All Title Author
Keywords Abstract

Publish in OALib Journal
ISSN: 2333-9721
APC: Only $99


Ca:Mg D, the Shield that Interdicts the Crown Viruses and Vaccines

DOI: 10.4236/oalib.1109249, PP. 1-24

Subject Areas: Pathology

Keywords: Magnesium, Parathormone, NHANES, Kallikrein-Kinin, Glutathione

Full-Text   Cite this paper   Add to My Lib


The calcium to magnesium ratio plus adequate vitamin D greatly determine success or not in the immune battle against pathogens and cancer, not to mention cardiovascular disease. Ionized calcium and magnesium in normal, healthy individuals can be calculated and a ratio determined from serum levels. Using widely accepted laboratory reference range values and NHANES data, the recommended daily allowances from the Institute of Medicine of the National Academy of Sciences for calcium, magnesium, and D3 (cholecalciferol) are objectively refuted mathematically and physiologically. Midrange values for both cations, despite RDA sufficiency, are shown to be unattainable without secondary hyperparathyroidism (high parathormone (PTH), low D) or hypoparathyroidism (low PTH, high iCa:iMg) at the officially designated level of 25(OH)D sufficiency (30 ng/mL). Calcium and magnesium utilize the same calcium sensing receptor (CaSR) not only on cell membranes but also on organelle membranes. Intramitochondrial hydroxylation of chole-calciferol can become compromised. An imbalanced intake of calcium and magnesium can impact the efficacy of vitamin D supplementation. Several pertinent articles underscoring these conclusions are analyzed in detail. The impact of an imbalanced Ca:Mg ratio on Covid-19, Long Covid and vaccination is also discussed.

Cite this paper

Chambers, P. (2022). Ca:Mg D, the Shield that Interdicts the Crown Viruses and Vaccines. Open Access Library Journal, 9, e9249. doi:


[1]  Workinger, J.L., Doyle, R.P. and Bortz, J. (2018) Challenges in the Diagnosis of Magnesium Status. Nutrients, 10, Article 1202.
[2]  Wacker, M. and Holick, M.F. (2018) Vitamin D—Effects on Skeletal and Extraskeletal Health and the Need for Supplementation. Nutrients, 5, 111-148.
[3]  Zhao, J., Giri, A., Zhu, X., et al. (2019) Calcium: Magnesium Intake Ratio and Colorectal Carcinogenesis, Results from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. British Journal of Cancer, 121, 796-804.
[4]  Dai, Q., Sandler, R., Barry, E., Summers, R., Grau, M. and Baron, J. (2012) Calcium, Magnesium, and Colorectal Cancer. Epidemiology, 23, 504-505.
[5]  Costello, R., Rosanoff, A., Dai, Q, Saldanha, L.G. and Potischman, N.A. (2021) Perspective: Characterization of Dietary Supplements Containing Calcium and Magnesium and Their Respective Ratio—Is a Rising Ratio a Cause for Concern? Advances in Nutrition, 12, 291-297.
[6]  Dai, Q., Motley, S.S., Smith Jr., J.A., Concepcion, R., Barocas, D., Byerly, S. and Fowke, J.H. (2011) Blood Magnesium, and the Interaction with Calcium, on the Risk of High-Grade Prostate Cancer. PLOS ONE, 6, e18237.
[7]  Zhu, X., Borenstein, A.R, Zheng, Y., Zhang, W., Seidner, D.L., Ness, R., et al. (2020) Ca:Mg Ratio, APOE Cytosine Modifications, and Cognitive Function: Results from a Randomized Trial. Journal of Alzheimer’s Disease, 75, 85-98.
[8]  Tulloch, J., Leong, L., Chen, S., Keene, C.D., Millard, S., Shutes-David, A., et al. (2018) APOE DNA Methylation Is Altered in Lewy Body Dementia. Alzheimer’s and Dementia, 14, 889-894.
[9]  Gröber, U., Schmidt, J. and Kisters, K. (2015) Magnesium in Prevention and Therapy. Nutrients, 7, 8199-8226.
[10]  Rooney, M.R., Rudser, K.D., Alonso, A., Harnack, L., Saenger, A.K. and Lutsey, P.L. (2020) Circulating Ionized Magnesium: Comparisons with Circulating Total Magnesium and the Response to Magnesium Supplementation in a Randomized Controlled Trial. Nutrients, 12, Article 263.
[11]  Mathew, A.A. and Panonnummal, R. (2021) ‘Magnesium’—The Master Cation—As a Drug—Possibilities and Evidence. Biometals, 34, 955-986.
[12]  Altura, B.T., Shirey, T.L., Young, C.C., et al. (1994) Characterization of a New Ion Selective Electrode for Ionized Magnesium in Whole Blood, Plasma, Serum, and Aqueous Samples. Scandinavian Journal of Clinical and Laboratory Investigation, 54, 21-36.
[13]  Micke, O., Vormann, J., Kraus, A. and Kisters, K. (2021) Serum Magnesium: Time for a Standardized and Evidence-Based Reference Range. Magnetic Resonance, 34, 84-89.
[14]  Rosanoff, A., West, C., Elin, R.J., et al. (2022) Recommendation on an Updated Standardization of Serum Magnesium Reference Ranges. European Journal Nutrition, 61, 3697-3706.
[15]  Rosanoff, A., Weaver, C.M. and Rude, R.K. (2012) Suboptimal Magnesium Status in the United States: Are the Health Consequences Underestimated? Nutrition Reviews, 70, 153-164.
[16]  Costello, R.B., Elin, R.J., Rosanoff, A., Wallace, T.C., Guerrero-Romero, F., Hruby, A., et al. (2016) Perspective: The Case for an Evidence-Based Reference Interval for Serum Magnesium: The Time Has Come. Advances in Nutrition, 7, 977-993.
[17]  Liebscher, D.H. and Liebscher, D.E. (2004) About the Misdiagnosis of Magnesium Deficiency. Journal of the American College of Nutrition, 23, 730S-731S.
[18]  Facchinetti, F., Borella, P., Fioroni, L., Pironti, T. and Genazzani, A.R. (1990) Reduction of Monocyte Magnesium in Patients Affected by Premenstrual Syndrome. Journal of Psychosomatic Obstetrics & Gynecology, 11, 221-229.
[19]  Thomas, J., Millot, J.M., Sebille, S., Delabroise, A.M., Thomas, E. and Manfait, M. (2000) Free and Total Magnesium in Lymphocytes of Migraine Patients—Effect of Magnesium-Rich Mineral Water Intake. Clinica Chimica Acta, 295, 63-75.
[20]  Razzaque, M.S. (2018) Magnesium: Are We Consuming Enough? Nutrients, 10, Article 1863.
[21]  Mulquiney, Peter J., and Kuchel, Philip W. (1997) Free Magnesium-Ion Concentration in Erythrocytes by 31P NMR: The Effect of Metabolite: Hemoglobin Interactions. NMR in Biomedicine, 10, 129-137.
[22]  Xiong, W., Liang, Y., Li, X., et al. (2016) Erythrocyte Intracellular Mg2 Concentration as an Index of recognition and Memory. Scientific Reports, 6, Article No. 26975.
