Folic Acid

World’s Most Depleted Vitamin

• Folic acid, also known as folate, is an important (read critical) member of the water-soluble B-group vitamins. It received its name from the Latin word folium, meaning ‘foliage’, because it is found in nature’s leafy green vegetables, such as spinach, kale and beet greens.
• Folic Acid carries out may and varied functions in the human body from assisting in the formation of nucleic acid, essential for growth and reproduction, to stimulating the production of hydrochloric acid in the stomach. It is also used in the manufacture of neurotransmitters (chemical hormonal messengers in the brain), in preventing heart disease and for synthesizing DNA. In fact, folate is so important for many metabolic processes in the body, it is hard to mention them all.
• Despite the wide occurrence of Folic Acid in food, it is still the most common vitamin deficiency in the world. In a clinical sense, I have found that a poor diet coupled with moderate to high alcohol intake is the most common cause of folate deficiency.
• In my opinion, one of the biggest contributing factors accounting for folate deficiency in New Zealand is alcohol consumption. But realistically, any condition that disturbs the small intestine can and will contribute to a folate deficiency.   High-dose aspirin, smoking, treatment for epileptic seizures, and oral contraceptives all increase the risk for folate deficiency.  Some studies have associated very high doses of folate with central nervous system disorders, zinc deficiency, and seizures in epileptics. Although the risk appears to be extremely low, these results indicate that megadoses (we are talking tens of thousands of micrograms daily for extended periods) of folic acid should be avoided.  High amounts of folic acid in the elderly may also mask symptoms of vitamin B12 deficiencies, but in my experience, the elderly never get enough of this critically important vitamin.

Folate Deficiency Affects The Body In Many Ways

• Rapid cell division – multiple areas affected. In Folic Acid deficiency all parts of the body are affected, particularly the rapidly dividing cells like red blood cells and cells of the gastrointestinal and genital tract. This results in retarded growth, diarrhoea, anaemia, gingivitis, and abnormal smears in women.
• Anaemias. Macrocytic anaemia as a result of folic acid deficiency is characterised by enlarged red blood cells, but folate deficiency can also cause megaloblastic anaemia. Symptoms include depression, insomnia, irritability, forgetfulness, loss of appetite, fatigue and shortness of breath.
• Neural tube defects – high spina bifida risk. Pregnant women who do not take folate supplements often have a folate deficiency, which places them at risk for neural tube defects in newborns.  Women who are planning to become pregnant should take 400 mcg of folic acid before conception, as well as during pregnancy and when breast-feeding.
• Cognition. Folate deficiency can also cause affect concentration and memory and may cause hearing loss.
• Homocysteine elevation. As with vitamins B6 and B12, folate deficiencies also elevate homocysteine, and recent studies suggest a strong link between low folate levels and the onset of heart disease.

Folate Is Required Most In Areas Of Growth And Cell Division

• Since folic acid is important to the division of cells in the body, it is even more essential during times of growth, such as pregnancy where rapid cell multiplication takes place. If there is a deficiency of folic acid at this time, the result is decreased nucleic acid synthesis (for RNA and DNA) and interrupted cell division. Folic acid is essential for the development of the foetal spinal cord and nervous system.

• During the first trimester of pregnancy, one of the biggest fears for a parent comes from the threat of congenital defects, such as spina bifida (incomplete closure of the spine), hydrocephaly and impaired brain development. Statistically neural tube defects occur in approximately one to two of every 1000 live births.

• Researchers from the University of Otago recommend the use of Folic Acid in pregnancy, used both several weeks before conception and in the first trimester of pregnancy. Supplementation with Folic Acid has been associated with a massive 70% reduction in neural tube defects. Wise supplementation with Folic Acid can lower the risks.

• The average RDI for pregnancy of Folic Acid is approximately 800 – 1200 mcgs (Obstetricians can recommended that high-risk women should receive up to 5mg of folic acid).

