Folate

3 imperatives to transform health care in America. You're invited to watch it live

Free

E-newsletter

Subscribe to Housecall

Our weekly general interest
e-newsletter keeps you up to date on a wide variety of health topics.

Sign up now

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Folate deficiency
Folate deficiency will occur if the body does not get the adequate amount of folic acid from dietary intake. Folic acid has been shown to be effective in the treatment of megaloblastic and macrocytic anemias due to folate deficiency. 		A
Folate deficiency in alcoholics
Folate deficiency has been observed in alcoholics. Alcohol interferes with the absorption of folate and increases excretion of folate by the kidney. Many alcohol abusers have poor quality diets that do not provide the suggested intake of folate. Increasing folate intake through diet, or folic acid intake through fortified foods or supplements, may be beneficial to the health of alcoholics. 		A
Hyperhomocysteinemia
Homocysteine is considered a significant risk factor for cardiovascular disease, and levels of homocysteine are modified by B vitamins, including folate. 		A
Megaloblastic anemia - due to folate deficiency
Folate deficiency may cause megaloblastic (or macrocytic) anemia. In this type of anemia, red blood cells are larger than normal, and the ratio of nucleus size to cell cytoplasm is increased. There are other potential causes of megaloblastic anemia, including vitamin B12 deficiency or various inborn metabolic disorders. If the cause is folate deficiency, then treatment with folate is the standard approach. Patients with anemia should be evaluated by a physician in order to diagnose and address the underlying cause. 		A
Prevention of pregnancy complications (neural tube defects)
Consuming a high dietary intake of folate and taking folic acid supplements orally during pregnancy reduces the risk of neural tube birth defects or cleft palate in the infant. 		A
Methotrexate toxicity
Folate supplementation is beneficial in patients being treated with long-term, low-dose methotrexate for rheumatoid arthritis (RA) or psoriasis. Development of folate deficiency is associated with increased risk of certain side effects, including gastrointestinal effects, stomatitis, alopecia, abnormal liver function tests, myelosuppression, megaloblastic anemia, and increased homocysteine levels, which are associated with cardiovascular disease. People who have experienced side effects may need to continue taking folic acid for the duration of methotrexate therapy. Patients receiving methotrexate for cancer should avoid folic acid supplements, unless suggested by their oncologist. There is some evidence that folic acid supplements reduce the efficacy of methotrexate in the treatment of acute lymphoblastic leukemia, and theoretically they could reduce its efficacy in the treatment of other cancers. 		B
Acute lymphocytic leukemia
Preliminary evidence suggests that vitamin use during pregnancy might protect against acute lymphoblastic leukemia. The effects of folate alone are not clear. Well-designed clinical trials of folate supplementation are needed before a conclusion may be drawn. 		C
Alzheimer's disease
Preliminary evidence indicates that low folate concentrations might be related to Alzheimer disease. Well-designed clinical trials of folate supplementation are needed before a conclusion may be drawn. 		C
Anemia
The effect of folic acid on iron-deficiency anemia is not clear. Well-designed clinical trials of folate supplementation are needed in iron-supplemented individuals before a conclusion may be drawn. 		C
Arsenic poisoning
Folate may lower blood arsenic concentrations and thereby contribute to the prevention of arsenic-induced illnesses. Additional research is needed in this area. 		C
Cancer (general)
Preliminary evidence surrounding the use of folate seems promising for decreasing the risk of breast, cervical, pancreatic, and gastrointestinal cancer. However, currently there is insufficient evidence available to suggest folate supplementation for any type of cancer prevention or treatment. Please follow the advice of a qualified healthcare provider in this area. 		C
Cardiovascular disease
Homocysteine is considered a significant risk factor for vascular disease and may be modified by B vitamins, including folate. However, the effect of B vitamins on clinical vascular outcomes such as CVD has been investigated, and the evidence for vascular disease outcomes is unlikely. 		C
Chronic fatigue syndrome
Some patients with chronic fatigue syndrome (CFS) also have decreased folic acid levels. Daily injections of a combination of folic acid, bovine liver extract, and vitamin B12 for three weeks were not beneficial for CFS in one study. 		C
Coronary artery disease
Folic acid might prevent nitroglycerin-induced nitrate tolerance and cross tolerance to endothelial nitric oxide, which plays a role in blood pressure control. These conditions need to be treated by a qualified healthcare provider. 		C
Depression
Folic acid deficiency has been found among people with depression and has been linked to poor response to antidepressant treatment. Folate supplements have been used for enhancing treatment response to antidepressants. Limited clinical research suggests that folic acid is not effective as a replacement for conventional antidepressant therapy. Depression should be treated by a qualified healthcare provider. 		C
Diabetes
The effect of folic acid on diabetes is not clear. Well-designed clinical trials of folate supplementation are needed before a conclusion may be drawn. 		C
Down's syndrome
One study does not show a protective effect of folic acid on heart anomalies among infants with Down syndrome. In Japan, decreased folate status was a maternal risk factor for Down syndrome. Further study is needed. 		C
Epilepsy
Early study does not show a protective effect of folic acid for epilepsy. Further study is needed. 		C
Fragile X syndrome
Folic acid supplementation has been shown not to improve symptoms of Fragile X syndrome. 		C
Growth
Use of multiple vitamins and minerals has been found to improve growth. The effect of folate alone is not clear. 		C
Hearing loss
Folic acid supplementation slowed the decline in hearing of speech frequencies associated with aging in a population from a country without folic acid fortification of food. The effect requires confirmation, especially in populations from countries with folic acid fortification programs. 		C
High blood pressure associated with pregnancy
A combination therapy, including folate, in women with high blood pressure during pregnancy made it possible to maintain pregnancy until delivery was beneficial for both the mother and child. More well-designed studies are needed to examine the role of folate monotherapy in this condition. 		C
High blood sugar/glucose intolerance
In individuals with high blood sugar, folic acid in combination with enalapril resulted in a greater reduction in blood glucose levels compared to enalapril alone. More trials are needed before a conclusion may be drawn. 		C
Hypertension
Some study suggests that folic acid supplementation might decrease systolic blood pressure and improve flow-mediated dilation. Further study is needed to confirm these results. 		C
Kidney disease (chronic)
Although homocysteine lowering with folic acid with or without other B vitamins does not appear to reduce the risk of cardiovascular disease in general populations, cardiovascular disease risk is reduced in patients with chronic kidney disease. Most included studies are small, and further study is needed. 		C
Lometrexol toxicity
Folic acid supplementation is unclear with respect to reduction of toxicity from the cancer drug lometrexol. 		C
Mucositis from cancer treatment (mouth ulcers/irritation)
The effect of folinic acid on mucositis associated with cancer treatment is not clear. Further study is required. 		C
Phenytoin-induced gingival hyperplasia
Early evidence shows that applying folic acid topically may inhibit gingival hyperplasia (overgrowth of gum tissue) secondary to phenytoin therapy. Oral folic acid supplementation has not been proven to be beneficial. More research is needed in this area. 		C
Pregnancy-related gingivitis
Based on preliminary data, applying folic acid topically may improve gingivitis in pregnant women. Well-designed clinical trials are needed to confirm these results. 		C
Stroke
Study results are mixed for the use of folate in stroke patients. Further research is needed in this area before a strong conclusion may be made. 		C
Vitiligo
Based on preliminary data, folic acid and vitamin B12 may improve the symptoms of vitiligo. Further research is needed to confirm these results. 		C
Cognitive function
Combined B vitamin supplementation did not delay cognitive decline among women with CVD or CVD risk factors. The possible cognitive benefits of supplementation among women with a low dietary intake of B vitamins warrant further study. 		D
Prevention of pregnancy complications (other)
Studies have proven that folate consumption during pregnancy prevents deficiency and associated anemia in pregnant women. Low folate levels during pregnancy may contribute to birth defects and pregnancy loss. However, folate does not appear to reduce the number of stillbirths. Use of folate during pregnancy is associated with increased twinning, although this is unlikely to be due to folate itself. Overall studies suggest that folate use does not significantly reduce the risk of cleft palate in the infant or severe congenital heart disease. Studies suggest that folate use does not prevent pregnancy complications other than neural tube defects. Further research is needed in this area before a strong conclusion may be made. 		D
Colorectal cancer
Evidence suggests that increased dietary folate intakes or folate status is associated with decreased risk of colorectal or colon cancer. However, folate supplementation studies in general indicate a lack of protective effect for colorectal cancer with increased risk found in one meta-analysis. Currently there is insufficient evidence available to suggest folate supplementation for any type of cancer prevention or treatment. 		F

