The annual conference of One carbon metabolism, B vitamins and Homocysteine has been recently held in Poland, on September 12-16, 2021, bringing experts and professionals from all over the globe to assist and share the newest scientific advances in this field.
The annual conference was the occasion to meet and discuss the future of one-carbon metabolism, offering plenary lectures, invited talks, contributed talks, poster sessions, round table discussions, and expert sessions, and Gnosis by Lesaffre has been a proud sponsor of the conference.
Part of the conference challenge is raising the scientific voices to translate reported advances in basic science into clinical application, presenting potential and future applications mainly focused on:
- Emerging and critical role of Homocysteine in health, CVD and neurodegeneration
- One-carbon Metabolism, in health and Life Span
- New developments in emerging roles of folate, enzyme polymorphisms in Health and Disease
- Perspective on UMFA risk in high folate administration (folic acid)
The central role of “one-carbon metabolism” in sustaining life
Often referred to as the Methylation Cycle, the One carbon metabolism is a network of interrelated biochemical reactions that involves the transfer of one carbon methyl groups from one compound to another. The one-carbon involves the conversion of dietary folate or folic acid into SAMe via several intermediary molecules, including L-methylfolate (5-methyltetrahydrofolate or 5-MTHF).
In the one carbon metabolism, the active form of folate 5-MTHF provides methyl groups to the S-adenosylmethionine (SAMe) cycle through the conversion of homocysteine (Hcy) to methionine. SAMe is the primary methyl donor of methyl groups in our body, required in the methylation of a diverse number of targets, including phospholipids, DNA, ribonucleic acid, neurotransmitters, and proteins. Homocysteine is a byproduct of the one-carbon cycle. Perturbations of one carbon metabolism, owing to low levels of 5-MTHF, critically contribute to decreasing the availability of SAMe and increase the levels of circulating homocysteine.
1) Emerging and critical role of Homocysteine in health, CVD and neurodegeneration
Impairment of methylation status and raised values of homocysteine (a non-protein forming amino acid) may be modifiable risk factors for cardiovascular disease, cognitive decline and dementia, and thus a potential target in preventive interventions. As a matter of fact, HHcy has been associated with several cerebrovascular and cardiovascular conditions.
The majority of cases of hyperhomocysteinemia (HHcy) are caused by a lack of several key B vitamins or their absorption with age, where folate has a big importance. The importance of diagnosing and treating nutritional deficiencies and inherited disorders to reverse intermediate/severe HHcy associated is today even more demanding as pointed out in the conference.
As reported by Prof. I.H. Rosenberg and Scott1 in their intervention, “there is now sufficient evidence to make an increasingly powerful argument for a cost-effective homocysteine lowering by B vitamins and omega-3 fatty acids for prevention and mitigation of age-related cognitive decline and dementia”.
Vitamin B12 and folate are essential vitamins for the remethylation of homocysteine to methionine and the subsequent formation of S-adenosylmethionine (SAMe), the primary methyl donor for many biochemical reactions involved in normal brain functions. Interference with this process may lead to impairment in the formation of methionine and an unfavorable methylation status and may result in the accumulation of serum total homocysteine (tHcy). Elevated tHcy levels may further impair the methylation status by converting to S-adenosyl homocysteine (SAH), a potent competitive inhibitor of several methyl transferases.
Guéant et al.2, presented a study pointing out the importance of diagnosing and treating nutritional deficiencies and inherited disorders to reverse intermediate/severe HHcy associated with CVD outcomes. The group performed a retrospective cross-sectional study on consecutive patients who underwent a homocysteine assay. Patients with CVD outcomes were assessed for vitamin B12, folate, Hcy, methylmalonic acid, and next-generation clinical exome sequencing. HHcy was related to vitamin B12 and/or folate deficiency in 55%, mutations in one or more genes of one-carbon and/or vitamin B12 metabolisms in 11%, and renal failure in 26% of the studied patients. HHcy was the single vascular risk retrieved in almost 9% of patients. 60% of patients received a supplementation to treat HHcy, with a significant decrease in median Hcy from 41 to 17 µmol/L. No recurrence of thromboembolic manifestations was observed after supplementation and antithrombotic treatment of patients who had HHcy as a single risk, after nearly 4-years of follow-up……….
- Irwin H. Rosenberg & Tammy Scott “It is well past time to apply our understanding of homocysteine metabolism to the treatment and prevention of age related vascular dementia and cognitive decline.” Tufts University
- Jean-Louis Guéant et al., ”Cardiovascular manifestations of intermediate and major hyperhomocysteinemia due to vitamin b12 and folate deficiency and/or inherited disorders of one-carbon metabolism: a 3.5-years retrospective cross-sectional study of consecutive patients”. INSERM U1256 and Department of Molecular Medicine, Division of Biochemistry, Molecular Biology, and Nutrition, University Hospital of Nancy.
2) One-carbon Metabolism, in health and Life Span …
3) New developments in emerging roles of folate, enzyme polymorphisms in Health and Disease …
4) Perspective on UMFA risk in high folate administration (folic acid2) …
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Folate is one of the most common vitamin deficiencies, also because body requires the conversion of folic acid to its active form, methylfolate.