key: cord-0801359-vqxd6cyc authors: Ibrahimagić, Omer Ć.; Kunić, Suljo title: COMMENT ON AN ARTICLE: ,High dose folic acid is a potential treatment for pulmonary hypertension, including when associated with COVID-19 pneumonia“ date: 2020-10-07 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110338 sha: 824c40c21e6dd72852f55510e2b73746b00d6b73 doc_id: 801359 cord_uid: vqxd6cyc nan We have read with great attention the article "High dose folic acid is a potential treatment for pulmonary hypertension, including when associated with COVID-19 pneumonia" written by pneumonia with pulmonary hypertension. Due to our studies and experiences, but also of rare opinions of other distinguish colleagues, we strongly agree with the hypothesis of Authors. Importantly, we welcome the opportunity to make a short comment as well. There is an evident connection between homocysteine and nitric oxide (NO) metabolism. Hyperhomocysteinemia leads to reduction in NO bioavailability (2) . Oxidative stress, impaired of NO synthase pathway and mitochondria dysfunction associated with impaired homocysteine metabolism leads to aging tissue degeneration (3) . Homocysteine increases activity of NO synthase and induces inhibition of nitric oxide production in platelets (4, 5) . Homocysteine is an independent risk factor for coronary heart disease and cerebrovascular disease. Hyperhomocysteinemia could play a key role through free radicals production by homocysteine oxidation. The high toxicity of these free radicals to vascular endothelial cells, could promote and increase synthesis of oxidized low-density lipoprotein (6) . In addition, vascular changes, caused by increased levels of homocysteine, may provoke pulmonary hypertension (7) . Furthermore, the Authors also note that hyperhomocysteinemia may occur in patients with pulmonary hypertension (1). Values of folic acid and B12 are in negative correlation with levels of homocysteine (8) . Fortunately, folates could protect blood vessels and prevent DNA damage caused by hyperhomocysteinemic oxidative stress (9) . A large prospective study reported a significant lowering effect on homocysteine levels of daily suplementation combining folic acid and vitamins B 12 / B 6 (10). Risk of side effects is minimal if the daily dose of folic acid is in between 1-5 mg (11) . In light of this facts, proper intake of vitamin and diet control should be established as early as possible, not only in COVID-19 population but also in other health individuals in the age of SARS-Cov-2. Importantly, for this purpose, it includes adequate dietary intake of folate and vitamins B 6 / B 12, intake of proteins rich in methionine that help to regulate homocysteine biochemical pathways, and avoid unhealthy lifestyle choices such High dose folic acid is potential treatment for pulmonary hypertension, including when associated with COVID-19 pneumonia Homocysteine-induced endothelial dysfunction Homocysteine and age-associated disorders Homocysteine and homocysteine-related compounds:an overview of the roles in the pathology of the cardiovascular and nervous systems Homocysteine: Its possible emerging role in at-risk population groups Plasmaendothelin-1, homocysteine and serum nitric oxide values in patients with left-to-right shunt Treatment Trialists' Collaboration. Homocysteine-lowering trials for prevention of cardiovascular events: A review of the design and power of the large randomized trials Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease Hyperhomocysteinemia recurrence in levodopa-treated Parkinson's disease patients Facts and reccomendations about total homocysteine determinations: An expert opinion