Folic acid
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The Role of Folic Acid in Health and Disease
Folic Acid and Neural Tube Defects (NTDs)
Folic acid, a synthetic form of the naturally occurring B vitamin folate, is crucial for preventing neural tube defects (NTDs) such as spina bifida. Research indicates that increasing folic acid intake significantly raises serum folate concentrations, which in turn reduces the risk of NTDs. For instance, a 0.1 mg/day increase in folic acid intake can raise serum folate by 0.94 ng/mL in women aged 20-35 years, and every doubling of serum folate concentration roughly halves the risk of an NTD 1. Consequently, higher doses of folic acid, such as 5 mg daily, are recommended for women planning pregnancy to maximize the preventive effect 1.
Folic Acid and Cognitive Function
The relationship between folic acid and cognitive function, particularly in the elderly and those with dementia, has been extensively studied. However, findings suggest that folic acid supplementation, with or without vitamin B12, does not significantly improve cognitive function or mood in healthy elderly individuals or those with mild to moderate cognitive impairment or dementia 2. Despite its effectiveness in reducing serum homocysteine levels, folic acid supplementation did not show a statistically significant benefit on cognitive measures such as the Mini-Mental State Examination (MMSE) or the Alzheimer's Disease Scale (ADAS-Cog) 2.
Folic Acid and Cardiovascular Health
Folic acid plays a role in lowering homocysteine levels, which are associated with cardiovascular diseases. Elevated homocysteine is a risk factor for conditions such as stroke and heart disease. While folic acid supplementation has been shown to reduce homocysteine levels, its impact on preventing fatal cardiovascular events remains inconclusive. Some studies suggest that folic acid, along with vitamins B12 and B6, can help in the secondary prevention of non-fatal strokes but not in preventing fatal cardiovascular diseases 8.
Folic Acid and Cancer
The role of folic acid in cancer prevention is complex. While folic acid can protect against the initiation of cancer, it may also facilitate the progression of pre-existing preneoplastic cells. High folate status has been linked to both protective and adverse effects, depending on the stage of cancer development 6. Therefore, the implications of folic acid supplementation in cancer prevention and progression require careful consideration and further research.
Folic Acid Supplementation in Pregnancy
High-dose folic acid supplementation during pregnancy is common to prevent NTDs. However, studies indicate that while high doses increase maternal serum folate levels, they do not significantly alter red blood cell folate concentrations, suggesting tissue saturation 5. Additionally, high doses may lead to elevated levels of unmetabolized folic acid, raising concerns about potential adverse effects on 1-carbon metabolism 5.
Public Health Implications of Folic Acid Fortification
Mandatory folic acid fortification of food has been a public health success in reducing the prevalence of NTDs. However, there are concerns about the potential risks of excessive folic acid intake, particularly in populations with mandatory fortification programs. Women taking additional folic acid supplements may exceed the upper tolerable limit, which could have implications for vitamin B12 deficiency and other health issues 10. Therefore, recommendations for folic acid supplementation and fortification policies need to be carefully reviewed to balance benefits and potential risks 10.
Conclusion
Folic acid is essential for preventing neural tube defects and has roles in cardiovascular health and potentially in cancer prevention. However, its benefits in cognitive function and other health conditions are less clear. Public health policies on folic acid supplementation and fortification should consider both the benefits and potential risks to ensure optimal health outcomes. Further research is needed to refine these recommendations and understand the broader implications of folic acid intake.
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Quantifying the effect of folic acid
Increased folic acid intake reduces neural-tube defect risk by about 20%, with greater preventive effect in women with low serum folate levels.
Meta-Analysis
Highly CitedFolic acid with or without vitamin B12 for cognition and dementia.
Folic acid supplementation, with or without vitamin B12, may improve cognitive function in elderly individuals at risk of cognitive decline or dementia.
Systematic ReviewHighly CitedFolic Acid.
Folic acid is essential for the formation of red blood cells, nerve function, and DNA replication in all body cells.
Highly CitedFolic acid: nutritional biochemistry, molecular biology, and role in disease processes.
Folic acid prevents neural tube defects and lowers homocysteine levels, potentially influencing various diseases and promoting good health.
Highly CitedImpact of high-dose folic acid supplementation in pregnancy on biomarkers of folate status and 1-carbon metabolism: An ancillary study of the Folic Acid Clinical Trial (FACT).
High-dose folic acid supplementation in early pregnancy increases maternal serum folate but not RBC folate concentrations, suggesting tissue-specific effects.
RCT
Very Rigorous JournalIs folic acid good for everyone?
High folic acid intake may be harmful for some people, and nations considering fortification should carefully research its effects before implementing it.
Very Rigorous JournalHighly CitedFolic acid and diseases - supplement it or not?
Folic acid supplementation is well-established for preventing neural tube defects, but its medicinal effects in treating other diseases require further detailed investigations.
Systematic ReviewFolic acid in general medicine and dermatology
Folic acid supplementation is beneficial in preventing neural tube defects, limiting methotrexate side effects, and may reduce the risk of colorectal cancer.
Highly CitedFolic acid in early pregnancy: a public health success story
Folic acid supplementation during early pregnancy significantly reduces neural tube defect prevalence, with mandatory food fortification programs in numerous countries contributing to this reduction.
Highly CitedWomen Taking a Folic Acid Supplement in Countries with Mandatory Food Fortification Programs May Be Exceeding the Upper Tolerable Limit of Folic Acid: A Systematic Review
Women in high-income countries with mandatory food fortification programs may be exceeding the upper tolerable limit of folic acid intake, potentially impacting their health during childbearing years.
Systematic ReviewVery Rigorous Journal