Methylation, Methylfolate, MTHFR Gene Mutation, Homocysteine Mentioned in Life Extension Magazine

[Lotus97]

Even though Life Extension Magazine could be viewed as just an advertisement to sell supplements, this is still (somewhat) newsworthy. I noticed in my recent Life Extension Magazine an ad for methylfolate. It's still a sign of progress that there is at least some press (albeit an advertisement) about how folic acid can be ineffective for many people.
http://www.lef.org/Vitamins-Supplem...hylfolate.html?source=search&key=methylfolate

Those who take ordinary folate supplements, however, may not be experiencing its full spectrum of effects. This is because once ingested, not everyone converts folate to its biologically active form called 5-methyltetrahydrofolate (5-MTHF).180 Research shows that in a large proportion of the population, genetic enzyme deficiencies prevent the conversion of folate to 5-MTHF, leaving many vulnerable to low blood folate levels (and higher than desired homocysteine).
A more useful approach is to take the bioactive folate 5-MTHF directly, which has been declassified as a drug and is now available as a dietary supplement. 5-MTHF has been shown to dramatically raise red blood cell folate concentration, an indicator of folate status181 compared with folic acid supplementation. This bioactive folate is up to seven times more bioavailable than folic acid. This greater bioavailability is especially important in people who have a genetic enzyme deficiency182 since it requires no conversion to become metabolically active.
People with elevated homocysteine levels have a greater risk of cognitive decline.184 Unlike folic acid, 5-MTHF is able to cross the blood-brain barrier, which is especially important for people with cognitive difficulties to enhance the synthesis of acetylcholine in the brain — the neurotransmitter associated with memory.
Studies also show that the effectiveness of 5-MTHF can be further enhanced by co-supplementing with methylcobalamin (the active form of vitamin B12),185 vitamin B6, and riboflavin.186,187

I decided to check online to see if there were any articles about methylfolate in past issues of Life Extension and came across one from 2009 about homocysteine and methylfolate.
http://www.lef.org/magazine/mag2009...aking-You-Sick_02.htm?source=search&key=5mthf

A New Bioactive Form of Folic Acid Can Lower Stubbornly High Homocysteine Levels When Ordinary B-Vitamins Fail
Emerging research suggests that elevated levels of homocysteine may be a risk factor for cancer.39 A number of studies suggest that folate, through its effect on regulating DNA methylation and reducing homocysteine levels, may prevent cancers of the breast, bladder, lung, lymph, and colorectum.40-44

Conflicting evidence with respect to prostate cancer45 raises questions about the efficacy of folate for prostate cancer prevention. Some experts believe that when it comes to taking folate supplements, timing is everything. For example, some have proposed that folate may be beneficial when taken prior to old age because it decreases the likelihood of DNA mutations.

Many people who take B vitamin supplements are unable to sufficiently lower their homocysteine levels low enough to prevent disease.46 One possible reason is that folic acid, the form of the vitamin used in most supplements and enriched foods, is not bioavailable enough to sufficiently increase plasma folate levels in people with certain health problems or genotypes.
Researchers recently found that giving bioactive 5-MTHF to patients with coronary artery disease resulted in a 700% higher plasma folate concentration compared with folic acid. This difference was irrespective of the patient’s genotype.23 Compared with bioactive 5-MTHF, folic acid supplements were relatively ineffective in increasing blood folate concentrations.
Cooking and food processing destroy natural folates. Although red blood cells can retain folate for 40-50 days following discontinuation of supplementation, folic acid is poorly transported to the brain and is rapidly cleared from the central nervous system.1

Even though folic acid-fortified foods are ubiquitous in our food supply, and despite peoples’ best efforts to ensure adequate intake of the vitamin through supplementation, many individuals run the risk of not achieving sufficient plasma folate levels unless they supplement with bioactive folate.Bioactive folate, or 5-MTHF, is the predominant biologically active form of folate in cells, the blood, peripheral tissues, and particularly the brain.1 Until recently, 5-methyltetrahydrofolate was available only in expensive prescription medicines and medicinal food products. Now, this active form of folate, which provides increased bioavailability together with protection against homocysteine-related health problems, is available as a dietary supplement. Since 5-MTHF is the only form of folate used directly by the body, it doesn’t have to be converted and metabolized to be clinically useful, as does regular folic acid.1

Folic acid, as used in ordinary dietary supplements and vitamin-fortified foods, must first be converted to bioactive 5-methyltetrahydrofolate in order to be clinically effective (Figure 3 to the Right). These steps require several enzymes, adequate liver and gastrointestinal function, and sufficient supplies of niacin (B3), pyridoxine (B6), riboflavin (B2), vitamin C, and zinc.1
Another advantage of 5-MTHF is that it is unlikely to mask a vitamin B12 deficiency, a shortcoming of folic acid. Folic acid, when administered as a single agent, may obscure the detection of vitamin B12 deficiency (specifically, folic acid may reverse the hematological manifestations of B12 deficiency, while not addressing the neurological manifestations). Research has shown that bioactive 5-MTHF (5-methyltetrahydrofolate) is less likely than folic acid to mask vitamin B12 deficiency.1

The low-dose requirements for 5-MTHF make it a relatively inexpensive supplement with superior clinical benefits over folic acid. People who would benefit from taking active folate include:

• Those who desire to take advantage of 5-MTHF as a part of their anti-aging strategy due to its potency, low cost, and bioavailability.
• Those with elevated risk factors for cardiovascular disease.
• Those taking drugs known to interfere with the absorption or metabolism of folate (See sidebar below: “Drugs That Raise Homocysteine Levels.”)
• People with the gene variant MTHFR C677T.
• Those who have stubbornly high homocysteine levels despite taking B-complex vitamins.

Individuals with the MTHFR C677T mutation are at higher risk of cardiovascular disease, stroke, pre-eclampsia (high blood pressure in pregnancy), and birth defects that occur during the development of the brain and spinal cord (neural tube defects).