EJBR2020v10i3art258


ISSN 2449-8955 
European Journal  

of Biological Research 
Review Article 

 

European Journal of Biological Research 2020; 10(4): 271-295 

DOI: http://dx.doi.org/10.5281/zenodo.3990659  

Vitamins, omega-3, magnesium, manganese, and thyme 

can boost our immunity and protect against COVID-19 

Afaf M. Hamada 

Botany and Microbiology Department, Faculty of Science, Assiut University, Assiut 71516, Egypt 

E-mail: afafhamada@yahoo.com; hamada@aun.edu.eg 

Received: 26 June 2020; Revised submission: 02 August 2020; Accepted: 15 August 2020 

 

http://www.journals.tmkarpinski.com/index.php/ejbr 

Copyright: © The Author(s) 2020. Licensee Joanna Bródka, Poland. This article is an open access article distributed under the 

terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/) 

ABSTRACT: A new coronavirus, SARS-CoV-2, has been recognized as a cause of severe acute respiratory 

syndrome (SARS) and COVID-19 disease. In the absence of stable treatments for COVID-19, the possibility 

that vitamins: B1, C, D, and E, omega-3, minerals (magnesium and manganese), and herb thyme may have 

unspecified effects on infection with COVID-19 would be considered. Various reports have revealed that 

vitamins B1, C, D, and E, omega-3, magnesium, manganese, and thyme may affect the human innate system, 

for example, thiamine may play beneficial roles in human immunodeficiency viruses (HIV), treating 

megadose ascorbic acid can assist prevent cold and flu symptoms, vitamin D can decrease the risk of 

developing COVID-19, vitamin E has been evaluated against the influenza virus in mice, and omega-3 fatty 

acids supplementation has been efficient in reducing the severity and frequency of sickle cell rate. Magnesium 

may be effective in patients with a mutation in the interleukin-2-inducible T-cell kinase, as well as manganese 

associates with the metabolism of glucose and fats, vitamin C, and B, accelerating protein synthesis, 

endocrine regulation, stimulating hematopoiesis, improving innate function, and reducing reactive oxygen 

species (ROS) generation. Moreover, thyme extract can have beneficial antiviral effects against human 

papillomavirus (HPV) and influenza A (IAV). The possibility that the vitamins B1, C, D, E, omega-3, 

magnesium, manganese, and thyme appear to affect the human innate system warrants further study, 

especially in light of the recent COVID-19 epidemic. 

Keywords: COVID-19; Vitamin B1; Vitamin C; Vitamin D; Vitamin E; Omega-3; Magnesium; Manganese; 

Thyme. 

Abbreviations: 

Acyl-coenzyme A - acyl-CoA; Adenosine triphosphate - ATP; α-Linolenic acid - ALA; α-tocopherol transfer protein -              

α-TTP; Calcium - Ca; Cholecalciferol - vit. D3; Disease caused by SARS-CoV-2 - COVID-19; Corticosterone - CORT; 

Damage-associated molecular patterns - DAMPs; Docosahexaenoic acid - DHA; Dynamin-related protein 1 - DRP1; 

Eicosapentaenoic acid - EPA; Ergocalciferol - vit. D2; Fatty acid - FA; Fatty acids - FAs; Glucocorticoid - GC;                    

Glucose-6-phosphate - G6PD; Herpes simplex virus - HSV; Human immunodeficiency virus - HIV;                                     

Human papillomavirus - HPV; Hypothalamic-pituitary-adrenal - HPA; Influenza A - IAV; Interferon - IFN; Iron - Fe;                   

L-Ascorbic acid - AsA; Magnesium - Mg; Manganese - Mn; Mitochondrial DNA - mtDNA; Omega-3 - �-3;                          

Open reading frame-9b - ORF-9b; Pathogen-associated molecular patterns - PAMPs; Pattern-recognition receptors - 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 272 

European Journal of Biological Research 2020; 10(4): 271-295 

PRRs; Phosphorus - P; Polyunsaturated fatty acids - PUFAs; Potassium - K; Reactive oxygen species - ROS;                                     

Red blood cells - RBC; Respiratory syndrome coronavirus -SARS-CoV; Selenium - Se; Severe acute respiratory 

syndrome coronavirus-2 - SARS-CoV-2; Sodium - Na; Thiamine adenosine diphosphate - AThDP; Thiamine adenosine 

triphosphate - AThTP; Thiamine diphosphate - ThDP; Thiamine monophosphate - ThMP; Thiamine pyrophosphate - TPP; 

Thiamine triphosphate - ThTP; Thiamine - vit. B1; Vitamin A - vit. A; Vitamin D - vit. D; Vitamin E - vit. E. 

1. INTRODUCTION 

In humans, the innate system composes of groups of effector systems that are able to destroy 

pathogenic microbes such as parasites, fungi, bacteria, and viruses [1]. It includes two types of effectors: an 

adaptive antigen-specific innate effector and a natural innate effector that identifies pathogen-associated 

molecular patterns (PAMPs) [2]. These PAMPs are determined by pattern-recognition receptors (PRRs), 

which are mostly expressed in natural innate cells. PRRs can also identify host particles that contain damage-

associated molecular patterns (DAMPs), which are mostly freed particles from dead cells damaged by 

invasive pathogens [3]. The natural innate system consists fundamentally of physical barriers (mucous 

membranes and skin), chemical barriers and antimicrobial peptides), natural innate cells, and soluble 

mediators (the complement system, natural antibodies, and associated-cytokines) [4-5]. The main goal of the 

natural innate system is (1) to prevent pathogens from entering the body by biophysical and biochemical 

barriers [4]; (2) avoid the prevalence of infection by the supplementary system and other humoral elements; 

(3) remove pathogens by phagocytosis and cytotoxicity processes [6]; and (4) activation of the adaptive innate 

system by synthesizing several cytokines and antigen presentation of T and B cells [7]. 

Various innate cell patterns use distinctive metabolic programs to realize their functions, such as 

responder T cells prefer aerobic glycolysis at anabolic metabolism to equilibrium the synthesis of 

macromolecules and create support energy [8]. On the contrary, memory and regulatory T cells prefer to 

oxidize fatty acids to support energy demand for survival and function [8]. In almost eukaryotic cells, 

mitochondrion mainly provides metabolic energy [9], and is also associated with various cellular activities, 

such as maintaining cellular balance, innate immunity, signaling pathways, aging, and cell apoptosis. 

Moreover, the mitochondrion is a dynamic organelle and can modify its position and morphology within cells 

through harmonious cycles of fusion and fission to regulate its activity, functioning, and cell metabolism [10]. 

Local reactive oxygen species (ROS) production is another significant function of mitochondria, which are 

also important signal molecules for cell activation [11-14]. Mitochondria can coordinate immunity by 

modifying both physiological and metabolic states in various kinds of innate cells. 

Various pathogens have developed ways to target mitochondria to influence their survival within cells 

or to spread them by mediating cell death caused by mitochondria, or by avoiding host immunity [15]. 

Mitochondria are a suitable target for infectious microbes, such as viruses, as they act as a force in the cell and 

have different important functions [16]. The mitochondrion is the objectives of ROS, which are generated 

within the cell when viral infections are present, and that mitochondrial DNA (mtDNA) is a primary objective 

of these ROS [17]. Mitochondrial adenosine triphosphate (ATP) production needs proteins from the 

mitochondrial and nuclear genomes. ROS deactivates the oxidative ATP generation needed for ordinary 

cellular function as mtDNA damage deactivates the normal biosynthesis of proteins required for 

mitochondrial functioning and makes them appropriate objectives for attack by ROS during viruses and 

infections of other microorganisms, although ROS also have other cellular objectives [16]. Influenza A's PB1-

F2 protein, which targets the mitochondria leads to mitochondrial fragmentation, and causes the 

mitochondrial membrane potential to be lost [18]. The virulence factor open reading frame-9b (ORF-9b) of 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 273 

European Journal of Biological Research 2020; 10(4): 271-295 

the severe acute respiratory syndrome coronavirus (SARS-CoV) causes proteasomal dissolution of dynamin-

related protein 1 (DRP1) that leads to the fusion mitochondrial that ultimately reduce interferon (IFN) host 

cell reactions against the virus [19]. These and other studies [20] appeared the function of mitochondria and 

their interaction with antiviral immunity when infected with viruses. 

In December 2019, the coronavirus disease (COVID-19) raised by the SARS-CoV-2, novel appeared in 

China and is now spreading almost all over the world. The cause of COVID-19 is SARS-CoV-2, a new type 

of encapsulated RNA coronavirus that can be transmitted from person to person through air and contact [21]. 

It is described by slight upper respiratory infection with cough, fever, and typical variations in radiation, while 

lower respiratory infections including non-life-threatening pneumonia, and life-threatening pneumonia with 

acute respiratory distress syndrome [22]. Generally, SARS-CoV-2 infection is vulnerable to all age groups, 

involving the elderly and newborns [21]. SARS-CoV-2 infection is a widespread challenge for the innate 

system, as there is as yet no efficient targeted treat for the virus, and persistent infection may include stages of 

silent and productive host-cellular infection [23]. 

There is a controversy that both macronutrient and micronutrient deficiencies cause impaired innate 

functions that can be inverted by depleting nutrients. While it is accepted that deficiency or under-nutrition 

requires it to be correct to ensure the innate system is functioning properly, increasing evidence indicates that 

for some nutrients, increasing absorption above the currently recommended standards may help improve 

innate function involving enhancing defense function and therefore impedance to infection whilst maintaining 

tolerance [24]. Many vitamins, minerals, and herbs have been exhibited to have a beneficial effect on 

mitochondrial function and thus the innate system. The most important effects of vitamins: B1, C, D, E, 

omega-3, minerals: magnesium and manganese, herbs: thyme on the innate system under the virus infection, 

especially the COVID-19 virus that received special attention to the newest discoveries and their interactions 

with the innate system in this review 

2. VITAMIN B1  

Vitamin B1 (thiamine) is recognized as thiamin and anurine and also the first type of vitamin B that has 

been identified. Thiamine participates in glycolysis, the tricarboxylic acid cycle, branched-chain amino acids, 

and nucleotide metabolism [25]. It includes a thiazole ring attached with a methylene bridge with a 

pyrimidine ring and is named a 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-5-(2-hydroxyethyl)-4-

methylthiazolium [26]. It is a water-soluble vitamin that mammalian cells cannot synthesize, but only plants 

and microorganisms can synthesize it [27]. It is found in various forms: free, monophosphate (ThMP), 

diphosphate (ThDP), or also recognized as pyrophosphate (TPP), triphosphate (ThTP), adenosine diphosphate 

(AThDP), and adenosine triphosphate (AThTP) [28]. Free and ThMP account for about 5-15% of total 

thiamine and have no known function yet, understanding the first stage of thiamine phosphorylation. ThTP, 

AThDP, and AThTP account for less than 1% of total thiamine in normal circumstances, but they appear to be 

likely to perform specific roles such as intracellular messengers or metabolic regulators [28-29]. ThDP 

accounts for about 80-90% of total thiamine and performs as a catalyst for many enzymes and thus plays 

important roles in all cells [30]. 

Thiamine shortage is more common than before and underlies acute cases in serious seriously sick 

patients [31]. Although B1 deficiency is uncommon in evolved societies, its deficiency may additionally show 

up in cases of alcohol, diet, some illnesses, and excessive use of certain medications [32-35]. Moreover, the 

hazard of B1 deficiency in advanced societies includes the elderly, after significant surgery, breastfeeding 

women and pregnant, diabetes, smokers, and young adults prefer high carbohydrates diets [36]. Also, 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 274 

European Journal of Biological Research 2020; 10(4): 271-295 

Anderson [37] stated that niacin and thiamine may become deficient during viral disease even if the patient 

has these vitamins at normal levels before the disease, because of the increased B1 vitamins, which are used 

due to metabolic requirements during the disease.  

However, at the present time in some developing countries, thiamine shortage and activity are not 

easily diagnosed, which is useful for diagnosis. Thiamine deficiency reduces oxygen consumption in different 

tissues by reducing the pyruvate dehydrogenase activity that converts the pyruvate into the acetyl-CoA, which 

enters the tricarboxylic acid cycle to provide ATP using oxygen. Thiamine deficiency has sub-deadly health 

effects such as reduced eating, metabolism changes in carbohydrates, proteins and fats, immunosuppression 

and blood-brain barrier damage, nerve and memory disorders, and ultimately it is lethal [38-41]. 

