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9 kinds of effects and side effects of folic acid (9 points of use contraindications be careful)

Folic acid is a type of vitamin B group, both water-soluble vitamins. The origin of the word folic acid is the Latin word folium, which means leaf. It is a nutrient molecule necessary for one-carbon metabolism. It is metabolized and methylated with amino acids. Process, DNA and RNA synthesis, neurotransmitter synthesis and gene expression are closely related

Folic acid plays an important role in protein synthesis, metabolism and other processes related to cell proliferation and tissue growth. Folic acid deficiency is often associated with insufficient dietary intake, alcohol abuse and liver disease, malabsorption, increased needs during pregnancy and lactation, and drug interference


What is the difference between Folate and Folic acid?

Dietary folic acid (folate) is a natural nutrient found in foods such as green leafy vegetables, beans, egg yolks, liver, and citrus fruits.

Folic acid refers to synthetic dietary supplements, found in artificially added foods (such as flour and breakfast cereals) and medicinal vitamins.

Neither folate nor Folic acid has metabolic activity, and must be converted into 5-methyltetrahydrofolate (5-MTHF) in the cell before it can be used by the human body, and 5-MTHF is also called active folic acid


What are the concerns about supplementing Folic acid?

Folic acid is in the form of general supplements. It is commonly found in multivitamins. After being ingested in the human body, it must undergo multiple steps to convert to become valuable active folic acid (5-MTHF). Studies have found that some people have gene mutations that cause MTHFR. Enzyme activity becomes worse, so the conversion process is less efficient

When the above subjects are supplemented in the form of Folic acid in large amounts, it will cause the accumulation of unmetabolized folic acid in the blood.

The literature also pointed out that unmetabolized folic acid may be related to certain adverse health conditions, including weakened immunity, decreased brain function, and cancer. Note 8

Although the above argument needs more research and verification, the best way to take folic acid before this is still to obtain it from natural foods. If you really have additional needs, you can choose to contain 5-MTHF (5-methyltetrahydrofolate) form of activity. Folic acid supplements, in addition to high human body rate, can also avoid possible metabolic problems. Note 9


What are the empirical effects (benefits) of folic acid?

  1. Folic acid is good for blood sugar regulation

Diabetes is the most common metabolic disease. It is estimated that more than 460 million people worldwide suffer from diabetes. There are 34.2 million patients in the United States alone, accounting for 10.5% of the total population.

High blood sugar is associated with frequent urination, thirst, blurred vision, fatigue, and recurrent infections…symptoms (patients are three times more likely to be hospitalized than non-diabetic patients.

In addition to relieving symptoms, the purpose of glycemic management is to reduce the long-term complications of diabetes. Good blood sugar management can reduce the occurrence and progression of microvascular complications.

A systematic literature review and meta-analysis (including 24 randomized controlled trials with 34,646 participants) pointed out that compared with the control group, folic acid supplementation reduced fasting blood glucose, fasting insulin and insulin resistance (HOMA-IR) ) Indicators, but there is no significant change in glycosylated hemoglobin (HbA1c). Note 1

In addition, subgroup analyses showed that the use of high doses (≥5 mg) improved blood sugar more significantly

*Conclusion: Folic acid supplementation may have a positive effect on blood sugar regulation, but because the improvement is relatively small, it may not have reached clinical importance


  1. Folic acid assists blood lipid regulation

Dyslipidemia refers to the disorder of one or more lipoproteins in the blood, such as increased total cholesterol, low-density lipoprotein cholesterol or triglycerides, or only low high-density lipoprotein cholesterol levels

In many countries, due to the westernization of diet, obesity, aging of the population, reduction in physical activity, and other unhealthy lifestyles, the incidence of dyslipidemia is high and continues to increase. It is the most important and changeable risk factor for cardiovascular disease one

A systematic literature review and meta-analysis (including 38 randomized controlled trials with a total of 21787 participants) pointed out that compared with placebo, folic acid supplementation can help reduce serum triglyceride and total cholesterol (Total cholesterol) concentration. Note 1

