Effects of folic acid: A Synthesis of Findings from 44 Studies

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Original Abstract of the Article

Major findings of the research

Folic acid supplementation has been shown to have a protective effect against neural tube defects (NTDs), a type of birth defect that affects the brain and spinal cord. 24 However, the effect of folic acid on other birth defects is less clear, with no statistically significant effects observed for cleft palate, cleft lip, congenital cardiovascular defects, miscarriages, or other birth defects. 24 In terms of maternal and infant outcomes, folic acid supplementation has not been shown to have any adverse effects. 24

Folic acid supplementation has been shown to reduce plasma homocysteine levels, which is an independent risk factor for occlusive vascular disease. 3 The study found that folic acid supplementation led to significant increases in serum folate and red cell folate, and a decrease in plasma homocysteine. 3 This suggests that folic acid supplementation may have a positive impact on cardiovascular health. 3

Folic acid supplementation can be beneficial for malnourished children, particularly for improving serum folate levels and promoting weight gain. 11 While there was no significant difference in weight increase between the study group and the control group, the study group showed significantly higher increases in weight and serum folate levels after six weeks of supplementation. 11 This indicates that folic acid supplementation can contribute to improving nutritional status in malnourished children. 11

Benefits and risks

Benefits summary

Folic acid supplementation has been shown to be beneficial for reducing the risk of neural tube defects, a serious birth defect that affects the brain and spinal cord. 24 It has also been linked to reduced levels of homocysteine, a substance that can increase the risk of cardiovascular disease. 3

Risks summary

While folic acid is generally considered safe, excessive intake can mask vitamin B12 deficiency, potentially leading to neurological damage. 5 Some studies have suggested a potential link between folic acid supplementation and increased cancer risk, but more research is needed to confirm this association. 29

Comparison between studies

Commonalities between studies

Many studies consistently demonstrate the effectiveness of folic acid in reducing the risk of neural tube defects. 24 Additionally, a reduction in homocysteine levels is frequently observed with folic acid supplementation. 3

Differences between studies

The effectiveness and potential risks of folic acid may vary depending on the dosage, intake method, and individual factors. 8 For instance, high doses of folic acid have been associated with masking vitamin B12 deficiency, as previously mentioned. 5

Consistency and inconsistencies of the findings

The results of the studies generally show a consistent positive impact of folic acid, particularly regarding neural tube defect prevention and homocysteine reduction. 24 3 However, the link between folic acid and cancer risk remains unclear and requires further investigation. 29

Points to note for applying the results to real life

Folic acid is a crucial nutrient for women planning pregnancy or in their early stages of pregnancy. 24 To ensure adequate intake, consider incorporating folic acid-rich foods into your diet or taking folic acid supplements. 24 However, due to the potential for masking vitamin B12 deficiency, it's crucial to discuss your folic acid intake with a healthcare professional to determine the appropriate dosage for your individual needs. 5

Limitations of current research

The research on the effects of folic acid is not yet comprehensive and more research is needed. 24 Specifically, further investigation is required to understand the potential relationship between folic acid intake and cancer risk. 29

Future research directions

Large-scale studies are needed to investigate the potential association between folic acid intake and cancer risk. 29 Further research is also warranted to explore the effects of folic acid on other aspects of health. 24

Conclusion

Folic acid plays a significant role in overall health, particularly for women planning pregnancy or in their early stages of pregnancy. 24 It has been proven to be effective in reducing the risk of neural tube defects, a serious birth defect affecting the brain and spinal cord. 24 However, it is important to consult with a healthcare professional to determine the appropriate dosage, as excessive intake may mask vitamin B12 deficiency. 5 Continued research is essential to further understand the nuances of folic acid's effects and ensure its safe and effective use for optimal health outcomes. 29