In HIV patients, it is essential to test the extent of thiamine, as it can play beneficial roles in these cases 

[42]. When Wallace and Weeks [43] examined three sufferers with chronic active hepatitis B and treated them 

with thiamine, they reported that thiamine treatment reduced the levels of aminotransferase to ordinary levels, 

while those levels increased when thiamine treatment was withdrawn. Lévy et al. [44] suggested that cirrhosis 

patients must be given thiamine regardless of its causes. They compared the thiamine shortage prevalence in 

40 cases with alcoholic-cirrhosis (group A), 48 cases with hepatitis C virus-related cirrhosis (group B), and 59 

cases with chronic-hepatitis-C without cirrhosis (group C) and concluded that thiamine shortage was similar 

in group A and group B. Not any of the group C (chronic hepatitis) cases had a thiamine shortage. Moreover, 

they added that thiamine shortage is not related to the activity or severity of liver diseases. Although recently 

reported that vitamins B1 and C with corticosteroids are active in stopping progressive organ dysfunction, an 

additional study is wanted to affirm this initial finding [45]. 

3. VITAMIN C  

L-ascorbic acid (vitamin C, AsA) is a water-soluble vitamin and necessary for many biological roles 

[46]. It is hexuronic acid with an enediol group combined in a five-membered heterocyclic lactone ring with 

the formula C6H8O6, (5R)-[(1S)-1,2-Dihydroxyethyl]-3,4-dihydroxyfuran-2(5H)-one). Plants and generality of 

animals can synthesize AsA, while humans and other primates cannot synthesize it [46]. In most organisms, 

AsA performs major roles in metabolism. In humans, AsA mainly acts as antioxidants and cofactors for mono- 

and di-oxygenases [47]. It renews other metabolites, such as α-tocopherols, from oxidative stresses and 

protects some enzymes from oxidation, which may be induced by active oxygen in cells [48]. Also, AsA can 

be utilized as substrates or cofactors for some enzymes in many biological reactions [49-50]. Plants, fungi, 

protozoa, and animals synthesize AsA through many biosynthetic pathways [51-54]. Due to the deprivation of 

the enzyme that stimulates the last stage of AsA biosynthesis, human has lost the capability to biosynthesize it 

[55-56]. 

The physiological roles of ascorbate are mainly dependent on oxidation-reducing properties. Ascorbate 

acts as a cofactor for mono-oxygen and hydroxyl enzymes associated with the biosynthesis of carnitine, 

neurotransmitters, and collagen [57-58]. Ascorbate plays an important function in conservation collagen that 

is the major proteins in the skin, cardiovascular valves, teeth, tendons, ligaments, bones, intervertebral discs, 

cartilage, eye lens, and corneal [58].  

Ascorbate is required for the biosynthesis of the β-hydroxybutyric acid (muscle carnitine) needful to 

transfer fatty acids into mitochondria for energy production [59]. It is essential for the biosynthesis of 

catecholamines, as it is a catalyst for the dopamine-β-hydroxylase enzyme that stimulates the neurotransmitter 

dopamine to norepinephrine [58]. Ascorbate stimulates the reactions of the hormonal activity of oxytocin, 

cholecystokinin, vasopressin, and α-melanotripin [60]. Moreover, its significant role is an antioxidant, which 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 275 

European Journal of Biological Research 2020; 10(4): 271-295 

helps prevent certain ailments such as cardiovascular ailments, age-related muscle declination, cataracts, 

cancer, and colds [61]. Additionally, this antioxidant may act roles in pathogens such as inhibiting the 

formation of carcinogenic nitrous compounds that predominate in the lumen of the gastrointestinal tract [62]. 

Naturally, inadequate AsA causes serious injuries to various organs, especially the brain and heart, as 

both are highly aerobic organs that produce more free oxygen species. On average, daily, about 3% of the AsA 

is lost from the man-body, which is the daily loss parallel to the first degree of AsA disposal assuming it is not 

ingested [63]. The half-life of AsA is about 16 days [64], and under the non-ingestion of AsA, a deficiency in 

blood is detected after about 35-40 days [65] and 12 weeks later Harvard felt tired in trying with a non-

ascorbate diet [66]. Therefore, the symptom of ascorbate deficiency develops very slowly. Besides the 

paradoxical consequences of the medical use of ascorbate for a broad variety of ailments [67], the shortage of 

AsA was a great health problem. Actually, the content of AsA can reduce by 20-40% under normal cooking of 

fruits and vegetables [68]. Furthermore, Carr and Maggini [69] stated that smokers, alcoholics, and drug users 

who do not use nutritional supplements have a high hazard of ascorbate deficiency. Air pollution can result in 

a deterioration of the respiratory system and increased hazard of respiratory diseases, especially in individuals 

at risk of weakened immunity and deficiency of AsA [70-71]. 

The antihistamine impact of ascorbate is related to improved chemotaxis [72]. AsA appears to have a 

considerable function in the maturity, development, and distinction of immature T-cells [73-74]. Some 

literature has indicated that incubating AsA with human fibroblasts and viruses has strengthened the output of 

antiviral interferon (IFN) [75-77]. The widespread complications of AsA deficiency (scurvy) and the main 

causing of death are the observed susceptibilities to viruses, especially pneumonia [78]. Cases of pneumonia 

have exhibited speedy clearance of chest X-rays following the giving of intravenous ascorbate [79-80]. 

Moreover, treatments for individuals with a deficiency of AsA reduced the occurrence of colds [81]. Gorton 

and Jarvis [82] stated that treating megadose AsA can help in preventing and therapeutical treatment cold and 

flu symptoms. Also, Cai et al. [83] found that the protective influences of AsA on pneumonia induced by the 

influenza virus may be linked with inhibition of corticosterone (CORT) biosynthesis, which lowers 

susceptibility to influenza virucidal in experimental restraint-stressed mice. CORT may modify the 

inflammatory reaction, but it may catalyze the infection [84]. 

4. VITAMIN D 

Vitamin D (vit. D) is one of the fat-soluble vitamins and secosteroids group responsible for elevated 

intestinal absorption, calcium and magnesium, and diverse other biological roles [85]. Vit. D is a cholesterol 

derivative and is linked with steroid hormones. Generally, cholecalciferol (vit. D3) and ergocalciferol (vit.D2) 

are the central groups of vit. D, in humans [86]. Vit. D is synthesized under skin epidermis by a 

photochemical reaction from pro-vitamin to cholecalciferol based on ultraviolet radiation (exposure to 

sunlight), vit. D3 and vit. D2 can be absorbed from the diet and nutritional supplements too [87-88]. Little 

foods are vit. D dietary sources such as fish, eggs, dairy, meat (animal-based), yeast, mushrooms, planktonic 

microalgae, and Solanaceae family, plant-based after UVB-exposure [89-90]. Although there is evidence that 

vit. D5 was discovered in the Arabidopsis thaliana plants, it has not been discovered whether vit. D5 or its 

derivatives show a biological function in plant growth similar to that in vit. D3 in humans [91].  

Hypovitaminosis D is increasing in the global and is related to many ailments caused by calcium 

stabilization disorder [92]. This deficiency is related to autoimmune ailments [92], cardiovascular diseases 

[93], and respiratory diseases [94]. Zosky et al. [95] clarified that a vit. D caused lung volume to decrease in 

mice without significantly affecting somatic growth. Vit. D organizes ROS levels through anti-inflammatory 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 276 

European Journal of Biological Research 2020; 10(4): 271-295 

actions and mitochondrial-based expression of antioxidants via cell signaling pathways [96-97]. Ricca et al. 

[98] appeared that the mitochondrial impacts of vit. D receptors not only control respiratory activity, however, 

also maintain oxidative damage and protect the safety of mitochondria and the survival of healthy and also 

cancerous cells. Soe et al. [99] stated that vit. D deficiency is prevalent in patients of sickle cells at any season 

or age. Moreover, Mocayar Marón et al. [100] stated that the chronic deficiency of vit. D and melatonin 

certainly causes pathophysiological consequences.  

Various studies have disclosed that vit.D plays important parts of the signals through adaptive and 

innate responses to bacterial and viral infections, such as influenza, in vitro respiratory syncytial virus, and 

tuberculosis [101-108]. Katz et al. [109] stated that aging is also related to raising the hazard of death from 

pneumonia and that persons up 65 years of age account for more than 90% of influenza-related deaths. 

Several observations reinforced that susceptibility to acute influenza related to the gradual accumulation of 

vitamin A (vit. A) with age [110-111], and vit. A absorption also increases in elderly humans [112-113]. 

Mawson [114] reviewed that a new pattern of influenza infection indicates that host resistance and sensitivity 

depend heavily on the ratio of vit. D to vit. A activity and vit.A at optimal concentration limits may prevent 

influenza disease while high concentration (i.e., very low vit. D: vit. A ratios) raise the hazard of acute 

influenza complications. Zhou et al. [115] studied infant (400 infants) therapies (3-12 months) with vit. D 

against influenza A infection, the study included viral loads, the period of fever, wheezing, and coughing. The 

researchers reported that the group treated with a high dose of vit. D (1200 IU/d) showed a rapid decrease in 

temperature compared to another group treated with a low dose of vit. D (400 IU/d). Gruber-Bzura [116] has 

shown that vit. D is definitely an aspect of the complex factors that influence innate responses, and therefore it 

is essential to maintain vit. D at optimal levels in children and all elderly adults to improve action against 

diseases.  

Goncalves-Mendes et al. [117] advised that nutrition vit. D supplementation in old aged persons isn't 

always an effective manner to enhance their antibody reaction to the influenza vaccine. Newly, Grant et al. 

[118] exhibited the action of vit. D in reducing the hazard of evolving of COVID-19, as the number of 

COVID-19 cases is less in late summer (Southern Hemisphere) than others cases living in winter (Northern 

Hemisphere); and that the death rate increases with chronic ailments and age, both attached to a vit. D 

deficiency. Further, diverse studies have established the correlation between vit. D deficiency and venous 

thromboembolism in the lower extremities, patients with pulmonary venous thrombosis and ischemic stroke 

[119-121]. 

5. VITAMIN E 

Vitamin E (Vit. E) is a class of amphiphilic soluble molecules, tocotrienols, and tocopherols, which are 

the head of a chromanol and side chain of a prenyl and biosynthesized by non-photosynthetic/photosynthetic 

organisms [122-123]. The difference between tocopherols and tocotrienols is the degree of saturation of the 

prenyl side chain, and four α-β-γ-δ-forms differ from tocotrienols and tocopherols in the position and number 

of methyl particles attached to the particle of chromanol.  

Vitamin E is an active antioxidant for the removal of lipophilic radicals, and tocopherols are the active 

form in human cells [124]. α-tocopherol can perform as a molecule in gene modulating and regulation signal 

pathways through membrane-linked integrated proteins [125]. It maintains red blood cells (RBC) from 

oxidation, as it saves polyunsaturated fatty acids (PUFAs) from oxidation [126]. Further, it modifies the 

activity of inflammatory cytokines and innate cells and prevents the proliferation of smooth muscle cells 

[127-128]. Vitamin E was reported to curb sarcopenia and muscle weakness in preclinical models [129].  An 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 277 

European Journal of Biological Research 2020; 10(4): 271-295 

integration of vit. E with omega-3 fatty acids increased the expression of sirtuin-1 genes from peripheral 

mononuclear cells in patients of coronary artery [130]. Tocopherols are antioxidants that have been assessed 

against the influenza virus in mice [131] due to their activity versus oxidative damage through their activity in 

the scavenging of ROS [132]. Various studies, in humans, have revealed the immune impacts of vit. E, which 

gives resistance to many infections [133]. Dworski et al. [134] stated that vit. E protects against allergies and 

asthmas. 

Tocotrienols have the potential to inhibit the mevalonate pathway, accountable for the biosynthesis of 

cholesterol, bone remodeling, and carcinogenesis [135-136]. Deficiency of vit. E is common in hereditary 

anemia, including anemia induced by a deficiency of glucose-6-phosphate (G6PD), a mutation in the gene for 

α-tocopherol transfer protein (α-TTP), and alcohol-induced ailments [126, 137-139]. In children with vit. E 

deficiency with cystic fibrosis, anemia is noticed in a short life span of red blood cells [140]. Vitamin E 

deficiency leads to progressive neurological disorders, spinal cerebellar ataxia, and death [141]. 

