…article continued:
Recently according to Hickey and Roberts (2008)46 and Davis et al (2016),48 vitamin C blood plasma concentration could exceed the oral barrier of 230 μMol/L if supplementation is taken with the liposomal form. Specifically, they observed that plasma concentrations of vitamin C >250 μMol/L could be obtained by a single one-gram dose of liposomal-encapsulated ascorbic acid. Most interesting is the fact that liposomal vitamin C can achieve plasma levels of 600 microM/L or more. Moreover, a combination of simple ascorbic acid with liposomal-encapsulated C are absorbed independently and can produce higher levels.47 A single dose of liposomal-encapsulated C can keep steady concentrations of reasonably high vitamin C concentrations in the plasma more than four hours.48 (See the graph, which was obtained from Dr. Hickey S. with permission of LipoLife Gold.)
The asymmetric behavior of COVID-19 and poor outcomes from patients appears to involve hemoglobin. This is probably due to the insult that red blood cells are up against from COVID-19 impairing hemoglobin, hence unlatching the iron atom. Scientists are trying to understand the biochemistry behind iron deposition and the pandemic virus.49 This is probably due to the fact that confirmed COVID-19 patients appear to have elevated levels of ferritin. For this reason, vitamin C could be an asset in regulating iron.50
Finally, a recent review argues that there is a high probability that the immune system will respond to vitamin C adjuvant utilization on COVID-19 patients.51 To be more specific, Boretti and Banik (2020) report that intravenous vitamin C seems to pose a dual function (antiviral-antioxidant) that may enhance immunity so as to cope with 1) the “cytokine storm” that characterizes the Acute Respiratory Distress Syndrome (ARDS) that appears in the later cycle of the COVID-19 infectious disease and 2) the oxidative stress that accompanies ARDS through the release of free radicals and cytokines.51 It appears that this new virus initiates a “storm” of cytokines since COVID-19 patients show an increase of C-reactive protein (hsCRP).52
There is no doubt that vitamin C pharmacodynamics has been observed to be clinically safe and successful in responding to viral ARDS and inhibiting the acceleration of a “cytokine storm” in critically-ill patients from infectious diseases such as COVID-19.53 Of course, subsequent clinical research is needed as soon as possible to utilize IV vitamin C (VC) and oral VC (such as liposomal-encapsulated VC) as an adjuvant intervention choice for COVID-19.
Vitamin D
Thirty years ago, Dr. Hope-Simpson theorized that “seasonal stimulus” linked to solar radiation could explain the remarkable seasonality of epidemic influenza. Solar radiation activates a vigorous seasonal vitamin D production in the skin that can have profound results in human immunity.54
1,25(OH)2D modulates our immune system to a point that can prevent excessive expression of inflammatory cytokines and increase the ‘oxidative burst’ potential of macrophages. Moreover, it stimulates the expression of anti-microbial peptides, present in neutrophils, monocytes, natural killer cells, and importantly in epithelial cells of the respiratory tract, which protect against lung infections.55 The release of pro-inflammatory cytokines with COVID 19 is dependent on the virulence of the virus. Similarly, recent research confirms that the clinical phenotype of influenza correlates well with the amount of cytokines released.55,56
Furthermore, 1,25(OH)2D induces gene expression that in turn can enhance immunity. Almost every human tissue has vitamin D receptors. In turn the vitamin D receptors control gene expression from homeostatic control of mineral metabolism to focal activities that are essential for growth and immune function.57 Vitamin D either directly or indirectly regulates the expression of up to 5% of the human genome or about 1250 genes. For example, vitamin D supplementation caused at least a 1.5-fold change in the expression of 291 genes that are involved in apoptosis, immune function, transcriptional regulation, epigenetic modification, response to stress, cell cycle activity and differentiation.58,59 In a recent study 66 genes showed a significant change in their expression when supplemented with 2,000 IUs vitamin D3. Of the 66 genes, 52 genes increased their expression in response to vitamin D3 supplementation. Specifically, in genes coded for T Cell intracellular antigen-1 (TIA1), there was a 26-fold increased expression; and in those coded for immune function and zinc finger protein 287(ZNF287), there was a 6.8-fold increase.58 Supplementing with vitamin D3 would be a prudent approach. There is, however, a caveat for vitamin D3 supplementation. The action of vitamin D3 depends upon the available magnesium levels since magnesium is required in eight crucial biochemical steps.60
A recent review reported that vitamin D supplementation reduced the risk of acute respiratory tract infection.61 The prevention of acute respiratory tract infection is a critically important indication for vitamin D supplementation. People, especially those who are very deficient, experience substantial benefit when receiving daily or weekly vitamin D without bolus dosages. In general, vitamin D treatment was linked with a substantial degree of protection against acute respiratory tract infection among those who took part in the analysis with baseline circulating 25-hydroxyvitamin D concentrations less than 25 nmol/L.61
In line with this is the very enlightening article by Ilie et.al (May 2020), stressing the potential relationship between the mean levels of vitamin D with COVID patients and mortality.62 It was revealed that in COVID-19 cases vitamin D levels were critically low, from the data acquired by 20 European countries. To be more specific the authors mention that not only in Nordic countries but in Southern Europe countries the levels were less than 30 nMol/L, but the aging population that experienced poor outcomes were those with the most deficit vitamin D levels. Thus, the potential association between COVID-19 therapy and vitamin D supplementation could not be ignored.