Keywords
Benefit Keywords
Cervical dysplasia treatment
1
Neural tube defect prevention
2
Reduced homocysteine
3
Lower homocysteine levels
Reduce neural tube defects risk
Reduce vascular disease risk
4
Folate supplementation
Homocysteine reduction
5
Homocysteine reduction
Vascular disease prevention
6
Increased RCF
Increased SF
Reduced Hcy
7
Homocysteine reduction
8
NTD prevention
9
Increased plasma folate
10
Increased serum folate level
Increased weight
11
Cognitive function improvement
Epilepsy treatment
12
Arteriosclerosis prevention
13
Neural tube defect prevention
14
Folate status
Homocysteine reduction
15
Cardiovascular risk reduction
16
Colorectal cancer prevention
17
Neural tube defect prevention
18
Reduced hemorrhage
Reduced sepsis
19
Colorectal adenoma recurrence prevention
20
Blood pressure reduction
Homocysteine reduction
21
Higher birthweight
Increased placental weight
Reduced preterm birth
22
Improved folate status
Lower homocysteine
23
Prevents NTDs
24
Lowered homocysteine concentrations
26
Cardiovascular outcome prevention
Homocysteine reduction
28
Infant health
Maternal health
30
Melanoma risk reduction
31
Neural tube defect prevention
32
Plasma homocysteine reduction
33
Reduces GI side effects
Reduces hepatic dysfunction
34
Congenital malformations
Neural tube defects
35
Lower homocysteine
36
folate status improvement
37
Prevented NTDs
38
Neurodevelopmental benefits
Prevents NTDs
39
Higher pregnancy rate
Improved sperm quality
40
Glycemic control
42
Increased milk folate
44
Risk Keywords
Toxic side effects
1
Vitamin B12 status
5
Vitamin B-12 deficiency masking
9
Dysfunctional labor
19
Dietary and lifestyle confounding
Folate supplementation
20
Cancer
Cardiovascular disease
Mortality
25
Attenuated ovarian response
27
Increased cancer risk
29
Cancer risk
32
Intracellular homocysteine increase
MTHFR inhibition
SAM dysregulation
33
Stroke risk
36
adverse effects
37
Harmful effect at high dose
39
Folic acid deficiency
40
Childhood cancer risk
41
Increased milk UMFA
Potential impact on folate metabolism
Potential impact on infant health
44
Literature analysis of 44 papers
Positive Content
38
Neutral Content
2
Negative Content
4
Article Type
26
16
9
10
44
1.

Zinc concentration in plasma and erythrocytes of subjects receiving folic acid supplementation.

Author: ButterworthC E, HatchK, ColeP, SauberlichH E, TamuraT, CornwellP E, SoongS J

Cervical dysplasia treatment
Toxic side effects

Folic acid supplementation did not deplete zinc levels in blood in women with cervical dysplasia. Erythrocyte folate levels increased significantly in the supplemented group, but plasma and erythrocyte zinc levels did not change significantly in either group.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

2.

Effect of increasing dietary folate on red-cell folate: implications for prevention of neural tube defects.

Author: CuskellyG J, McNultyH, ScottJ M

Neural tube defect prevention

The UK Department of Health recommends an extra 400 micrograms daily of folate/folic acid for neural tube defect prevention, assuming that natural food, fortified foods, and supplements have equal effects on folate status.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

3.

The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study.

Author: SchorahC J, DevittH, LucockM, DowellA C

Reduced homocysteine

This randomized double-blind placebo-controlled intervention study found that folic acid fortification of cereals led to significant increases in serum folate and red cell folate, and a decrease in plasma homocysteine in a general population. The study suggests that food fortification with physiological levels of folic acid should have a significant impact on the prevalence of occlusive vascular disease.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women.

Author: BrönstrupA, HagesM, Prinz-LangenohlR, PietrzikK

Lower homocysteine levels
Reduce neural tube defects risk
Reduce vascular disease risk

Plasma homocysteine concentrations can be lowered by folic acid. Preliminary evidence indicates that vitamin B-12 may be beneficial when included in supplements or in a food-fortification regimen together with folic acid.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

5.

Low-dose folic acid supplementation does not influence plasma methionine concentrations in young non-pregnant women.

Author: BrouwerI A, van DusseldorpM, DuranM, ThomasC M, HautvastJ G, EskesT K, Steegers-TheunissenR P

Folate supplementation
Homocysteine reduction
Vitamin B12 status

Low-dose folic acid supplementation significantly decreased total homocysteine concentrations but did not affect plasma methionine or vitamin B12 concentrations.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Lowering blood homocysteine with folic acid-based supplements: meta-analysis of randomised trials.

