Vitamin B9 (Folate/Folic Acid)

Effects and Benefits

Core Identification

Common Names:
- Folate (natural food form)
- Folic acid (synthetic form)
- Vitamin B9
- Pteroylglutamic acid
- Folacin
- L-methylfolate (active form)
- 5-MTHF (5-methyltetrahydrofolate)
- Metafolin (branded active form)

Latin Name: N/A (Vitamin compound)

Category: Vitamin

Uses

Traditional Uses

• Treatment of anemia - Recognized since the 1930s-1940s when isolated from spinach
• General tonic for weakness and fatigue - Historical use in various cultures
• Support during pregnancy - Long recognized importance for maternal health

Modern Uses

• Neural Tube Defect Prevention - Critical for preventing spina bifida and anencephaly in pregnancy | Research quality: Strong
• Key findings: A landmark 1997 study and subsequent research showed 72-75% reduction in neural tube defects with supplementation; defects arise between days 24-28 after conception when the neural tube fails to close properly

• Source citations: Medical Research Council Vitamin Study Research Group; Moyad - The Supplement Handbook

• Cardiovascular Health (Homocysteine Regulation) - Works with B6 and B12 to convert homocysteine to cysteine | Research quality: Strong

• Key findings: Elevated homocysteine is an independent risk factor for heart disease and stroke comparable to high cholesterol; folic acid supplements of 400-650 mcg daily effectively lower homocysteine levels; the Nurses' Health Study found supplements can reverse cardiovascular damage

• Source citations: Brewer - TDT Encyclopedia of Vitamins; Moline - The Doctors Book of Natural Health Remedies

• Megaloblastic Anemia Treatment - Corrects abnormally large red blood cells from deficiency | Research quality: Strong

• Key findings: Folate deficiency causes production of enlarged, abnormal red blood cells (megaloblasts); supplementation reverses anemia, typically within 6 weeks

• Source citations: Merck Manual Home Health Handbook

• Cognitive Function & Alzheimer's Prevention - May protect against cognitive decline | Research quality: Moderate

• Key findings: Low blood folate levels associated with 3.3 times greater risk of Alzheimer's disease; believed related to vascular protection from homocysteine reduction

• Source citations: Brewer - TDT Encyclopedia of Vitamins; Gladstar - Herbal Recipes for Vibrant Health

• Depression Support - Helps produce neurotransmitters | Research quality: Moderate

• Key findings: Folate helps stabilize mood through serotonin and dopamine production; deficiency associated with depression symptoms

• Source citations: Moline - The Doctors Book of Natural Health Remedies

• Bone Health - Reduces fracture risk by lowering homocysteine | Research quality: Moderate

• Key findings: Two-year Japanese study of 559 elderly women showed B12 and folate supplementation reduced hip fractures by 33 compared to control group

• Source citations: Cordain - The Paleo Answer

• Hearing Loss Prevention - May slow age-related hearing decline | Research quality: Preliminary

• Key findings: Dutch study of 728 older adults showed 800 mcg folic acid daily reduced hearing loss after three years

• Source citations: Stewart - Living the Good Long Life

• Fertility Support - Important for both male and female reproductive health | Research quality: Moderate

• Key findings: Low B12 and folate status increases homocysteine, which is toxic to sperm and egg cells; adequate status improves conception rates
• Source citations: Cordain - The Paleo Answer

Active Compounds

Primary Active Ingredients:
- Tetrahydrofolate (THF) - The active coenzyme form in the body; essential for one-carbon metabolism
- 5-methyltetrahydrofolate (5-MTHF) - The predominant circulating form; directly usable by cells without conversion
- Polyglutamates - The natural form found in foods; requires conversion to monoglutamate for absorption
- Monoglutamate (folic acid) - The synthetic supplemental form; more readily absorbed than food folate

Dosage Information

Standard Dosage:
- Form: Tablet, capsule, or fortified foods
- Amount: 400 mcg (0.4 mg) daily
- Frequency: Once daily

Therapeutic Dosage:
- Form: Tablet or capsule
- Amount: 400-800 mcg daily for general supplementation; 4-5 mg daily for women with previous neural tube defect pregnancy
- Purpose: Neural tube defect prevention, homocysteine reduction
- Duration: For pregnancy: Begin 2-3 months before conception, continue through first trimester (ideally first 12 weeks)

Maximum Safe Dosage:
- Daily maximum: 1,000 mcg (1 mg) from supplements for most adults
- Warning threshold: Doses above 1,000 mcg may mask vitamin B12 deficiency, potentially allowing nerve damage to progress undetected

Bioavailability Notes:
- Synthetic folic acid in supplements is 50-80% more bioavailable than natural food folate
- Food folate bioavailability is approximately 50% of supplement folic acid
- A threefold increase in dietary folate would be needed to match 400 mcg from supplements
- Individuals with MTHFR gene mutations (affecting approximately 10% of population) may benefit from L-methylfolate (5-MTHF) form, which bypasses the need for conversion
- Cooking destroys much of the folate in foods; prolonged cooking significantly reduces content