6. OMEGA-3  

Omega-3 (�-3) is a main human fatty acid (FA), long-chain PUFAs, belonging to a family of fats that 

the body can’t biosynthesize and absorb through diet [142-144]. The name Omega is associated with the 

location of the double bond in relation to the methyl group present in a molecule of FAs. α-Linolenic Acid 

(ALA) is a short-chain �-3 FA that polymerizes into long-chain �-3 FAs such as eicosapentaenoic acid (EPA) 

and docosahexaenoic acid (DHA), which is a very weak step in the body [145]. Plant source is rich in �-3 FA, 

especially ALA that can be an inexpensive, sustainable, renewable, and suitable source for vegetarians, 

compared to fatty fish acids [146]. 

In humans, there is strong evidence that adequate �-3 are essential in maintaining health and can 

minimize the risks of inflammatory and chronic ailments [147]. In a 20-year study of 80,000 volunteers, 

women, increased consumption of PUFA was linked with a lower hazard of coronary heart ailment when 

replacing carbohydrates [148-149]. Moreover, �-3 and docosahexaenoic acid are needed for healthy growth, 

improving children's brain and eye development, and continuing ordinary brain function for adults [150]. The 

literature also revealed the advantages of �-3 in protecting and treating digestive, rheumatic, respiratory and 

bone disorders [151-152]. Also, �-3 is related to enhance vascular endothelial function, decreased 

triglycerides, levels of residual lipoprotein, risk of thrombosis, blood pressure, and unequal heartbeat [153]. 

The literature revealed the benefits of �-3 in reducing the hazard of breast, prostate, and lung cancer [154-

155]. Daak et al. [156] reported that �-3 supplementation for homozygous sickle cells (SCD) patients was 

active in reducing the severity and frequency of vascular blockages, blood transfusion rate, and severe 

anemia. Moreover, there are several studies that indicate defects in membranous fatty acids, red blood cells 

flow defects, inflammation, and hemolysis in SCD cases are improved with �-3 treatments [157-159]. Daak 

et al. [160] reported that SCD studies did not confirm the critical role of anomalies in the blood cell 

membrane lipids in causing disease, and the therapeutic potential of �-3 FAs proven in pioneering and 

randomized studies [161-164]. In contrast, Schwerbrock et al. [165] reported that PUFA consumption, in 

mice, has the possibility to raise the risk of influenza virus infection and possibly other viral diseases as well. 

Torrinhas et al. [166] reported that �-3 FAs are precursors of quite potent specialized pro-resolution 

mediators (SPMs), including resolvins, protecting, and maresins, which are related to a less attacker 

inflammatory inception, after competing together with �-6 FAs for eicosanoid biosynthesis, thus, it is used for 

the clinical management of COVID-19 patients. They added that the resolvins, protectins and maresins of �-3 

FAs can inactivate polymorphonuclear leukocyte and stimulate the mobilization of non-inflammatory 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 278 

European Journal of Biological Research 2020; 10(4): 271-295 

leukocytes, which eliminates programmed cell death (efferocytosis). These SPMs also contribute to the pro-

inflammatory cytokine “carry off” and remove other residues (such as invasive microorganisms) that provide 

restoration of the natural structure and tissue stabilization [167-171]. With its role in preventing pro-

inflammatory mediators, it has appeared that SPMs reduce the extent and duration of inflammation, improve 

reepithelization, tissue regeneration, and wound healing in experimental models [172]. Moreover, Souza et al. 

[173] demonstrated that �-3 leads to increased rapid regulation of SPM contents in peripheral blood and 

reprogramming of peripheral blood cell responses to sterile and infectious stimulants, adjustments that were 

managed to continuo after SPM contents returned to normal. 

7. MAGNESIUM 

Magnesium (Mg) is an important cation of crops, humans, and animals, and its deficiency decreases 

the sustainability of agrarian output and development and has long-term period negative consequences on 

animal and human health [174-175]. It is significant to keep the Mg content in agrarian products within an 

appropriate range because these products are the main source of Mg for animals and humans [176].  

In humans, Mg plays several roles, stimulating many enzymes, and regulating basic roles such as 

neuromuscular conduction, muscle contraction, myocardial contraction, blood sugar control, and blood 

pressure [177-178]. Furthermore, Mg has a significant function in energy metabolism, bone development, and 

transfer of ions across membranes [178], and consequently, Mg deficiency is related to many diseases [179]. 

Regulating the intracellular Mg is key to maintaining tissue integrity and cellular functions, as Mg plays a 

significant role in immunity and metabolism [180-185].  

Hypomagnesemia is unknown because its levels are not often evaluated as in which deficiency or 

surplus may occur, and data in developed countries reveal that about 10-30% inhabitance suffers from 

subclinical Mg deficiency [186-187]. Many diseases are related to Mg deficiency such as metabolic diseases, 

cardiovascular diseases, respiratory diseases, neurological abnormalities, and skeletal disorders [188]. 

Usually, hypomagnesemia is caused by decreasing consumption or insufficient absorption and/or excessive 

excretion and it is not easy to diagnose clinical, as symptoms related to it are not specific and generally 

confusing, due to down consuming other nutrients [188]. Hypomagnesemia was observed in patients treated 

with a proton pump inhibitor [189-190], thiazide diuretics, elevated doses of vit.D, and alcoholism [191]. 

Various studies have manifested that Mg deficiency is common in clinical cases, in particular in patients 

admitted to the comprehensive care unit as it has been observed to be related to increased hospital stay and 

deaths [192-194]. Magnesium deficiency may lead to reduced lung function, in particular in asthma cases 

[195]. Traviesa [196] confirmed that hypomagnesemia leads to thiamine deficiency, which sometimes appears 

in cases with Wernicke-Korsakoff encephalopathy. Magnesium is necessary to uptake thiamine [197], 

phosphorylation of thiamine phosphate [198], and action of enzymes that depend on thiamine in the cell [199-

200]. Uwitonze and Razzaque [201] also added that Mg is needed for vit.D because all metabolic vit.D 

enzymes require Mg that represents as a stimulus for reactions in the liver and kidneys. In adults, 

hypomagnesemia leads to unspecified clinical type with relevant central and peripheral neuromuscular 

markers, such as chronic fatigue syndrome, idiopathic Barlow's ailments, spasmophilia, hypoventilation 

syndrome, neurocirculatory asthenia [202]. Cross et al. [203] stated that MgSO4 may be useful in preventing 

fetal membranes inflammation produced by polymicrobial viral-bacterial infection. It is known that Mg is 

related to many protein kinases and additional Mg may indirectly stimulate T-cell receptor signals [204]. 

Howe et al. [205] added that oral Mg may also be efficient in patients with a mutation in the Interleukin-2-

inducible T cell kinase. 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 279 

European Journal of Biological Research 2020; 10(4): 271-295 

The function of Mg in the lung can be interpreted at three standards: Mg has an acute vasodilator and 

bronchodilator impact; Mg controls the liberation of acetylcholine and histamine; magnesium represents as an 

anti-inflammatory [175]. Studies on X-linked immunodeficiency with Mg deficiency disease (XMEN) have 

shown that deficiency of Mg leads to a poor immune reaction that can lead to increased viral load by Epstein - 

Barr (EBV) [206]. Lately,  it was found that 93% of acute and seriously ill patients with COVID-19 have 

hypokalemia [207], where hypokalemia is a widespread outcome in cases with hypomagnesemia [208]. 

8. MANGANESE 

Manganese (Mn) is a fundamental element in almost all organisms as it acts as an enzymatic catalyst 

and as a catalyst in the activities of biological groups [209]. Manganese is significant for plant growth because 

it participates in photosynthesis, respiration, defense of pathogens, hormone signals and ROS scavenger 

[210]. In plants, it has been noticed that only the evolution of O2 in photosynthesis, oxalate oxidase, and Mn 

superoxide dismutase (MnSOD) exclusively require Mn. MnSODs are located in mitochondria and 

peroxisomes and give protection against ROS that cause oxidative stress [211-212]. The oxalate oxidase is 

located in the oblast and stimulates the breakdown of oxalate into CO2 and H2O2, where it participates in 

defense by generating H2O2, which involves the biosynthesis of lignin that appears as an impediment against 

pathogens [213]. 

In humans, Mn is an essential microelement, distributed throughout the body, and high concentrations 

are found in mitochondrial-rich organs such as the thyroid, pituitary, liver, pancreas, bones, and kidneys [214-

215]. Mn catalyzes many enzymes, inclusive MnSOD, glutamine synthetase, arginase, and pyruvate 

carboxylase. It activates and synthesizes many enzymes participated with the metabolism of glucose and fats, 

ascorbate and thiamine, accelerate protein synthesis, endocrine regulation, stimulate hematopoiesis, improve 

innate function, and reduce ROS [216-217]. Interestingly, research points out that levels of Mn in the blood 

depend on sex and age, for example, the level is lower in adulthood than in childhood, and men have 

somewhat lower levels than women [218]. Moreover, Mn levels in non-pregnant women are lower compared 

to pregnant women [219], and individuals with high blood Mn levels have lower levels of iron (Fe) [220-222]. 

Compared to other essential micronutrients, Mn deficiency is rare, while Mn toxicity may occur more 

frequently when overexposed to Mn that causes polycythemia, dystonia, liver cirrhosis, and signs similar to 

Parkinson's ailment [217]. Accumulation and excessive exposure to Mn cause harm to the central nervous 

system that favors Mn absorption, while prolonged exposure to low Mn levels leads to Parkinson's disease 

[223]. However, the in vivo experiments in Mn-deficient mice increase the question of whether Mn depletion 

in humans is able to reduce response versus DNA viruses, resulting in reduced antiviral defense in people with 

Mn deficiency [224]. Haase [224] pointed out that THP1 cells, a cell line derived from peripheral blood, 

acquired antiviral activity while Mn averaged 2 mM, and Mn concentrations required to stimulate innate 

immunity. 

Both Fe and Mn are transitional minerals and have opposite effects, which may alter the absorption of 

Mn, excretion, or distribution of tissues/cells, and thus change Mn standards in the blood [225]. Common 

causes of high Fe concentrations, which can harm a number of different organs, especially the liver, in 

humans are alcohol addiction, cytolysis, inflammation, and metabolic syndrome [226]. Fernandez-Real et al. 

[227] reviewed that excess Fe in the blood is related to the development of type two diabetes. Various 

researches have also reported that the hazard of developing diabetes-related to high Fe intake is not 

considered by hemochromatosis or inflammation, but is fully linked to excessive Fe diet [228-229]. Bowers et 

al. [230] and Qiu et al. [231] noticed that the risk of gestational diabetes is especially associated with heme-



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 280 

European Journal of Biological Research 2020; 10(4): 271-295 

Fe, which is absorbed more efficiently than Fe-heme-Fe. Moreover, Cunningham et al. [232] and 

Memişoğullari and Bakan [233] reported that greater ceruloplasmin levels and lower transferrin [233] noticed 

in type two diabetic cases could lead to increased free copper (Cu) and Fe levels, respectively. 

Furthermore, it was found that Mn was heavily involved and wanted for the host's defense versus DNA 

viruses in mice [234]. As Mn accumulation stimulates the prominent innate immunity, which leads to the 

production and secretion of cytokines [234]. However, excessive accumulation or exposure to Mn damages 

the central nervous system as a result of preferential absorption of magnesium through brains and spinal 

cords. It is found that Manganism appears in response to sever manganese exposures, whereas Parkinsonism 

may outcome from long-time exposure into low concentrations of Mn [223]. Moreover, colloidal Mn salt 

(MnJ) showed significant adjunctive effects for all of the antigens tested including recombinant proteins, 

peptides, and inactivated viruses either by intramuscular or nasal immunization, which these results may have 

participations for the development of robust and safe Mn vaccines [235]. Manganese also participates with 

tumor immunology, as it is represented in dendritic cells to stimulate an anti-tumor reaction by cytotoxic T 

cells [236]. More studies are needed to clarify the relationship between influenza viruses and Mn. 

9. THYME 

Thyme is a prevalent semi-evergreen or evergreen shrub originated from the Mediterranean area and 

characterized by different species that differ in flavors [237]. The species are commonly used as ornamental, 

flavoring agents in culinary, and medicinal. It belongs to the Lamiaceae, the mint family has been used in 

traditional medicines to treat many diseases with many therapeutic effects related to volatile compounds and 

essential oils that have been used as anti-bacterial, anti-fungal, and anti-inflammatory properties [238-240]. 