Author: ClarkeR

Homocysteine reduction
Vascular disease prevention

This meta-analysis evaluated the reduction in homocysteine concentrations produced by dietary supplementation with folic acid and vitamins B12 or B6. The study suggests that folic acid supplementation reduces homocysteine concentrations, with an additional reduction observed with vitamin B12 but not vitamin B6.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

7.

Effect of folic acid and vitamin C supplementation on folate status and homocysteine level: a randomised controlled trial in Italian smoker-blood donors.

Author: CafollaA, DragoniF, GirelliG, TostiM E, CostanteA, De LucaA M, FunaroD, ScottC S

Increased RCF
Increased SF
Reduced Hcy

Supplementation with 5 mg/day folic acid is able to significantly increase both RCF and SF levels and reduce Hcy level in Italian smoker-blood donors.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease.

Author: NealBruce, MacMahonStephen, OhkuboTakayoshi, TonkinAndrew, WilckenDavid,

Homocysteine reduction

Folic acid supplementation, both at pharmacological doses (2.0 mg daily) and dietary supplementation levels (0.2 mg daily), effectively reduces homocysteine levels in individuals with a history of myocardial infarction or unstable angina. While both doses are beneficial, higher doses produce a significantly greater reduction in homocysteine levels.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid.

Author: VennBernard J, GreenTimothy J, MoserRudolf, McKenzieJoanne E, SkeaffC Murray, MannJim

NTD prevention
Vitamin B-12 deficiency masking

This randomized, placebo-controlled, double-blind trial compared the effects of [6S]-5-MTHF and folic acid supplementation on blood folate levels in women of childbearing age. Both supplements increased blood folate indices to a similar extent, suggesting that [6S]-5-MTHF may be a safe alternative to folic acid for neural tube defect prevention.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

A comparison of the effect of advice to eat either '5-a-day' fruit and vegetables or folic acid-fortified foods on plasma folate and homocysteine.

Author: Ashfield-WattP A L, WhitingJ M, ClarkZ E, MoatS J, NewcombeR G, BurrM L, McDowellI F W

Increased plasma folate

Both fortified folic acid and natural folate increased plasma folate levels in healthy individuals with the wild-type CC genotype for C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR). However, the increase in folate intake from fortified foods was greater than from natural sources. Neither intervention significantly reduced homocysteine levels in this group.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

Effects of multivitamin and folic acid supplementation in malnourished children.

Author: Ratanachu-EkSuntaree

Increased serum folate level
Increased weight

Folic acid supplementation in malnourished children resulted in significant increases in serum folate levels and weight gain. Folic acid deficiency is common in malnourished children, and supplementation is recommended.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

[Decrease of folic acid and cognitive alterations in patients with epilepsy treated with phenytoin or carbamazepine, pilot study].

Author: HernándezRaul, FernándezM de los Angeles, MirandaGabriela, SuásteguiRoberto

Cognitive function improvement
Epilepsy treatment

This study explores the potential benefits of supplementing with folic acid for patients with epilepsy who are taking phenytoin or carbamazepine, two commonly used anti-seizure medications. These medications can lower folate levels in the blood, which has been linked to cognitive problems. The study suggests that adding folic acid to treatment could potentially improve cognitive function in these patients.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : Spanish

13.

The effect of folic acid supplementation in beta-thalassemia major: a randomized placebo-controlled clinical trial.

Author: MojtahedzadehFereidoon, KosaryanMehrnoush, MahdaviMohammad-Reza, AkbariJafar

Arteriosclerosis prevention

Folic acid is essential for various biochemical reactions and is recommended for infants and children. Although the effects of excess folic acid are unknown, daily consumption of 1 mg with 5-100 mg of pyridoxine may decrease thrombotic events associated with slightly elevated homocysteine levels in adults.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

14.

Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis.

Author: Ingrid GohY, BollanoEnkelejd, EinarsonThomas R, KorenGideon

Neural tube defect prevention

Folic acid-fortified multivitamin supplements have been associated with a decreased risk of neural tube defects. Several studies have proposed the effectiveness of these supplements in preventing other birth defects, but this has not been systematically examined.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

15.