From a pharmacodynamic angle, there is solid scientific background that favors its utilization in early and later phases of the severe acute respiratory syndrome coronavirus 2, thus, reducing the impact of COVID-19 in populations that are characterized to be deficient in vitamin D. It appears that the data promotes supplementation so as to attenuate serious COVID-19 incidences.63
Magnesium
Approximately 800 enzyme systems require magnesium for their optimal functioning. It is well documented that magnesium deficiency is common reaching even 80% in some groups.64 Mitochondrial dysfunction is attributed to low levels of magnesium. Six out of the eight steps that produce ATP (adenosine triphosphate) in the mitochondria via the Krebs cycle require adequate levels on magnesium (magnesium is a cofactor for ATP production). We need optimum cellular energy to cope with viral disease because it comes with great metabolic and energetic costs. Incidentally, magnesium also seems to be able to insult the avian influenza PA endopolymerase and provides an anti-influenza target with optimum levels of magnesium.65
The potential role of magnesium in the development and activation of the immune system is profound.66 Magnesium is a cofactor in most immune responses.67 Magnesium is an option for someone wanting to boost their immune system in a viral epidemic.
Zinc
The essentiality of zinc on immune function has been well documented.68 The results of more than three decades of work indicate that zinc deficiency rapidly diminishes antibody- and cell-mediated responses in both humans and animals.69 Zinc deficiency has been linked to immune dysfunctions mainly affecting T-helper cells and decreasing natural killer (NK) cell activity. Moreover, zinc supports innate immunity and not only facilitates normal development and function of macrophages, NK cells, and neutrophils but also affects T and B cells function and growth.70 Subsequently studies have revealed that macrophages and monocytes are stressed during zinc deficiency, as a result generating inflammatory cytokines such as TNF-a and IL-1b.70
In a Cochrane review, 13 randomized placebo-controlled trials revealed that, when taking zinc immediately upon appearance of common cold symptoms, there was a significant reduction not only in the duration but also the severity of symptoms.71
It has been referred that excess zinc is not stored in the human body, thus consumption of this mineral, through diet or supplementation, is important in maintaining not only the integrity of the immune system but also body homeostasis since zinc deficiency is responsible for serious respiratory infections worldwide.72,73
Finally, a recent exemplary study argues the prophylactic effect that zinc may pose on COVID-19 (SARS-CoV-2).74 Specifically, the article discusses how changes in zinc homeostasis could be linked with most of the common symptoms of COVID-19. Zinc’s direct anti-infectious properties will only benefit against viral and respiratory tract cases; zinc is vital so as to 1) safeguard the respiratory epithelium inhibiting any pathogen entry, 2) increase ciliary length and movement, 3) balance every immune cells function multifariously, 4) prevent the formation of platelet aggregates and 5) inhibit viral replication, to mention a few effects.74 The article presents numerous studies that reveal its effectiveness in coping with respiratory infections; but severity, frequency, and duration of the illness depends on the concentration, zinc’s compound structure, and the time it is taken after the initial symptoms.74
Conclusion
This open letter is designed to bring light and hope to the dying and afflicted patients and to the devastated economies around the world. Given the above, and since we are in the midst of a global pandemic, time is of the essence. Exhaustive, randomized controlled trials cannot replace successful clinical results when it is necessary to act quickly and prevent physical and economic death and destruction. The methods we propose have been in use for many decades and in some cases over a century.
Wisdom involves making rational decisions.75,76 We must endorse the plethora of available quantitative and qualitative data and the efficacy of “the obvious,” which in turn will definitely enhance clinical decisions especially when objective evidence has been collectively accumulated and revealed to us over generations.77
Our group is in support of any proposal that has been shown safe by government or academia, provided it is in accordance with the Helsinki Declaration. We respectfully request from all authorities that they allow all schools of thought to be employed against this common COVID-19 enemy.
We are facing a formidable viral epidemic. We must not limit the fight to drugs and vaccines, especially where strong evidence exists to back micronutritional support and other medical interventions. Our group strongly endorses the use of pharmaceuticals and vaccines in combination with micronutrient protocols and the use of anecdotal remedies that have a good clinical track record. We need methods that work!
1*Professor and Chairman, Lab. of Public Health Medical School University of Patras. University Campus, 26504, Greece; email: micleon@upatras.gr.
2*Medical Director Kotsanis Institute-Health Clinic, Grapevine, Dallas Texas, USA; email: gusatwork@aol.com
3*Research Assistant and Micronutrient Scientific Advisor Kotsanis Institute – Palladion Rehabilitation Centre Tripoli Arcadia, Greece; email: aktouariosp@gmail.com
*Corresponding Author: E-mail address:gusatwork@aol.com (Kotsanis K.)
