Nitric Oxide & Inflammation: Education for Healthcare Professionals During The Pandemic

 

Healthcare professionals and those they care for can be left with few options to manage mild and moderate Covid-19 care, especially since healthcare systems are burdened beyond capacity and since presumably-infected patients to manage their own symptoms at home. Here, we adapt elements of current critical care treatment and cautiously extrapolate preliminary data from previous outbreaks to inform strategies for symptom management in the absence of better evidence and better options. Resync Recovery and Resync Collagen is a unique inorganic nitrate-based nitric oxide and antioxidant/anti-inflammatory supplement that adhere to the highest standards in the supplement industry (BSCG; NSF Sport), making the use of these products an attractive possibility for mitigating features of Covid-19 pathophysiology. 

Disclaimer

This content is for general informational purposes only, and does not constitute the practice of any professional healthcare service, including the giving of medical advice. 

The use of this information and the materials linked to this content is at the user's own risk, and should never replace sound clinical judgement.

This content is not intended to diagnose, treat, or prevent any disease. Regardless of the contents herein, users should abide by government recommendations and policy, professional medical organization guidelines, and the policies of the organizations to which they are affiliated.

These statements have not been evaluated by the Food and Drug Administration. Products manufactured, marketed, distributed, sold, or otherwise affiliated with Resync, LLC are not intended to diagnose, treat, cure, or prevent any disease.

Key Takeaways:

  • The burden that Covid-19 is placing on medical systems leaves healthcare providers and patients looking for additional treatment options.
  • There is considerable overlap between those at highest risk for severe illness and mortality due to Covid-19 and those at risk for nitric oxide insufficiency, deficiency, and dysregulation.
  • Inhaled nitric oxide is one approach to increase oxygenation and gas exchange in pneumonia and in mechanically ventilated acute respiratory distress syndrome. Aerosolized drug delivery should be approached with extreme caution due to risk of spreading SARS-CoV-2.
  • Nitric oxide can be enzymatically synthesized from arginine/citrulline, or non-enzymatically synthesized via the nitrate-nitrite-nitric oxide pathway.
  • Resync Recovery and Resync Collagen contain the most highly concentrated source of natural nitrates in addition to a spectrum of natural antioxidant and anti-inflammatory ingredients.  These products adhere to the strictest purity and consistency standards in the industry.
  • Oral natural nitrate supplements (must be tested by 3rd party) may be an attractive option for reducing comorbidities and some symptoms associated with severe Covid-19.

Covid-19 Pathophysiology

SARS-CoV-2 is a novel coronavirus that causes Covid-19. SARS-CoV-2 originated in Wuhan, China in November or December of 2019, was declared a pandemic on 11 March 2020, and has contributed significantly to worldwide morbidity and mortality at an alarming rate.  As of 26 March 2020, 465,915 infections and 21,031 deaths have been reported worldwide; 68,440 infections and 994 deaths have been reported in the United States.1,2

Outcomes of Covid-19 fall into three categories: mild, severe, and critical.3 Of SARS-CoV-2 infected individuals, 50.5% may be asymptomatic.4 In a cohort of suspected and confirmed cases in Wuhan, 81% appeared to be mild lower respiratory tract infections including mild pneumonia.  14% were severe cases requiring hospitalization, and 5% of cases required critical care.3

Clinical characteristics of mild Covid-19 are difficult to pinpoint considering the widespread lack of validating testing options.  Case reports of mild Covid-19 include a disparate range of respiratory symptoms, compounding this lack of specificity is the fact that many cases may go unnoticed.

