiency can cause megaloblastic anemia, where the red blood cells are larger and fewer than normal. This can impair the delivery of oxygen to the tissues and organs and cause various symptoms, such as fatigue, weakness, pale skin, jaundice (yellowing of skin or eyes), shortness of breath, and heart palpitations.
• Mental health issues. Folic acid deficiency can also affect the function of the brain (cognitive impairment) and cause mental health issues, such as depression, anxiety, irritability, confusion, memory loss, dementia, and psychosis.

A swollen, inflamed tongue, skin disorders or related symptoms, and anorexia are other symptoms that might be present in someone with folate deficiency. If tested, higher than usual homocysteine levels may be present, yet they may also be normal if levels of other B vitamins are sufficient.

Risk Factors for Folic Acid Deficiency

Folate metabolism is a complicated yet crucial part of our overall health. Deficiency is most often thought to be caused by a lack of intake, yet even when supplementing folic acid or folate, there are several other nutrients that are required to ensure it can be used properly by the body.

Of these, vitamin B12 is one of the most important as it helps the active form of folate to function properly and lower homocysteine levels. When vitamin B-12 is deficient, folate remains inactive, even when converted into an optimal form, leading to pseudo deficiency and high homocysteine. ^[18]

Most of the other B vitamins enhance the action of folate in the body as well, including vitamins B6, B3, B2, and B1. This is why it is optimal to take a vitamin B complex that makes use of the active forms of each vitamin for the best results.

Other common risk factors for folic acid deficiency are:

• Consuming a low-folate diet
• Frequently consuming overcooked food and avoiding a balanced diet with complementary raw wholefoods.
• Alcoholism
• Dialysis or kidney failure
• Pregnancy
• Hemolytic anemia
• Digestive disorders or problems including IBS/IBD, celiac disease, tropical sprue, short bowel syndrome, amyloidosis, and gastric bypass.
• Elevated gut pH and low levels of digestive enzymes, stomach acids, and bile.
• The medications methotrexate, phenytoin, sulfasalazine, and trimethoprim can lower their conversion into active forms of folate, leading to deficiency.
• Inherited congenital enzyme deficiencies that impair its proper metabolism

Can Menopause Cause Folic Acid Deficiency?

It is not likely for menopause to cause a folate deficiency. Studies show that folate levels can become deficient roughly 15 years after menopause in elderly women^[19], which coincides with an increase in homocysteine and a higher risk for stroke, heart disease, and dementia. This is likely due to age-related changes.

How Much Folic Acid Do You Need?

The body holds between 1000-20 000 mcg of folate, and the recommended daily intake is about 400 mcg per day to replenish lost stores. However, the amount of folic acid you need may vary depending on your age, gender, health status, and lifestyle.

Supplements tend to offer folic acid in amounts that vary from 680 - 1360 mcg. The body absorbs roughly 85% of a folic acid supplement with food and nearly 100% without.^[20]

Folic Acid for Women

The usual dose is adequate for most women. Women planning to conceive and pregnant women need 600 mcg of folic acid per day. Breastfeeding women need 500 mcg of folic acid per day. There is no folic acid dosage for menopause. However, menopausal women may want to supplement with folic acid to maintain their health.

How Much Folic Acid Should A Man Take A Day?

Men who are having fertility problems, low sperm quality, or are attempting to conceive should take 400–800 mcg of folic acid daily, as this can help improve their sperm parameters and chances of fathering a healthy child. Recent research has begun to show that men absorb about 10% less folate than women and that their requirements may be higher due to having a larger body mass.^[21] Thus, healthy men may also wish to supplement 400 - 800 mcg of folate per day.

Folic Acid for Megaloblastic Anemia

People who have megaloblastic anemia or other conditions that cause folate deficiency should take 1 milligram (mg) of folic acid per day or as prescribed by their doctor. If signs of anemia are present, it is important to supplement with both folate and vitamin B12. Folate can mask the symptoms of cobalamin deficiency-induced anemia, yet it does not treat the underlying cause of the problem. Neglecting to treat a deficiency can lead to long-term health problems and complications.

Other Medical Conditions

People with certain medical conditions, such as kidney disease, liver disease, or malabsorption syndromes, may need higher doses of folic acid, such as 400 to 800 mcg daily. People who smoke, drink alcohol, or take certain medications, such as anticonvulsants, methotrexate, or sulfasalazine, may also need more folic acid, as these factors can interfere with the absorption or metabolism of folic acid.

Can One Take Too Much Folic Acid? Risks and Side Effects

Consuming folic acid in excess can lead to health problems, involving risks and side effects such as:

• Masking of vitamin B12 deficiency. This is the main adverse effect associated with a high folic acid intake. Folic acid corrects anemia symptoms, which might conceal the signs of a vitamin B12 shortage. However, folic acid cannot prevent the neurological damage caused by vitamin B12 deficiency, such as nerve damage, cognitive impairment, and dementia. Therefore, it is important to check your vitamin B12 levels before taking high doses of folic acid and to take both vitamins together if you are deficient in both.
• Digestive problems. Folic acid supplements may cause digestive problems, such as nausea, loss of appetite, bloating, gas, diarrhea, or constipation, in some people.
• Cancer risk. It seems that both low and high levels of folate can contribute to increasing the risk of cancer. In terms of high levels, cancer risk appears more connected to supplementing with very high doses of folic acid versus the active form 5-methyltetrahydrofolate.

