<strong>Pyridoxal 5'-phosphate to mitigate immune dysregulation and coagulopathy in COVID-19</strong>

Abstract

Although most cases of COVID-19 are paucisymptomatic, severe disease is characterized by immune dysregulation, with a decreased type I interferon response, increased inflammatory indicators, surging IL-6, IL-10 and TNF&amp;alpha; suggestive of cytokine storm, progressive lymphopenia, and abnormal blood clotting. Factors determining susceptibility to severe disease are poorly understood, although mortality correlates with increasing age and co-morbidities including diabetes and cardiovascular disease (CVD). Pyridoxal 5'-phosphate (PLP) tends to be insufficient in populations particularly vulnerable to COVID-19, including the elderly, the institutionalized, and people with diabetes and CVD, and PLP becomes further depleted during infection and inflammation. In turn, low PLP results in immune imbalance, as PLP is an essential cofactor in pathways regulating cytokine production, in particular type I interferons and IL-6, and in lymphocyte trafficking and endothelial integrity. Furthermore, normalizing PLP levels attenuates abnormalities in platelet aggregation and clot formation. Finally, PLP insufficiency induces excess secretion of renin and angiotensin, and hypertension. In inflammatory disease, pharmacological doses of PLP decrease circulating TNF&amp;alpha;, IL-6 and D-dimer, and animal studies demonstrate that supplemental PLP shortens the duration and severity of viral pneumonia. Severe COVID-19 manifests as an imbalance in the immune response and the clotting system. Pharmacological PLP supplementation may therefore mitigate COVID-19 symptoms by alleviating both the immune suppression underlying viral spread and the pathological hypersecretion of inflammatory cytokines, as well as directly bolstering endothelial integrity and preventing hypercoagulability.

Be well: A potential role for vitamin B in COVID-19

“…Dysregulation of immune responses and increased risk of coagulopathy have also been noted among COVID-19 patients. In a recent preprint it is suggested that PLP supplementation mitigates COVID-19 symptoms by regulating immune responses, decreasing pro-inflammatory cytokines, maintaining endothelial integrity and preventing hypercoagulability [22]. In fact, it was shown three decades ago that PLP levels reduce abnormalities in platelet aggregation and blood clot formation [23].…”

Clinical Impact Potential of Supplemental Nutrients as Adjuncts of Therapy in High-Risk COVID-19 for Obese Patients

“…The utilization of vitamin B6 rapidly increases under inflammatory conditions, and COVID-19 patients probably may have vitamin B6 deficiency (156). Vitamin B6 downregulated the pulmonary inflammation by inhibiting macrophage activation, as reduced production of IL-1β, IL-6, and TNF-α in macrophages challenged with LPS of mice (155). In a rat model of systemic inflammation, orally administered 500 mg/kg riboflavin and 600 mg/kg thiamine increased the anti-inflammatory activity of dexamethasone, along with reducing TNF-α and IL-6 production (157).…”

“…Vitamin B6 levels and the severity of inflammatory reactions are inversely correlated (154,155). The utilization of vitamin B6 rapidly increases under inflammatory conditions, and COVID-19 patients probably may have vitamin B6 deficiency (156).…”

Vitamin B6 in Health and Disease

“…When there is PLP deficiency, this lyase is inhibited, and when the lyase is deficient, lymphocytes are arrested in secondary lymphatic organs and in places where inflammatory processes take place [ 5 , 6 ]. This leads to lymphopenia and immunosuppression as well as to local exacerbation of inflammatory processes and to an increase in the secretion of pro-inflammatory cytokines [ 5 ].…”

“…Descriptions of the mechanisms of these reactions can be found in any textbook on biochemistry. The key pathways for human health with the regulatory involvement of vitamin B6 include the metabolism of sphingosine phosphate [ 5 ], tryptophan catabolism [ 6 ], and the action of the transcription factor NF-κB. According to the latest research, it has the effect of reducing inflammation in the body by influencing the activity of inflammasomes and specifically its component, the NLRP3 sensory protein [ 7 ].…”