Covid-19 progresses from mild symptoms and mild pneumonia to severe pneumonia, then to acute respiratory distress syndrome (ARDS), septic shock, and finally death. Of a subset of hospitalized patients, 40.3% developed ARDS.5,6

Symptoms most commonly reported by patients presenting to hospitals are dyspnea (3-76%), fever (52-98%), fatigue (11-52%) and cough (46-82%).6,7,8 In a retrospective analysis of Chinese patients, lymphocytopenia was present in 83.2% of patients, with greater prevalence among severe cases.5

Risk factors for increased severity and mortality of Covid-19 include: advanced age, type two diabetes mellitus, chronic kidney disease, acute kidney injury, cancer, pulmonary disease (chronic obstructive pulmonary disease, asthma) and various diseases of the cardiovascular system (congestive heart failure, hypertension, and coronary heart disease). 5,6,9 Rigorous epidemiological data is not able to confirm the observation that age and cardiovascular comorbidity are the most significant risk factors for death.

Covid-19 Treatment

Pharmaceutical interventions to treat the SARS-CoV-2 infection itself are currently being investigated in clinical trials,10 and have been summarized elsewhere.11,12 Intensive care guidelines have been developed by the CDC,12 and have been succinctly summarized for clinical practice elsewhere.13

Interventions to treat severe Covid-19 symptoms and sequelae (i.e. ARDS) in adult and pediatric populations include intravenous antibiotics, vasopressors, protective ventilation, oxygen therapy, inhaled prostacyclins, neuromuscular blockers, continuous renal replacement therapy, extracorporeal oxygen therapy, pulmonary surfactant, and inhaled nitric oxide, among others.5,12,14–16 Strong caution is warranted with the use of nebulized pharmaceuticals due to risk of aerosolization and transmission of SARS-CoV-2.17,18

Reduced availability of arginine for NO production during sepsis may lead to altered immune response and loss of microcirculatory regulation. Due to conflicting evidence on mortality, especially in cases of infection, the use of arginine to support endogenous nitric oxide production in pediatric populations is not recommended.19 Arginine affects the healing process, immune system, and NO production via a multiplicity of enzyme pathways, some of which may also promote infection and disease progression.19,20 Interestingly, these enzymatic pathways are distinct from the process by which NO is produced from inorganic nitrates.21

Notably, clinical practice guidelines for the at-home management of mild Covid-19, which account for most cases, are almost wholly absent.  This leaves the majority of patients to seek alternative means to manage mild symptoms. Considering current and anticipated widespread shortages of common pharmaceuticals, shortage of clinical providers, and the growing number of patients left to manage their care alone, clinicians may need to consider alternative means to manage Covid-19 symptoms.

Nitric Oxide (NO): Physiological Relevance and Application

Nitric Oxide Production From Endogenous and Exogenous Sources

Nitric oxide (NO) is a signaling molecule that plays a critical vasodilating role in the endothelial system, among other vital functions. NO can be produced via three different enzymes from the substrate L-arginine and indirectly from l-citrulline: inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase.22Enzymatic production of nitric oxide is rate-limited, depends on the presence of cofactors and substrates, and is subject to dysregulation in the setting of endothelial nitric oxide synthase dysfunction.21

Nonenzymatic production of NO is via a different pathway. Oral nitrate, commonly from beet, celery, arugula, red spinach, aronia berry, or synthetic sodium nitrate, is absorbed, distributed via the cardiovascular system, converted to nitrite by oral and gut microflora, and then reduced to NO with hemoglobin, myoglobin, xanthine oxidoreductase, ascorbate, polyphenols and protons.22

Pharmacological strategies to enhance nitric oxide are numerous and summarized elsewhere.21 Briefly, substrates to enhance nitric oxide include inhaled nitric oxide, oral L-arginine/L-citrulline, nitrosothiols, nitro-fatty acids, nitroglycerin/organic nitrates, novel NO hybrid drugs, and oral nitrate/nitrite.