However, folic acid supplementation does not affect the serum concentration of low-density lipoprotein cholesterol or high-density lipoprotein cholesterol, and the observation between the folic acid supplement dose and the serum high-density lipoprotein cholesterol concentration To a significant dose-response relationship

*Conclusion: Folic acid supplementation may have a positive effect on blood lipid regulation, but more research is still needed to observe the effect on different groups of people


  1. Folic acid reduces the incidence of autism

Autism spectrum disorder (Autism spectrum disorder) is a multifactorial neurodevelopmental disorder caused by a combination of genetic and environmental factors. Possible environmental factors include folic acid deficiency, neonatal hypoxia, maternal obesity, and gestational diabetes (8 years old). The prevalence of autism in children is 1/54, and the male to female ratio is 4.3:1)

People with autism exhibit problem behaviors, such as aggression, self-harm, resistance to order, and inability to talk normally, usually accompanied by social anxiety, attention deficit, hyperactivity, sleep disorders, and obsessive-compulsive disorder. Therefore, it is difficult for patients to obtain the same level of education as their peers and maintain an independent life

A literature meta-analysis (Meta-analysis, including 10 observational studies) pointed out that folic acid supplementation in early pregnancy is associated with a lower risk of autism. Note 1

In addition, subgroup analysis found that the minimum dose of folic acid is estimated to be at least 400 μg per day for protection.

*Conclusion: Prenatal folic acid supplementation in pregnant women (especially in the first trimester) is associated with a lower risk of autism spectrum disorder in the offspring.


  1. Folic acid reduces the risk of preterm birth

Preterm birth is defined as being born within the 20th and 37th weeks of pregnancy. It is a major obstetric health care problem and an important factor in perinatal morbidity, mortality and long-term disability.

It is estimated that about 15 million babies are born prematurely every year in the world, causing 1 million of them to die

Preterm birth is considered a multifactorial syndrome. Nearly 70% of preterm births are caused by natural delivery or rupture of membranes, and the rest are caused by iatrogenic causes. Therefore, it can be broadly divided into spontaneous preterm birth and indicative preterm birth

A literature meta-analysis (Meta-Analysis, including 27 observational studies) pointed out that blood folic acid levels, folic acid supplementation, and dietary folic acid intake are negatively correlated with the risk of preterm birth (but there is a relationship between folic acid in the diet and the risk of spontaneous preterm birth No obvious connection). Note 1

*Conclusion: Folic acid supplementation during pregnancy is significantly associated with lower risk of preterm birth and higher maternal folic acid levels


  1. Folic acid reduces the incidence of stroke

Stroke can be divided into hemorrhagic or occlusive/ischemic stroke. Most (80%) belong to the latter. In terms of mortality, stroke is the fourth leading cause after heart disease, cancer and chronic lower respiratory diseases. The cause of death is also the biggest cause of disability. About 50% of survivors are permanently disabled

Risk factors related to stroke, including history of hypertension, smoking history, diabetes, waist-to-hip ratio, dietary risk score, lack of exercise, drinking, psychosocial stress and depression, cardiac causes, and the ratio of apolipoprotein B to A1

A systematic literature review and integrated analysis (meta-analysis, including 12 randomized controlled trials, with a total of 47,523 cardiovascular disease patients) pointed out that compared with patients receiving controlled treatment, folic acid treatment significantly reduced the risk of stroke (especially The daily dose is less than 2 mg, and the follow-up time ≥ 40 months is most significant). Note 1

In addition, there were no significant differences in all-cause mortality, cardiovascular mortality, and coronary heart disease risks between the two groups.

*Conclusion: For patients with cardiovascular disease, oral folic acid can help reduce the risk of stroke, but more large-scale trials with precise design are still needed to prove it


  1. Folic acid prevents neural tube defects

Neural tube defects (NTDs) are congenital malformations of the brain and spinal cord caused by the failure to close the neural tube within 21 – 28 days after pregnancy. It is the second most common serious birth defect. It accounts for every 1,000 pregnancies worldwide. About 0.5 to 2 cases are affected.

