Folic acid

Scientific studies (review articles) on the relationship between folic acid and disease prevention:
One swallow does not make a summer. A famous Dutch saying that could not be any more obvious. Just because one single scientific study about a certain topic makes certain claims, it does not necessarily mean it is true. On the other hand, a review article (a collection of scientific studies on a specific topic) of randomized, placebo-controlled double blind clinical trials (RCTs) will answer the following question:
"Do taking dietary supplements make sense?" Yes for a positive conclusion and no for a negative conclusion.

One swallow does not make a summer. A famous Dutch saying that could not be any more obvious. Just because one single scientific study about a certain topic makes certain claims, it does not necessarily mean it is true. On the other hand, a review article (a collection of scientific studies on a specific topic) of cohort studies or case-control studies will answer the following question:
"Should I change my diet?".

1. 0.8-10 mg/d folic acid supplements decrease CRP levels
2. Dietary intake of vitamin B6 and folate reduces stroke
3. Oral vitamin B supplementation does not prevent cognitive decline in cognitively unimpaired individuals
4. Low folate levels increase risk of depression among the aged people
5. Preterm birth and low birthweight are strongest risk factors associated with increased case fatality of infants with spina bifida
6. 400 μg folic acid during pregnancy reduce offspring's autism spectrum disorders
7. Maternal folic acid supplementation reduces childhood acute lymphoblastic leukaemia
8. Maternal folic acid supplementation is associated with an increased birth weight
9. Large-scale food fortification reduces goiter, anemia and neural tube defects in low- and middle-income countries
10. Steady-state red blood cell folate concentrations can be reached with 375-570 µg folic acid/day
11. 1 μg/day dietary B12 intake increases esophageal cancer
12. Folate supplementation lowers HOMA-IR
13. Folic acid supplementation reduces both fasting glucose level, fasting insulin level and HOMA-IR
14. High folate dietary intake reduces colon cancer in people with medium or high alcohol consumption
15. High dietary vitamin B9, D, B6 and B2 intake reduces risk of colorectal cancer
16. Decreased folate level is a risk factor for schizophrenia
17. Reduced serum levels of folate and vitamin B12 increase peripheral neuropathy risk among patients with type 2 diabetes
18. Daily 200-320 micrograms dietary folate intake reduce breast cancer risk
19. Higher vitamin B2 and B6 dietary intake decreases ER-/PR- breast cancer
20. A high plasma folate level does not reduce breast cancer
21. Daily 100 μg dietary folate intake reduce oestrogen-receptor-negative breast cancer

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• Folic acid (also known as folate, vitamin M, vitamin B9, vitamin Bc (or folacin), pteroyl-L-glutamic acid, pteroyl-L-glutamate and pteroylmonoglutamic acid) is a water-soluble member of the B-complex family of vitamins.
• Folic acid derives its name from the Latin word folium, which means "leaf".
• Folate plays a crucial role in the one-carbon metabolism for physiological nucleic acid synthesis and cell division, regulation of gene expression, amino acid metabolism and neurotransmitter synthesis.
• Pregnancy is associated with a marked acceleration in one-carbon transfer reactions, including those required for nucleotide synthesis and thus cell division, which is the basis for the substantial increase in folate requirements during pregnancy.
  Folate requirements are 5- to 10-fold higher in pregnant than in non-pregnant women.
• Low dietary intake of folic acid during pregnancy increases the risk of developing birth defects, likes delivery of a child with a neural tube defect (NTD). Birth defects occur within the first 3-4 weeks of pregnancy.
  To reduce the risk of developing birth defects, experts recommend to take 400 micrograms (mcg) of folic acid per day, beginning at least a month before the pregnancy until the first 2 months of pregnancy.
• It is impossible to get 400 mcg of folic acid from food.
• Dietary folic acid, or the form naturally found in foods, is actually a complex and variable mixture of folate compounds, such as polyglutamate (multiple glutamate molecules attached) conjugate compounds, reduced folates and tetrahydrofolates.
• Cooking or processing destroys folic acid.
• The recommended daily allowance is 200-300 mcg.
• The best folate sources in foods are green, leafy vegetables, sprouts, fruits, brewer’s yeast, liver and kidney.
• Signs and symptoms of folate deficiency include macrocytic anemia, fatigue, irritability, peripheral neuropathy, tendon hyper-reflexivity, restless legs syndrome, diarrhea, weight loss, insomnia, depression, dementia, cognitive disturbances and psychiatric disorders.
  Elevated plasma homocysteine can also indicate a dietary or functional deficiency of folic acid.
• Homocysteine metabolism is regulated by the nutritional status of folate, vitamin B12, and vitamin B6. Folate status has the strongest influence on plasma homocysteine concentration.
• At least 200 mcg folic acid per day is needed to prevent a high (> 12 μmol/L) plasma homocysteine concentration.
  A high plasma homocysteine concentration is an independent risk factor for cardiovascular disease.
• Folate deficiency can be treated with supplemental oral folate of 400 to 1000 mcg per day.
• The serum (or plasma) folate concentration and red blood cell (RBC) concentration of folate were the two most commonly used indicators of folate status.
  Red cell folate concentration, which reflects liver folate concentration and is considered to be an indicator of long-term folate status.
• Synthetic folic acid is 100% bioavailable when consumed under fasting conditions on an empty stomach.
• The bioavailability of food folate was 50% that of synthetic folic acid because synthetic folic acid (found in dietary supplements and folate-fortified foods) is free and the human body is only able to absorb “free form” folic acid.
• Monoglutamate folates (often found in dietary supplements and folate-fortified foods) are absorbed by an active energy-dependent, carrier-mediated process at physiological concentrations and by passive absorption at higher concentrations.
  Absorption takes place mainly in the jejunum and is markedly influenced by pH with a maximum absorption at pH 6.3.
  The polyglutamic folates (often found in diet) must be cleaved to their monoglutamate forms by a pteroylpolyglutamate hydrolase, referred to as folate deconjugase, before uptake can take place in the intestinal epithelial cells (primarily in the jejunum).
• Folic acid intakes in excess of the tolerable upper intake level (UL) (1 mg/day) may mask the symptoms associated with a vitamin B12 deficiency and allow for the progression of irreversible neurological damage.
• The total body pool size is estimated between 12-28 mg or 3-4 weeks.
  The liver contains about 50% of the body stores of folate.
• 1 µg dietary folate equivalent (DFE) = 1 µg food folate = 0.5 µg folic acid on an empty stomach = 0.6 µg folic acid with meals or as fortified foods.
• The tolerable upper intake level (UL) for folic acid (but not total food folate) is 1000 micrograms (1 mg) of folic acid, only because of possible neurological damage of vitamin B12 deficiency at levels exceeding 1000 micrograms.