Nitric Oxide Deficiency

NO deficiency has been suggested to underlie the pathology of numerous conditions, including advanced age,23 sedentary lifestyle,24 obesity,25 chronic kidney disease,26 inflammatory pulmonary disease (e.g. asthma, COPD),27 pulmonary arterial hypertension,28 essential hypertension29, atherosclerosis,30 heart failure31, endothelial dysfunction,32 and cardiovascular and cardiometabolic diseases.24,33

Additionally, males appear to have lower levels than age-matched pre-menopausal females.23 Antibacterial mouthwash use disrupts the oral microfloral ability to generate nitrite from nitrate.34,35 Use of the proton pump inhibitor omeprazole may elevate asymmetric dimethylarginine and lower nitric oxide levels.36 Interestingly, long term use of proton pump inhibitors is associated with increased risk for community-acquired pneumonia in older adults.37

Overlap between risk for severe Covid-19 outcomes and risk for NO deficiency

The epidemiology of severe and critical Covid-19 outcomes reveals substantial overlap with populations at risk for decreased nitric oxide levels. Most risk factors for severe Covid-19 illness, including cardiovascular disease, hypertension, chronic kidney disease, chronic pulmonary disease, compromised immune system, and diabetes, but not cancer, are associated also with deficient, insufficient, or dysregulated nitric oxide. Advanced age and cardiovascular diseases are the most significant risk factors for severe illness, and are also the most well-documented conditions associated with decreased NO.

Resync, LLC Leads the Industry in Quality and Innovation

Resync, LLC produces two inorganic nitrate-containing products: Resync Recovery and Resync Collagen Blend.  Both products contain high levels of a proprietary natural nitrate blend of beet powder and extracts of red spinach (Oxystorm®) and aronia berry. Other active ingredients in Resync Recovery include inulin fiber, bioavailable turmeric root extract (AcuminTM), hyaluronic acid, ginger root extract, and mango fruit (CareflowTM). Besides the aforementioned natural nitrate blend, Resync Collagen (aka, Resync Your Joints) contains the active ingredients calcium fructoborate (FruiteX-B®), ascorbic acid, and hyaluronic acid.[1]

Resync, LLC is committed to exceeding industry standards in purity and consistency.  Resync Recovery is NSF Sport certified and Banned Substances Control Group (BSCG) Certified Drug Free; Resync Collagen Blend is BSCG Certified Drug Free. These are among the highest purity and consistency certifications available in the supplement industry, ensuring freedom from mycotoxin, manufacturing contamination, heavy metals, banned substances, and other foreign contamination. Certification is particularly important for nitrate supplements because of the wide variability of nitrate content in source ingredients. Resync Recovery delivers 544.0 μmol/ mL, more nitrate than any other popular nitrate supplement on the market.38,39

NO and Pulmonary Function

Endogenous NO may be decreased in the lungs of patients with ARDS.40 Inhaled nitric oxide (iNO, not to be confused with iNOS, “inducible nitric oxide synthase”) is notable as a possible treatment option to increase gas exchange in mechanically ventilated acute respiratory distress syndrome, although this is a contentious application due to a demonstrated lack of effect on mortality.41,42 iNO may have a similar effect on gas exchange in the setting of severe pneumonia.43 Additionally, the use of a INOmaz DSIR system is an FDA approved treatment for persistent neonatal pulmonary hypertension to increase the oxygen exchange capacity of the alveola.44 Risk of rebound pulmonary hypertension upon abrupt withdrawal can be mitigated by appropriate tapering of iNO, however other limitations of this therapy include the short-term nature of the intervention and lack of data on its efficacy for survival.45

Despite limitations, iNO has been investigated for previous coronavirus infections and is currently being investigated in the treatment of mechanically-ventilated Covid-19 patients.46 In one study of 14 patients, inhaled NO treatment for severely sick patients with SARS resulted in improvement of arterial oxygenation and allowed noninvasive pressure support to be discontinued.47 Another study among 32 mechanically-ventilated ARDS patients showed that 69% of patients responded to iNO therapy.48 iNO therapy appears to be especially promising in the setting of dysregulated arginine/nitric oxide synthase signaling.49