Best Folate Sources

• Brewer’s yeast, Green beans, leek, parsnip, cabbage, beetroot, green peas, spinach, capsicum, cauliflower, chick peas, oranges, orange juice, peanuts, oats, wholegrain bread, wheat germ & wheat bran, cos lettuce, banana, avocado, carrot, parsley, tomato, strawberry, canned salmon, hazelnuts, cashews, walnuts, almonds.
• For more information on your best dietary sources of folic acid go to this link.

Folic Acid Is Required In Your Body 

1. Prevention of neural tube defects and cleft palate

• Women of childbearing age should consume 0.4 mg/day of folic acid to prevent spina bifida and possibly other neural tube defects. Folic acid from supplements appears to be better utilised than folic acid from food.

2. Cervical dysplasia

• At a dose of between 1000 – 5000 mcg/day for 3 months, folic acid induced regression of cervical dysplasia and cervical intraepithelial neoplasia in women taking oral contraceptives (double-blind trials). Smaller doses, such as 0.4 mg/day, may help prevent cervical dysplasia resulting from human papilloma virus infection (theoretical, based on observational study). I recommend high dose for 12 weeks when women present with high grade smear test results – excellent results. More study needs to be done here, could prevent cases of cervical cancer in New Zealand folks.

3. Homocysteine-Related Conditions

• By reducing homocysteine levels, folic acid (0.4 to 5.0 mg/day) may help prevent both atherosclerosis and osteoporosis (theoretical for osteoporosis, intervention trials for atherosclerosis).

4. Gout

• Go here to learn more about gout. Doses of 40-80 mg/day, when combined with unspecified doses of vitamin C, have been reported reduce serum uric acid levels, through inhibition of xanthine oxidase (clinical observation – Oster K), although others have been unable to confirm that observation.

5. Restless Legs Syndrome

Doses of up to 5000mcg day are effective for some individuals with familial restless legs syndrome and other associated familial neurological problems (uncontrolled trial). Take with a good B-Complex.

6. Gingivitis

• A 0.1 % solution of folic acid, used as a mouthwash (5 ml twice a day for 2 months), reduced the severity of gingivitis (double-blind trial). Research on folic acid administered orally in tablet form (4-5 mg/day) is conflicting, I recommend 4 – 5 drops of folic acid solution a day. Take in about 1 half a glass of water, rinse your (clean) mouth thoroughly before you go to bed – then swallow. Do this nightly for 2 – 3 weeks. And presto – gingivitis is sorted in most cases. Try this, it works.

7. Depression

• Go here to read more about mood disorders. Folic acid at a dose of 500 mcg/day enhanced the antidepressant effect of fluoxetine (Prozac) in women, but not in men, with major depression (double-blind trial). Laboratory findings (e.g., serum folate and homocysteine) suggested that men may require a higher dose of folic acid than 500 mcg/day.

8. Psoriasis

•  Go here to read more about psoriasis. At a dose of 50-150 mg/day, folic acid was effective in approximately 75% of cases (Oster K, small uncontrolled trial; Elson B, clinical observation), typically producing improvements of 80% or more. Initial improvement is usually seen after 2-3 weeks. Dosage may be tapered, as improvement occurs.

9. Cancer prevention

• Go here to read the cancer articles. Numerous studies suggest that folic acid reduces the risk of various cancers, particularly those of the gastrointestinal tract.

Dosage and Administration of Folic Acid:

• The usual dosage range is between 400mcg (0.4mg) right up to 5000mcg (5mg) per day. Doses of a very high 80 mg/day or more have been used for very specific conditions.

Drug Interactions:

• l. Large doses(15 mg/day) may interfere with the anticonvulsant effect of phenytoin and may also have a mild epileptogenic effect. Conversely, administration of phenytoin may promote folic acid deficiency. Smaller doses of folic acid, such as 1 mg/day, do not appear to promote seizures in patients taking phenytoin and may, in fact, improve their clinical condition.
• 2. Folic acid may interfere with the anti-cancer effect of methotrexate. However, when methotrexate is being used to treat rheumatoid arthritis, administration of l mg of folic acid 5 days a week (taken when methotrexate is not being ingested) has been shown to reduce methotrexate toxicity without diminishing its efficacy.
• 3. Sulfasalazine, oral contraceptives, trimethoprim, alcohol, and tobacco smoke each may promote folic acid deficiency.