Fortified mineral water improves folate status and decreases plasma homocysteine concentration in pregnant women.

Author: JärvenpääJouko, SchwabUrsula, LappalainenTiina, PäkkiläMervi, NiskanenLeo, PunnonenKari, RyynänenMarkku

Folate status
Homocysteine reduction

This study investigated the effects of mineral water fortified with folic acid, vitamins B6, B12, D, and calcium on serum and erythrocyte folate concentrations, serum vitamin B12, and plasma homocysteine concentrations in pregnancy. The study found that fortified mineral water improved folate status and reduced plasma homocysteine concentrations in pregnant subjects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

16.

Global improvement of vascular function and redox state with low-dose folic acid: implications for folate therapy in patients with coronary artery disease.

Author: ShirodariaCheerag, AntoniadesCharalambos, LeeJustin, JacksonClare E, RobsonMatthew D, FrancisJane M, MoatStuart J, RatnatungaChandi, PillaiRavi, RefsumHelga, NeubauerStefan, ChannonKeith M

Cardiovascular risk reduction

While dietary folate helps lower homocysteine levels and may reduce heart disease risk, high-dose folic acid supplements don't appear to improve health outcomes. Both folic acid and its active form, 5-methyltetrahydrofolate, improve blood vessel function, but how the amount of folic acid affects this is unclear. This study compared the effects of high-dose folic acid (like supplements) with low-dose folic acid (like in fortified foods) on blood vessels.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Responses of biomarkers of folate and riboflavin status to folate and riboflavin supplementation in healthy and colorectal polyp patients (the FAB2 Study).

Author: PowersHilary J, HillMarilyn H, WelfareMark, SpiersAlison, BalWendy, RussellJean, DuckworthYvonne, GibneyEileen, WilliamsElizabeth A, MathersJohn C

Colorectal cancer prevention

A double-blind study investigates the effects of folic acid and riboflavin supplements on biomarkers of colorectal cancer risk. Riboflavin supplementation enhances the response to low-dose folate in individuals with colorectal polyps.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Effect of different dosage and administration schedules of folic acid on blood folate levels in a population of Honduran women of reproductive age.

Author: RosenthalJ, MillaG, FloresA, YonM, PfeifferC, UmañaE, SkerretteN, BarahonaF,

Neural tube defect prevention

Periconceptional folic acid supplementation is effective in preventing neural tube defects, and the Honduran government should implement a supplementation program.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

19.

Effects of prenatal micronutrient supplementation on complications of labor and delivery and puerperal morbidity in rural Nepal.

Author: ChristianParul, KhatrySubarna K, LeClerqSteven C, DaliSanu Maiya

Reduced hemorrhage
Reduced sepsis
Dysfunctional labor

Prenatal folic acid-iron supplementation reduced the risk of postpartum hemorrhage by 41% in rural Nepal.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

20.

Folic acid supplementation for the prevention of recurrence of colorectal adenomas: metaanalysis of interventional trials.

Author: IbrahimEzzeldin M, ZekriJamal M

Colorectal adenoma recurrence prevention
Dietary and lifestyle confounding
Folate supplementation

This meta-analysis found that folate supplementation had no protective effects on the recurrence of colorectal adenomas. However, the two studies that have used folic acid as 1 mg/day favored folic acid over placebo.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

21.

Homocysteine lowering with folic acid supplements in children: effects on blood pressure.

Author: PapandreouD, MalindretosP, ArvanitidouM, MakedouA, RoussoI

Blood pressure reduction
Homocysteine reduction

Oral folic acid supplementation was found to reduce homocysteine levels and blood pressure in children with hyperhomocysteinemia, suggesting its potential benefit in preventing cardiovascular disease.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

22.

[Effects of folic acid supplementation on pregnancy outcomes: a review of randomized clinical trials].

Author: ChiaffarinoF, AsconeG B, BortolusR, Mastroia-CovoP, RicciE, CiprianiS, ParazziniF

Higher birthweight
Increased placental weight
Reduced preterm birth

While observational studies suggest a link between folate deficiency and pregnancy complications, clinical trials have not consistently shown a benefit of folate supplementation.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : Italian

23.