The aerosolized nature of iNO delivery may contraindicate its use among patients with Covid-19, which begs the question as to whether oral supplementation may yield a similar advantage.  Research comparing nitrates and arginine/citrulline supplementation has clearly shown an advantage with the use of nitrates.50 Three randomized clinical trials have revealed that in animals, healthy subjects, and in patients with pulmonary hypertension, enhancing NO with oral nitrate doses at 16mmol per day or 0.1mmol/kg body weight/day significantly improved pulmonary oxygenation.51–53 No less than five randomized trials have investigated the effect of dietary nitrate on physical performance, oxygenation, and hypertension among patients with COPD.54–58 One trial revealed uniformly null results, but the other four trials demonstrated some benefit to lung function in this population.

NO and Cardiovascular Function

Nitrates and Cardiovascular Disease

Nitrates have been most thoroughly investigated in the management of cardiovascular diseases. A systematic review and meta-analysis showed that nitrates can lower systolic blood pressure by 4 to 10 points and diastolic blood pressure by 1 to 3 points. The effects are highest with the use of a higher nitrate dose or for those with lower pre-existing nitric oxide levels.59Nitrates may increase exercise capacity by lowering the amount of effort during exercise among cardiac rehab patients.60Nitrates may increase the artery flexibility, increase capillary microcirculation, and don’t pose the same risk for nitrate tolerance as organic nitrate drugs.61 Dietary nitrates may reduce inflammation-induced atherosclerosis,62 improve heart function after a heart attack,61 and confer other cardiometabolic benefits like reducing triglycerides and cholesterol.63

Resync is currently investigating the blood pressure lowering effects of its unique nitrate blend the Canadian study has been temporarily halted in the last week of testing due to the 2019-coronavirus pandemic. Unpublished results appear in line with other published data on natural inorganic nitrate supplements, and preliminary results suggest that Resync Recovery may be used as a natural supplement to support cardiovascular health and help lower high blood pressure.

Nitrates, NO, and relationship to Cardiovascular Determinants of Covid-19 Mortality

Cardiovascular disease and advanced age are the strongest predictors of mortality in critical cases of COVID-19.5,6,9

SARS-CoV-2 infiltrates via the angiotensin converting enzyme 2 (ACE2), essentially using it and a coenzyme as a receptor.64Antihypertensive ACE inhibitor olmesartan can lead to ACE upregulation, but the role of other hypertensives in ACE2 expression is either unclear or null. This suggests a possible therapeutic target and one possible contributor to the increased mortality in hypertensive patients.65

NO can decrease blood pressure via an alternate pathway. NO operates on the renin-angiotensin-aldosterone system outside of the arginine-NO pathway.  NO from nitrate is not an enzymatically-capped process, resistance or adaptation to nitrates doesn’t seem to occur, and the level of endothelial benefit is in proportion to dose of nitrates, suggesting that nitrates may be considered for improving cardiovascular health while minimizing ACE expression.  This is an active area of discussion, with a wide range of clinical perspectives; at the time of writing, every medical society suggests that that benefit of remaining on prescribed ACE inhibitors is greater than the possible risk of ACE upregulation.

NO in the Immune Response

NO is Critical in Immune Response

Nitric oxide is a key component of the immune system’s defense mechanism. Classically, NO derived from arginine via inducible nitric oxide synthase and nitric oxide synthase 2 provides cytokine-activated macrophages with reactive species, essentially the immune system’s “stopping power”.  Beyond this, since it’s activity is not limited to a receptor or a particular type of molecule, diffusible NO displays paracrine activity on a vast number of biological molecules, affecting the regulation environment during immune inflammation.22

Nitrate Supplementation May Alleviate Symptoms in Mild Seasonal Cold Infection

In a randomly-assigned clinical trial including 60 healthy young adults and 14 young adults with asthma, supplementation with beet root juice containing 400mg dietary nitrate was associated with 26% reduced symptomology of stress-exacerbated cold and sickness, an effect that was accentuated among the participants with asthma and among those with higher production of NO from dietary nitrate.66

NO may have direct anti-coronavirus activity

Although the effect that SARS-CoV-2 may have on NO has not been investigated, experimental models suggests that other, less-pathogenic coronaviruses “Connecticut A-5968” and “IBV M41” suppress host NO production during infection.67 NO may also play a role in inhibiting porcine circovirus type 2,68 reovirus,69 and murine coronavirus,70 among others.

