Folic Acid

The basic mechanism of action underlying folic acid is its role in cellular division and DNA synthesis. Without folic acid cells do not divide properly. Folic acid is critical in the nervous system development of the foetus and for healthy red blood cell production. Folate is also required for the regeneration of methionine from homocysteine and plays a key role as a 'methyl-donor'.

NEURAL TUBE PROTECTION - Folic acid supplementation of 400µgs daily in early pregnancy has been shown to reduce the incidence of neural tube defects by 48% to 80%. Numerous studies have suggested that it would appear prudent to utilise folic acid pre-conceptually and throughout pregnancy. The Government's Chief Medical Officer recommends all women to supplement with 400µg daily from 12 weeks prior to conception.
CARDIOVASCULAR PROTECTION - Folic acid plays a key role in protecting the cardiovascular system by regulating body concentrations of homocysteine, an intermediate in the conversion of the amino acid methionine to cysteine. The lower the folic acid intake the higher homocysteine levels rise increasing the risk of atherosclerosis (artery furring). Homocysteine would appear to promote atherosclerosis by directly damaging the artery and reducing the integrity of the vessel wall. Elevated levels of homocysteine are found in 20% to 40% of patients with heart disease.
DEPRESSION - Folic acid exerts a mild anti-depressant effect and correcting deficiency has brought about dramatic results in mental and psychological symptoms in patients, especially the elderly suffering from impaired mental function. Its anti-depressant effects are due to its function as a methyl donor and increasing the brain content of serotonin, SAM (S-adenosyl-methionine), and BH4 (tetrahydrobiopterin). BH4 functions as an essential coenzyme in the activation of enzymes that manufacture monoamine neurotransmitters like serotonin and dopamine from their corresponding amino acids. E.g. tryptophan > 5HTP > serotonin.
OSTEOPOROSIS - Elevated levels of homocysteine in the blood of postmenopausal women have an adverse effect on collagen cross-linking, leading to defective bone matrix development. Given that osteoporosis is a condition characterised by both a loss of the protein structure and well as the mineral content of the bone it is likely that the homocysteine theory carries validity. Folic acid supplementation has been shown to lower homocysteine levels in postmenopausal women even when their folic acid status was within the normal range.
CERVICAL DYSPLASIA - This is an abnormal condition of the cells of the cervix. It is generally regarded as a pre-cancerous lesion and has risk factors similar to those of cervical cancer. It is suggested that oral contraceptives interfere with folate metabolism resulting in cervical tissue deficiency of folate.

Docosahexaenoic Acid (DHA)

Docosahexanoic acid (C22:6, DHA) is a highly unsaturated omega-3 fatty acid that forms part of the central nervous and visual system structures. DHA is synthesized from its precursor, alpha-linolenic acid that is also an omega-3 fatty acid and can be obtained from vegetable oils. Marine organisms, especially fish, are good nutritional sources of DHA and eicosapentanoic acid (EPA), another omega-3 fatty acid that has a role in vascular homeostasis. DHA increases membrane fluidity, improving neurogenesis, synaptogenesis and the activity of retinal photoreceptors. The fetus has high DHA requirements particularly during the last trimester of pregnancy.

EYE HEALTH - DHA is essential for eye and brain development. It is an important dietary nutrient for infants. DHA comprises about 60 percent of the rod outer segments of the eyes. The percentage of DHA in retinal tissue increases rapidly in the last half of pregnancy. Cell membranes of the retina and visual cortex, highly enriched in DHA, develop rapidly during the last trimester -- the period of most rapid eye development -- and in the first 6 months of infancy.
BRAIN DEVELOPMENT - Beyond development, the eyes and the brain need plentiful stores of DHA to function optimally. Cells in the retina, brain and other parts of the nervous system have connecting arms that transport electrical currents, sending visual information from the retina to the brain and messages from the brain throughout the body. DHA supplementation ensures the optimal composition of cell membranes necessary for the most effective transmission of these signals.
MENTAL FUNCTION - Studies have shown that pre-term infants, born without the benefit of the maternal delivery of DHA during the period of most rapid brain growth in the last trimester of pregnancy, did not perform as well on cognitive mental tests later in life (by up to 20 IQ points) as those who were breast-fed. Specific behavioural and learning problems have also been shown to correlate significantly with low DHA levels.
DYSLEXIA - Dyslexia, a learning disorder marked by impairment of the ability to recognize and comprehend written words, has been correlated with sub optimal DHA levels. Stordy (1995) reported that DHA supplementation in adult dyslexics improved rod dark adaptation or night vision. Stordy also reported anecdotal evidence that DHA supplementation improves dyslexics' reading ability and behaviour.
ATTENTION DEFICIT HYPERACTIVITY DISORDER - Children with ADHD also have low DHA levels and experience essential fatty acid deficiency symptoms including hyperactivity and short attention span. Studies are under way to determine whether DHA supplementation can alleviate these symptoms.

