FOLATE – Folic Acid

Folate is the Natural source; Folic Acid is synthetic.

Folate is an essential member of the vitamin B complex family that is naturally present in grains, green leafy vegetables, and liver. Folic acid and the L-methylfolate derivative are synthetic supplemental forms that have higher bioavailability ⁽¹⁾. Folate is important for cell growth and division, and is involved in methylation and DNA

synthesis. Inadequate intake can cause deficiency leading to megaloblastic anemia.

Folate is essential during pregnancy, with supplementation shown to reduce risks of neural tube birth defects ⁽¹⁰⁾ and medulloblastoma in offspring ⁽¹¹⁾. A study among South American populations suggests the protective effect against neural tube defects may be greater in female than male infants ⁽⁶⁵⁾. In high doses (5 mg/day), it reduced homocysteine levels at time of delivery and may lessen pregnancy complications ⁽⁴³⁾. Supplementation may also benefit women with polycystic ovary syndrome ⁽⁴²⁾ along with improving BMI ⁽⁸⁹⁾, but supplements taken beyond the first trimester did not prevent pre-eclampsia in women at high risk for this disorder ⁽⁷²⁾. In a large multicenter trial, folic acid and zinc supplementation by male partners of couples seeking infertility treatment did not improve semen quality or live birth rates ⁽⁸¹⁾. In postmenopausal women, folic acid may help reduce hot flushes, but confirmatory data are needed ⁽⁸⁶⁾.

In older adults, folate supplementation may improve cognitive function ⁽²⁶⁾. In patients with Alzheimer’s disease, it improved response to cholinesterase inhibitors ⁽²⁷⁾, cognition, and inflammatory markers ⁽⁴⁶⁾.

Folate decreases homocysteine levels, a risk factor for cardiovascular disease (CVD) mortality ^{(13) (14) (15)}, improves BMI in those with high homocysteine levels ⁽⁸⁹⁾ along with lowering blood pressure in smokers ^(5) (16) and in patients with CVD and overweight individuals ⁽⁹⁰⁾. A combination of folic acid and vitamin B12 supplements also decreased homocysteine levels and improved anemia in patients with multiple sclerosis ⁽⁷⁴⁾, but evidence is limited on whether supplementation has an effect on anemia in patients with sickle cell disease ⁽⁶⁸⁾. Among hypertensive adults, folic acid therapy reduced risk of first stroke ^{(44) (45) (66)}, but smoking status may affect efficacy ⁽⁶⁷⁾. Other trials on stroke risk have yielded mixed results ^{(17) (18) (19) (20)} with meta-analyses confirming reductions in the risks of cardiovascular disease and stroke ^(73) (91).

In other studies, folate lowered blood arsenic concentrations of chronically exposed individuals by facilitating its urinary excretion ⁽²⁸⁾. It was also associated with lower risk of progression of early-to-late age-related macular degeneration ⁽⁹²⁾ and when added to antipsychotics, may improve symptoms in schizophrenic patients ⁽⁷⁵⁾, but did not have any significant effects on memory ⁽⁹³⁾.