The thyme plant contains many proteins, fats, fiber, flavonoids, and phenolic antioxidants, which are the 

highest levels of antioxidants among herbs, such as lutein, luteolin, naringenin, pigenin, zeaxanthin, 

thymonin, and vitamins such as A, B, C, and is considered the richest source of minerals such as K, Fe, Ca, 

Mn, Mg and Se, Na, and P [241-243]. 

Thyme phytochemical ingredients contain terpenoids, phenolic compounds, and usually, thymol, 

saponins, eugenol [244], and the essential oil appeared a high level of oxygenated monoterpenes (56.53%), 

monoterpene hydrocarbons (28.69%), sesquiterpene hydrocarbons (5.04%), and oxygenated sesquiterpenes 

(1.84%) [245]. The spicy aroma of thyme is an essential oil, as the dried plant contains about 1-2.5% of the 

essential oil [246]. The dominant essential oil is thymol (γ-terbene; 51.34%) while other essential oil 

components are less than 19% [245]. Most essential thyme oil belongs to monoterpene: linalol, myrcene, 

camphor, borneol, β-pinene, β-caryophyllene, p-cymene, carvacrol, thymol, γ-terpinene, thymyl methyl ether, 

limonene, α-terpinol, γ-terpinol, carvacryl methyl ether, and sabinene hydrate [245]. Also, thyme has 

triterpenes oleanolic acid (0.37%) and ursolic acid (0.94%) [247]. Thyme phenolic compounds are rosmarinic 

acid, p-hydroxybenzoic acid, caffeic acid, ferulic acid, syringic acid, gentisic acid, and p-coumaric acid [245, 

248-249]. Thyme flavonoids are about 25 among them flavones: apigenin, luteolin, 6-hydroxyluteolin; and 

methylflavones: cirsilineol, 8-methoxycirsilineol, cirsimaritin, 5-desmethylnobiletin, 5-desmethylsinensetin, 

gardenin B, genkwanin, 7-methoxyluteolin, salvigenin, sideritoflavone, thymonin, thymusin, and 

xanthomicrol [245, 250-251].  

The essential oil of thyme is characterized by its ability to scavenging free radicals, and therefore it is a 

natural antioxidant factor [252]. Thyme extracts appeared to fix the impacts on behavioral and memory 

disorders generated by scopolamine in mice, suggesting their beneficial effect in treating Alzheimer's ailment 

[253]. Thyme contains anti-inflammatory activities, where thymol, a major component of thyme, has been 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 281 

European Journal of Biological Research 2020; 10(4): 271-295 

notified to show anti-inflammatory impacts in the laboratory and in vivo [254]. Thyme extracts have been 

stated for their anti-inflammatory activities, as they reduce the inflammatory mediators: alpha tumor necrosis 

factor, beta-interleukin-1, and interleukin-6, and increase the expression of the anti-inflammatory cytokine, 

interleukin-10 [255]. Moreover, Vigo et al. [256] illustrated that thyme has anti-inflammatory activity by 

significantly inhibiting the expression of nitric oxide synthase mRNA. The antimicrobial mechanisms of 

carvacrol and thymol rely on their potentiality to degrade the outer membrane of Gram-negative bacteria, 

increase the permeability of the cytoplasmic membrane to ATP and release lipopolysaccharides [257]. 

Essential oils of Thymus vulgaris and T. zygis, which contain an elevated content of carvacrol and thymol, 

exhibited anti-fungal activities against seven Candida app. strains [258]. Thyme essential oil was a powerful 

antifungal against Aspergillus flavus, A. parasiticus, A. ochraceus, and Fusarium moniliforme [259]. It also 

has antioxidant action and has a protecting effect versus aflatoxin toxicity [260]. 

Regular and mostly critical bronchitis is induced by viral diseases, which are commonly treated by 

self-medication without a prescription, and herbal medicines, such as thyme extraction, with known efficiency 

and safety [261-264]. Thymus extracts (80% ethanol) have been stated for their antiviral activities against the 

Newcastle ailment virus, decreasing the potency of the virus more than 56-fold [265], and against herpes 

simplex virus (HSV) 1 and 2, and against HSV strains 1 Acyclovir Resistance [266]. Recently, Lenz et al. 

[267] reported that the tested standard thyme extract can have beneficial antiviral effects against HPV, leading 

to common cold ailments and possibly against flu A virus, leading to respiratory complications. The broad 

antimicrobial activity can be associated with phenol and its derivatives have antimicrobial effects by 

denaturation proteins, and thymol is 30-fold more active compared to phenol [267-268]. 

10. CONCLUSION 

The multiple roles of vitamin B1, vitamin C, vitamin D, vitamin E, omega-3, Mg, Mn, and thyme in 

humans provide these compounds with essential functions in defense against pathogens. While several open 

queries continue, there is an agreement that these compounds can be employed for medicinal advantage. It 

will be significant to assess the net impacts of these agents, as these factors seem to have a function in 

enhancing innate responses. The result of this review will visualize potential strategies that may benefit the 

host's innate system and improve the human defense. 

Conflict of Interest: The author declares no conflict of interest. 

Acknowledgment: Thanks to my brothers for encouraging me to publish this work. It is hoped that this work 

will assist in treating COVID-19 and provide a reference for future studies 

Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or 

not-for-profit sectors. 

REFERENCES 

1. Williams AE. Basic concepts in immunology. In: Immunology: mucosal and body surface defences. 

Chichester, UK: John Wiley & Sons, Ltd; 2011: 1-19. 

2. Koenderman L, Buurman W, Daha MR. The innate immune response. Immunol Lett. 2014; 162: 95-102.  

3. Lamb TJ. Notes on the immune system. In: Lamb TJ, ed. Immunity to parasitic infection. Chichester, 

UK: John Wiley & Sons, Ltd; 2012: 13-57. 

4. Williams AE. The innate immune system. In: Immunology: mucosal and body surface defences. 

Chichester, UK: John Wiley & Sons, Ltd; 2011: 20-40. 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 282 

European Journal of Biological Research 2020; 10(4): 271-295 

5. Lee JS, Bukhari SN, Fauzi NM. Effects of chalcone derivatives on players of the immune system. Drug 

Des Devel Ther. 2015; 9: 4761-4778. 

6. Tosi MF. Innate immune responses to infection. J Allergy Clin Immunol. 2005; 116: 241-249. 

7. Beutler B. Innate immunity: An overview. Mol Immunol. 2004; 40: 845-859.  

8. Pearce EJ, Pearce EJ. Metabolic pathways in immune cell activation and quiescence. Immunity. 2013; 

38: 633-643. 

9. O'Rourke B. From bioblasts to mitochondria: ever expanding roles of mitochondria in cell physiology. 

Front Physiol. 2010; 1: 7. 

10. Wa T, Langer, T. Mitochondrial dynamics and metabolic regulation. Trends Endocrinol Metabol. 2016; 

27: 105-117. 

11. Hamanaka RB, Chandel, S. Mitochondrial reactive oxygen species regulate cellular signaling and dictate 

biological outcomes. Trends Biochem Sci. 2010; 35: 505-513. 

12. Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell. 2012; 

48: 158-167. 

13. Kamiński MM, Röth D, Krammer PH, Gülow K. Mitochondria as oxidative signaling organelles in T-

cell activation: physiological role and pathological implications. Arch Immunol Ther Exp. 2013; 61: 

367-384. 

14. Rashida Gnanaprakasam JN, Wu R, Wang R. Metabolic reprogramming in modulating T cell reactive 

oxygen species generation and antioxidant capacity. Front Immunol. 2018; 9: 1075. 

15. Tiku V, Tan MW, Dikic I. Mitochondrial functions in infection and immunity. Trends Cell Biol. 2020; 

30: 263-275. 

16. Reshi L, Wang H-V, Hong J-R. Modulation of mitochondria during viral infections. Mitoch Dis. 2018; 

2018: 443. 

17. Reshi L, Wang H-V, Hui CF, Su YC, Hong JR. Anti-apoptotic genes Bcl-2 and Bcl-xL overexpression 

can block iridovirus serine/threonine kinase-induced Bax/mitochondria-mediated cell death in GF-1 

cells. Fish Shellfish Immun. 2017; 61: 120-129. 

18. Yoshizumi T, Ichinohe T, Sasaki O, Otera H, Kawabata S-I, Mihara K, et al. Influenza A virus protein 

PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity. Nat Commun. 

2014; 5: 4713. 

19. Shi CS, Qi HY, Boularan C, Huang NN, Abu-Asab M, Shelhamer JH, et al. SARS-coronavirus open 

reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 

signalosome. J Immunol. 2014; 193: 3080-3089. 

20. Kim SJ, Ahn DG, Syed GH, Siddiqui A. The essential role of mitochondrial dynamics in antiviral 

immunity. Mitochondrion. 2018; 41: 21-27. 

21. Liu J, Zheng X, Tong Q, Li W, Wang, B, Sutter, K, et al. Dittmer, D. Yang, Overlapping and discrete 

aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, 

MERS-CoV, and 2019-nCoV. J Med Virol. 2020; 92: 491-494. 

22. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 

2019 in China. N Engl J Med. 2020: doi: 10.1056/NEJMoa200203.  

23. Boldogh I, Albrecht T, Porter DD. Persistent viral infections. In: Baron S, ed. Medical Microbiology, 4th 

edn. University of Texas Medical Branch at Galveston, Galveston, TX, 1996: 585-596. 

24. Wu D, Lewis ED, Pae M, Meydani SN. Nutritional modulation of immune function: Analysis of 

evidence, mechanisms, and clinical relevance. Front Immunol. 2019; 9: 3160. 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 283 

European Journal of Biological Research 2020; 10(4): 271-295 

25. Donnino M. Gastrointestinal beriberi: a previously unrecognized syndrome. Ann Intern Med. 2004; 141: 

898-899. 

26. Funk C. The etiology of the deficiency. Anal Chim Acta. 1975; 76: 176-177. 

27. Pourcel L, Moulin M, Fitzpatrick TB. Examining strategies to facilitate vitamin B1 biofortification of 

plants by genetic engineering. Front Plant Sci. 2013; 4: 160. 

28. Frédérich M, Delvaux D, Gigliobianco T, Gangolf M, Dive G, Mazzucchelli G, et al. Thiaminylated 

adenine nucleotides. Chemical synthesis, structural characterization and natural occurrence. FEBS J. 

2009; 276: 3256-3268. 

29. Bettendorff L, Wirtzfeld B, Makarchikov AF, Mazzucchelli G, Frédérich M, Gigliobianco T, et al. 

Discovery of a natural thiamine adenine nucleotide. Nat Chem Biol. 2007; 3: 211-212. 

30. Bettendorff L, Lakaye B, Kohn G, Wins P. Thiamine triphosphate: a ubiquitous molecule in search of a 

physiological role. Metab Brain Dis. 2014; 29: 1069-1082.  

31. Singer M. The role of mitochondrial dysfunction in sepsis-induced multiorgan failure. Virulence. 2014; 

5: 66-72. 

32. Shimon I, Almog S, Vered Z, Seligmann H, Shefi M, Peleg E, et al. Improved left ventricular function 

after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide 

therapy. Am J Med. 1995; 98: 485-490. 

33. Suter PM, Haller J, Hany A, Vetter W. Diuretic use: a risk for subclinical thiamine deficiency in elderly 

patients. J Nutr Health Aging. 2000; 4: 69-71. 

34. Katta N, Balla S, Alpert MA. Does long-term furosemide therapy cause thiamine deficiency in patients 

with heart failure? A focused review. Am J Med. 2016; 129: 753.e7-753.e11. 

35. Teigen LM, Twernbold DD, Miller WL. Prevalence of thiamine deficiency in a stable heart failure 

outpatient cohort on standard loop diuretic therapy. Clin Nutr. 2016; 35: 1323-1327. 

36. Malecka SA, Poplawski K, Bilski B. Profilaktyczne i terapeutyczne zastosowanie tiaminy (witaminy B1) 

- nowe spojrzenie na stary lek. Wiad Lek. 2006; 59: 383-387. 

37. Anderson P. Influenza, and viral resistance. https://www.advancedmedicaltherapies.com/influenza-viral-

resistance/ 

38. Singleton CK, Martin PR. Molecular mechanisms of thiamine utilization. Curr Mol Med. 2001; 1: 197-

207. 