Nutrient Interactions

• Administration of large doses of folic acid may promote a deficiency of zinc or vitamin B 12; however, it is not clear whether this interaction is clinically significant when typical doses of folic acid are being used. Large doses of vitamin 136, vitamin B12, or zinc may increase the requirement for folic acid. Folic acid supplementation may interfere with the laboratory diagnosis of pernicious anemia.

• Toxicity

Rare hypersensitivity reactions have been reported. Very large doses may provoke seizures in epileptics.

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Folic Acid Studies

1. – Functional and psychic deterioration in elderly people

• The deterioration of functional and mental capacity is one of the major problems of the elderly. This deterioration may be caused or worsened by folate deficiency. The aim of this investigation was to analyse the relationship between mental and functional capacities and folate status in a group of 177 elderly Spanish people. Folate deficiency is common in the Spanish population. In this study, 48.6% of the elderly subjects had folate intakes below recommended values (200 microg/day), 34.9% had serum concentrations < 14 nmol/L and 6.6% had <360 nmol/L erythrocyte folate.
• Subjects took part in a series of tests: Katz’s scale of activities of daily living, Lawton’s scale of instrumental activities of daily living, Pfeiffer’s mental status questionnaire, Folstein’s Mini-Mental State Test and the Geriatric Depression scale of Yesavage. The results for Lawton’s scale of instrumental activities of daily living were significantly better (indicating greater independence and capacity) when folate intake and serum or erythrocyte folate concentrations were adequate (i.e., folate intake no less than recommended, > or = 14 nmol/L serum folate or > or = 360 nmol/L erythrocyte folate). Subjects with adequate Mini-Mental State Exam results (> or = 28 points) had serum and erythrocyte folate concentrations significantly higher than those with less adequate results (<28 points).

• Thus, there is evidence to suggest that the folate status of the elderly should be monitored
• Ref: Ortega RM, Manas LR, Andres P, et al. J Nutr 1996;126:1992-1999.
  

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2. – Folic acid may halve the risk of developing Alzheimer’s disease in the elderly.

• A significant correlation has been found between the risk of developing Alzheimer’s disease and high plasma levels of homocysteine, as well as low levels of folic acid and vitamins B6 and B12.
•  Homocysteine is a metabolic by-product of methionine metabolism. There are numerous nutrient cofactors (including those mentioned above) involved in the methionine cycle. A deficiency of, or a metabolic dysfunction involving any of these nutrients could affect how well homocysteine is either recycled or broken down.
•  There is evidence that hyperhomocysteinemia may promote different types of dementia by more than one mechanism, including cerebral microangiopathy, endothelial dysfunction, oxidative stress, neuronal DNA damage, enhancement of beta-amyloid peptide-mediated vascular smooth muscle toxicity, neurotoxicity and apoptosis.

• In the present study, elderly people who consumed at least 400 mcg of folate each day were shown to more than halve their risk of developing Alzheimer’s disease. 579 non-demented volunteers from the Baltimore Longitudinal Study of Ageing completed dietary diaries and recorded supplement intake for a 7-day period. The researchers followed these individuals for over 9 years and found that those who consumed at least 400 mcg of folate each day had a 55% reduction in risk of the disease.
• The researchers commented that most people who reached these levels of folate intake did so by taking folic acid supplements.

References

• Corrada MM, Kawas CH, Hallfrisch J, et al. Reduced risk of Alzheimer’s disease with high folate intake: The Baltimore Longitudinal Study of Ageing. Alzheimer’s & Dementia July 2005;1(1):11-18.
• Miller AL. The methionine-homocysteine cycle and its effects on cognitive diseases. Altern Med Rev 2003;8(1):7-19.