Worse Course and Bad Prognosis of COVID-19 in Hyper-Homocysteinemia: Role of Some B-Group Vitamins and of Other Compounds

Review Article

J Cardiovasc Disord. 2021; 7(1): 1045.

Worse Course and Bad Prognosis of COVID-19 in Hyper-Homocysteinemia: Role of Some B-Group Vitamins and of Other Compounds

Cacciapuoti F*

Department of Internal Medicine, “Luigi Vanvitelli”- Campania-University, Italy

*Corresponding author: Federico Cacciapuoti, Department of Internal Medicine, “Luigi Vanvitelli” Campania University, Piazza L. Miraglia, 2 Naples, Italy

Received: June 22, 2021; Accepted:July 15, 2021; Published: July 22, 2021


Background: Increased homocysteine serum levels (HHcy) induce Endothelium Dysfunction (ED), responsible of the activation of some proinflammatory agents (“cytokine storm”), the imbalance between vasodilation and vasoconstriction with vasoconstrictive prevalence, increased oxidative stress and hyper-coagulability.

Methods: All these events can worsen the course of COVID-19 in HHcy- patients, favoring the evolution towards vasculitis, thromboembolic complications, multi-organ dysfunction until acute respiratory distress and failure.

Results: Therefore, Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) also called COVID-19, elapses more dangerously in patients affected by HHcy and can easily complicate with thromboembolic events. But, some vitamins of B-group and other substances could positively affect both high Hcy levels and thrombotic complications of SARS-CoV-2 happening in lungs and other districts.

Conclusions: COVID-19 can have a dangerous evolution and a bad prognosis in patients with HHcy. Concerning this, some compounds seem to exert beneficial effects on HHcy, inflammatory and coagulopathic complications.

Keywords: Homocysteine; COVID-19; Endothelial dysfunction; Thromboticlungs complications; B-group vitamins; Vitamin D; Magnesium; N-Acetyl- Cysteine


Hcy: Homocysteine; Met: Methionine; MTHFR: Methylene-Tetra- Hydro-Folate Reductase; MAT: Methionine; Adenosyl Transferase; ROS: Reactive Oxygen Species; TMG: Tri-Methyl-Glycine; HHcy: Hyper Homocysteine; CβS: Cystationine-Beta-Synthase; CGL: Cystationine-Gamma-Lyase; COVID-19: Corona-Virus Disease 2019; HRCT: High Resolution Computed Tomography; IL: Inter- Leukin; ED: Endothelial Dysfunction; NO: Nitric Oxide; ADMA: Asymmetric-Di-Methyl Arginine; DDAH: Dimethylarginine- Dimethyl-Amino Hydrolase; VCAM: Vascular Adeshion Molecule; SARS-CoV-2: Severe Acute Respiratory Syndrome-Coronavirus-2; ACE: Angiotensin Converting Enzyme; PE: Pulmonary Embolism; NAC: N-Acetyl-Cysteine



Homocysteine (Hcy) is an intermediate, sulfur amino acid produced by the Methionine (Met) demethylation. This amino-acid (Met) is present in meat, fish, eggs, grains and dairy diet products and plays a critical role in DNA methylation [1]. Hcy metabolization happens via two major pathways: re-methylation and trans-sulfuration [2]. About 50% of Hcy is re-converted back to Met via two enzymes: Methylene-Tetra-Hydrofolate Reductase (MTHFR) and Methionine- Adenosyl-Transferase (MAT) respectively having folate (vit.B9) and vit. B12 as cofactors. In trans-sulfuration pathway, Hcy condenses with serine to form Cystathionine. Afterwards, this is synthesized in Cysteine that rises to Glutathione, a powerful antioxidant of the body, able to prevent damage induced by Reactive Oxygen Species (ROS) (Figure 1). In this pathway, vit.B6 acts as a cofactor for the enzymes employed [3]. The enzymes coming in this pathway are respectively: Cystathionine-beta-Synthase (CβS) and Cystathionine-Gamma- Lyase (CGL). A third route for the conversion back of Hcy to Met happens in the liver and kidney involving Trimethylglicine (TMG) or betaine as a methyl donor via trimethyltransferase [3].