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Vitamin B9 (Folate, Folic Acid)

Vitamin B9 (Folate) Functions

Vitamin B9 is a water soluble vitamin, an essential nutrient, which is required for [1]:

  • Synthesis of DNA and RNA and thus production of new cells, including red blood cells (folate deficiency causes megaloblastic anemia)
  • Prevention of malformation of the neural tube (the tissue in a fetus, from which the brain and spinal cord develop)
  • Synthesis of the amino acids
  • Lowering blood homocysteine levels by converting homocysteine to methionine

The general name for vitamin B9 is folate, which refers to several vitamin B9 forms: folate–a salt of folic acid (naturally present in foods and in the human body), and synthetic forms: folic acid (in supplements and fortified foods), folinic acid or leucovorin, and levomefolic acid [1]. In the human body, all mentioned forms are converted to folate, which is the only active form of vitamin B9.

Folate has got its name from the Latin folium, which means leaf, since it can be obtained from green leafy vegetables.

Recommended Daily Intake

The Recommended Dietary Allowance (RDA) for folate for adults is 400 DFE (Dietary Folate Equivalents), during pregnancy 600 DEF and during breastfeeding 500 DEF [1]. 1 DFE = 1 mcg folate from foods, or 0.6 mcg folic acid from fortified foods or supplements.

Foods Sources of Folate

Folate-rich foods image

Picture 1. Foods high in folate

Examples of foods rich in folate:

  • PLANT FOODS: fortified ready-to-eat cereals, cornmeal, rice and wheat (bread and other baked products), legumes, quinoa, orange/juice, dark green leafy vegetables (spinach, Brussel’s sprouts), avocado, asparagus, artichokes, beets, sunflower seeds
  • ANIMAL FOODS: liver, mollusks (conch); other animal foods have only moderate amounts of folate
  • OTHER: yeast extract spread, baker’s yeast
  • Human breast milk contains sufficient amount of folate to meet the needs of infants 0-6 months of age.
  • References: [1,2]

In the U.S. and Canada, plain grain products, like white bread, white rice, pasta and cornmeal, are enriched with folic acid [5].

Drying can reduce the folate content of foods by up to 50% and cooking by 70% [6].

Absorption and Bioavailability

Folate is absorbed in the upper small intestine [12].

Folate absorption effectiveness: about 50% of folate naturally present in foods, 85% of folic acid from fortified foods or supplements when taken with food, and up to 100% of folic acid from supplements on an empty stomach is absorbed [1,11].

Vitamin C stimulates folate absorption [1].

Normal Blood Levels

Normal blood folate concentrations are above 3 ng/mL [11]. Recent folate intake from foods can greatly affect the blood folate levels, which may therefore not be the best indicator of the adequate amount of folate in the body.

Erythrocyte folate concentration has been proposed as a better indicator of the body folate stores; levels above 140 ng/mL are currently considered adequate [4,11].

Folate body stores in healthy adults may range from 0.5 to 20 mg [11].

Folate Deficiency: Causes, Symptoms

Causes

  • Low folate intake in starvation, chronic alcohol abuse, anorexia nervosa. Smoking also lowers blood folate levels.
  • Impaired intestinal absorption  in celiac disease, Crohn’s disease, tropical sprue, partial gastric removal [7], gastric bypass (bariatric surgery as a treatment of obesity) [8], small intestinal bacterial overgrowth (SIBO) [9]zinc deficiency, fructose malabsorption [10]
  • Increased folate requirements in infancy, pregnancy, lactation, infections, cancer, chronic hemolytic anemia
  • Genetic predisposition
  • Increased folate loss in hemodialysis and vitamin B12 deficiency
  • Medications with anti-folate effects: methotrexate, phenytoin, trimethoprim, pyrimethamine, triamterene, sulfasalazine, metformin, barbiturates
  • References: [3]

Symptoms and Signs

Symptoms and signs of folate deficiency may develop within 4-5 months after cessation of folate intake [11] and may include:

  • Anorexia, nausea, abdominal pain, diarrhea
  • Neurological problems: abnormal sensations (paresthesia: tingling and numbness), memory loss, insomnia
  • Red, sore, swollen, shiny tongue, difficulty swallowing (dysfagia), cracks in the lips corners (cheilosis)
  • Patchy brownish discoloration of the hands and feet (upper side of fingers and toes, palm creases)
  • Low-grade fever
  • Fatigue and shortness of breath due to megaloblastic anemia
  • Depression

Complications

Folate deficiency has been associated with increased risk of atherosclerosis, heart disease and Alzheimer’s disease [1,4].

Complications of low folate deficiency during pregnancy [11]:

  • Fetus: neural tube defects (resulting in serious spinal cord and brain disorders), low birth weight, miscarriage, cardiovascular malformations; severe language delay in children
  • Mother: preeclampsia (high blood pressure and edema in pregnancy), placental abruption

Diagnosis is made by a blood tests that show low folate and high homocysteine levels [5].

Treatment

  • Folate supplements
  • Potassium and iron supplements may be needed to prevent low blood potassium (hypokalemia) and iron levels caused by high folate doses [13].

Folic Acid Supplements

Without prescription (over-the-counter):

  • Folic acid
  • Folic acid is also included in B-complex, multivitamin and prenatal supplements.