Effects of folic acid supplementation on serum folate and plasma homocysteine concentrations in older adults: a dose-response trial.

Author: AndersonCheryl A M, JeeSun Ha, CharlestonJeanne, NarrettMatthew, AppelLawrence J

Improved folate status
Lower homocysteine

This study investigated the changes in serum folate and homocysteine concentration that resulted from 6 weeks of supplementation with folic acid. Folic acid supplementation increased serum folate levels. There was no dose-response relation with homocysteine level among all participants.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

24.

Effects and safety of periconceptional folate supplementation for preventing birth defects.

Author: De-RegilLuz Maria, Fernández-GaxiolaAna C, DowswellTherese, Peña-RosasJuan Pablo

Prevents NTDs

This review assessed the effects of periconceptional folic acid supplementation on neural tube defects (NTDs) and other birth defects. Folic acid supplementation was effective in preventing NTDs, but no clear effect on other birth defects was observed.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

25.

Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37 485 individuals.

Author: ClarkeRobert, HalseyJim, LewingtonSarah, LonnEva, ArmitageJane, MansonJoAnn E, BønaaKaare H, SpenceJ David, NygårdOttar, JamisonRex, GazianoJ Michael, GuarinoPeter, BennettDerrick, MirFraz, PetoRichard, CollinsRory,

Cancer
Cardiovascular disease
Mortality

The study found that folic acid supplementation had no significant effect on cardiovascular events, cancer incidence, cancer mortality, or all-cause mortality in individuals at increased risk of cardiovascular disease.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

26.

A dose-finding trial of the effect of long-term folic acid intervention: implications for food fortification policy.

Author: TighePaula, WardMary, McNultyHelene, FinneganOwen, DunneAdrian, StrainJj, MolloyAnne M, DuffyMaresa, PentievaKristina, ScottJohn M

Lowered homocysteine concentrations

This study compared the effectiveness of different doses of folic acid in lowering homocysteine concentrations. A dose as low as 0.2 mg/d was effective in lowering homocysteine concentrations over a 6-month period. Higher doses may not be necessary.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

27.

Preconception folic acid use modulates estradiol and follicular responses to ovarian stimulation.

Author: TwigtJohn M, HammicheFatima, SinclairKevin D, BeckersNicole G, VisserJenny A, LindemansJan, de JongFrank H, LavenJoop S E, Steegers-TheunissenRégine P

Attenuated ovarian response

This randomized trial found that low-dose folic acid use (0.4 mg/d) attenuated follicular and endocrine responses to conventional ovarian stimulation in subfertile women. The study found that the estradiol response was higher in nonfolic acid users receiving conventional treatment, and this effect was independent of serum anti-Müllerian hormone (AMH) levels and the preovulatory follicle count.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

28.

Effect of folic acid supplementation on cardiovascular outcomes: a systematic review and meta-analysis.

Author: ZhouYu-Hao, TangJian-Yuan, WuMei-Jing, LuJian, WeiXin, QinYing-Yi, WangChao, XuJin-Fang, HeJia

Cardiovascular outcome prevention
Homocysteine reduction

This review and meta-analysis examined the effects of folic acid supplementation on cardiovascular outcomes. The review concluded that the effects of folic acid supplementation on cardiovascular events are not clear.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

29.

Meta-analysis of cancer risk in folic acid supplementation trials.

Author: BaggottJoseph E, OsterRobert A, TamuraTsunenobu

Increased cancer risk

This meta-analysis investigated the association between folic acid supplementation and cancer incidence. The results suggest a potential increased cancer risk with folic acid supplementation, highlighting the need for careful monitoring of cancer incidence in these trials.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

30.

Micronutrient supplementation and pregnancy outcomes: double-blind randomized controlled trial in China.

Author: LiuJian-meng, MeiZuguo, YeRongwei, SerdulaMary K, RenAiguo, CogswellMary E

Infant health
Maternal health

The study aims to investigate the maternal and infant health effects of iron plus folic acid and multiple micronutrient supplements compared to folic acid alone in pregnant women with no or mild anemia.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

31.

Folic acid supplementation and cancer risk: a meta-analysis of randomized controlled trials.

