Homocysteine (HCY) is an essential amino acid that contains sulfur whose value in the blood should be between 4 and 8 moles/liter. The condition in which the plasma HCY exceeds 9 μmol/liter is hyperhomocysteinemia, a cardiovascular risk factor independent of that of hypercholesterolemia. If the HCY exceeds 15 μmol/l, the daily intake of cardio aspirin to thin the blood is recommended by the doctor; in the USA the limit threshold is set at 9 μmol/l. According to the best MTHFR test, the accumulation of homocysteine in the blood correlates with the presence of genetic mutations concerning the MTHFR enzyme and in cases of deficiency of folates, vitamin B12, and B6.
Homocysteine is formed by removing a methyl group (CH3) from methionine (MAT). The methionine is formed of the homocysteine giving it a methyl group. To the homocysteine-methionine cycle participate enzymes (MTHFR, MTRR, MTR, and DHPR), B vitamins (6, 9 and 12), minerals (zinc) and substrates in methylation processes and demethylation. These substances work together to determine more or less resistance and susceptibility to environmental toxins and microbes. It should be noted that the SAM (S-adenosyl methionine) is also formed from methionine, which together with the other transferases catalyze more than 40 metabolic reactions essential for life.
The MTR enigma catalyzes the final step of regeneration of methionine from homocysteine. The whole reaction takes a methyl group (CH3) from N5-Methyltetrahydrofolate N5-MeTHF, transforming it into tetrahydrofolate (THF), and passes it to cyanocobalamin which is activated becoming Methylcobalamin (MeB12). Activated vitamin B12 is in the possession of the methyl group which, again thanks to the same enzyme and the presence of Zinc, can be donated in turn to the homocysteine making it return methionine.
If a substrate or an enzyme is not correctly present there can be an alteration of the more or less serious methylating capacity depending on the combination of problems that each expresses. Having a polymorphism of the MTHFR enzyme can increase the frequency of errors with which the enzyme is transcribed and cause a weakness in the homocysteine-methionine cycle. And it can cause a multiplicity of pathologies of the cardiovascular system, of the protein metabolism, to develop or worsen, of the reproductive system, in the development of the embryo and the newborn, of the cancerous processes, of the immune system, of the skin and much more. Modern society with its deficient diet full of anti-nutrients, it’s sedentary and stressful lifestyle, the alteration of sleep, methylation needs and causes the appearance of problems in those with methylation deficiency.
There is a mutation that affects the activity of the MTHFR enzyme and is therefore correlated with some malfunctions of the homocysteine-methionine cycle. This mutation has a significant incidence (around 40%) and therefore represents an objective problem. Without adequate methylation skills, health is compromised. It is also true that epigenetics is more important than genetics and therefore a mutation is not enough to mark the fate of a person, it becomes dangerous if the lifestyle and food of that person are not enough to make up for the genetic deficit.
The best MTHFR website says the genetic polymorphism of the MTHFR enzyme is associated with many variants, including the C677T and the A1298C. The first is determined by the substitution of the amino acid Cytosine (C) in Thymine (T), the second by the substitution of an Adenine (A) with a cytosine (C). The C677T variant affects heterozygosity 42-46℅ of Italians, in homozygosity 8-15%. Those with the A1298C variant are able to maintain an enzymatic activity equal to 50-60% while the double heterozygotes (carriers of two mutations, the C677T and the A1298C) manage to maintain 50%. If the mutation is homozygous, it is more likely to manifest symptoms first.
If this polymorphism occurs, the homocysteine values can rise. For highs, it is intended to be superior to 7, not only to 15 as generically indicated in laboratory reports. It is therefore important to monitor homocysteine and if higher than 7, perform genetic screening for thrombophilia with MTHFR mutation to verify the entire genetic profile for thrombophilia.
It is possible to have methylation deficiency but have laboratory values of the same B12 in the limits because certain vitamins can go around in the blood without being activated and without being used. All of this obviously does not diminish the thrombophilia risk.
When you have a positive family history of certain cardiovascular diseases, if elderly relatives take anticoagulants, if you get very poor blood when you get injured, and if you take a lot of alpha lipoic acid that consumes a greater quantity of B vitamins you have to check more regularly homocysteine and methylmalonic acid (MMA). In dermatitis, the positivity to the Homozygous MTHFR A1298C gene may inhibit the action of the enzyme that degrades histamine.