[23]  Ulger, Z., Ariogul, S., Cankurtaran, M., et al. (2020) Intra-Erythrocyte Magnesium levels and Their Clinical Implications in Geriatric Outpatients. Journal of Nutrition, Health and Aging, 14, 810-814.
[24]  Mansmann, H.C. (1993) Consider Magnesium Homeostasis: II: Staging of Magnesium Deficiencies. Pediatric Allergy, Immunology and Pulmonology, 7, 211-215.
[25]  Kisters, K., Niedner, W., Fafera, I., and Zidek, W. (1990) Plasma and Intracellular Mg2 Concentrations in Pre-Eclampsia. Journal of Hypertension, 8, 303-306.
[26]  Sales, C.H., Nascimento, D.A., Medeiros, A.C.Q., Lima, K.C., and Pedrosa, L.F.C. (2014) There Is Chronic Latent Magnesium Deficiency in Apparently Healthy University Students. Nutricion Hospitalaria, 30, 200-204.
[27]  Cheung, M.M., DeLuccia, R., Ramadoss, R.K., Aljahdali, A., Volpe, S.L., Shewokis, P.A. and Sukumar, D. (2019) Low Dietary Magnesium Intake Alters Vitamin D— Parathyroid Hormone Relationship in Adults Who Are Overweight or Obese. Nutrition Research, 69, 82-93.
[28]  Veugelers, P.J. and Ekwaru, J.P. (2014) A Statistical Error in the Estimation of the Recommended Dietary Allowance for Vitamin D. Nutrients, 6, 4472-4475.
[29]  Reddy, P. and Edwards, L.R. (2019) Magnesium Supplementation in Vitamin D Deficiency. American Journal of Therapeutics, 26, e124-e132.
[30]  Ginde, A.A., Wolfe, P., Camargo, C.A., et al. (2012) Defining Vitamin D Status by Secondary Hyperparathyroidism in the U.S. Population. Journal of Endocrinological Investigation, 35, 42-48.
[31]  Dai, Q., Zhu, X., Manson, J.E., Song, Y., Li, X., Franke, A., et al. (2018) Magnesium Status and Supplementation Influence Vitamin D Status and Metabolism: Results from a Randomized Trial. The American Journal of Clinical Nutrition, 108, 1249-1258.
[32]  Kimball, S.M., Burton, J.M., O’Connor, P.G., and Vieth, R. (2011) Urinary Calcium Response to High Dose Vitamin D3 with Calcium Supplementation in Patients with Multiple Sclerosis. Clinical Biochemistry, 44, 930-932.
[33]  Dai, Q., Shu, X.O., Deng, X., Xiang, Y.B., Li, H., Yang, G., et al. (2013) Modifying Effect of Calcium/Magnesium Intake Ratio and Mortality: A Population-Based Cohort Study. BMJ Open, 3, e002111.
[34]  Huang, F., Wang, Z., Zhang, J., Du, W., Su, C. and Jiang, H. (2018) Dietary Calcium intake and Food Sources among Chinese Adults in CNTCS. PLOS ONE, 13, e0205045.
[35]  Wark, P.A., Lau, R., Norat, T. and Kampman, E. (2012) Magnesium Intake and Colorectal Tumor Risk: A Case-Control Study and Meta-Analysis. The American Journal of Clinical Nutrition, 96, 622-631.
[36]  Connor, T. (2020) The Importance of the Calcium-to-Magnesium Ratio.
[37]  Martineau, A.R., Jolliffe, D.A., Hoope, R.L., Greenberg, L., Aloia, J.F. and Bergman, P. (2017) Vitamin D Supplementation to Prevent Acute Respiratory Tract Infections: Systematic Review and Meta-Analysis of Individual Participant Data. BMJ, 356, i6583.
[38]  CDC. Centers for Disease Control and Prevention. Influenza (Flu).
[39]  Matsuoka, H. (2005) Aldosterone and Magnesium. Clinical Calcium, 15, 187-191.
[40]  Pickering, G., Mazur, A., Trousselard, M., Bienkowski, P., Yaltsewa, N., Amessou, M., et al. (2020) Magnesium Status and Stress: The Vicious Circle Concept Revisited. Nutrients, 12, Article 3672.
[41]  Kelly, O.J., Gilman, J.C. and Ilich, J.Z. (2018) Utilizing Dietary Micronutrient Ratios in Nutritional Research May Be More Informative than Focusing on Single Nutrients. Nutrients, 10, Article 107.
[42]  DiNicolantonio, J.J. and O’Keefe, J.H. (2021) Magnesium and Vitamin D Deficiency as a Potential Cause of Immune Dysfunction, Cytokine Storm and Disseminated Intravascular Coagulation in Covid-19 Patients. Missouri Medicine, 118, 68-73.
[43]  Bird, L. (2022) Magnesium: Essential for T Cells. Nature Reviews Immunology, 22, 144-145.
[44]  Vardhana, S. and Dustin, M.L. (2022) Magnesium for T Cells: Strong to the Finish! Trends in Immunology, 43, 277-279.
[45]  Polonikov, A. (2020) Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients. ACS Infectious Diseases, 6, 1558-1562.
[46]  Shchetinin, E., Baturin, V., Arushanyan, E., Bolatchiev, A. and Bobryshev, D. (2022) Potential and Possible Therapeutic Effects of Melatonin on SARS-CoV-2 Infection. Antioxidants, 11, Article 140.
[47]  Shi, Z., and Puyo, C.A. (2020) N-Acetylcysteine to Combat COVID-19: An Evidence Review. Therapeutics and Clinical Risk Management, 16, 1047-1055.
