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High dose folic acid is a potential treatment for pulmonary hypertension, including when associated with COVID-19 pneumonia

Wiltshire et al., Medical Hypotheses, doi:10.1016/j.mehy.2020.110142
Jul 2020  
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Hypothesis that high-dose folic acid (5-10mg daily) may be beneficial for COVID-19 related pulmonary hypertension and hypoxemia, based on systemic vascular effects showing improved endothelial function and prevention of nitrate tolerance with high-dose folic acid. Authors propose testing as an adjunct therapy for severe COVID-19 pneumonia patients being considered for inhaled nitric oxide, expecting potential improvements in oxygenation and prevention of tachyphylaxis.
Wiltshire et al., 26 Jul 2020, peer-reviewed, 5 authors. Contact: esko.wiltshire@otago.ac.nz.
This PaperVitamin B9All
High dose folic acid is a potential treatment for pulmonary hypertension, including when associated with COVID-19 pneumonia
Esko Wiltshire, Alexia Sophie Peña, Karen Mackenzie, Geoffrey Shaw, Jennifer Couper
Medical Hypotheses, doi:10.1016/j.mehy.2020.110142
Background: Pulmonary hypertension is a significant complication for some patients with COVID-19 pneumonia, especially those requiring intensive care. Tachyphylaxis to the current therapy, inhaled nitric oxide (iNO), is also common. In vitro, folic acid directly increases nitric oxide (NO) production and extends its duration of action; effects which could be of benefit in reversing pulmonary hypertension and severe hypoxaemia. Our work has shown that, in the systemic circulation, folic acid in high dose rapidly improves nitric oxide mediated vasodilation, by activating endothelial nitric oxide synthase (eNOS). Hypothesis: A similar effect of high dose folic acid on pulmonary endothelial function would be expected from the same mechanism and would lead to improvement in pulmonary perfusion. We therefore hypothesise that folic acid, 5 mg or greater, is a useful therapeutic option for pulmonary hypertension and/or refractory severe hypoxaemia, in patients with severe COVID-19 associated pneumonia in whom NO therapy is considered, with a very low risk of adverse effects.
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.mehy.2020.110142.
References
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