Folate/Folic Acid

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Folate/Folic Acid (Vitamin B9)
  Evaluated for:
Effectiveness Rating Effectiveness Rating
Anemia caused by folate deficiency
+3 (Strong Evidence)
Neural tube birth defects (such as spina bifida)
+3 (Strong Evidence)
Migraine
+1 (Slight Evidence)
Depression
+1 (Slight Evidence)
Frequent Early Miscarriage
+1 (Slight Evidence)

PRO

  • Folate, vitamin B9, is found in many whole foods, especially leafy greens like spinach, kale, chard, and lettuce (think FOL-iage). Other good sources include broccoli, asparagus, okra, mushrooms, and tomatoes, whole grains, legumes, yeast, and fruits.  Folic acid, the synthetic form of folate, is added to flour used for commercial baking.
  • Folate is beneficial for treating folate deficiency, associated megaloblastic anemia. It lowers homocysteine levels. Its widespread addition to flour has decreased the incidence of spinal bifida and other neural tube defects by 80%. It has also decreased the risk of certain cancers.
  • Folate is often used for arthritis patients who take the medication methotrexate to control symptoms.
  • Folate may help decrease migraines, depression, and miscarriages. 

CON

  • Folic acid, the synthetic form of folate, may, in high doses, be associated with an increased risk of prostate and colon cancer. These differences are significant; folate and folic acid are not the same supplement. Unfortunately packaging materials do not always reflect accurately their contents, so be aware.
  • Methotrexate is a chemotherapy medication that kills cancer cells by interfering with their metabolism of folate. So patients taking methotrexate specifically to treat cancer should NOT take folate.
  • Green tea may interfere with absorption of folic acid from supplements.

* *ADVISORY* *
Prostate cancer patients cancer should not take folate or folic acid.
Individuals with cancer who take a cancer-treating agent called methotrexate (MTX) should not take folate unless it is specifically prescribed by their oncologist (cancer specialist).  This is because MTX works by interfering with pathways that rely on folate for proper functioning.  However, individuals taking low-dose MTX for psoriasis or rheumatoid arthritis often use folate to reduce side effects.  In all cases, check with your doctor.

DOSAGE: To prevent folate deficiency, take 400 mcg twice a day.

CONCLUSION: We conclude that folate is a safe and effective supplement for folate deficiency and for prevention of neural birth tube defects. While it shows some promise for treating migraines and depression, and for preventing miscarriage, there is not enough evidence for us to support its use for these indications. The harm to health and possible increase in cancer risk comes with use of large doses of synthetic folic acid. Intake of folate from food has been shown to be beneficial. It is also associated with cancer prevention. A metabolized form of folate, called L-methyl folate or metafolin, is also beneficial. Consumers should be careful to understand that folate and folic acid are different products with different health profiles.

REFERENCES
“Folic Acid.” ConsumerLab.com. ConsumerLab.com LLC, 2013. 3 August 2013
“Folate.” Natural Standard –The Authority on Integrative Medicine. Natural Standard, 2013.
“Folic Acid.” Natural Standard –The Authority on Integrative Medicine. Natural Standard, 2013.
“Folic Acid.” Natural Medicines Comprehensive Database. Therapeutic Research Faculty, 2013. 8 November 2013.
Qian, X. et al. A meta-analysis of association between C677T polymorphism in the methylenetetrahydrofolate reductase gene and hypertension. European Journal of Human Genetics (2007) 15, 1239-1245
Rossi, M. et al. Folate Production by Probiotic Bacteria. Nutrients (2011) 3, 118-134
Figueiredo, J. et al. Folic Acid and Risk of Prostate Cancer: Results From a Randomized Clinical Trial. J Natl Cancer Inst (2009) 101:432-435
Park, Y. et al. Intakes of vitamins A, C, and E and use of multiple vitamin supplements and risk of colon cancer: a pooled analysis of prospective cohort studies. Cancer Causes Control (2010) 21:1745-1757
Farah, A. et al. The Role of L-Methylfolate in Depressive Disorders. CNS Spectrums (2009) 14(1):2
Rodriguez-Guillen, M. et al. Maternal MTHFR polymorphisms and risk of spontaneous abortion. Salud Public Mex (2009) 51:19-25
Samaan, Z. et al. Methylenetetrahydrofolate Reductase Gene Variant (MTHFR C677T) and Migraine: A Case Control Study and Meta-Analysis. BMC Neurology (2011) 11:66
Gupta, N. et al. Strong Association of 667 C>T Substitution in the MTHFR Gene with Male Infertility – A Study on an Indian Population and a Meta-Analysis. PLoS ONE (2011) 6(7):e22277
Crider, K. et al. MTHFR 677C  T genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation. The American Journal of Clinical Nutrition (2011) 93:1265-72
Lewis, S.J. et al. The thermolabile variant of MTHFR is associated with depression in the British Women’s Heart and Health Study and a meta-analysis. Molecular Psychiatry (2006) 11, 352-360


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