In an animal model of SARS-Cov, the organic NO-donor S-nitroso-N-acetylpenicillamine was shown to inhibit SARS-Cov via iNOS upregulation.70 In cell culture, the same compound significantly inhibited the replication cycle of SARS CoV in a concentration-dependent manner. This study also revealed that IL-1β inducible nitric oxide synthase inhibited viral protein and RNA synthesis.71 The same group later demonstrated that NO can reduce SARS-CoV activity in vitro by inhibiting RNA replication and reducing the palmitoylation of nascently expressed spike protein. Interestingly, it is this latter mechanism that may affect the fusion between the S protein and its receptor, ACE2.72

NO and SARS Cytokine Storm

Inducible nitric oxide synthase contributes to formation of anti-microbial inflammasomes,73 yet excessive, unregulated pro-inflammatory cytokines contribute to the “cytokine storm” characteristic of advanced SARS, MERS, and SARS-CoV-2 disease.74Animal research reveals the contribution of inducible nitric oxide synthase to H1N1 and 1918-virus pathogenesis.75 Inhaled nitric oxide does not affect clinical outcomes in experimental severe influenza infection.76 Additionally NO has pleiotropic roles in regulating apoptosis, which itself results in both pro-viral and anti-viral immune activity.77 

On the other hand, iNO plus IV steroid might protect renal function in an experimental model of endotoxemia.78 Curiously, resistance to inhaled NO therapy may be improved by nitric oxide synthase 2 inhibition by aminoguanidine in a dose dependent manner in rats.79

The use of inhaled nitric oxide in mechanically ventilated pediatric patients calls into question the effect that NO-enhancing interventions aimed at endothelial nitric oxide synthase may have on the separately-regulated role of inducible nitric oxide synthase in viral pathogenesis.

The dual role of inducible NO production in inflammation regulation, the dual role that inflammation plays in Covid-19 pathogenesis, and the likelihood of endothelial NO insufficiency in many populations at risk for severe Covid-19 outcomes all suggest an uncertainty in clinical practice that should best be approached conservatively.  Due to lack of clear evidence, Resync does not recommend the use of its products in the setting of terminal illness.

Antioxidant and Anti-inflammatory Benefits

In addition to the unique natural nitrate blend made from beet powder and extracts of red spinach (Oxystorm®) and aronia berry, Resync products contain other ingredients with a history of research.  Other active ingredients in Resync Recovery include inulin fiber, bioavailable turmeric root extract (AcuminTM), hyaluronic acid, ginger root extract, and mango fruit (CareflowTM). Other active ingredients in Resync Collagen Blend are calcium fructoborate (FruiteX-B®), ascorbic acid, and hyaluronic acid.

Side stream benefits of nitrate blend

Beet powder and aronia extract contain a number of anti-inflammatory phytochemicals besides their nitrate content. Beet phytochemicals are suggested to provide a spectrum of natural antioxidants, enhance nitric oxide bioavailability, and enhance cardiovascular benefits.80

Aronia berry is one of the most potent antioxidants studied to date, measured by ORAC score by the USDA (publicly available data). Aronia may have promising effects on inflammation in athletes and may lower cholesterol and triglycerides.81,82Additionally, aronia berry may have anti-diabetic effects and may alleviate symptoms of cardiovascular and cardiometabolic diseases.83,84