39. Combs GF. The Vitamins. Elsevier 2008: 265-280. 

40. Manzetti S, Zhang J, van der Spoel D. Thiamin function, metabolism, uptake, and transport. 

Biochemistry 2014; 53: 821-835. 

41. Mkrtchyan G, Aleshin V, Parkhomenko Y, Kaehne T, Di Salvo ML, Parroni A, et al. Molecular 

mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway 

analysis. Sci Rep. 2015; 5: 12583.  

42. Luo’ng K, Nguyễn LT. The role of thiamine in HIV infection. Int J Infect Dis. 2013; 17: e221-e227. 

43. Wallace AE, Weeks WB. Thiamine treatment of chronic hepatitis B infection. Am J Gastroenterol. 2001; 

96: 864-868. 

44. Lévy S, Hervé C, Delacoux E, Erlinger S. Thiamine deficiency in hepatitis C virus and alcohol-related 

liver diseases. Dig Dis Sci. 2002; 47: 543-548. 

45. Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, vitamin C, and thiamine for 

the treatment of severe sepsis and septic shock. Chest. 2017; 151: 1229-1238. 

 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 284 

European Journal of Biological Research 2020; 10(4): 271-295 

46. Smirnoff N, Conklin PL, Loewus FA. Biosynthesis of ascorbic acid in plants: a renaissance. Annu Rev 

Plant Physiol Plant Mol Biol. 2001; 52: 437. 

47. Padayatty SJ, Levine M. Vitamin C: the known and the unknown and Goldilocks. Oral Dis. 2016; 22: 

463-493. 

48. Locato V, Cimini S, Gara LD. Strategies to increase vitamin C in plants: from plant defense perspective 

to food biofortification. Front Plant Sci. 2013; 4: 152. 

49. Lodge JK. Molecular actions of ascorbic acid. Curr Top Nutraceut Res. 2008; 6: 1-13. 

50. De Gara L, Locato V, Dipierro S, de Pinto MC. Redoxhome-ostasis in plants. The challenge of living 

with endogenous oxygen production. Respir Physiol Neurobiol. 2010; 173: S13-S19. 

51. Bleeg HS, Christensen F. Biosynthesis of ascorbate in yeast. Purification of L-galactono-1,4-lactone 

oxidase with properties different from mammalian L-gulonolactone oxidase. Eur J Biochem. 1982; 127: 

391-396. 

52. Banhegyi G, Braun L, Csala M, Puskas F, Mandl J. Ascorbate metabolism and its regulation in animals. 

Free Radic Biol Med. 1997; 23: 793-803. 

53. Wheeler GL, Jones MA, Smirnoff N. The biosynthetic pathway of vitamin C in higher plants. Nature. 

1998; 393: 365-369. 

54. Loga FJ, Taylor MC, Wilkinson SR, Kaur H, Kelly JM. The terminal step in vitamin C biosynthesis in 

Trypanosoma cruzi is mediated by a FMN-dependent galactonolactone oxidase. Biochem J. 2007; 407: 

419-426. 

55. Nishikimi M, Kawai T, Yagi K. Guinea pigs possess a highly mutated gene for L-gulono-gammalactone 

oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species. J Biol Chem. 1992; 

267: 21967-21972. 

56. Nishikimi M, Fukuyama R, Minoshima S, Shimizu N, Yagi K. Cloning and chromosomal mapping of 

the human nonfunctional gene for L-gulonoγ-lactone oxidase, the enzyme for L-ascorbic acid 

biosynthesis missing in man. J Biol Chem. 1994; 269: 13685-13688. 

57. Levin M. New concepts in the biology and biochemistry of ascorbic acid. New Engl J Med. 1986; 31: 

892-902. 

58. Naidu KA. Vitamin C in human health and disease is still a mystery? An overview. Nutr J. 2003; 2: 7. 

59. Hulse JD, Ellis SR, Henderson LM. Carnitine biosynthesis-beta hydroxylation of trimethyllysine by an 

α-keto glutarate dependent mitochondrial dioxygenase. J Biol Chem. 1978; 253: 1654-1659. 

60. Cameron E, Pauling L. Ascorbic acid and the glycosaminoglycans. Oncology. 1973; 27: 181-192. 

61. Devaki SJ, Raveendran RL. Vitamin C: sources, functions, sensing and analysis. In: Amal H. Hamza 

Vitamin C. InTech., 2017. 

62. Mirvish SS. Effects of vitamins C and E on N-nitroso compound formation, carcinogenesis, and cancer. 

Cancer. 1986; 58(8 Suppl): 1842-1850. 

63. Delanghe JR, Langlois MR, De Buyzere ML, Na N, Ouyang J, Speeckaert MM, et al. Vitamin C 

deficiency: more than just a nutritional disorder. Genes Nutr. 2011; 6: 341-346. 

64. Yung S, Mayersohn M, Robinson JB. Ascorbic acid elimination in humans after intravenous 

administration. J Pharm Sci. 1978; 67: 1491-1492. 

65. Willet W. Nutritional epidemiology, 2nd edn. Oxford University Press, New York, 1998. 

66. Crandon JH, Lund CC, Dill DB. Experimental human scurvy. N Engl J Med. 1940; 223: 353-369. 

67. Cahill LE, El-Sohemy A. Haptoglobin genotype modifies the association between dietary vitamin C and 

serum ascorbic acid deficiency. Am J Clin Nutr. 2010; 92: 1494-1500. 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 285 

European Journal of Biological Research 2020; 10(4): 271-295 

68. Hirschmann JV, Raugi GJ. Adult scurvy. J Am Acad Dermatol. 1999; 41: 895-906. 

69. Carr AC, Maggini S. Vitamin C and immune function. Nutrients. 2017; 9: 1211. 

70. Kelly F, Dunster C, Mudway I. Air pollution and the elderly: Oxidant/antioxidant issues worth 

consideration. Eur Respir J. 2003; 21: 70s-75s. 

71. Haryanto B, Suksmasari T, Wintergerst E, Maggini S. Multivitamin supplementation supports immune 

function and ameliorates conditions triggered by reduced air quality. Vitam Miner. 2015; 4: 1-15. 

72. Johnston CS, Martin LJ, Cai X. Antihistamine effect of supplemental ascorbic acid and neutrophil 

chemotaxis. J Am Coll Nutr. 1992; 11: 172-176.  

73. Manning J, Mitchell B, Appadurai DA, Shakya A, Pierce LJ, Wang H, et al. Vitamin C promotes 

maturation of T-cells. Antioxid Redox Signal. 2013; 19: 2054-2067.  

74. Huijskens MJ, Walczak M, Koller N, Briede JJ, Senden-Gijsbers BL, Schnijderberg MC, et al. Technical 

advance: Ascorbic acid induces development of double-positive T cells from human hematopoietic stem 

cells in the absence of stromal cells. J Leukoc Biol. 2014; 96: 1165-1175. 

75. Siegel BV. Enhancement of interferon production by poly(rI)-poly(rC) in mouse cell cultures by ascorbic 

acid. Nature. 1975; 254: 531-532.  

76. Dahl H, Degre M. The effect of ascorbic acid on production of human interferon and the antiviral 

activity in vitro. Acta Pathol Microbiol Scand B. 1976; 84b: 280-284. 

77. Karpinska T, Kawecki Z, Kandefer-Szerszen M. The influence of ultraviolet irradiation, L-ascorbic acid 

and calcium chloride on the induction of interferon in human embryo fibroblasts. Arch Immunol Ther 

Exp. 1982; 30: 33-37. 

78. Hemila H. Vitamin C and Infections. Nutrients. 2017; 9: 339. 

79. Bharara A, Grossman C, Grinnan D, Syed AA, Fisher BJ, De Wilde C, et al. Intravenous vitamin C 

administered as adjunctive therapy for recurrent acute respiratory distress syndrome. Case Rep Crit Care. 

1016; 2016: 8560871. 

80. Fowler AA, Kim C, Lepler L, Malhotra R, Debesa O, Natarajan R, et al. Intravenous vitamin C as 

adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome. World J Crit 

Care Med. 2017; 6: 85-90.  

81. Johnston CS, Barkyoumb GM, Schumacher SS. Vitamin C supplementation slightly improves physical 

activity levels and reduces cold incidence in men with marginal vitamin C status: A randomized 

controlled trial. Nutrients. 2014; 6: 2572-2583.  

82. Gorton HC, Jarvis K. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-

induced respiratory infections. J Manipulative Physiol Ther. 1999; 22: 530-533. 

83. Cai Y, Li Y-F, Tang L-P, Tsoi B, Chen M, Chen H, et al. A new mechanism of vitamin C effects on 

A/FM/1/47(H1N1) virus-induced pneumonia in restraint-stressed mice. BioMed Res Int. 2015; 2015: 

675149. 

84. Colunga Biancatelli RM, Berrill M, Marik PE. The antiviral properties of vitamin C. Expert Rev Anti 

Infect Ther. 2020; 18: 99-101.  

85. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and 

cardiovascular disease. Am J Clin Nutr. 2004; 80(6 Suppl): 1678S-1688S. 

86. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 

2006; 81: 353-373. 

87. Calvo MS, Whiting SJ, Barton CN. Vitamin D intake: a global perspective of current status. J Nutr. 

2005; 135: 310-316. 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 286 

European Journal of Biological Research 2020; 10(4): 271-295 

88. Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential 

for good health. Am J Clin Nutr. 2008; 88: 491S-499S. 

89. Jäpelt RB, Jakobsen J. Vitamin D in plants: a review of occurrence, analysis, and biosynthesis. Front 

Plant Sci. 2013; 4: 136. 

90. Black LJ, Lucas RM, Sherriff JL, Björn LO, Bornman JF. In pursuit of vitamin D in plants. Nutrients. 

2017; 9: 136. 

91. Silvestro D, Villette C, Delecolle J, Olsen CE, Motawia MS, Geoffroy P, et al. Vitamin D5 in 

Arabidopsis thaliana. Sci Rep. 2018; 8: 16348. 

92. Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 357: 266-281. 

93. Kilkkinen A, Knekt P, Aro A, Rissanen H, Marniemi J, Heliovaara M, et al. Vitamin D status and the risk 

of cardiovascular disease death. Am J Epidemiol. 2009; 170: 1032-1039. 

94. Janssens W, Bouillon R, Claes B, Carremans C, Lehouck A, Buysschaert I, et al. Vitamin D deficiency is 

highly prevalent in COPD and correlates with variants in the vitamin D-binding gene. Thorax. 2010; 65: 

215-220. 

95. Zosky GR, Berry LJ, Elliot JG, James AL, Gorman S, Hart PH. Vitamin D deficiency causes deficits in 

lung function and alters lung structure. Am J Respir Crit Care Med. 2011; 183: 1336-1343. 

96. Shelton RC, Claiborne J, Sidoryk-Wegrzynowicz M, Reddy R, Aschner M, Lewis DA, et al. Altered 

expression of genes involved in inflammation and apoptosis in frontal cortex in major depression. Mol 

Psychiatry. 2011; 16: 751-762. 

97. Berridge MJ. Vitamin D cell signalling in health and disease. Biochem Biophys Res Commun. 2015; 

460: 53-71.  

98. Ricca C, Aillon A, Bergandi L, Alotto D, Castagnoli C, Silvagno F. Vitamin D receptor is necessary for 

mitochondrial function and cell health. Int J Mol Sci. 2018; 19: 1672. 

99. Soe HH, Abas AB, Than NN, Ni H, Singh J, Said AR, et al. Vitamin D supplementation for sickle cell 

disease. Cochrane Database Syst Rev. 2017; 1: CD010858. 

100. Mocayar Marón FJ, Ferder L, Reiter RJ, Manucha W. Daily and seasonal mitochondrial protection: 

Unraveling common possible mechanisms involving vitamin D and melatonin. J Steroid Biochem Mol 

Biol. 2020; 199: 105595. 

101. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering on a vitamin 

D-mediated human antimicrobial response. Science. 2006; 311: 1770-1773. 

102. Bikle DD. Vitamin D and the immune system: role in protection against bacterial infection. Curr Opin 

Nephrol Hypertens. 2008; 17: 348-352. 

103. Hansdottir S, Monick MM, Hinde SL, Lovan N, Look DC, Hunninghake GW. Respiratory epithelial 

cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol. 2008; 

181: 7090-7099. 

