We previously published an article titled FOLATE INGREDIENTS – FOLINIC ACID & 5-MTHF in which we discuss how coenzyme folate vitamins are far superior to the synthetic folic acid form. In today’s article, I take a more in-depth look at how homocysteine is formed from methionine, how genetics affects the metabolic pathways, and how B vitamins are used in metabolic pathways.
One way to look at the metabolic pathways of methionine (an essential amino acid) is that it provides a way for the body to convert this sulfur containing amino acid either to cysteine and its key by-products glutathione, taurine, and sulfates or allows remethylation back to methionine to occur using either the Folate Cycle or the Trimethyl glycine (betaine) pathways.
Figure 1 shows these metabolic pathways including the vitamins required at each step including vitamin B6 (as P-5-P), methylcobalamin, and 5-methyltetrahydrofolate (5-MTHF). In addition, it shows the key enzymes produced by the body at each step. These enzymes include CBS (cystathione beta synthase), BHMT (betaine homocysteine methyltransferase), MS (methionine synthase), and MTHFR (methylene tetrahydrofolate reductase).
HEALTH ISSUES ASSOCIATED WITH HIGH HOMOCYSTEINE LEVELS
It is highly important that the various metabolic pathways function correctly to keep homocysteine at healthy levels (6–8 µmol/L). Unfortunately, high levels of homocysteine in the body (10–20 µmol/L) are a factor in a wide range of health issues, including:
- Greater risk for heart problems, including coronary artery disease, heart attacks, stroke, high blood pressure, congestive heart failure, and abnormal cholesterol levels. This is due to increased inflammation, sometimes due to blood clotting spontaneously, and because of blockages of the major arteries.
- Mental abnormalities such as depression, anxiety, bipolar disorder, and other mental problems are more common among people with high homocysteine
- Migraines and headaches in a significant percentage of the population
- In those who suffer from high homocysteine due to having nutritional deficiencies anemia, aches and pains, hearing loss, age-related macular degeneration (ARMD), slowed development, and birth defects might also be possible
- Greater risk for dementia, Alzheimer’s disease, brain atrophy, and other cognitive problems
- In children, skeletal and developmental abnormalities including having a curved spine or protruding chest and rib cage. Some patients appear very tall and thin, and some might also have very long, thin “spider-like” toes and fingers.
- Behavioral problems, including ADHD, autism and other learning disabilities
ROLE OF GENETICS IN HOMOCYSTEINE METABOLISM
Ten or more years ago, questions of how genetics enters into homocysteine metabolism were unlikely to be asked. However, in recent years DNA testing has advanced and is now available to everyone (for example, see my article about Bodysync’s genetic test, DISCOVERING NUTRITIONAL NEEDS THROUGH ADVANCED GENETIC TESTING.
You may have heard a great deal about MTHFR (methylene tetrahydrofolate reductase). This gene is involved in folate metabolism and has a central role in methylation processes like repair of and building new DNA in dividing cells.
In the remethylation pathway for conversion of homocysteine to methionine, MTHFR plays a key role in converting folate into 5-MTHF which is needed along with B12 as methylcobalamin in order for the conversion to take place. Genetic variations in MTHFR have been studied in depth. Of the many variations studies the most significant ones appear to be variations of C677C such as C677T (referred to as heterozygous) or T677T (referred to as homozygous). The heterozygous variant appears in about 30–50% of the population and causes somewhat less efficiency in the conversion of folic acid to 5-MTHF. However, the homozygous variation occurs in about 10% of the population and can have serious effects due to converting little homocysteine back to methionine.
Another variation in MTHFR is called A1298A. These variations are A1298C and C1298C and will have similar effects to the C677C variations. It was interesting to me when I recently analyzed my Bodysync genetic test results showing I carry the variation A1298C (heterozygous), which indicates I may not be effectively converting homocysteine back to methionine.
Additionally, my Bodysync genetic test results also indicate that I have heterozygous variations in the CBS enzyme shown in Figure 1, as well as heterozygous variations in MTR and MTRR enzymes, which are involved with B12 levels in the remethylation pathway. These results indicate that I need to take higher levels of methylcobalamin and 5-MTHF.
IMPORTANCE OF COENZYME FORMS AND PROPER AMOUNTS OF B VITAMINS
Many of the B vitamins on the market today unfortunately are in synthetic form. The body can only use the natural coenzyme forms effectively. For example, the body needs vitamin B6 in the form of P-5-P (pyridoxal-5-phosphate), folate in the form of L-5-MTHF, and B12 in the form of methylcobalamin for proper metabolism of methionine. In some cases the body can use the synthetic forms of pyridoxine HCl, folic acid, and cyanocobalamin but pays a cost (e.g., in time and energy) by having to convert synthetic forms to coenzyme forms.
Add to the prevalence of synthetic B vitamins, the fact that genetic deficiencies are more common than previously assumed, and it becomes clear that the coenzyme forms of B vitamins in the proper amounts are extremely important.
Fortunately, I have always believed it best to include as many coenzyme forms as possible in the nutritional supplements I formulate (over the past 27 years). For example, all HPDI multivitamins include coenzymes of B1, B2, B6, B12, and folate (as 5-MTHF and folinic acid). This is uncommon in most multivitamin formulas on the market. For this reason our supplements are ideally suited to the prevention or resolution of most genetic problems regarding homocysteine.
In addition, I have always chosen to include higher amounts than most multivitamins on the market. We also make available 5-MTHF one milligram (1 mg) capsules and methylcobalamin five milligram (5 mg) sublingual tablets. When genetic variations are in play as discussed above, then providing relatively higher amounts of coenzyme B vitamins that support important requirements in the body seems necessary.
Interestingly, several other nutrients are involved in the pathways involving methionine and homocysteine. These include zinc, magnesium, and Vitamin B2. Our multivitamin formulas and magnesium formulas, especially Myo-Mag with its coenzyme B1, B2, and B6, are recommended to support these nutrient needs. Finally, it has been found that N-Acetyl-L-Cysteine (NAC) can significantly lower homocysteine (by up to 50%), most likely because its gives the body an excellent source of cysteine without have to use methionine.
In this article, I have shown the value of the use of genetic testing and high-quality coenzyme B vitamins in resolving health issues associated with high values of homocysteine in the body.
SOURCES & RESOURCES
DISCOVERING NUTRITIONAL NEEDS THROUGH ADVANCED GENETIC TESTING.
FOLATE INGREDIENTS – FOLINIC ACID & 5-MTHF
The Homocysteine Revolution by Kilmer S. McCully, MD
“Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease“
(Cell Death and Differentiation 11, S56–S64)