Key to grades
A Strong scientific evidence for this use
B Good scientific evidence for this use
C Unclear scientific evidence for this use
D Fair scientific evidence against this use (it may not work)
F Strong scientific evidence against this use (it likely does not work)

Grading rationale

Uses based on tradition or theory

The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

AIDS, anemia (associated with inflammatory bowel disease), anti-aging (preventing signs of aging), aphthous ulcers (canker sore), appetite stimulation, arsenic poisoning, autism, cardiovascular disease risk, celiac disease, colorectal adenoma, critical illness (supplementation due to refusal of blood transfusion), Crohn's disease, dental conditions, fistula (abnormal connection in the blood vessel), fracture (risk reduction), gastritis (atrophic), genetic damage (X-ray-induced chromosomal damage), infertility, inflammatory bowel disease, insomnia, ischemic heart disease, lichen planus (itchy rash in the mouth), liver disease, low birth weight, macular degeneration, memory enhancement, mood, myofascial pain (pain in muscles and fascia), osteoporosis, peripheral neuropathy, restless leg syndrome, retinal vein occlusion (blocked vein in the eye), schizophrenia, sickle cell anemia, spinal cord injury (myelopathy), thrombosis, ulcerative colitis, weight loss.

Dosing Related terms
NS_patient-folate Portions of this document last updated: Sept. 1, 2012

THIS EVIDENCE-BASED MONOGRAPH WAS PREPARED BY
THE NATURAL STANDARD RESEARCH COLLABORATION
(www.naturalstandard.com)

Advertisement


Text Size: smaller largerlarger