How to reasonably supplement folic acid in clinical practice? Please listen to the advice and suggestions of experts

Folic acid, as a B vitamin, was first extracted from spinach leaves, hence the name folic acid. This drug is mainly used clinically to correct folic acid deficiency caused by various reasons, and is given preventively to pregnant and lactating women; long-term folic acid supplementation can also help prevent "sneak attacks" of cardiovascular and cerebrovascular diseases such as hypertension and stroke. At present, scientific research reports on folic acid are emerging in an endless stream, but the quality of research and results vary, resulting in the screening and prevention of folic acid deficiency, the population suitable for folic acid supplementation, timing, dosage and course of treatment, etc. There has never been a unified standard and specification, which has brought troubles to the clinical use of folic acid.

In this regard, Li Weimin, Chairman of the Chinese Heart Failure Center Alliance and Life-long Professor of Cardiovascular Medicine at the First Affiliated Hospital of Harbin Medical University, while interpreting a "Chinese Multidisciplinary Expert Consensus on Rational Clinical Folic Acid Supplementation" (co-authored by eight authoritative academic organizations and institutions including the Professional Committee of Clinical Rational Drug Use of the Chinese Medical Education Association, the Hypertension Branch of the China Medical and Healthcare International Exchange Promotion Association, the Perinatal Nutrition and Metabolism Professional Committee of the Chinese Maternal and Child Health Association, and the Therapeutic Drug Monitoring Research Professional Committee of the Chinese Pharmacological Society), proposed evidence-based basis and reference opinions on the relationship between rational folic acid supplementation and the occurrence and development of related diseases, as well as how to rationally apply it in clinical practice.

Folic acid should be taken half an hour after a meal

Professor Li Weimin believes that the method of taking folic acid should be implemented in accordance with the recommendations of the "Consensus" on the evaluation of folic acid status. This is because folic acid has a stimulating effect on the stomach. If taken before meals, it is likely to cause stomach discomfort and affect appetite, so it is better to take the medicine half an hour after breakfast. After oral administration, folic acid is mainly absorbed in the proximal jejunum, and the peak blood concentration can be reached after half an hour to one hour. Serum folic acid and red blood cell folate are specific indicators for evaluating clinical folic acid deficiency or insufficiency. Plasma homocysteine ​​(Hcy) levels greater than 13 micromoles/liter are non-specific indicators for evaluating functional folic acid deficiency.

Improper cooking causes loss of folic acid

The consensus emphasizes that a balanced diet is the first choice to improve folic acid nutrition. The human body cannot synthesize folic acid by itself and can only obtain it from food. Li Weimin introduced that there are many foods containing folic acid, including green leafy vegetables, soy products, animal liver, lean meat, and eggs. Folic acid easily loses its activity when exposed to light and heat, so the human body does not actually get much folic acid from food. For example, if vegetables are stored for 2-3 days, the loss of folic acid can reach 50-70%; cooking methods such as soup will cause the loss of folic acid by 50-95%; vegetables soaked in salt water will lose more folic acid. This reminds people to try to change their cooking habits and minimize the loss of folic acid.

Accurately grasp the safe dose of folic acid

For people at high risk of folate deficiency and special populations, further measures such as folic acid supplementation or food fortification can be taken to effectively improve folic acid nutrition. Professor Li Weimin warned that folic acid should not be blindly exaggerated or deified, and clinical application should be scientific and standardized and just right. The effective and safe dose of folic acid supplementation for the general population is 0.4-1.0 mg/day. Long-term high-dose (greater than 1 mg/day) folic acid supplementation may pose health risks, such as increasing the incidence of colorectal cancer, prostate cancer and other tumors, masking the early manifestations of vitamin B12 deficiency, aggravating degenerative lesions of the nervous system, interfering with other drugs, and affecting the absorption rate of zinc and folic acid, and leading to a "slippery" immunity.

How to use it during pregnancy and delivery

According to the consensus, for women who are preparing for pregnancy or in early pregnancy, if they do not have high-risk factors, Professor Li Weimin recommends supplementing folic acid by 0.4 mg/day or 0.8 mg/day starting from the time of possible pregnancy or at least 3 months before pregnancy until the 3rd month of pregnancy. For women who have the following conditions, such as living in northern regions (especially rural areas in the north), consuming less fresh vegetables and fruits, having low blood folic acid levels, and having a short period of time to prepare for pregnancy, the folic acid dose can be increased or the pre-pregnancy supplementation time can be extended as appropriate.