104. Hansdottir S, Monick MM, Lovan N, Powers L, Gerke A, Hunninghake GW. Vitamin D decreases 

respiratory syncytial virus induction of NFkB-linked chemokines and cytokines in airway epithelium 

while maintaining the antiviral state. J Immunol. 2010; 184: 965-974. 

105. Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D 

supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010; 91: 1255-

1260. 

106. Beard JA, Bearden A, Striker R. Vitamin D and the anti-viral state. J Clin Virol. 2011; 50: 194-200. 

 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 287 

European Journal of Biological Research 2020; 10(4): 271-295 

107. Belderbos ME, Houben ML, Wilbrink B, Lentjes E, Bloemen EM, Kimpen JL, et al. Cord blood vitamin 

D deficiency is associated with respiratory syncytial virus bronchiolitis. Pediatrics. 2011; 127: e1513-

1520. 

108. Chadha MK, Fakih M, Muindi J, Tian L, Mashtare T, Johnson CS, et al. Effect of 25-hydroxyvitamin D 

status on serological response to influenza vaccine in prostate cancer patients. Prostate. 2011; 71: 368-

372. 

109. Katz JM, Plowden J, Renshaw-Hoelscher M, Lu X, Tumpey TM, Sambhara S. Immunity to influenza: 

the challenges of protecting an aging population. Immunol Res. 2004; 29: 113-124. 

110. Garry PJ, Hunt WC, Bandrofchak JL, VanderJagt D, Goodwin JS. Vitamin A intake and plasma retinol 

levels in healthy elderly men and women. Am J Clin Nutr. 1987; 46: 989-994. 

111. Comstock GW, Menkes MS, Schober SE, Vuilleumier JP, Helsing KJ. Serum levels of retinol, beta-

carotene, and alpha-tocopherol in older adults. Am J Epidemiol. 1988; 127: 114-123. 

112. Hollander D, Dadufalza V. Influence of aging on vitamin A transport into the lymphatic circulation. Exp 

Gerontol. 1990; 25: 61-65. 

113. Krasinski SD, Kohn JS, Schaefer EJ, Russell RM. Post prandial plasma retinyl ester response is greater 

in older subjects compared with younger subjects. J Clin Invest. 1990; 85: 883-892. 

114. Mawson AR. Role of fat-soluble vitamins A and A in the pathogenesis of influenza: a new perspective. 

Int Sch Res Notices. 2013; 2013: 246737. 

115. Zhou J, Du J, Huang L, Wang Y, Shi Y, Lin H. Preventive effects of vitamin D on seasonal influenza A in 

infants: A multicenter, randomized, open, controlled clinical trial. Pediatr Infect Dis J. 2018; 37: 749-

754. 

116. Gruber-Bzura BM. Vitamin D and influenza-prevention or therapy? Int J Mol Sci. 2018; 19: E2419. 

117. Goncalves-Mendes N, Talvas J, Dualé C, Guttmann A, Corbin V, Marceau G, et al. Impact of vitamin D 

supplementation on influenza vaccine response and immune functions in deficient elderly persons: a 

randomized placebo-controlled trial. Front Immunol. 2019; 10: 65. 

118. Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, et al. Evidence that vitamin 

D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020; 

12: E988. 

119. Wu WX, He DR. Low vitamin D levels are associated with the development of deep venous 

thromboembolic events in patients with ischemic stroke. Clin Appl Thromb Hemost. 2018; 24(9S): 69S-

75S. 

120. Dehghani K, Nowrouzi A, Pourdavood AH, Rahmanian Z. Effect of vitamin D deficiency in lower 

extremity and pulmonary venous thromboembolism. Biomed Res Ther. 2019; 6: 3017-3112. 

121. Ehsanian R, Timmerman MA, Wright JM, McKenna S, Dirlikov B, Crew J. Venous thromboembolism is 

associated with lack of vitamin D supplementation in patients with spinal cord injury and low vitamin D 

levels. PMR. 2019; 11: 125-134. 

122. Munné-Bosch S, Alegre L. The function of tocopherols and tocotrienols in plants. Crit Rev Plant Sci. 

2002; 21: 31-57. 

123. Mène-Saffrané L. Vitamin E biosynthesis and its regulation in plants. Antioxidants. 2018; 7: 2. 

124. Niki E. Role of vitamin E as a lipid-soluble peroxyl radical scavenger: in vitro and in vivo evidence. 

Free Radic Biol Med. 2014; 66: 3-12. 

125. Galli F, Azzi A, Birringer M, Cook-Mills JM, Eggersdorfer M, Frank J, et al. Vitamin E: Emerging 

aspects and new directions. Free Radic Biol Med. 2017; 102: 16-36.  



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 288 

European Journal of Biological Research 2020; 10(4): 271-295 

126. Chan AC, Chow CK, Chiu D. Interaction of antioxidant and their implication in genetic anemia. Proc 

Soc Exp Biol Med. 1999; 222: 274-282. 

127. Zou T, Liu N, Li SD, Su YC, Man Y, Lu D. Vitamin E inhibits homocysteine-mediated smooth muscle 

cell proliferation. Nan Fang Yi Ke Da Xue Xue Bao. 2007; 27: 783-786. 

128. Huey KA, Fiscus G, Richwine AF, Johnson RW, Meador BM. In vivo vitamin E administration 

attenuates interleukin-6 and interleukin-1beta responses to an acute inflammatory insult in mouse 

skeletal and cardiac muscle. Exp Physiol. 2008; 93: 1263-1272. 

129. Khor SC, Abdul Karim N, Ngah WZ, Yusof YA, Makpol S. Vitamin E in sarcopenia: current evidences 

on its role in prevention and treatment. Oxid Med Cell Longev. 2014; 2014: 914853. 

130. Saboori S, Koohdani F, Nematipour E, Yousefi Rad E, Saboor-Yaraghi AA, Javanbakht MH, et al. 

Beneficial effects of omega-3 and vitamin E coadministration on gene expression of SIRT1 and PGC1α 

and serum antioxidant enzymes in patients with coronary artery disease. Nutr Metab Cardiovasc Dis. 

2015; 26: 489-494.  

131. Mileva MM, Bakalova RB, Zlateva GA, Galabov AS, Ohba H, Ishikawa M, et al. Еffect of rutin and 

quercetin and the “oxidative stress” induced by influenza virus infection in mice alveolocytes. In: 

Izumori K, ed. Proceedings of the 2nd Symposium of the International Society of Rare Sugars. 

Takamatsu, Japan: Kagawa University Press, 2005: 64-69. 

132. Blaner WS. Vitamin E: the enigmatic one. J Lipid Res. 2013; 54: 2293-2294. 

133. Lee GY, Han SN. The role of vitamin E in immunity. Nutrients. 2018; 10: 1614. 

134. Dworski R, Han W, Blackwell TS, Hoskins A, Freeman ML. Vitamin E prevents NRF2 suppression by 

allergens in asthmatic alveolar macrophages in vivo. Free Radic Biol Med. 2011; 51: 516-521. 

135. Mo H, Yeganehjoo H, Shah A, Mo WK, Soelaiman IN, Shen C-L. Mevalonate-suppressive dietary 

isoprenoids for bone health. J Nutr Biochem. 2012; 23: 1543-1551. 

136. Shen CL, Klein A, Chin KY, Mo H, Tsai P, Yang RS, et al. Tocotrienols for bone health: a translational 

approach. Ann N Y Acad Sci. 2017; 1401: 150-165.  

137. Hasanato RM. Zinc and antioxidant vitamin deficiency in patients with severe sickle cell anemia. Ann 

Saudi Med. 2006; 26: 17-21. 

138. Kaur J, Shalini S, Bansal MP. Influence of vitamin E on alcohol-induced changes in antioxidant defenses 

in mice liver. Toxicol Mech Methods. 2010; 20: 82-89. 

139. Desrumaux CM, Mansuy M, Lemaire S, Przybilski J, Guern NL, Givalois L, et al. Brain vitamin E 

deficiency during development is associated with increased glutamate levels and anxiety in adult mice. 

Front Behav Neurosci. 2018; 12: 310. 

140. Farrell PM, Bieri JG, Fratantoni JF, Wood RE, di Sant’Agnese PA. The occurrence and effects of human 

vitamin E deficiency: a study in patients with cystic fibrosis. J Clin Invest. 1977; 60: 233-241. 

141. El Euch-Fayache G, Bouhlal Y, Amouri R, Feki M, Hentati F. Molecular, clinical and peripheral 

neuropathy study of Tunisian patients with ataxia with vitamin E deficiency. Brain. 2014; 137: 402-410. 

142. Schmidt EB, Dyerberg J. Omega-3 fatty acids: current status in cardiovascular medicine. Drugs. 1994; 

47: 405-424. 

143. Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, 

molecular pathways, and clinical events. J Am Coll Cardiol. 2011; 58: 2047-2067. 

144. Khan WA, Chun-Mei H, Khan N, Iqbal A, Lyu SW, Shah F. Bioengineered plants can be a useful source 

of omega-3 fatty acids. BioMed Res Int. 2017; 2017: 7348919. 

 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 289 

European Journal of Biological Research 2020; 10(4): 271-295 

145. Lakra N, Mahmood S, Marwal A, Sudheep NM, Anwar Kh. Bioengineered plants can be an alternative 

source of omega-3 fatty acids for human health. In: Plant and human health, Vol. 2 Phytochemistry and 

molecular aspects. Springer, Cham, 2019: 361-382. 

146. Guillen MD, Ruiz A, Cabo N, Chirinos R, Pascual G. Characterization of Sacha Inchi (Plukenetia 

volubilis L.) oil by FTIR spectroscopy and 1H NMR. Comparison with linseed oil. J Am Oil Chem Soc. 

2003; 80: 755-762. 

147. Welch AA, Shakya-Shrestha S, Lentjes MA, Wareham NJ, Khaw KT. Dietary intake and status of n-3 

polyunsaturated fatty acids in a population of fish-eating and non-fish-eating meat-eaters, vegetarians, 

and vegans and the product-precursor ratio [corrected] of α-linolenic acid to long-chain n-3 

polyunsaturated fatty acids: results from the EPIC-Norfolk cohort. Am J Clin Nutr. 2010; 92: 1040-1051. 

148. Oh K, Hu FB, Manson JE. Dietary fat intake and risk of coronary heart disease in women: 20 years of 

follow up of the nurses’ health study. Am J Epidemiol. 2005; 161: 672-679. 

149. Mente A, de Koning L, Shannon HS, Anand SS. A systematic review of the evidence supporting a causal 

link between dietary factors and coronary heart disease. Arch Intern Med. 2009; 169: 659-669. 

150. Birch EE, Garfield S, Castañeda Y, Hughbanks-Wheaton D, Uauy R, Hoffman D. Visual acuity and 

cognitive outcomes at 4 years of age in a double-blind, randomized trial of long-chain polyunsaturated 

fatty acid-supplemented infant formula. Early Hum Dev. 2007; 83: 279-284. 

151. Sakaguchi K, Morita I, Murota S. Eicosapentaenoic acid inhibits bone loss due to ovariectomy in rats. 

Prostagl Leukot Essent Fatty Acids 1994; 50: 81-84. 

152. Ambrosone CB, Freudenheim JL, Sinha R. Breast cancer risk, meat consumption and N-

acetyltransferase (NAT2) genetic polymorphisms. Int J Cancer. 1998; 75: 825-830. 

153. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and 

cardiovascular disease. Circulation 2002; 106: 2747-2757. 

154. Veierod MB, Laake P, Thelle DS. Dietary fat intake and risk of lung cancer: a prospective study of 

51,452 Norwegian men and women. Eur J Cancer Prev. 1997; 6: 540-549.  

155. Freeman MP, Hibbeln JR, Wisner KL, Davis JM, Mischoulon D, Peet M, et al. Omega-3 fatty acids: 

evidence basis for treatment and future research in psychiatry. J Clin Psychiatry. 2006; 67: 1-14.  

156. Daak AA, Ghebremeskel K, Mariniello K, Attallah B, Clough P, Elbashir MI. Docosahexaenoic and 

eicosapentaenoic acid supplementation does not exacerbate oxidative stress or intravascular haemolysis 

in homozygous sickle cell patients. Prostagl Leukot Essent Fatty Acids. 2013; 89: 305-311. 