Other side effects associated with a high folic acid intake across preliminary and animal studies include obesity and insulin resistance in children born from mothers who overdosed with folic acid during pregnancy^[22], increased risk of liver fibrosis in rats, lower immune cell activity in elderly women, higher risk for cancer of the retina in women who cannot metabolize folic acid (due to deletion in DHFR gene), and lower memory and cognition in elderly women (with the same DHFR gene mutation).^[23] These results are a few of many that have yet to be confirmed.

It is important not to overdose on any supplement and to be aware of any side effects that occur if taking an ordinary folic acid or folate dose, as it may mean you are more sensitive to folate.

Folic Acid Contraindications

A folic acid supplement is contraindicated for individuals allergic or sensitive to folic acid or any ingredients in the supplement. So far, there have not been any documented reactions towards folic acid, and the chances are very slim.

Various medications can inhibit the absorption or conversion of folic acid into its active form, as can several gene mutations. Those on the following medications ought to supplement folate as either tetrahydrofolate or 5-methyltetrahydrofolate^[24]:

• Large doses of NSAIDs (non-steroidal anti-inflammatory drugs)
• Anticonvulsants 
• Cholesterol-lowering drugs cholestyramine and colestipol
• Folate antagonists methotrexate, aminopterin, pemetrexed, pralatrexate, and raltitrexed
• Trimethoprim
• Pyrimethamine
• Triamterene
• Sulfasalazine
• High doses of oral contraceptives

Does a MFTHR Gene Variant 667C>T Increase the Risk for Folic Acid Toxicity?

When folic acid is metabolized by the body, it undergoes two prime transformations in the liver to turn into a form the body can use. In the first step, folic acid is changed to tetrahydrofolate by the enzyme dihydrofolate reductase. In the second step, it is converted into its active form 5-10- methylenetetrahydrofolate due to the enzyme methylenetetrahydrofolate reductase. When in this form, it can be used to lower homocysteine to produce methionine or to produce DNA.

The pathway that makes use of folic acid for DNA synthesis is known to recycle folic acid, making dietary folic acid requirements for DNA synthesis and repair very low. The same cannot be said for the folate used to lower homocysteine.^[25]

Some people carry a variant of the MTHFR gene known as 667C>T, which causes them to convert less active folate into the methionine-producing form that lowers homocysteine. This means that these people are at risk of folate deficiency, high homocysteine levels, and possibly cancer unless they take a supplement in the active form that handles homocysteine: 5-methyl-tetrahydrofolate (5-MTHF). This form has additional benefits, such as better absorption and less interaction with contraindicated medications^[26].

Food Sources of Folic Acid

By consuming foods high in folate, you can obtain folic acid through your diet, such as^[27]:

• Leafy green vegetables (turnip greens, spinach, lettuce asparagus, brussels sprouts, broccoli)
• Beans
• Peanuts and other nuts
• Citrus and other fruits
• Whole grains
• Liver
• Seafood
• Eggs
• Fortified cereals, pastas, and other fortified foods

It may be difficult to get enough folic acid from food alone, as folate is easily destroyed by heat, light, and oxygen. Therefore, you may need to take a folic acid supplement to meet your needs.

You can find folic acid supplements in the form of pills, tablets, capsules, or liquids in various doses and formulations. You can also find folic acid combined with other vitamins and minerals, such as prenatal vitamins or multivitamins.

How to Choose and Use Folic Acid Supplements

If you decide to take folic acid supplements, you might like to consult with your doctor first to determine the right dose and duration. Your doctor can also assess whether you have anemia, are required to take other B vitamins to balance folic acid, or if you would do best on a folate supplement instead. You should also inform your doctor about any other medications or supplements you are taking, as they may interact with folic acid.

Some of the factors to consider when choosing and using folic acid supplements are:

• Folic Acid Supplement Form. Folic acid supplements come in different forms, such as folic acid pills, tablets, capsules, or liquids. Liquids are more bioavailable and easier to swallow, while pills or tablets are more portable and discreet. Check the supplement for any additives or fillers that may cause allergic reactions or side effects.
• If you experience symptoms from a folic acid supplement or notice that after several weeks, your homocysteine levels remain unchanged, you might want to consider the most active form: 5-methyltetrahydrofolate (5-MTHF). You may also need to get checked for vitamin B12 deficiency.
• Timing. Supplements should be taken with food at the same time daily to ensure consistent intake and absorption. Avoid taking folic acid with supplements that inhibit its absorption, including calcium, iron, zinc^[28], or antacids. Waiting a minimum of 2 hours apart from these supplements ought to be sufficient to allow for optimal absorption.
• Supplement Quality. Choose folic acid supplements that are made by reputable manufacturers and that have been tested and certified by independent third-party organizations. Also, check the label for the expiration date and avoid folic acid supplements that are too old or that contain artificial colors, flavors, preservatives, or sweeteners, as they may cause adverse reactions or side effects.

Conclusion

Folic acid is a vital nutrient for your health, and it has many benefits for both men and women beyond pregnancy. Folic acid can help prevent folate deficiency, anemia, birth defects, cancer, cardiovascular disease, stroke, and neurological and mental health problems. However, folic acid excess can also have negative effects on your health, such as masking vitamin B-12 deficiency. Some people may be more sensitive towards folic acid than others and may require a 5-MTHF folate supplement instead.

Before taking folic acid pills, especially if you are thinking about using them to treat anemia or symptoms associated with it, speak with your doctor. By doing so, you can enjoy the benefits of folic acid and improve your health and well-being.

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