Red spinach extract is the single most highly concentrated source of nitrates hitherto discovered; the source used in Resync is standardized to 9% natural nitrates. It contains extremely high levels of vitamin E and is high in iron and phytoecdysteroids. It has been shown to delay the ventilatory threshold, which means that you can exercise at a higher rate before your breathing increases. Red spinach extract may improve blood flow and increase the amount of oxygen to the brain in cell studies, which can have implications on lowering fatigue and stress.85,86

In vitro studies of have revealed a promising inhibitory effect of Resync’s proprietary blend on adhesion molecule expression of ICAM-1. The nitrate blend in Resync may even more effectively suppress VCAM-1, suggesting that the combination is likely to improve vascular function in the setting of cardiovascular inflammation. These yet-unpublished results await conformation in human trials.

Calcium Fructoborate

A highly bioavailable source of calcium, calcium fructoborate has been investigated for its use in reducing inflammation, particularly CRP, in cardiovascular and musculoskeletal disease.87

Vitamin C

Vitamin C may lessen the severity and duration of the common cold at regular, high doses.88 Doses in line with the recommended dietary allowance (48mg) help keep BH4, a cofactor of nitric oxide synthase genes, in its reduced state so that immune cells are able to generate NO from arginine.89

Bioavailable Curcumin (AcuminTM)

Resync uses a turmeric-root derived extract that delivers 45-50% curcumin and other curcuminoids in a bioavailable form. Turmeric and/or curcumin may help control dyslipidemia,90 hypertension, and cardiovascular inflammation.91 Curcumin can also upregulate nitrate-synthesis enzymes in healthy adults.92

Ginger

Ginger has rich research supporting its anti-inflammatory activity and has been shown to help alleviate nausea in patients with cancer.93,94 Ginger may also regulate inflammatory pathways, as demonstrated by its ability to lower CRP and modulate NO biosynthetic pathways.95

Mango Fruit Powder (CareflowTM)

Components of mango, including mangiferin, various antioxidants, pectin,  flavonoids, omega-3 and omega-6 fatty acids, fibers, and micronutrients and minerals may contribute to control of inflammation and fatigue.96

Clinical research on the Careflow product, a proprietary Mangifera indica fruit powder, shows that it may activate eNOS, increase superoxide dismutase by 45%, and enhance microcirculation. These effects can contribute to increased nitric oxide, enhanced hemoglobin saturation and veneous oxygen saturation, and a more robust antioxidant, anti-inflammatory system.97,98

Mango may also help regulate blood sugar, especially for people with heart disease.99

Contraindications

Hyaluronic acid, a component of previous formulations of the Resync Recovery product, has been suggested to play a role in cancer progression, though this association is not consistent and has not been verified in any clinical trial.100 The role of carcinogenic nitrosamine-production via nitrate consumption is an active area of scholarly debate, with no clear association having ever been established between natural nitrates from vegetables and cancer risk.101

NO may decrease platelet aggregation and number in vitro and in animal models.102

The role that nitrates play in acute inflammatory bowel disease exacerbation is unclear. Nitrates may feed gut dysbiosis and exacerbate flareups in animal models and elevated NO levels are associated with worsened disease exacerbation.103 The role of antioxidants and supplemental nitrate, which may have positive epithelial and gut microbiome benefits, has not been investigated in humans.

Due to the unclear role that NO may have on unregulated cytokine production in the setting of virally induced ARDS, use of Resync products is not recommended for disease states characterized by the “cytokine storm”.

Adverse Effects

No adverse events have been reported in clinical trials using nitrates to enhance NO. Other ingredients in Resync products have a demonstrated record of safety and collagen has “Generally Regarded As Safe” status.