The most common types of neural tube defects are spina bifida and anencephaly. Spina bifida is due to failure of posterior (caudal) neural tube fusion, and anencephaly is due to failure of anterior (cranial) neural tube fusion.

Congenital anencephaly is fatal, and many children with anencephaly are stillborn or die shortly after birth. And spina bifida has a high probability of life-long survival in physical and intellectual disabilities, and only a few of these children can live independently in adulthood

A Cochrane Review (Cochrane Review, containing 4 studies, with a total of 6425 female participants) pointed out that folic acid supplementation from pre-pregnancy to early pregnancy (Periconceptional) can reduce the incidence of neural tube defects by 72%. Note 1

*Conclusion: Supplementing folic acid from before to the early stage of pregnancy has a positive effect on the prevention of neural tube defects


  1. Folic acid reduces the incidence of hypertension in pregnancy

Hypertension in pregnancy, including preeclampsia (preeclampsia) and gestational hypertension (gestational hypertension), is the most common complication during pregnancy and is related to the adverse health outcomes of the mother and her children.

Preeclampsia is diagnosed as a new increase in blood pressure and proteinuria after 20 weeks of pregnancy. It is an important cause of fetal death, premature delivery, and intrauterine growth restriction.

Hypertension during pregnancy refers to a new increase in blood pressure without proteinuria after 20 weeks of pregnancy. It is found in 6% to 17% of pregnancies and is associated with premature delivery and small for gestational age babies

A meta-analysis of literature (including 13 queued studies and 1 randomized controlled trial, with more than 300,000 female participants) pointed out that the risk of hypertension in pregnancy has nothing to do with folic acid supplementation during pregnancy. However, folic acid supplementation during pregnancy can significantly reduce the risk of preeclampsia. Note 2

In addition, the results of the subgroup analysis showed that the reduction in the risk of preeclampsia was related to supplementation of multivitamins containing folic acid (folic acid supplementation alone was not related).

*Conclusion: Supplementing multivitamins containing folic acid during pregnancy may help reduce the risk of preeclampsia, but due to the high heterogeneity between studies, more randomized controlled trials are still needed to support it.


  1. Folic acid reduces the risk of congenital heart disease

Congenital heart disease is the most common type of congenital malformations. It is mainly defined as a large number of structural and functional defects that occur during cardiac embryogenesis, accounting for one third of all major congenital malformations.

Worldwide, 1.35 million babies are born with congenital heart disease each year, and it is considered to be the substantial cause of early fetal death.

The etiology is usually divided into two categories: genetic and non-hereditary. Non-genetic causes include environmental teratogens (dioxin, PCBs, pesticides), maternal contact (alcohol, isotretinoin, thalidomide, anti-epileptic drugs), and infectious pathogens

A comprehensive literature analysis (Meta-Analysis, including 20 case control studies) pointed out that in Chinese and European patients, supplementation of folic acid during pregnancy is a protective factor to prevent congenital heart defects and can reduce congenital heart defects by about 40% Risk, and no association has been found in the United States. Note 3

*Conclusion: According to observations in China and Europe, folic acid supplementation during pregnancy can significantly reduce the risk of congenital heart defects in newborns.


  1. Folic acid reduces cleft lip and palate events

Cleft lip and palate (oral clefts) is a kind of congenital cleft lip deformity caused by abnormal facial development during pregnancy, including: cleft lip only, cleft lip with palate and cleft palate only. The most common orofacial congenital malformations, accounting for 65% of all head and neck deformities, are usually non-fatal.

It is estimated that cleft lip occurs in about 1/700 to 1/1000 of live births in different populations around the world, and there is great variability depending on geographic origin, ethnicity, and socio-economic conditions.

About 70% of cleft lip cases are nonsyndromic, that is, the patient has no other physiological or developmental abnormalities

When cleft lip and palate occurs, it has a great impact on infant feeding, speech, language and speech formation, breathing, oral function, bite, tooth formation and other functions.

