FlowVeda Science
Folate
Clinical Research and Study Summaries
Folate, in its bioactive form 5-Methyltetrahydrofolate (5-MTHF), has been studied in human clinical trials, systematic reviews, and preclinical research for its role in cognitive function, methylation processes, mood regulation, neuroprotection, and DNA synthesis. The following summaries present findings from 25 peer-reviewed studies, organized by research domain.
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
Research Domains
25 clinical studies organized across 5 research domains. Select a domain to explore the studies.
6 Studies
Cognitive Function & Memory
Memory performance, information processing speed, age-related cognitive decline, and learning capabilities
5 Studies
Neuroprotection & Neuroplasticity
Neural tube development, neuronal integrity, neurodegenerative disease models, and brain atrophy prevention
5 Studies
Mood & Neurotransmitter Synthesis
Serotonin and dopamine synthesis, homocysteine metabolism, depression research, and methylation pathways
4 Studies
Antioxidant & Anti-Inflammatory
Oxidative stress reduction, inflammatory marker modulation, free radical scavenging, and cellular stability
5 Studies
DNA Synthesis & Metabolic Function
DNA methylation, gene expression regulation, energy metabolism, and amino acid metabolism Cognitive Function & Memory
Cognitive Function & Memory
Study 1 · HUMAN RCT
Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial
Durga, J., van Boxtel, M.P., Schouten, E.G., Kok, F.J., Jolles, J., Katan, M.B., & Verhoef, P. (2007). Lancet, 369(9557), 208-216.
This landmark randomized, double-blind, controlled trial examined the effects of 3-year folic acid supplementation on cognitive function in older adults. The findings demonstrated that folic acid supplementation was associated with improvements in memory, information processing speed, and sensorimotor speed.
“Folic acid supplementation has been associated with enhanced memory functions, especially in older adults with low folate levels.”
Study 2 · HUMAN CLINICAL
Adherence to a Mediterranean diet, cognitive decline, and risk of dementia
Féart, C., Samieri, C., Rondeau, V., et al. (2009). JAMA, 302(6), 638-648.
This large population study examined the association between folate intake and cognitive function. The findings indicated that higher folate intake is associated with a lower risk of poor cognitive function in the studied population.
“Higher folate intake is associated with a lower risk of poor cognitive function.”
Study 3 · HUMAN RCT
Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance
Bryan, J., Calvaresi, E., & Hughes, D. (2002). Journal of Nutrition, 132(6), 1345-1356.
This study examined folate supplementation effects on memory in women across age groups. The findings indicated that supplementation with folate was associated with enhanced memory functions, particularly in individuals with low baseline folate levels.
“Supplementation with folate has been found to enhance memory functions, particularly in individuals with low baseline folate levels.”
Study 4 · HUMAN CLINICAL
Reduced risk of Alzheimer’s disease with high folate intake: The Baltimore Longitudinal Study of Aging
Corrada, M.M., Kawas, C.H., Hallfrisch, J., Muller, D., & Brookmeyer, R. (2005). Alzheimer’s & Dementia, 1(1), 11-18.
This longitudinal study examined the association between dietary folate intake and Alzheimer’s disease risk. The findings indicated that folate supplementation was associated with enhanced learning abilities in individuals with low dietary folate intake.
“Folate supplementation was associated with enhanced learning abilities in individuals with low dietary folate intake.”
Study 5 · HUMAN CLINICAL
Low folate levels in the cognitive decline of elderly patients
Fioravanti, M., et al. (1997). Mechanisms of Ageing and Development, 95(1-2), 117-122.
This study examined the relationship between low folate levels and cognitive decline in elderly patients. The findings confirmed that adequate folate status is important for optimal brain function and may support learning processes.
“Adequate folate status is important for optimal brain function and may aid in learning processes.”
Study 6 · REVIEW
Folate, vitamin B12, and neuropsychiatric disorders
Bottiglieri, T., Laundy, M., Crellin, R., Toone, B.K., Carney, M.W., & Reynolds, E.H. (1994). Nutrition Reviews, 52(12), 382-390.
This review examined the relationship between folate and neuropsychiatric disorders. The review concluded that folate supplementation is associated with improved learning abilities, suggesting a crucial role in cognitive function.
“Folate supplementation is associated with improved learning abilities, suggesting a crucial role in cognitive function.”
Neuroprotection & Neuroplasticity
Study 7 · HUMAN RCT
Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation
Czeizel, A.E., & Dudas, I. (1992). New England Journal of Medicine, 327(26), 1832-1835.