By prescription:

  • Folica cid in doses 1 mg or higher require prescription.

Possible Folic Acid Supplements Benefits

Folic acid supplements are EFFECTIVE in:

  • Treatment and prevention of folate deficiency [4]. Folic acid supplements can prevent and treat megaloblastic anemia caused by either folate or vitamin B12 deficiency, and can thus mask the vitamin B12 deficiency. Untreated vitamin B12 deficiency can lead to a permanent neurological disorder, so it is important to determine the exact cause of megaloblastic anemia before starting treatment.

Folic acid supplements are LIKELY EFFECTIVE in [4]:

  • Treatment (with folinic acid) of certain hereditary disorders of folate metabolism [1]
  • Lowering homocysteine levels in people with kidney disease. High homocysteine were once considered as a risk factor for coronary heart disease and stroke but evidence is lacking.
  • Reducing nausea and vomiting in patients with rheumatoid arthritis or psoriasis treated with methotrexate
  • Decreasing the risk of neural tube defects in fetus, when taken by pregnant women. The Office of Dietary Supplements at the US National Health Institute recommends taking 400 mg folate from supplements or fortified foods (along with folate rich diet) to all pregnant women and to those who plan pregnancy, since they may lower the risk neural tube defects, which occurs in first month of the fetus life [5].

Folic acid supplements are POSSIBLY EFFECTIVE in:

  • Treatment of depression (in combination with conventional antidepressant medicines) [5]
  • Cerebral folate deficiency syndrome [1]
  • Reducing the risk of stroke by lowering homocysteine levels [11]

Folic acid supplements are POSSIBLY INEFFECTIVE or there is INSUFFICIENT EVIDENCE about their effectiveness in prevention or treatment of age-related hearing loss, age-related macular degeneration (AMD), alcoholism, Alzheimer’s disease, bipolar disorder, cancer (breast, cervical, colorectal, esophageal, lung, prostate, stomach), cleft lip, chronic fatigue syndrome (CFS), coronary heart disease, diabetes mellitus, epilepsy (seizures), fragile-X syndrome, gout, gum disease, heart attack or stroke, HIV/AIDS, infertility in men, insomnia, liver disease, muscle pain, nerve pain, osteoporosis, re-blockage of blood vessels after angioplasty, restless leg syndrome, sickle cell anemia, side effects of lometrexol, vitiligo, or improving memory and thinking skills in older people [1,4].

Folate Supplements Safety: Toxicity, Side Effects

According to Institute of Medicine in the US, the Tolerable Upper Intake Level (UL) for folic acid for adults is 1 mg/day [1].

Side effects of high doses of folate supplements include nausea, abdominal cramps, flatulence, diarrhea, rash, sleep disorders, confusion, irritability, behavior changes and seizures [4]. Doses 0.8-1.2 mg/day might increase the risk of heart attack, lung or cancer, especially prostate cancer [4,11]. Doses 5 mg/day or higher may cause neurological damage.

No side effects from folate from foods were observed so far [1].

Folic Acid Interactions With Drugs and Herbs

  • Foods and drugs that may reduce folate absorption: green tea, large doses of nonsteroid antiinflamatory drugs (NSAIDs), such as aspirin and ibuprofen, anticonvulsants phenytoin, phenobarbital, primidone, cholesterol-lowering drugs cholestiramine and colestipol.
  • Other drugs with anti-folate effects: methotrexate, trimethoprim, pyrimethamine, triamterene, sulfasalazine
  • Folic acid taken with 5-fluorouracil or capecitabine may cause stomach problems.
  • Folic acid may decrease the effectiveness of fosphenytoin, methotrexate, phenobarbital, phenytoin, primidone and pyrimethamine [4].
  • References: [1,4]

  1. Folate  Linus Pauling Institute
  2. List of foods high in folate  US Department of Agriculture
  3. Folic Acid Deficiency, Clinical Presentation  Emedicine
  4. Folic acid  MedlinePlus
  5. Folate  National Institutes of Health, Office of Dietary Supplements
  6. Nutritional effects of food processing; folate  SELF NutritionData
  7. Beyan C et al, 2007, Post-gastrectomy anemia: evaluation of 72 cases with post-gastrectomy anemia  PubMed
  8. Shah M et al, 2006, Long-Term Impact of Bariatric Surgery on Body Weight, Comorbidities, and Nutritional Status  The Journal of Clinical Endocrionology & Metabolism
  9. Bacterial Overgrowth Syndrome Clinical Presentation  Emedicine
  10. Ledochowski M et al, 1999, Fructose Malabsorption Is Associated with Lower Plasma Folic Acid Concentrations in Middle-Aged Subjects  Clinical Chemistry
  11. Folic acid deficiency  Emedicine
  12. Folate: Physiology of Absorption, Metabolism, and Excretion  The National Academic Press
  13. Megaloblastic Anemia Treatment  Emedicine

One Response to "Vitamin B9 (Folate, Folic Acid)"

  1. Pete Nelson says:

    Very helpful! I have been managing celiac disease for 20 years and had a gastric bypass 3 years ago due to a duodenum that was blocked by scar tissue due to long use of NSAIDS (old athletic injuries). Due to 3 volvuli I lost the entire ascending colon and about 18″ of small intestine. Recovery time has been long and arduous.

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