Folic acid is a vital nutrient in diet. Its primary action is on formation of red blood cells and also in the formation of chemicals essential for DNA manufacture.
How does folate function in the body?
Folic acid’s primary mechanisms of action are through its role as a one carbon donor. Folate helps in the transfer of a single methyl group in various metabolic reactions in the body and in the functioning of the nervous system. It is essential for DNA synthesis. For the reactions the following steps are important:
- Amino acid Serine reacts with tetrahydrofolate to form 5,10-methylenetetrahydrofolate. This is the folate derivative involved in DNA synthesis.
- A methyl group is donated to cobalamin (B12) by 5-methyltetrahydrofolate to form methylcobalamin.
- With the help of the enzyme methionine synthase, methylcobalamin donates a methyl group to the amino acid metabolite homocysteine. This homocysteine is then converted to amino acid methionine
- Methionine is then converted to S-adenosyl-methionine (SAMe), a methyl donor involved in numerous biochemical processes.
Folate deficiency
Folic acid deficiency is considered to be one of the most common nutritional deficiencies. It is seen in those with excess demands or in those with excess losses of folate. Causes of deficiency include:
- excess demand states e.g. pregnancy and breast feeding mothers and in cancer patients on certain drugs like Methotrexate
- deficient food supply
- deficient absorption for example in HIV disease
- defects in utilization e.g. in alcoholics and those with liver disease
- certain drugs that interfere with folate utilization like diuretics, anti-cancer drugs
- folate losses in hemodialysis
- deficiencies in enzymes or cofactors needed for the generation of active folic acid
Signs and symptoms of folate deficiency
Signs and symptoms of folate deficiency include symptoms of:
- anemia
- fatigue
- irritability
- diarrhea
- weight loss
- insomnia
- depression
- nerve damage
- tingling and numbness of fingers and toes
- tendon hyper-reflexivity
- cognitive disturbances
- loss of memory
- behavioral disorders and psychiatric disorders
What is folate needed for?
Folate is beneficial for:
Pregnancy
Low dietary intake of folic acid increases the risk for delivery of a child with a neural tube defect. As the fetus develops its spine and nerve form rapidly during the first few weeks of pregnancy, its requirements of folate is also high. Folate supplementation early in pregnancy can prevent nerve damage in the unborn child.
Lack of folate may give rise to several disorders like malformations of the spine (spina bifida), malformations of brain (anencephaly – small of absent brain) and nerve damage.
Folates also increase birth weight, prevent congenital heart defects, mental retardation, cleft lip, limb defects, and urinary tract abnormalities.
Folates in men
Folic acid may also reduce chromosomal defects in sperm among men. A benefit is indicated even for more than 700 mcg folate per day.
Anemia
Lack of folate and vitamin B12 leads to macrocytic anemia. This can be corrected by combined supplementation of diet with folate, vitamin B 12 and iron supplements. Therapeutic doses are usually 1 mg folate daily. It may take as little as 15 days of supplementation to correct anemia.
Homocysteinemia and heart disease
Homocysteine is a protein in blood that is raised in heart disease and raises risk of heart attacks and stroke. Elevated plasma homocysteine has been connected to increased risk of neural tube defects and other birth defects as well as to mental ailments like schizophrenia, Alzheimer’s disease, cognitive decline and other disorders like osteoporosis, rheumatoid arthritis, kidney failure and cancer. Folate supplementation has been found to reduce the amounts of homocysteine in blood.
Inflammatory Bowel Disease
Those with inflammatory bowel disease (IBD) like Crohn’s disease and ulcerative colitis often have folate deficiencies. This could be due to their medication like sulfasalazine, prescribed for IBD and also lowered absorption of folates. Folic acid supplementation might lower the risk of colon cancer in these patients.
Mental ailments
Folate deficiencies are seen in several mental ailments like dementia, schizophrenia, insomnia, irritability, forgetfulness, depression, psychosis, peripheral neuropathy (damage of smaller nerves of the limbs and extremities), myelopathy (nerve damage), and restless legs syndrome.
Gum disease
Folic acid can increase the resistance of the gums to local irritants and prevent inflammation.
Folic acid in obesity prevention
Folic acid increases breakdown of fats. This may help in prevention of` obesity and type 2 diabetes. Folic acid supplements may also reduce the accumulation of cholesterol in the liver and in the blood.
Folic acid in allergy
Folic acid supplementation may also help in decreasing features of allergy, atopy, wheeze, and asthma.
Folic acid in rheumatoid arthritis
Folic acid supplementation has been seen to have a protective effect against rheumatoid arthritis
Health risk of too much folic acid
Risk of overdosage of folates is low since this is a water soluble vitamin and can be easily removed from the body through urine.
The Institute of Medicine has established a tolerable upper intake level (UL) for folate of 1 mg for adult men and women, and a UL of 800 µg for pregnant and breast feeding women. Excess folates may unmask vitamin B 12 deficiency and lead to nerve damage.
Further Reading
The effects of high maternal folate intake on the health outcomes of offspring