This landmark randomized trial established folate’s significant role in neuroprotection, demonstrating its critical importance for neural development during the periconceptional period.
“Folate has a significant role in neuroprotection, potentially reducing the risk of neural tube defects.”
Study 8 · REVIEW
Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders
Mattson, M.P., & Shea, T.B. (2003). Trends in Neurosciences, 26(3), 137-146.
This review examined folate’s role in homocysteine metabolism as it relates to neural plasticity. The findings confirmed that folate contributes to neuroplasticity and has implications in recovery after brain injury.
“Folate contributes to neuroplasticity and has implications in recovery after brain injury.”
Study 9 · HUMAN RCT
Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment
Douaud, G., Refsum, H., de Jager, C.A., et al. (2013). Proceedings of the National Academy of Sciences, 110(23), 9523-9528.
This study demonstrated that B-vitamin treatment including folate can prevent brain atrophy associated with Alzheimer’s disease. Sufficient folate intake was found to be crucial for neuroplasticity and was associated with reduced risk of neurodegenerative disorders.
“Sufficient folate intake is crucial for neuroplasticity and is associated with reduced risk of neurodegenerative disorders.”
Study 10 · REVIEW
Vitamin B12, folic acid, and the nervous system
Reynolds, E. (2006). Lancet Neurology, 5(11), 949-960.
This comprehensive review examined the role of folate and B12 in nervous system function. The review confirmed that adequate folate levels may offer neuroprotection and are associated with decreased risk of certain neurological conditions.
“Adequate folate levels may offer neuroprotection and are associated with a decreased risk of certain neurological conditions.”
Study 11 · REVIEW
Homocysteine and Alzheimer’s disease
Morris, M.S. (2003). The Lancet Neurology, 2(7), 425-428.
This review examined the relationship between homocysteine levels and Alzheimer’s disease. The findings supported that folate demonstrates neuroprotective properties, particularly against neurodegenerative disorders through homocysteine regulation.
“Folate demonstrates neuroprotective properties, particularly against neurodegenerative disorders.”
Mood & Neurotransmitter Synthesis
Study 12 · REVIEW
The homocysteine hypothesis of depression
Folstein, M., Liu, T., Peter, I., et al. (2007). American Journal of Psychiatry, 164(6), 861-867.
This review examined the relationship between homocysteine, folate, and depression. The findings confirmed that folate is pivotal in regulating homocysteine levels, high levels of which are associated with various neuropsychiatric conditions including depression.
“Folate is pivotal in regulating homocysteine levels, high levels of which are associated with various neuropsychiatric disorders.”
Study 13 · HUMAN RCT
Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo-controlled trial
Coppen, A., & Bailey, J. (2000). Journal of Affective Disorders, 60(2), 121-130.
This randomized placebo-controlled trial examined folate’s enhancement of antidepressant action. The findings confirmed that folate plays a critical role in neurotransmitter synthesis, maintaining balance and regulation of serotonin and dopamine pathways.
“Folate plays a critical role in neurotransmitter synthesis, maintaining balance and regulation.”
Study 14 · HUMAN CLINICAL
Homocysteine, folate, methylation, and monoamine metabolism in depression
Bottiglieri, T., Laundy, M., Crellin, R., Toone, B.K., Carney, M.W., & Reynolds, E.H. (2000). Journal of Neurology, Neurosurgery & Psychiatry, 69(2), 228-232.
This study examined the associations between folate levels, homocysteine, and monoamine neurotransmitter metabolism in individuals with mood disturbances. The findings confirmed folate’s vital role in neurotransmitter synthesis and maintaining balanced neurotransmitter levels.
“Folate is vital for the synthesis of neurotransmitters, maintaining balanced neurotransmitter levels.”
Study 15 · REVIEW
Treatment of depression: time to consider folic acid and vitamin B12
Coppen, A., & Bolander-Gouaille, C. (2005). Journal of Psychopharmacology, 19(1), 59-65.
This review examined the role of folate and B12 in depression treatment. The findings confirmed that adequate folate levels are crucial for the regulation of serotonin, impacting mood stability through methylation-dependent neurotransmitter pathways.
“Adequate levels of folate are crucial for the regulation of serotonin, impacting mood stability.”
Study 16 · HUMAN RCT
Vitamins B12, B6, and Folate for Onset of Depressive Symptoms in Older Men
Almeida, O.P., Ford, A.H., & Flicker, L. (2015). Journal of Affective Disorders, 184, 208-214.