A literature meta-analysis (including 6 queue studies and 31 case-control studies) pointed out that folic acid supplementation in parturients can reduce the risk of all types of cleft lip and palate. Note 4

And further subgroup analysis (Subgroup Analysis) found:

Supplementing folic acid alone can reduce the risk of non-syndromic cleft lip and palate by 27% and 25% of the risk of single cleft palate (cleft palate only)

Supplementation of multivitamins containing folic acid reduces the risk of non-syndromic cleft palate and 31% (cleft palate only)

The timing of use is the most protective effect from before pregnancy to the first 3 months of pregnancy (compared to those not ingested)

*Conclusion: Continuous folic acid supplementation (or folic acid comprehensive vitamins) from before pregnancy to 3 months after pregnancy can help reduce neonatal cleft lip and palate events


Pregnancy/Pregnancy Folic Acid Dosage?

According to the US Centers for Disease Control and Prevention (Centers for Disease Control and Prevention) recommendations, all women planning to become pregnant or of childbearing age should consume 400 micrograms (mcg) of folic acid a day to get enough folic acid to help prevent certain birth defects

This is because about half of the pregnancies are unplanned, and the major birth defects of the baby’s brain or spine appear early in pregnancy (3-4 weeks after pregnancy), which is usually before you realize that you are pregnant.

If you have the following conditions, it is generally recommended to use a dose higher than 400 micrograms (mcg) during pregnancy or pregnancy. Please consult your doctor for the exact dose to ensure safety

The mother or the child’s biological father has a neural tube defect

Have a history of pregnancy with neural tube defects

You or your child’s biological father has a family history of neural tube defects

Have diabetes

Taking medications for epilepsy, type 2 diabetes, lupus, psoriasis, rheumatoid arthritis, asthma, or inflammatory bowel disease

Have kidney disease and need hemodialysis (dialysis)

Have sickle cell disease (sickle cell disease, a genetic disease, also known as sickle-type anemia)

Abnormal liver function

Drink more than one alcoholic beverage a day


What are the side effects of folic acid?

Excessive intake of folic acid from food has no adverse effects, but additional supplements should be noted that most adults have few side effects when they take a daily dose of less than 1000 micrograms (mcg).

However, long-term high-dose folic acid may cause abdominal cramps, bitter mouth, diarrhea, skin rash, sleep disturbance, irritability, confusion, nausea, stomach upset, loss of appetite, difficulty concentrating, skin reactions, seizures, exhaust, and excitement Wait


What are the safety precautions for folic acid?

  1. If you have ever had any abnormal allergic reaction to food or medicine, please be careful. Allergic reactions may occur. Symptoms include rash, itching, redness, and difficulty breathing.
  2. It is safe to take oral folic acid in proper amount during pregnancy and lactation, the dosage is about 300 to 400 mcg per day
  3. Excessive serum folic acid levels are associated with an increased risk of prostate cancer. Note 6
  4. Taking folic acid supplements may worsen seizures, especially at high doses.
  5. Those who have undergone coronary angioplasty should use caution. Early studies have found that the use of folic acid, vitamin B6 and vitamin B12 in related patients after surgery may increase the risk of in-stent restenosis and increase the target vessel reconstruction ( target vessel revascularization). Note 7
  6. Do not use in combination with anticonvulsant (used to treat epilepsy). Folic acid can increase the speed at which the body breaks down the drug, thereby reducing the effectiveness of the drug. Related drug names are: Fosphenytoin, phenytoin, and primidone (Primidone)
  7. Do not use in combination with the anti-cancer drug Methotrexate (Methotrexate), because the drug is a folic acid antagonist, so the combined use may reduce the efficacy of the drug
  8. Do not use with central nervous system depressants: Barbiturates (Barbiturates) drugs may reduce the effectiveness of drugs
  9. Do not use in combination with the antimalarial agent Pyrimethamine (pyrimidine), which may reduce the effectiveness of the drug