Nitrate-containing dietary supplements have been investigated in the treatment of hypertension among pregnant women with little success but without significant harm,104 although potential for harm has been suggested in pre-clinical experiments.105

In spite of this relative safety, adverse events are possible when using a physiologically active supplement in high doses. For example, a consumer report of orthostatic hypotension has been documented with the use of nitrate-containing dietary supplements. Always consider the effects of polypharmacy, especially when considering patients prescribed antihypertensive medications.

Limitations, Knowledge Gaps

The following include questions to which research has not supplied a clear answer.

  • Due to the impossibility of rigorously controlled trials, to what extent do major risk factors for critical Covid-19 illness actually contribute to pathogenesis?
  • Significant individual variability of NO production via nitrate-nitrite-NO pathway suggests that dose titration may be necessary for optimal effects.
  • What role does ACE2 and hypertension play in Covid-19 pathogenesis?106
  • To what extent can results from studies on SARS-CoV and other coronaviruses be extrapolated to SARS-CoV-2, taking into account the 80% genetic homology between SARS-CoV and SARS-CoV-2?107
  • How important is L-arginine-NO pathway in pathophysiology of covid-19?
  • How effective is NO in mild cases of Covid-19?

We hope that clearer answers to these questions can be arrived at sooner than later, but in the absence of evidence we can only attempt to make perfect decisions with imperfect knowledge.

Resync Products and Covid-19 Management

Potential benefits of Resync stratified by health topics & body systems for severe Covid-19

Body Systems 

Possible effect of ingredients in Resync

Cardiovascular Systems

May have positive effect on atherosclerosis, nitrates have been used safely in research on severe heart disease, nitrates may decrease triglycerides & cholesterol, may improve microcirculation, may correct NO deficiency

Healthy Blood Pressure Regulation

Resync supports BP in healthy levels (unpublished results), systematic reviews show that beetroot (less potent) can lower blood pressure, may correct NO deficiency, may promote endothelial function

Lung Function

May increase gas exchange, may improve oxygenation, may correct NO deficiency

Glucose Management

May help regulate glucose, may have a positive effect on inflammation markers, may promote endothelial health

Immune Support

May enhance ability of immune function, may correct NO deficiency

Weight Management

May have a positive effect on inflammation markers, may promote favorable blood lipids, may correct NO deficiency

Gene Expression / Inflammation Balance

Anti-inflammatory activity of a spectrum of phytochemicals in beets, red spinach extract, aronia berry, ginger, and turmeric extract may be beneficial


Key Takeaways:

  • The burden that Covid-19 is placing on medical systems leaves healthcare providers and patients looking for additional treatment options.
  • There is considerable overlap between those at highest risk for severe illness and mortality due to Covid-19 and those at risk for nitric oxide insufficiency, deficiency, and dysregulation.
  • Inhaled nitric oxide is one approach to increase oxygenation and gas exchange in pneumonia and in mechanically ventilated acute respiratory distress syndrome. Aerosolized drug delivery should be approached with extreme caution due to risk of spreading SARS-CoV-2.
  • Nitric oxide can be enzymatically synthesized from arginine/citrulline, or non-enzymatically synthesized via the nitrate-nitrite-nitric oxide pathway.
  • Resync Recovery and Resync Collagen contain the most highly concentrated source of natural nitrates in addition to a spectrum of natural antioxidant and anti-inflammatory ingredients.  These products adhere to the strictest purity and consistency standards in the industry.
  • Oral nitrate supplements may be an attractive option for reducing comorbidities and some symptoms associated with severe Covid-19.

References

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[1]Future Resync batches will not contain hyaluronic acid, though it is present in current commercially-available products. Due to synthetic hyaluronic acid now being regulated as a pharmaceutical for injection use, an alternative natural, vegan source from fermented potato was identified. However, due to its manufacturing origin in China and the 2019 coronavirus pandemic, its safe and reliable production is under scrutiny. At the present time, Resync will no longer include hyaluronic acid in their products.

 Written by registered dietitian, Detrick Snyder, MPH, RDN. Updated 09/22/2020

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