Monday, January 28, 2008

Folic Acid as Cinderella and Homocysteine as the Evil Stepmother

Folic Acid as Cinderella and Homocysteine as the Evil Stepmother
By: Cristina Berard, RPh, MEd

Folic acid or folate as it is also called, is found in green leafy vegetables. Folate from vegetables is about 40-50% less bioavailable than synthetic folic acid, which is almost 100% bioavailable. After it is absorbed by the body it is converted into tetrahydrofolate. Tetrahydrofolate based coenzymes play a major role in intracellular(within the cell) metabolism. Folic acid reduces errors to DNA and prevents replication errors. Folate deficiency disturbs the cycling of the cells and induces and increases the rate ofcell aptopsis (cell death). It is involved in the metabolism of homocysteine (high levels cause inflammation). Low levels of Folate are associated with an increase plasma homocysteine levels. High levels of homocysteine (hyperhomocysteinemia) is a risk factor for coronary, cerebral, and peripheral atherosclerosis; recurrent thromboembolism; deep vein thrombosis; myocardial infarction; and ischemic stroke.

Why are high homocysteine plasma levels a risk factor for certain diseases? The mechanism of action isn't fully understood, but it might include vascular endothelial cell damage(deterioration of the blood vessels), impaired endothelium dependent vasodilation (blood vessels don't dilate properly) due to reduced nitric oxide activity, arterial stiffening due to increase in oxidation(arteries become stiff) and arterial deposition of low density lipoproteins (LDL cholesterol deposits in the lining of the artery), increase of platelet adhessiveness (blood thickens becomes less viscous), and activation of the clotting cascade (increase in clots formed in the vessels).

All vitamins are essential and play important roles in metabolic pathways. Folic acid is an especially important vitamin. The following description of it's role may at times be a bit technical, but it is important in helping you to understand just how imperative it is to ensure that you are not deficient in folic acid or in any steps along the way.

Homocysteine is metabolized via two pathways. One is called "remethylation" the other "transsulfuration".

Homocystein-----------------------> methionine

This reaction is facilitated by folate and Vitamin B12 (cofactors). Without these two cofactors, this processes would not take place and homocystein would remain in tact, thus increase homocystein levels in blood stream. There is another factor that can impede this process. Some people homozygous fo the mutations of the gene MTHFR(5,10 methyltetrahydrofolate reductase). This is an enzyme involved in the conversion of homocysteine to methionine. When you are homozygous for this gene most often you need to take higher doses of folate, usually 1mg per day.

Transsulfuration usually occurs after an individual ingests a meal high in animal protein (a methionine load).
via pyrodoxine(vit B6)

Deficiency of pyrodoxine impairs the pathway raising homocysteine levels as well. In addition to folic acid, vitamin B12 and B6 are important for successful conversion of homocysteine.

What does all of this mean and why is it important to health? Well plays an important role in pregnancy and the healthy development of the fetus. Low levels are associated with neural tube defects in the fetus.

Low levels might play a role in Alzeihmers Disease. It seems to be associated with atrophy of the cerebral cortex.

Homocysteine is thought to be neurotoxic, causing DNA damage and cell apoptosis which is associated with functional and mental deterioration in the elderly.

Folic acid deficiency is common in people with depression. Low levels have been linked to poor response to antidepressant treatment.

Folic acid is required for the conversion of homocysteine------->SAMe. SAMe in turn is associated with an increase in serotonin turnover, increase in dopamine, and norepinephrine levels. All of these play a role in mood.

When you go to the pharmacy, you will find that there are individual B vitamins and then there are products that provide a combination of all B vitamins. The previous pathways might have given you a clue as to why these B vitamin complexes are so popular. Various B vitamins played a key role in these homocysteine conversion pathways. Where folic acid is the work horse, the other B vitamins are its helpers. Just like Cinderella was the hard worker of the family she couldn't have made it to the ball without her little helpers. By working together they were able to stop the evil stepmother (homocysteine) from getting her way.

Folic acid supplementation is helpful in treating and or preventing the following conditions: End-stage renal disease, hyperhomocysteinemia (11 micromoles/L or higher), methotrexate toxicity, neural tube defects, breast cancer, colorectal cancer, depression, Alzheirmers, risk of cervical cancer, cognitive function, infertility, and restless leg syndrome.

Typical doses are: 250mcg-1000mcg/Day
Severe disorders and under medical supervision(1000-5000mcg/Day)

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