157. Daak AA, Ghebremeskel K, Hassan Z, Attallah B, Azan HH, Elbashir MI, et al. Effect of omega-3 (n-3) 

fatty acid supplementation in patients with sickle cell anemia: randomized, double-blind, placebo-

controlled trial. Am J Clin Nutr. 2013; 97: 37-44.  

158. Daak AA, Elderdery AY, Elbashir LM, Mariniello K, Mills J, Scarlett G, et al. Omega 3 (n-3) fatty acids 

down-regulate nuclear factor- kappa B (NF- kB) gene and blood cell adhesion molecule expression in 

patients with homozygous sickle cell disease. Blood Cells Mol Dis. 2015; 55: 48-55. 

159. Kalish BT, Matte A, Andolfo I, Iolascon A, Weinberg O, Ghigo A, et al. Dietary ω-3 fatty acids protect 

against vasculopathy in a transgenic mouse model of sickle cell disease. Haematologica. 2015; 100: 870-

880. 

160. Daak A, Rabinowicz A, Ghebremeskel K. Omega-3 fatty acids are a potential therapy for patients with 

sickle cell disease. Nat Rev Dis Primers. 2018; 4: 15. 

 

 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 290 

European Journal of Biological Research 2020; 10(4): 271-295 

161. Ren H, Okpala I, Ghebremeskel K, Ugochukwu CC, Ibegbulam O, Crawford M. Blood mononuclear 

cells and platelets have abnormal fatty acid composition in homozygous sickle cell disease. Ann 

Hematol. 2005; 84: 578-583. 

162. Kuypers FA. Membrane lipid alterations in hemoglobinopathies. Hematol Am Soc Hematol Educ 

Program. 2007; 2007: 68-73.  

163. Daak AA, Ghebremeskel K, Hassan Z, Attallah B, Azan HH, Elbashir MI, et al. Effect of omega-3 (n-3) 

fatty acid supplementation in patients with sickle cell anemia: randomized, double-blind, placebo-

controlled trial. Am J Clin Nutr. 2012; 97: 37-44.  

164. Sins JWR, Mager DJ, Davis SC, Biemond BJ, Fijnvandraat K. Pharmacotherapeutical strategies in the 

prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review. Blood Adv. 2017; 1: 

1598-1616. 

165. Schwerbrock NMJ, Karlsson EA, Shi Q, Sheridan PA, Beck MA. Fish oil-fed mice have impaired 

resistance to influenza infection. J Nutr. 2009; 139: 1588-1594. 

166. Torrinhas RS, Calder PC, Lemos GO, Waitzberg DL. Parenteral fish oil, an adjuvant pharmacotherapy 

for COVID-19? Nutrition. 2020; 81: 110900. 

167. Fredman G, Serhan CN. Specialized proresolving mediator targets for RvE1 and RvD1 in peripheral 

blood and mechanisms of resolution. Biochem J. 2011; 437: 185-197. 

168. Spite M, Norling L., Summers L, Yang R, Cooper D, Petasis NA, et al. Resolvin D2 is a potent regulator 

of leukocytes and controls microbial sepsis. Nature. 2009; 461: 1287-1291. 

169. Hasturk H, Kantarci A, Goguet-Surmenian E, Blackwood A, Andry C, Serhan CN, et al. Resolvin E1 

regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J 

Immunol. 2007; 179: 7021-7029. 

170. Titos E, Rius B, González-Périz A, López-Vicario C, Morán-Salvador E, Martínez-Clemente M, et al. 

Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation 

by eliciting macrophage polarization toward an M2-Like phenotype. J Immunol. 2011; 187: 5408-5418. 

171. Serhan CN, Yang R, Martinod K, Kasuga K, Pillai PS, Porter TF, et al. Maresins: novel macrophage 

mediators with potent anti-inflammatory and proresolving actions. J Exp Med. 2009; 206: 15-23. 

172. Dalli J, Zhu M, Vlasenko NA, Deng B, Haeggström JZ, Petasis NA, Serhan CN. The novel 13S,14S-

epoxy-maresin is converted by human macrophages to maresin 1 (MaR1), inhibits leukotriene A4 

hydrolase (LTA4H), and shifts macrophage phenotype. FASEB J. 2013; 27: 2573-2583. 

173. Souza PR, Marques RM, Gomez EA, Colas RA, Matteis RD, Zak A, et al. Enriched marine oil 

supplements increase peripheral blood specialized pro-resolving mediators concentrations and reprogram 

host immune responses: A randomized double-blind placebo-controlled study. Circ Res. 2020; 126: 75-

90. 

174. Robert KR, Helen EG. Magnesium deficiency and osteoporosis: animal and human observations. J Nutr 

Biochem. 2004; 15: 710-716. 

175. de Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in man: implications for health and disease. Physiol 

Rev. 2015; 95: 1-46. 

176. Wang Z, Hassan MU, Nadeem F, Wu L, Zhang F, Li X. Magnesium fertilization improves crop yield in 

most production systems: a meta-analysis. Front Plant Sci. 2020; 10: 1727. 

177. Bertinato J, Xiao CW, Ratnayake WM, Fernandez L, Lavergne C, Wood E, et al. Lower serum 

magnesium concentration is associated with diabetes, insulin resistance, and obesity in South Asian and 

white Canadian women but not men. Food Nutr Res. 2015; 59: 25974. 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 291 

European Journal of Biological Research 2020; 10(4): 271-295 

178. Grober U, Schmidt J, Kisters K. Magnesium in prevention and therapy. Nutrients. 2015; 7: 8199-8226.  

179. Al Alawi AM, Majoni SW, Falhammar,H. Magnesium and human health: Perspectives and research 

directions. Int J Endocrinol. 2018; 2018: 9041694. 

180. Rubin H. The logic of the membrane, magnesium, mitosis (MMM) model for the regulation of animal 

cell proliferation. Arch Biochem Biophys. 2007; 458: 16-23. 

181. Wolf FI, Trapani V, Cittadini A. Magnesium and the control of cell proliferation: looking for a needle in 

a haystack. Magnes Res. 2008; 21: 83-91. 

182. Wu N, Veillette A. Immunology: magnesium in a signalling role. Nature. 2011; 475: 462-463.  

183. Brandao K, Deason-Towne F, Perraud AL, Schmitz C. The role of Mg2+ in immune cells. Immunol Res. 

2013; 55: 261-269. 

184. Chaigne-Delalande B, Lenardo MJ. Divalent cation signaling in immune cells. Trends Immunol. 2014; 

35: 332-344. 

185. Yamanaka R, Tabata S, Shindo Y, Hotta K, Suzuki K, Soga T, et al. Mitochondrial Mg2+ homeostasis 

decides cellular energy metabolism and vulnerability to stress. Sci Rep. 2016; 6: 30027. 

186. Henzel JH, DeWeese MS, Ridenhour G. Significance of magnesium and zinc metabolism in the surgical 

patient. Arch Surg. 1967; 95: 974-990. 

187. Durlach J. Recommended dietary amounts of magnesium: Mg RDA. Magnes Res. 1989; 2: 195-203. 

188. Razzaque MS. Magnesium: are we consuming enough? Nutrients. 2018; 10: 1863. 

189. Janett S, Camozzi P, Peeters GG, Lava SA, Simonetti GD, Goeggel Simonetti B, et al. Hypomagnesemia 

induced by long-term treatment with proton-pump inhibitors. Gastroenterol Res Pract. 2015; 2015: 

951768. 

190. William JH, Danziger J. Magnesium deficiency and proton-pump inhibitor use: a clinical review. J Clin 

Pharmacol. 2016; 56: 660-668. 

191. Reddy P, Edwards LR. Magnesium supplementation in vitamin D deficiency. Am J Ther. 2019; 26: e124-

e132. 

192. Chernow B. Hypomagnesemia in intensive care correction of units. Chest 1989; 95: 1362. 

193. Schimatschek HF, Rempis R. Prevalence of hypomagnesemia in an unselected German population of 

16,000 individuals. Magnes Res. 2001; 14; 283-290. 

194. Cheungpasitporn W, Thongprayoon C, Qian Q. Dysmagnesemia in hospitalized patients: prevalence and 

prognostic importance. Mayo Clin Proc. 2015; 90: 1001-1010. 

195. Emelyanov A, Fedoseev G, Barnes PJ. Reduced intracellular magnesium concentration in asthmatic 

patients. Eur Respir J. 1999; 13: 38-40. 

196. Traviesa DC. Magnesium deficiency: a possible cause of thiamine refractoriness in Wernicke-Korsakoff 

encephalopathy. J Neurol Neurosurg Psychiatry. 1974; 37: 959-962. 

197. Osiezagha K, Ali S, Freeman C, Barker NC, Jabeen S, Maitra S, et al. Thiamine deficiency and delirium. 

Innov Clin Neurosci. 2013; 10: 26-32. 

198. Onozuka M, Nosaka K. Steady-state kinetics and mutational studies of recombinant human thiamin 

pyrophosphokinase. J Nutr Sci Vitaminol. 2003; 49: 156-162. 

199. Sevostyanova IA, Yurshev VA, Solovjeva ON, Zabrodskaya SV, Kochetov GA. Effect of bivalent cations 

on the interaction of transketolase with its donor substrate. Proteins. 2008; 71: 541-545. 

200. Peake RW, Godber IM, Maguire D. The effect of magnesium administration on erythrocyte transketolase 

activity in alcoholic patients treated with thiamine. Scott Med J. 2013; 58: 139-142. 

 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 292 

European Journal of Biological Research 2020; 10(4): 271-295 

201. Uwitonze AM, Razzaque MS. Role of magnesium in vitamin D activation and function. J Am Osteopath 

Assoc. 2018; 118: 181-189. 

202. Durlach J, Bac P, Durlach V, Bara M, Guiet-Bara A. Neurotic, neuromuscular and autonomic nervous 

form of magnesium imbalance. Magnes Res. 1997; 10: 169-195. 

203. Cross SN, Nelson RA, Potter JA, Norwitz ER, Abrahams VM. Magnesium sulfate differentially 

modulates fetal membrane inflammation in a time-dependent manner. Am J Reprod Immunol. 2018; 80: 

e12861. 

204. Nolen B, Taylor S, Ghosh G. Regulation of protein kinases; controlling activity through activation 

segment conformation. Mol Cell. 2004; 15: 661-675. 

205. Howe MK, Dowdell K, Roy A, Niemela JE, Wilson W, McElwee JJ, et al. Magnesium restores activity 

to peripheral blood cells in a patient with functionally impaired Interleukin-2-inducible T cell kinase. 

Front Immunol. 2019; 10: 2000. 

206. Gile J, Ruan G, Abeykoon J, McMahon MM, Witzig T. Magnesium: the overlooked electrolyte in blood 

cancers? Blood Rev. 2020; 100676. 

207. Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012; 5: i3-14. 

208. Galland L. Magnesium and immune function: an overview. Magnesium. 1988; 7: 290-299. 

209. Andresen E, Peiter E, Küpper H. Trace metal metabolism in plants. J Exp Bot. 2018; 69: 909-954. 

210. Alejandro S, Höller S, Meier B, Peiter E. Manganese in plants: From acquisition to subcellular 

allocation. Front Plant Sci. 2020; 11: 300. 

211. Bowle C, Slooten, L, Vandenbranden S, De Rycke R, Botterman J, Sybesma C, et al. Manganese 

superoxide dismutase can reduce cellular damage mediated by oxygen radicals in transgenic plants. 

EMBO J. 1991; 10: 1723-1732. 

212. Allen RD. Dissection of oxidative stress tolerance using transgenic plants. Plant Physiol. 1995; 107: 

1049-1054.  

213. Lane BG. Oxalate, germins, and higher-plant pathogens. IUBMB Life. 2002; 53: 67-75. 

214. Watts DL. Nutrient interrelationships minerals - vitamins - endocrines. J Orthomol Med. 1990; 5: 1990. 

215. Deng Q, Liu J, Li Q, Chen K, Liu Z, Shen Y, et al. Interaction of occupational manganese exposure and 

alcohol drinking aggravates the increase of liver enzyme concentrations from a cross-sectional study in 

China Environ Health. 2013; 12: 30. 

216. Aschner JL, Aschner M. Nutritional aspects of manganese homeostasis. Mol Aspects Med. 2005; 26: 

353-362. 

217. Li L, Yang X. The essential element manganese, oxidative stress, and metabolic diseases: links and 

interactions. Oxid Med Cell Longev. 2018; 2018: 7580707. 

