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INFORMATION ON METHYLATION REACTIONS AND GENETIC MUTATIONS

Vitamin deficiency and its relation with the Methylation pathway

  

Methylation reactions are extremely important to avoid many diseases like heart problems, cancer, atherosclerosis, Alzheimer and dementia, etc. The process requires vitamins of the B family as cofactors. 


Vitamins B6, B9, B12 are obtained from what we eat, but many people have a mutation in one of the genes related with the metabolism of these vitamins. Simply explained, after consumption these vitamins still need to be activated in the body through a few metabolic reactions. After numerous genetic analysis, we found that half of the world population has problems with the metabolic reactions and the activation of the vitamins is decreased. This further leads to an inefficient methylation process.


FOLIC ACID AND L-5-MTHF ARE NOT THE SAME THING. FOLIC ACID IS NOT BIOLOGICALLY ACTIVE, IT HAS TO BE CONVERTED TO L-5-MTHF IN THE BODY.


If you have a blood test to check for your vitamin levels in plasma, it can show high levels of folic acid, but this does not mean that you have a sufficient amount of the active form of the vitamin L-5-MTHF. If your body does not convert the folic acid to L-5-MTHF, it is not available to do its job, which really means you have a vitamin deficiency, but it is not detected in the blood analysis.


The actual information if your body can metabolise vitamins can ONLY be determined through genetic testing!

Why is a balanced Methylation pathway so important?

  

The methylation cycle importance is so extensive that a library of books could be written on its functions in the human body. Methylation reactions are the most important metabolic processes that occur in every cell of your body and they control almost everything.  Malfunctioning undeniably leads to premature aging and premature death. 


It is directly linked to our nervous system and nerve function highly depends on proper methylation. Methylation mobilizes cholesterol and fats and declined methylation has a huge negative effect on  cholesterol levels. Methylation is responsible for hormone regulation, histamine levels, allergic reactions, anaphylactic reactions, food allergies and it has a crucial role in detoxing the body. It converts the toxic amino acid “homocysteine” into a beneficial amino acid “methionine” , and thus avoids toxins build up in your bloodstream which eventually could cause disease and premature death. Methylation has a significant impact on liver health, fat metabolism, eye health, neurotransmitter production, DNA production, cellular energy and the list goes on and on…

Extra note about pregnancy


Most Doctors prescribe folic acid supplements for women, several months before they are trying to get pregnant. They do so for good reasons because folic acid is necessary for DNA methylation and deficiency in methylation highly increases the risk for miscarriage and neural tube defects in the baby. Unfortunately, most Doctors don’t understand that folic acid is actually doing absolutely nothing for many women because it is not biologically active. It has to be converted to L-5-MTHF in the body to be functional. For about 50% of the woman this is not a problem but for the other 50% their body cannot sufficiently activate the folic acid prenatal supplement, leaving them at high risk. 


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Scientific references

[1] N. M. J. van der Put et al., “A Second Common Mutation in the Methylenetetrahydrofolate Reductase Gene: An Additional Risk Factor for Neural-Tube Defects?,” Am. J. Hum. Genet., vol. 62, no. 5, pp. 1044–1051, 1998.

[2] E. J. Servy, L. Jacquesson-fournols, M. Cohen, Y. J. R. Menezo, C. Natecia, and L. Clement, “MTHFR isoform carriers . 5-MTHF ( 5- methyl tetrahydrofolate ) vs folic acid : a key to pregnancy outcome : a case series Authors ’ contributions,” J. Assist. Reprod. Genet., pp. 1–10, 2018.

[3] L. Leemans, “[Does 5-methyltetrahydrofolate offer any advantage over folic acid?].,” Le 5-methyltetrahydrofolate a-t-il des Avantag. par Rapp. a l’acide folique?, no. 4, pp. 16–22, 2012.

[4] B. S. Trippe, L. W. Barrentine, M. V. Curole, and E. Tipa, “Nutritional management of patients with diabetic peripheral neuropathy with L-methylfolate-methylcobalamin-pyridoxal-5-phosphate: results of a real-world patient experience trial,” Curr. Med. Res. Opin., vol. 32, no. 2, pp. 219–227, 2016.

[5] M. J. Walker, L. M. Morris, and D. Cheng, “Improvement of cutaneous sensitivity in diabetic peripheral neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5’-phosphate.,” Rev. Neurol. Dis., vol. 7, no. 4, pp. 132–9, 2010.

[6] V. Medici and C. H. Halsted, “Folate, alcohol, and liver disease,” Mol. Nutr. Food Res., vol. 57, no. 4, pp. 596–606, 2013.

[7]  B. Akoglu et al., “The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total serum homocysteine level in orthotopic liver transplant recipients: A double-blind placebo-controlled study,” Eur. J. Clin. Nutr., vol. 62, no. 6, pp. 796–801, 2008.

[8] F. Scaglione and G. Panzavolta, “Folate, folic acid and 5-methyltetrahydrofolate are not the same thing,” Xenobiotica, vol. 44, no. 5, pp. 480–488, 2014.

[9] S. Sharma and A. Litonjua, “Asthma, Allergy and Responses to Methyl Donor Supplements and Nutrients,” J. Allergy Clin. Immunol., vol. 133, no. 1, pp. 1–23, 2014.

[10] F. F. Willems, G. H. J. Boers, H. J. Blom, W. R. M. Aengevaeren, and F. W. A. Verbeugt, “Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease,” Br. J. Pharmacol., vol. 141, no. 5, pp. 825–830, 2004.

[11] A. Cribbs, M. Feldmann, and U. Oppermann, “Towards an understanding of the role of DNA methylation in rheumatoid arthritis: Therapeutic and diagnostic implications,” Ther. Adv. Musculoskelet. Dis., vol. 7, no. 5, pp. 206–219, 2015.

[12] E. Miranda-Morales, K. Meier, A. Sandoval-Carrillo, J. Salas-Pacheco, P. Vázquez-Cárdenas, and O. Arias-Carrión, “Implications of DNA Methylation in Parkinson’s Disease,” Front. Mol. Neurosci., vol. 10, no. July, pp. 1–13, 2017.

[13] L. Knowles, A. Morris, and J. Walter, “Treatment with Mefolinate (5-Methyltetrahydrofolate) but Not Folic Acid or Filinic Acid, Leads to Measurable 5-Methyltetrahydrofolate in Cerebrospinal Fluid in Methylenetetrahydrofolate Reductase Deficiency.,” JIMD Rep., pp. 103–107, 2016.

[14] F. Lombardo et al., “Treatment of erectile dysfunction due to C677T mutation of the MTHFR gene with vitamin B6 and folic acid in patients non responders to PDE5i,” J. Sex. Med., vol. 7, no. 1 PART 1, pp. 216–223, 2010.

[15] P. Tsamatropoulos, E. Jannini, L. Gandini, F. Dondero, A. Lenzi, and F. Lombardo, “T01-P-09 MTHFR gene and erectile dysfunction,” Sexologies, vol. 17, p. S59, 2008.