Author: QinXianhui, CuiYimin, ShenLin, SunNingling, ZhangYan, LiJianping, XuXin, WangBinyan, XuXiping, HuoYong, WangXiaobin

Melanoma risk reduction

Folic acid supplementation has no significant effect on total cancer incidence, colorectal cancer, prostate cancer, lung cancer, breast cancer or hematological malignancy. However, it reduces the risk of melanoma. Higher total cancer incidence risk was observed among trials with higher percent use of lipid-lowering drugs (>60%) or with lower percent baseline hypertension (≤70%).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

32.

Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals.

Author: VollsetStein Emil, ClarkeRobert, LewingtonSarah, EbbingMarta, HalseyJim, LonnEva, ArmitageJane, MansonJoAnn E, HankeyGraeme J, SpenceJ David, GalanPilar, BønaaKaare H, JamisonRex, GazianoJ Michael, GuarinoPeter, BaronJohn A, LoganRichard F A, GiovannucciEdward L, den HeijerMartin, UelandPer M, BennettDerrick, CollinsRory, PetoRichard,

Neural tube defect prevention
Cancer risk

This study assessed the effects of folic acid supplementation on site-specific cancer rates in randomized trials. Overall, folic acid supplementation at doses higher than those from fortification had no significant effect on total cancer incidence, but reduced the risk of melanoma.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

33.

Folic acid supplementation does not reduce intracellular homocysteine, and may disturb intracellular one-carbon metabolism.

Author: SmithDesirée E C, HornstraJacqueline M, KokRobert M, BlomHenk J, SmuldersYvo M

Plasma homocysteine reduction
Intracellular homocysteine increase
MTHFR inhibition
SAM dysregulation

Folic acid supplementation did not reduce intracellular homocysteine levels or change other one-carbon metabolites, suggesting that its effects on plasma homocysteine may not translate to intracellular levels. Folic acid may disrupt intracellular one-carbon metabolism by interfering with SAM's inhibitory effect on MTHFR activity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

34.

Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis.

Author: SheaBeverley, SwindenMichael V, GhogomuElizabeth Tanjong, OrtizZulma, KatchamartWanruchada, RaderTamara, BombardierClaire, WellsGeorge A, TugwellPeter

Reduces GI side effects
Reduces hepatic dysfunction

Folic acid or folinic acid supplementation while receiving methotrexate (MTX) therapy for rheumatoid arthritis (RA) reduced the incidence of gastrointestinal side effects by 26%, abnormal serum transaminase elevation by 76.9%, and discontinuation of MTX treatment for any reason by 60.8%.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

35.

Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid: community-based randomized clinical trial in Italy and the Netherlands.

Author: BortolusRenata, BlomFenneke, FilippiniFrancesca, van PoppelMireille N M, LeonciniEmanuele, de SmitDenhard J, BenetolloPier Paolo, CornelMartina C, de WalleHermien E K, MastroiacovoPierpaolo,

Congenital malformations
Neural tube defects

This project aims to assess the effect of higher doses of peri-conceptional folic acid (FA) supplementation on reducing the occurrence of all congenital malformations (CMs). It will also compare rates of specific CMs, miscarriage, pre-eclampsia, preterm birth, and other complications.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

36.

The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis.

Author: ZengRui, XuChun-Hua, XuYuan-Ning, WangYa-Li, WangMian

Lower homocysteine
Stroke risk

This meta-analysis investigates the effect of folic acid supplementation on homocysteine levels and stroke risk, considering different folate fortification statuses.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

37.

The impact of MTHFR 677 C/T genotypes on folate status markers: a meta-analysis of folic acid intervention studies.

Author: ColsonNatalie J, NaugHelen L, NikbakhtElham, ZhangPing, McCormackJoanna

folate status improvement
adverse effects

This study assessed the influence of methylenetetrahydrofolate reductase (MTHFR) genotype on folate status and response to supplementation. The study found that the T variant of the MTHFR gene increases the risk of low folate status, particularly in individuals with low folate intake. Adequate folate intake is crucial to override genetic effects and ensure optimal folate status.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

38.

Effects and safety of periconceptional oral folate supplementation for preventing birth defects.