How to Take It

Timing:
- Can be taken any time of day
- May be taken with or without food
- Best taken consistently at the same time daily
- For pregnancy prevention: Begin supplementation 2-3 months before trying to conceive

Synergies - What It Works Well With

Complementary Supplements:
1. Vitamin B12 - Essential partner for DNA synthesis and homocysteine metabolism; folic acid should always be taken with B12 to prevent masking B12 deficiency symptoms | Protects nerves, prevents anemia
2. Vitamin B6 - Works together with folate and B12 to regulate homocysteine; supports enzyme function in folate metabolism | Cardiovascular protection, neurotransmitter production
3. Iron - Both needed for red blood cell production; folate helps iron absorption | Anemia prevention and treatment
4. Vitamin C - Enhances folate stability and absorption | Improved bioavailability
5. Zinc - Combined supplementation studied for male fertility | Improved sperm quality and count

Avoidance - What NOT to Combine With

Supplement Interactions:
1. High-dose Vitamin B12 with low B12 status - Supplementing folate alone when B12 is deficient can mask the anemia of B12 deficiency while nerve damage progresses silently | Always take together

Drug Interactions:
1. Methotrexate - Folic acid is a direct antagonist; methotrexate works by inhibiting folate metabolism | May reduce drug effectiveness for cancer treatment; however, folic acid supplementation (5-50 mg weekly) can reduce side effects in rheumatoid arthritis treatment without affecting efficacy | Severity: Moderate to Severe - consult prescriber
2. Anticonvulsants (Phenytoin, Phenobarbital, Carbamazepine, Valproic Acid) - These drugs reduce folate levels; however, folic acid above 0.8-1 mg may increase seizure frequency in some patients | Severity: Moderate - requires medical supervision; pregnant women on anticonvulsants need specialist guidance on proper supplementation (typically 1-5 mg)
3. Sulfasalazine - Decreases folate absorption | May need supplementation | Severity: Mild
4. Metformin - Can deplete folate levels with long-term use | Monitor levels, consider supplementation | Severity: Mild
5. Trimethoprim-sulfamethoxazole (Bactrim) - Interferes with folate metabolism | Severity: Mild to Moderate
6. Triamterene (diuretic) - Weak folic acid antagonist; associated with folate-deficiency anemia in at-risk individuals | Severity: Mild

Food Interactions:
- Alcohol - Significantly interferes with folate absorption and metabolism; heavy drinking is a major cause of deficiency
- Prolonged cooking of folate-rich foods destroys the vitamin

Safety Information

Contraindications:
- Untreated vitamin B12 deficiency (supplement B12 first or concurrently)
- History of seizures - use only under medical supervision
- Allergic reaction to folic acid (rare)

Side Effects:
- Common: Generally well tolerated; rarely causes digestive upset
- Rare: Allergic reactions, skin rash
- Note: High doses may cause sleep disturbances, irritability, or gastrointestinal symptoms

Long-Term Use:
- Generally safe for long-term use at recommended doses (400-800 mcg)
- Doses exceeding 1,000 mcg daily require medical supervision
- Some research suggests very high long-term folic acid intake from fortification plus supplements may be associated with increased risk of certain cancers (prostate, breast, colorectal), though findings are debated
- Natural food folate does not carry the same concerns as synthetic folic acid
- Regular B12 monitoring recommended with long-term high-dose use

Special Precautions:
- Pregnancy: Essential supplement; begin before conception; higher doses (4-5 mg) for women with previous affected pregnancy
- Epilepsy: Use cautiously; can interact with anticonvulsant medications
- MTHFR Mutations: Those with genetic variants affecting folate metabolism may benefit from L-methylfolate form
- Elderly: Often deficient due to reduced dietary intake and absorption; up to 30% may be deficient

Primary Uses At-a-Glance

Primary: Neural tube defect prevention, megaloblastic anemia, homocysteine reduction, cardiovascular support, pregnancy support

Secondary: Cognitive function, depression support, bone health, hearing preservation, fertility support

Sources

Local Library:
- Brewer, Sarah - TDT Encyclopedia of Vitamins
- Cordain, Loren - The Paleo Answer
- Moyad, Mark - The Supplement Handbook
- Weil, Andrew - Eating Well for Optimum Health
- Gaby, Alan R. - A-Z Guide to Drug-Herb-Vitamin Interactions 2nd Ed.
- Gehring, Abigail - The Illustrated Encyclopedia of Natural Remedies
- Moline, Peg - The Doctors Book of Natural Health Remedies
- Merck - The Merck Manual Home Health Handbook
- Stewart, Martha - Living the Good Long Life
- Gladstar, Rosemary - Herbal Recipes for Vibrant Health
- Tessmer, Kimberly A. - Your Nutrition Solution to Type 2 Diabetes
- Ali, Naheed - Diabetes and You
- Bartram, Thomas - Bartrams Encyclopedia of Herbal Medicine

General Knowledge:
- Clinical reference materials on B vitamins and pregnancy nutrition
- Standard nutritional biochemistry references