COVID-19 pathophysiology: interactions of gut microbiome, melatonin, vitamin D, stress, kynurenine and the alpha 7 nicotinic receptor: Treatment implications

2020 ◽  
Vol 3 (3) ◽  
pp. 322-345 ◽  
Author(s):  
George Anderson ◽  
Russel J Reiter

As data emerges on the pathophysiological underpinnings of severe acute respiratory syndrome coronavirus (SARS-CoV)-2, it is clear that there are considerable variations in its susceptibility and severity/fatality, which give indications as to its pathophysiology and treatment. SARS-CoV-2 modulatory factors include age, vitamin D levels, cigarette smoking, gender and ethnicity as well as premorbid medical conditions, including diabetes, cancer, obesity, cardiovascular disease, and immune-compromised conditions. A complex picture is emerging, with an array of systemic physiological processes interacting including circadian, immune, intestinal, CNS and coagulation factors. This article reviews data on SARS-CoV-2 pathoetiology and pathophysiology. It is proposed that a decrease in pineal and systemic melatonin is an important driver of SARS-CoV-2 susceptibility and severity, with the loss of pineal melatonin's induction of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) in pulmonary epithelial cells and immune cells being a powerful regulator of susceptibility and severity, respectively. Stress, including discrimination stress, and decreased vitamin D also regulate SARS-CoV-2, including via gut dysbiosis and permeability, with a resultant decrease in the short-chain fatty acid, butyrate, and increase in circulating lipopolysaccharide. Stress and cytokine induction of the kynurenine pathways, leads to aryl hydrocarbon receptor activation, which primes platelets for heightened activity, coagulation and thrombin production, thereby driving elevations in thrombin that underpin many SARS-CoV-2 fatalities. On the basis of these pathophysiological changes, prophylactic and symptomatic treatments are proposed, including the use of melatonin and α7nAChR agonism. 

Author(s):  
Maryam Mosavat ◽  
Aisling Smyth ◽  
Diana Arabiat ◽  
Lisa Whitehead

AbstractVitamin D contributes to numerous physiological processes within the body but primarily calcium and bone homeostasis. Emerging evidence highlights a novel role for vitamin D in maintaining and regulating optimal sleep. Sleep is a known regulator of bone health, highlighting the interconnectedness between vitamin D concentrations, sleep duration and bone metabolism. It is possible that the relationship between sleep length and vitamin D is bidirectional, with vitamin D playing a role in sleep health and conversely, sleep affecting vitamin D levels. Nevertheless, limited information on the direction of the interaction is available, and much remains to be learned concerning the complex relationship between insufficient sleep duration and vitamin D deficiency. Given the potential to implement interventions to improve sleep and vitamin D supplementation, understanding this relationship further could represent a novel way to support and improve health.


2019 ◽  
Vol 25 ◽  
pp. 199-200
Author(s):  
Prathyusha Chitrapu ◽  
Shilpa Jain ◽  
Aaron Thrift ◽  
Maya Balakrishnan ◽  
Ruchi Gaba

Author(s):  
Jeniffer Danielle M. Dutra ◽  
Quelson Coelho Lisboa ◽  
Silvia Marinho Ferolla ◽  
Carolina Martinelli M. L. Carvalho ◽  
Camila Costa M. Mendes ◽  
...  

Abstract. Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were < 30 ng/mL in 78% of the patients, and < 20 ng/mL in 35%. The mean vitamin D level was 24.3 ± 6.8 ng/mL. The comparison between the clinical, biochemical and histological characteristics of the patients according to the levels of vitamin D showed no significant difference. Most patients with NAFLD had hypovitaminosis D, but low vitamin D levels were not related to disease severity and the presence of comorbidities.


2020 ◽  
Vol 90 (3-4) ◽  
pp. 346-352
Author(s):  
Vincenzo Pilone ◽  
Salvatore Tramontano ◽  
Carmen Cutolo ◽  
Federica Marchese ◽  
Antonio Maria Pagano ◽  
...  

Abstract. We aim to assess the prevalence of vitamin D deficiency (VDD) in patients scheduled for bariatric surgery (BS), and to identify factors that might be associated with VDD. We conducted a cross-sectional observational study involving all consecutive patients scheduled for BS from 2017 to 2019. The exclusion criteria were missing data for vitamin D levels, intake of vitamin D supplements in the 3 months prior to serum vitamin D determination, and renal insufficiency. A total of 206 patients (mean age and body mass index [BMI] of 34.9 ± 10.7 years, and 44.3 ± 6.99 kg/m2, respectively) met the inclusion criteria and were enrolled for data analysis. VDD (<19.9 ng/mL), severe VDD (<10 ng/mL), and vitamin D insufficiency (20–29.9 ng/mL) were present in 68.8 %, 12.5 %, and 31.2 % of patients, respectively. A significant inverse correlation was found between vitamin D levels and initial BMI, parathyroid hormone, and homeostatic model assessment of insulin resistance (r = −0.280, p < 0.05; r = −0.407, p = 0.038; r = −0.445, p = 0.005), respectively. VDD was significantly more prevalent in patients with higher BMI [−0.413 ± 0.12, CI95 % (−0.659; −0.167), p = 0.006], whereas no significant association between hypertension [−1.005 ± 1.65, CI95 % (−4.338; 2.326), p = 0.001], and diabetes type 2 (T2D) [−0.44 ± 2.20, CI95 % (−4.876; 3.986), p = 0.841] was found. We observed significant association between female sex and levels of vitamin D [6.69 ± 2.31, CI95 % (2.06; 11.33), p = 0.006]. The present study shows that in patients scheduled for BS, VDD deficiency is common and was associated with higher BMI, and female sex.


Author(s):  
Seyed Mostafa Parizadeh ◽  
Majid Rezayi ◽  
Reza Jafarzadeh-Esfehani ◽  
Amir Avan ◽  
Hamideh Ghazizadeh ◽  
...  

Abstract. Background: Vitamin D deficiency (VDD) is a major public health problem. There are few comprehensive systematic reviews about the relationship between Vitamin D status and liver and renal disease in Iran. Methods: We systemically searched the following databases: Web of Science; PubMed; Cochrane Library; Scopus; Science Direct; Google Scholar and two Iranian databases (Scientific Information Database (SID) and IranMedex) up until November 2017 to identify all randomized control trials (RCTs), case control, cross-sectional and cohort studies investigating the association between vitamin D and any form of liver or kidney disease. Results: Vitamin D insufficiency, or deficiency (VDD), is highly prevalent in Iran, reports varying between 44.4% in Isfahan to 98% in Gorgan. There is also a high prevalence of VDD among patients with liver or kidney disease, and the administration of vitamin D supplements may have beneficial effects on lipid profile, blood glucose, liver function and fatty liver disease, and bone health. Low serum vitamin D levels are related with abnormalities in these laboratory and clinical parameters. Conclusion: VDD is prevalent in patients with chronic liver or renal disease in Iran. There appear to be several beneficial effects of vitamin D supplementation in vitamin D deficient patients with liver or kidney disease.


2013 ◽  
Vol 51 (01) ◽  
Author(s):  
F Grünhage ◽  
M Krawczyk ◽  
C Stokes ◽  
M Langhirt ◽  
C Reichel ◽  
...  

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