Dosage

Folic acid: 400-1200µg daily. Folic acid is well tolerated and can be used at high doses, however it may cause increased flatulence, nausea and loss of appetite.
DHA: Supplementation of DHA up to several grams has been used in chronic conditions. For health maintenance purposes lower levels are utilised. Optimal levels of intake for DHA are difficult to equate but healthy traditional diets would indicate a level of 2-2.5% of calories from omega 3 fatty acids.

Potential applications

The main applications of folic acid are prevention of neural tube defects, atherosclerosis (reduces elevated homocysteine levels), osteoporosis, and cervical dysplasia. Other applications include depression, anemia, crohn's disease, fatigue, restless leg syndrome, epilepsy, fatigue, and infertility. DHA is particularly needed in eye and brain development. Other applications include - cardiovascular protection including cholesterol and triglyceride reduction, rheumatoid arthritis and other auto-inflammatory disorders, behavioural disorders such as ADHD, and mental function. DHA deficiency plays an important role in a group of congenital diseases called peroxisomal disorders, which damage the protective covering (myelin) around the nerves.

Known contraindications

High doses of folic acid should be used with caution in epileptics as it may increase the risk of seizures. Those on diabetic or cardiovascular medication should consult their doctor prior to supplementing DHA or other omega-3 fatty acids at levels more than 3 or 4 grams of fish oil (or equivalent).

Interactions

Folic acid works together with vitamin B12, B12, SAM, and choline. Oral contraceptives, anti-convulsants, alcohol, various chemotherapy drugs, sulfasalazine, and barbiturates, all interfere with folic acid absorption or function. DHA is commonly found along with EPA in fish oils. The use of vitamin E supplementation concurrently may help protect DHA from oxidation.

Use in conjunction with

Prenatal nutrition - hemp seed oil, 'high-five' multi-vitamin/mineral
Depression - B complex, EFAs, Rhodiola / St. John's Wort, zinc complex
Osteoporosis - Calcium/Magnesium and Boron powder, B complex, black cohosh, EFAs
Cardiovascular health - Flax seed oil, grape seed/pycnogenol, hawthorn berry, multi-vitamin/mineral, antioxidant formula
Cervical dysplasia - antioxidants, grapeseed/pycnogenol, EFAs, beta-carotene, trace minerals, oregon grape root

Note

DHA is a highly purified form of DHA extracted from micro-algae and represents the closest match to the DHA found in mother's milk. This single-nutrient, vegetarian source of DHA does not contain eicosapentaenoic acid (EPA) found in fish oils, which is not recommended for pregnant and lactating women or their infants.

References

Daly LE, Kirke PN, Molloy A, et al. Folate levels and neural tube defects. JAMA 1995;274:1698-702.
Ubbink JB, Vermaak WJH, van der Merwe A, Becker PJ. Vitamin B12, vitamin B6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr 1993;57:47-53.
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991;338(8760):131-7.
Conquer JA, Holub BJ. Supplementation with an algae source of docosahexaenoic acid increases (n-3) fatty acid status and alters selected risk factors for heart disease in vegetarian subjects. J Nutr 1996;126:3032-9.
Stevens LJ, Zentall SS, Deck JL, et al. Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am J Clin Nutr 1995;62:761-8.
Kelley DS, Taylor PC, Nelson GJ, et al. Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids 1999;34:317-24.
Martinez M, Vazquez E. MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders. Neurology 1998;51:26-32.

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