218. Baldwin,M, Mergler D, Larribe F, Belanger S, Tardif R, Bilodeau L, et al. Bioindicator and exposure 

data for a population based study of manganese. Neurotoxicology. 1999; 20: 343-353. 

219. Zota AR, Ettinger AS, Bouchard M, Amarasiriwardena CJ, Schwartz J, Hu H, et al. Maternal blood 

manganese levels and infant birth weight. Epidemiology. 2009; 20: 367-373.  

220. Mena K, Horiuchi K, Burke K, Cotzias GC. Chronic manganese poisoning: individual susceptibility and 

absorption of iron. Neurology. 1969; 19: 1000-1006. 

221. Meltzer HM, Brantsaeter AL, Borch-Iohnsen B, Ellingsen DG, Alexander J, Thomassen Y, et al. Low 

iron stores are related to higher blood concentrations of manganese, cobalt and cadmium in non-

smoking, Norwegian women in the HUNT 2 study. Environ Res. 2010; 110: 497-504. 

 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 293 

European Journal of Biological Research 2020; 10(4): 271-295 

222. Lee BK, Kim Y. Effects of menopause on blood manganese levels in women: analysis of 2008-2009 

Korean National Health and Nutrition Examination Survey data. Neurotoxicology. 2012; 33: 401-405. 

223. Martinez-Finley EJ, Gavin CE, Aschner M, Gunter TE. Manganese neurotoxicity and the role of reactive 

oxygen species. Free Radic Biol Med. 2013; 62: 65-75. 

224. Haase H. Innate immune cells speak manganese. Immunity 2018; 48: 616-618. 

225. Claus Henn B, Kim J, Wessling-Resnick M, Téllez-Rojo MM, Jayawardene I, Ettinger AS, et al. 

Associations of iron metabolism genes with blood manganese levels: a population-based study with 

validation data from animal models. Environ Health. 2011; 10: 97.  

226. Grochowski C, Blicharska E, Baj J, Mierzwińska A, Brzozowska K, Forma A, et al. Serum iron, 

magnesium, copper, and manganese levels in alcoholism: a systematic review. Molecules. 2019; 24: 

E1361. 

227. Fernandez-Real JM, Lopez-Bermejo A, Ricart W. Cross-talk between iron metabolism and diabetes. 

Diabetes. 2002; 51: 2348-2354. 

228. Fleming DJ, Jacques PF, Tucker KL, Massaro JM, D’Agostino RB, Wilson PW, et al. Iron status of the 

free-living, elderly Framingham Heart Study cohort: an iron-replete population with a high prevalence of 

elevated iron stores. Am J Clin Nutr. 2001; 73: 638-646.  

229. Fleming DJ, Tucker KL, Jacques PF, Dallal GE, Wilson PW, Wood RJ. Dietary factors associated with 

the risk of high iron stores in the elderly Framingham Heart Study cohort. Am J Clin Nutr. 2002; 76: 

1375-1384.  

230. Bowers K, Yeung E, Williams MA, Qi L, Tobias DK, Hu FB, et al. A prospective study of prepregnancy 

dietary iron intake and risk for gestational diabetes mellitus. Diabetes Care. 2011; 34: 1557-1563.  

231. Qiu C, Zhang C, Gelaye B, Enquobahrie DA, Frederick IO, Williams MA. Gestational diabetes mellitus 

in relation to maternal dietary heme iron and nonheme iron intake. Diabetes Care. 2011; 34: 1564-1569.  

232. Cunningham J, Leffell M, Mearkle P, Harmatz P. Elevated plasma ceruloplasmin in insulin-dependent 

diabetes mellitus: evidence for increased oxidative stress as a variable complication. Metabolism. 1995; 

44: 996-999. 

233. Memişoğullari R, Bakan E. Levels of ceruloplasmin, transferrin, and lipid peroxidation in the serum of 

patients with Type 2 diabetes mellitus. J Diabetes Complic. 2004; 18: 193-197. 

234. Wang C, Guan Y, Lv M, Zhang R, Guo Z, Wei X, et al. Manganese increases the sensitivity of the 

cGAS-STING pathway for Double-Stranded DNA and is required for the host defense against DNA 

viruses. Immunity 2018; 48: 675-687. 

235. Zhang R, Wang C, Guan Y, Wei X, Sha M, Jing M, et al. The Manganese salt (MnJ) functions as a potent 

universal adjuvant. bioRxiv. 2019; doi: 10.1101/783910. 

236. Chen Q, Sun L, Chen ZJ. Regulation and function of the cGAS-STING pathway of cytosolic DNA 

sensing. Nat Immunol. 2016; 17: 1142-1149. 

237. Pirbalouti AG, Bistghani EZ, Malekpoor F. An overview on genus Thymus. J Herb Drugs. 2015; 6: 93-

100. 

238. Cowan MM. Plant products as antimicrobial agents. Clin Microbiol Rev. 1999; 12: 564-582. 

239. Zuzarte M, Gonçalves MJ, Cavaleiro C, Cruz MT, Benzarti A, Marongiu B, et al. Antifungal and anti-

inflammatory potential of Lavandula stoechas and Thymus herba-barona essential oils. Ind Crops Prod. 

2013; 44: 97-103. 

 

 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 294 

European Journal of Biological Research 2020; 10(4): 271-295 

240. Alves-Silva JM, Zuzarte M, Gonçalves J, Cavaleiro C, Cruz MT, Cardoso SM, et al. New claims for 

wild carrot (Daucus carota subsp. carota) essential oil. Evid Based Complem Altern Med. 2016; 2016: 

1-10.  

241. Aksel B. Bioactive compounds in plants-benefits and risks for man and animals. The Norwegian 

Academy of Science and Letters, Oslo 2008: 13-14. 

242. Sharangi AB, Guha S. Wonders of leafy spices: Medicinal properties ensuring human health. Sci Int. 

2013; 2013: 312-317.  

243. Komaki A, Hoseini F, Shahidi S, Baharlouei N. Study of the effect of extract of Thymus vulgaris on 

anxiety in male rats. J Tradit Complem Med. 2016; 6: 257-261. 

244. Ekoh S, Akubugwo E, Chibueze Ude V, Edwin N. Anti-hyperglycemic and anti-hyperlipidemic effect of 

spices (Thymus vulgaris, Murraya koenigii, Ocimum gratissimum and Piper guineense) in alloxan-

induced diabetic rats. Int J Biosci. 2014; 4: 179-187. 

245. Reddy P, Kandisa R, Varsha P, Satyam S. Review on Thymus vulgaris traditional uses and 

pharmacological properties. Med Aromat Plants. 2014; 3: 164. 

246. Stahl-Biskup E, Venskutonis R. 27 - Thyme. In: Peter KV, ed. Handbook of herbs and spices. 2nd edn. 

Woodhead Publishing, Abington, Cambridge, UK, 2012: 499-525. 

247. Jäger S, Trojan H, Kopp T, Laszczyk MN, Scheffler A. Pentacyclic triterpene distribution in various 

plants-rich sources for a new group of multi-potent plant extracts. Molecules. 2009; 14: 2016-2031. 

248. Proestos C, Chorianopoulos N, Nychas GJ, Komaitis M. RP-HPLC analysis of the phenolic compounds 

of plant extracts. investigation of their antioxidant capacity and antimicrobial activity. J Agric Food 

Chem. 2005; 53: 1190-1195. 

249. Kivilompolo M, Hyotylainen T. Comprehensive two-dimensional liquid chromatography in analysis of 

Lamiaceae herbs: characterisation and quantification of antioxidant phenolic acids. J Chromatogr A. 

2007; 1145: 155-164. 

250. Wang M, Li J, Ho G, Peng X, Ho C. Isolation and identification of antioxidative flavonoid glycosides 

from thyme (Thymus vulgaris L.). J Food Lipids. 1998; 5: 313-321. 

251. Vila R. Flavonoids and further polyphenols in the genus Thymus. In: Stahl-Biskup E, Saez F, eds. Thyme 

- The Genus Thymus. Taylor & Francis, London, 2002: 144-176. 

252. Miladi H, Slama R, Mili D, Zouari S, Bakhrouf A, Ammar E. Essential oil of Thymus vulgaris L. and 

Rosmarinus officinalis L.: gas chromatography-mass spectrometry analysis, cytotoxicity and antioxidant 

properties and antibacterial activities against foodborne pathogens. Nat Sci. 2013; 5: 729-739. 

253. Rabiei Z, Mokhtari S, Asgharzade S, Gholami M, Rahnama S, Rafieian-kopaei M. Inhibitory effect of 

Thymus vulgaris extract on memory impairment induced by scopolamine in rat. Asian Pac J Trop 

Biomed. 2015; 5: 845-851. 

254. Zhou E, Fu Y, Wei Z, Yu Y, Zhang X, Yang Z. Thymol attenuates allergic airway inflammation in 

ovalbumin (OVA)-induced mouse asthma. Fitoterapia. 2014; 96: 131-137. 

255. Ocaña A, Reglero G. Effects of thyme extract oils (from Thymus vulgaris, Thymus zygis, and Thymus 

hyemalis) on cytokine production and gene expression of oxLDL-stimulated THP-1-macrophages. J 

Obes. 2012; 2012: 104706. 

256. Vigo E, Cepeda A, Gualillo O, Perez-Fernandez R. In-vitro anti-inflammatory effect of Eucalyptus 

globulus and Thymus vulgaris: nitric oxide inhibition in J774A.1 murine macrophages. J Pharm 

Pharmacol. 2004; 56: 257-263. 

 



Hamada   Vitamins, omega-3, magnesium, manganese, and thyme against COVID-19 295 

European Journal of Biological Research 2020; 10(4): 271-295 

257. Lambert RJW, Skandamis PN, Coote PJ, Nychas GJ. A study of the minimum inhibitory concentration 

and mode of action of oregano essential oil, thymol and carvacrol. J Appl Microbiol. 2001; 91: 453-462. 

258. Pina-Vaz C, Goncalves-Rodrigues A, Pinto E, Costa-de-Oliveira S, Tavares C, Salgueiro L, et al. 

Antifungal activity of thymus oils and their major components. J Eur Acad Dermatol Venereol. 2004; 18: 

73-78. 

259. Soliman KM, Badeaa RI. Effect of oil extracted from some medicinal plants of different mycotoxigenic 

fungi. Food Chem Toxicol. 2002; 40: 1669-1675. 

260. El-Nekeety AA, Mohamed SR, Hathout AS, Hassan NS, Aly SE, Abdel-Wahhab MA. Antioxidant 

properties of Thymus vulgaris oil against aflatoxin-induce oxidative stress in male rats. Toxicon. 2011; 

57: 984-991. 

261. ESCOP. Thymi Herba/Thyme. ESCOP monographs. Georg Thieme Verlag, 2003. 

262. Blaschek W, Ebel S, Hackenthal E, Holzgrabe U, Keller K, Reichling J, Schulz V, eds. Hagers 

Enzyklopädie der Arzneistoffe und Drogen, 14, Rut-Suf, 6. Auflage, Wissenschaftliche 

Verlagsgesellschaft mbH Stuttgart, 2007. 

263. Peltola V, Waris M, Osterback R, Susi T, Hyypia T, Ruuskanen O. Clinical effects of rhinovirus 

infections. J Clin Virol. 2008; 43: 411-414. 

264. Winther B. Rhinovirus infections in the upper airway. Proc Am Thorac Soc. 2011; 8: 79-89. 

265. Rezatofighi SE, Seydabadi A, Seyyed Nejad SM. Evaluating the efficacy of Achillea millefolium and 

Thymus vulgaris extracts against Newcastle Disease Virus in ovo. Jundishapur J Microbiol. 2014; 7: 

e9016. 

266. Nolkemper S, Reichling J, Stintzing FC, Carle R, Schnitzler P. Antiviral effect of aqueous extracts from 

species of the Lamiaceae family against herpes simplex virus type 1 and type 2 in vitro. Planta Med. 

2006; 72: 1378-1382. 

267. Lenz E, Müller C, Mostafa A, Dzieciolowski J, Kanrai P, Dam S, et al. Authorised medicinal product 

Aspecton ® Oral Drops containing thyme extract KMTv24497 shows antiviral activity against viruses 

which cause respiratory infections. J Herb Med. 2018; 13: 26-33. 

268. Aktories K, Förstermann U, Hofmann FB, Starke K. Allgemeine und Spezielle Pharmakologie und 

Toxikologie: Urban & Fischer in Elsevier, 2005.