Author: De-RegilLuz Maria, Peña-RosasJuan Pablo, Fernández-GaxiolaAna C, Rayco-SolonPura

Prevented NTDs

This Cochrane review examines whether periconceptional folate supplementation reduces the risk of neural tube and other congenital anomalies without causing adverse outcomes in mothers or babies. Daily folic acid supplementation, alone or in combination with other vitamins and minerals, was found to be effective in preventing neural tube defects. However, there was no clear evidence that it affected other birth defects, such as cleft palate or congenital cardiovascular defects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

39.

New Perspective on Impact of Folic Acid Supplementation during Pregnancy on Neurodevelopment/Autism in the Offspring Children - A Systematic Review.

Author: GaoYunfei, ShengChao, XieRi-Hua, SunWen, AsztalosElizabeth, ModdemannDiane, ZwaigenbaumLonnie, WalkerMark, WenShi Wu

Neurodevelopmental benefits
Prevents NTDs
Harmful effect at high dose

Folic acid supplementation during pregnancy is known to prevent neural tube defects (NTDs). This review explores the potential benefits of folic acid on other aspects of neurodevelopment, including autism spectrum disorders (ASDs). While evidence suggests potential benefits, further research is needed to confirm the impact of folic acid on neurodevelopment beyond NTDs.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

40.

Effects of folic acid on oligozoospermia with MTHFR polymorphisms in term of seminal parameters, DNA fragmentation, and live birth rate: a double-blind, randomized, placebo-controlled trial.

Author: HuangWen-Jie, LuXi-Lan, LiJun-Tao, ZhangJian-Min

Higher pregnancy rate
Improved sperm quality
Folic acid deficiency

Folic acid supplementation had a beneficial effect on oligozoospermia with MTHFR 677 TT genotype in terms of seminal parameters, seminal MDA, sperm DNA fragmentation, and pregnancy outcome.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

41.

The Protective Effect of Maternal Folic Acid Supplementation on Childhood Cancer: A Systematic Review and Meta-analysis of Case-control Studies.

Author: Wan IsmailWan Rosmawati, Abdul RahmanRaudah, RahmanNur Ashiqin Abd, AtilAzman, NawiAzmawati Mohammed

Childhood cancer risk

Folic acid is a vitamin that is important for pregnant women. It is recommended that all pregnant women take a folic acid supplement to prevent birth defects. This study investigated the relationship between maternal folic acid intake and the risk of childhood cancer.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

42.

Folic Acid Supplementation Improves Glycemic Control for Diabetes Prevention and Management: A Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

Author: AsbaghiOmid, Ashtary-LarkyDamoon, BagheriReza, MoosavianSeyedeh Parisa, OlyaeiHadi Pourmirzaei, NazarianBehzad, Rezaei KelishadiMahnaz, WongAlexei, CandowDarren G, DutheilFrédéric, SuzukiKatsuhiko, Alavi NaeiniAmirmansour

Glycemic control

Folic acid supplementation significantly reduces some markers of glycemic control in adults, including fasting blood glucose, fasting insulin, and hemoglobin A1C. However, these reductions are small and may not have significant clinical applications for adults with type II diabetes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

43.

The Effects of Folic Acid Supplementation on Pro-inflammatory Mediators: a Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

Author: ZargarzadehNikan, SeveroJuliana Soares, PizarroAna Beatriz, PersadEmma, MousaviSeyed Mohammad

This study provides a comprehensive review of the effects of folic acid supplementation on inflammatory biomarkers in adults. Existing research on this topic has been controversial and inconclusive, so the study aims to summarize findings from available clinical trials and assess the overall impact of folic acid supplementation on inflammation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

44.

Human milk unmetabolized folic acid is increased following supplementation with synthetic folic acid as compared to (6S)-5-methyltetrahydrofolic acid.

Author: CochraneKelsey M, ElangoRajavel, DevlinAngela M, HutcheonJennifer A, KarakochukCrystal D

Increased milk folate
Increased milk UMFA
Potential impact on folate metabolism
Potential impact on infant health

Folic acid supplementation increased unmetabolized folic acid (UMFA) in human milk compared to (6S)-5-MTHF supplementation. Further research is needed to assess the impact of increased UMFA on infant health outcomes.

Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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