In 1969, Dr. Kilmer McCully suggested that elevated homocysteine levels (hyperhomocysteinemia) were associated with heart issues. Since then, thousands of studies have confirmed his theory of homocysteine as a cardiovascular risk factor. As a result, many practitioners recognize the importance of keeping levels of homocysteine in a healthy range. Normal homocysteine levels require a functioning methylation cycle, which depends on the activity of multiple enzymes.

The body maintains healthy homocysteine levels by regulating the activity of a number of enzymes. These enzymes are located in your methylation cycle. They collectively work to convert homocysteine into either methionine or cysteine, which are beneficial amino acids.^†

The human body carries out methylation reactions in every single cell. The methylation cycle begins with the amino acid methionine. Via the MAT1A enzyme, methionine is converted into SAMe (S-adenosylmethionine). Once SAMe donates its methyl group to make creatine, phosphatidylcholine (PC), melatonin, or hundreds of other compounds, it becomes homocysteine. If the cycle slows down here, homocysteine levels can build up and become problematic.^†

It is essential to keep the methylation cycle moving to maintain healthy homocysteine levels. The most critical enzymes involved in homocysteine metabolism include:^†

• CBS (Cystathionine Beta Synthase): Converts homocysteine into cystathionine, and then cysteine. About half of this cysteine is used to make glutathione, the body’s most important antioxidant compound. Both the CBS enzyme and the following CTH enzyme need adequate levels of vitamin B6 in the form of pyridoxal-5'-phosphate (P-5-P) to function.^†


• BHMT (Betaine Homocysteine Methyl Transferase): This enzyme facilitates the donation of a methyl group from trimethylglycine (TMG) to homocysteine to recycle it into methionine.^†


• MTHFR (MethyleneTetraHydroFolate Reductase): This is the final enzyme that carries out the manufacturing of 5-MTHF. A form of folate called 5-Methyltetrahydrofolate (5-MTHF) first donates a methyl group to cobalamin (B12) to make methylcobalamin. Then, methylcobalamin donates the methyl group to homocysteine, converting it into harmless methionine.^†


• Unfortunately, the manufacturing of 5-MTHF is not easy. In addition, over 50% of the general population has an MTHFR gene mutation slowing down their MTHFR enzyme. Thus, taking only L-5-methylfolate is often insufficient for those with MTHFR mutations. Riboflavin in the form of riboflavin 5’-phosphate (R-5-P) is needed as a coenzyme for the MTHFR enzyme to work. If you have a gene mutation in this enzyme, having adequate amounts of R-5-P becomes increasingly important.^†


• MTR (Methionine Synthase): This is the last enzyme in the methylation cycle. It accepts the methyl group from 5-MTHF and adds it back to homocysteine to synthesize methionine. This provides the body with more methionine to start the methylation cycle all over again.^†

Each of these enzymes relies on specific nutrients as coenzymes. These coenzymes act like a key to ignite methylation enzymes to work and run at an optimal pace. It is well known that deficiency can slow the function of these enzymes. With slower enzyme function, homocysteine levels may rise.^†

Most research focuses on vitamin B12 and folate (5-MTHF) deficiencies in relation to elevated homocysteine levels. However, riboflavin (R-5-P), betaine (TMG), and vitamin B6 (P-5-P) play equally important roles in maintaining healthy homocysteine levels.^†

Did your doctor say you have high homocysteine? This is a sign of poor methionine recycling. If you want to support proper methylation recycling, you may want to look at HomocysteX Plus or Methylate. Each was designed to support healthy homocysteine levels.^†

If you’re looking to support healthy homocysteine levels and optimal methylation, look no further than HomocysteX Plus by Seeking Health.^†