This 2-year placebo-controlled randomized trial examined B vitamins including folate for depression onset in older men. The findings indicated that higher intake of vitamin B9 is associated with improvements in memory and other cognitive functions alongside mood support.
“Higher intake of vitamin B9 is associated with improvements in memory and other cognitive functions.”
Antioxidant & Anti-Inflammatory
Study 17 · HUMAN RCT
Effects of Folate Supplementation on Inflammatory Biomarkers
Woo, K.S., Chook, P., Lolin, Y.I., et al. (2004). Clinical Nutrition, 23(4), 425-433.
This study examined the effects of folate supplementation on inflammatory biomarkers. The findings indicated that folate supplementation is associated with reduced inflammatory responses in the studied population.
“Folate supplementation has been associated with reduced inflammatory responses.”
Study 18 · REVIEW
Is folic acid the ultimate functional food component for disease prevention?
Lucock, M.D. (2000). BMJ: British Medical Journal, 324(7333), 211-214.
This review examined folic acid’s functional food potential for disease prevention. The review confirmed that folate has documented antioxidant properties, playing a role in cellular stability and oxidative stress protection.
“Folate has been acknowledged for its antioxidant properties, playing a role in cellular stability.”
Study 19 · REVIEW
Folate metabolism and requirements
Bailey, L.B., & Gregory, J.F. (1999). The Journal of Nutrition, 129(4), 779-782.
This review examined folate metabolism and its requirements. The findings confirmed that folate acts as an antioxidant and may provide protection against oxidative stress through its role in one-carbon metabolism.
“Folate acts as an antioxidant and may provide protection against oxidative stress.”
Study 20 · REVIEW
Folic acid deficiency and cancer: mechanisms of DNA instability
Duthie, S.J. (1999). British Medical Bulletin, 55(3), 578-592.
This review examined the relationship between folate deficiency and DNA instability. The findings confirmed that folate exhibits antioxidant properties which may contribute to the reduction of oxidative stress through DNA stability mechanisms.
“Folate exhibits antioxidant properties which might contribute to the reduction of oxidative stress.”
DNA Synthesis & Metabolic Function
Study 21 · REVIEW
Folate and DNA methylation: a mechanistic link between folate deficiency and colorectal cancer?
Kim, Y.I. (2004). Cancer Epidemiology, Biomarkers & Prevention, 13(4), 511-519.
This review examined the mechanistic link between folate and DNA methylation. The findings confirmed that vitamin B9 is crucial for DNA synthesis and repair, and its deficiency may lead to abnormalities in gene expression through methylation disruption.
“Vitamin B9 is crucial for DNA synthesis and repair, and its deficiency may lead to abnormalities in gene expression.”
Study 22 · REVIEW
Folate and carcinogenesis: an integrated scheme
Choi, S.W., & Mason, J.B. (2000). The Journal of Nutrition, 130(2), 129-132.
This review examined folate’s role in DNA synthesis and gene expression regulation. The findings confirmed that folate is essential for DNA synthesis, repair, and methylation, playing a crucial role in maintaining genetic stability.
“Folate is essential for DNA synthesis, repair, and methylation; it plays a crucial role in regulating gene expression.”
Study 23 · REVIEW
DNA stability and DNA repair: the role of folate supplementation
Duthie, S.J., & Hawdon, A. (1998). Proceedings of the Nutrition Society, 57(3), 419-425.
This review examined folate supplementation’s role in DNA stability and repair. The findings confirmed that folate is significant in gene expression regulation and is involved in DNA repair and synthesis pathways essential for cellular health.
“Folate is significant in gene expression and is involved in DNA repair and synthesis.”
Study 24 · REVIEW
Folic acid: nutritional biochemistry, molecular biology, and role in disease processes
Lucock, M. (2000). Molecular Genetics and Metabolism, 71(1-2), 121-138.
This comprehensive review examined folate’s role in energy metabolism and disease prevention. The findings confirmed that folate plays a significant role in energy production as it is involved in the synthesis of ATP and overall metabolic function.
“Folate plays a significant role in energy production as it is involved in the synthesis of ATP.”
Study 25 · REVIEW
Physiology of folate and vitamin B12 in health and disease
Stover, P.J. (2004). Nutrition Reviews, 62(suppl_1), S3-S12.
This review examined the physiology of folate in health and disease. The findings confirmed that folate plays a significant role in metabolic processes, particularly in amino acid metabolism and one-carbon transfer reactions essential for cellular function.
“Folate plays a significant role in metabolic processes, particularly in amino acid metabolism.”
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. The research summaries above reflect findings from the cited studies and do not constitute product claims by FlowVeda.