There are some tips for supplementing special pregnancy groups

For special groups in the process of preparing for pregnancy and early pregnancy, such as one of the spouses suffering from neural tube defects in the fetus, or the man and woman have a history of neural tube defects in the past, Li Weimin recommends that women preparing for pregnancy should supplement folic acid by 4 mg/day from the time of possible pregnancy or at least 1 month before pregnancy until the pregnancy is 3 months; due to domestic dosage forms, folic acid can be supplemented by 5 mg/day. Women with congenital diseases or family history, diabetes, obesity, epilepsy, gastrointestinal malabsorption diseases, and women who are taking drugs that are likely to increase the risk of fetal neural tube defects are advised to supplement folic acid by 0.8-1.0 mg/day from the time of possible pregnancy or at least 3 months before pregnancy until the pregnancy is 3 months. For women with high homocysteine ​​(Hcy) blood, it is recommended to supplement folic acid by at least 5 mg/day, and to conceive after the Hcy level drops to normal, and to continue to supplement folic acid by 5 mg/day until the pregnancy is 3 months. For women in the middle and late stages of pregnancy and during lactation, in addition to regular intake of foods rich in folic acid, folic acid can continue to be supplemented by 0.4 mg/day.

Folic acid helps reduce cardiovascular events

Although the existing evidence-based medicine is not sufficient to prove that folic acid supplementation can reduce the risk of sudden cardiovascular events, the increase in Hcy levels caused by decreased folic acid levels is still a risk factor for cardiovascular disease. Professor Li Weimin suggested that for patients with high Hcy accompanied by hypertension, folic acid alone or fixed combination preparations containing folic acid can be used to reduce the risk of first stroke. However, relying solely on folic acid supplementation, about 50% of high Hcy cases still cannot meet the standard. Taking 0.8 mg of folic acid daily or taking vitamin B12 in combination can achieve the best effect of lowering Hcy levels. Professor Li recommends a daily Hcy-lowering regimen of 1000 mg of natural betaine, 0.8 mg of folic acid, 2. 8 mg of vitamin B2, 2.8 mg of vitamin B6 and 4.8 micrograms of vitamin B12.

Effective in reducing the risk of stroke

According to the consensus, Professor Li Weimin suggested that for patients with simple high Hcy, in order to reduce the risk of first stroke, folic acid supplementation of 0.8 mg/day can be considered, or folic acid combined with vitamin B6 and vitamin B12 can be used for treatment; for patients who have recently suffered ischemic stroke or transient ischemic attack and have mild to moderately elevated Hcy levels, folic acid, vitamin B6, and vitamin B12 can be considered to reduce the risk of stroke recurrence. A meta-analysis of this consensus showed that patients who took ≤0.8 mg of folic acid daily had a significantly reduced incidence of stroke; while patients who took >0.8 mg of folic acid daily had no significant improvement in their stroke incidence, suggesting that 0.8 mg of folic acid may benefit more.

Professor Li Weimin concluded that human folic acid deficiency may bring different health risks. The Chinese population still has wrong understandings or misunderstandings about folic acid supplementation, which often makes people feel at a loss. The above-mentioned "Consensus" is based on existing research evidence, and unifies and standardizes the screening and prevention of clinical folic acid deficiency and the applicable population, timing, dosage and course of treatment, and combination medication of folic acid supplementation. Through the discussion of multidisciplinary experts and the screening of a large amount of evidence-based medicine, the recommendations for folic acid supplementation are summarized. With the continuous deepening of research and the generation of more evidence in the future, I believe that people will have a deeper understanding of folic acid, and its use will be more scientific, reasonable and precise.

Introduction of Professor Li Weimin

Chief physician of the First Affiliated Hospital of Harbin Medical University, second-level professor, doctoral supervisor, and famous doctor in Heilongjiang.

He is currently the director of the Institute of Cardiovascular Diseases of Harbin Medical University, the honorary dean of the Cardiovascular Hospital of Harbin Medical University First Hospital, a tenured professor, a recipient of the State Council Special Allowance, and an expert with outstanding contributions from the National Health Commission (formerly the Ministry of Health). He is also the chairman of the China Heart Failure Center Alliance, the vice chairman of the China Elderly Cardiovascular Prevention Alliance, the vice president of the Hypertension Branch of the Chinese Geriatrics Society, and a fellow of the American College of Cardiology (FACC).