[48]  Schwalfenberg, G.K. (2021) N-Acetylcysteine: A Review of Clinical Usefulness (An Old Drug with New Tricks). Journal of Nutrition and Metabolism, 2021, Article ID: 9949453.
[49]  Twelve Steps to Optimize Your Methylation Process.
[50]  Liu, R.M., Liu, Y., Forman, H.J., Olman, M. and Tarpey, M.M. (2004) Glutathione Regulates Transforming Growth Factor-β-Stimulated Collagen Production in Fibroblasts. American Journal of Physiology-Lung Cellular and Molecular Physiology, 286, L121-L128.
[51]  Deumer, U.-S., Varesi, A., Floris, V., Savioli, G., Mantovani, E., López-Carrasco, P., et al. (2021) Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): An Overview. Journal of Clinical Medicine, 10, Article 4786.
[52]  Björkand, S., Ernberg, M. and Bileviciute-Ljungard, I. (2022) Reduced Immune System Responsiveness in Fibromyalgia—A Pilot Study. Clinical Immunology Communications, 2, 46-53.
[53]  Morrison, T.E., Mauser, A., et al. (2001) Inhibition of IFN-γ Signaling by an Epstein-Barr Virus Immediate-Early Protein. Immunity, 15, 787-799.
[54]  Sinclair, E., Black, D., Epling, C.L., Carvidi, A., Josefowicz, F.Z., Bredt, B.M., et al. (2004) CMV Antigen-Specific CD4 and CD8 T Cell IFNγ Expression and Proliferation Responses in Healthy CMV-Seropositive Individuals. Viral Immunology, 17, 445-454.
[55]  Crook, H., Raza, S., Nowell, J., Young, M. and Edison, P. (2021) Long Covid-Mechanisms, Risk Factors, and Management. BMJ, 374, n1648.
[56]  Ghorbani, Z., Rafiee, P., Haghighi, S., et al. (2021) The Effects of Vitamin D3 Supplementation on TGF-β and IL-17 Serum Levels in Migraineurs: Post Hoc Analysis of a Randomized Clinical Trial. Journal of Pharmaceutical Health Care and Sciences, 7, Article No. 9.
[57]  Yasuda, K., Takeuchi, Y. and Hirota, K. (2019) The Pathogenicity of Th17 Cells in Autoimmune Diseases. Semin Immunopathol, 41, 283-297.
[58]  Dankers, W., Colin, E.M., van Hamburg, J.P. and Lubberts, E. (2017) Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential. Frontiers in Immunology, 7, Article 697.
[59]  Wang, K., Chen, W., Zhang, Z., et al. (2020) CD147-Spike Protein Is a Novel Route for SARS-CoV-2 Infection to Host Cells. Signal Transduction and Targeted Therapy, 5, Article 283.
[60]  Chambers, P.W. (2021) Basigin Binds Spike S on SARS-CoV2. Open Access Library Journal, 8, e8064.
[61]  Bivona, G., Agnello, L. and Ciaccio, M. (2018) The Immunological Implication of the New Vitamin D Metabolism. Central-European Journal of Immunology, 43, 331-334.
[62]  Watanabe, M., Nakamura, K., Kato, M., Okada, T., and Iesaki, T. (2021) Chronic Magnesium Deficiency Causes Reversible Mitochondrial Permeability Transition Pore Opening and Impairs Hypoxia Tolerance in the Rat Heart. Journal of Pharmacological Sciences, 148, 238-247.
[63]  Fan, L., Zhu, X., Zheng, Y., Zhang, W., et al. (2021) Magnesium Treatment on Methylation Changes of Transmembrane Serine Protease 2 (TMPRSS2). Nutrition, 89, Article ID: 111340.
[64]  Tian, J., Tang, L., Liu, X., Li, Y., Chen, J., Huang, W. and Liu, M. (2022) Populations in Low-Magnesium Areas Were Associated with Higher Risk of Infection in COVID-19’s Early Transmission: A Nationwide Retrospective Cohort Study in the United States. Nutrients, 14, Article 909.
[65]  Wang, E., Chen, H., Sun, B., Wang, H., Qu, H.Q., Liu, Y., et al. (2021) TGF Beta Levels Correlate with Covid-19 Severity. FEBS Letters, 595, 2844-2844.
[66]  Sun, J. and Lanier, L. (2011) NK Cell Development, Homeostasis and Function: Parallels with CD8 T Cells. Nature Reviews Immunology, 11, 645-657.
[67]  Ferreira-Gomes, M., Kruglov, A., Durek, P., et al. (2021) SARS-CoV-2 in Severe COVID-19 Induces a TGF-β-Dominated Chronic Immune Response that Does Not Target Itself. Nature Communications, 12, Article 1961.
[68]  Witkowski, M., Tizian, C., Ferreira-Gomes, M., et al. (2021) Untimely TGFβ Responses in COVID-19 Limit Antiviral Functions of NK Cells. Nature, 600, 295-301.
[69]  Bi, J. (2022) NK Cell Dysfunction in Patients with COVID-19. Cellular and Molecular Immunology, 19, 127-129.
[70]  Jiang, F., Yang, Y., Xue, L., Li, B. and Zhang, Z. (2017) 1α,25-Dihydroxyvitamin D3 Attenuates TGF-β-Induced Pro-Fibrotic Effects in Human Lung Epithelial Cells through Inhibition of Epithelial-Mesenchymal Transition. Nutrients, 9, Article 980.
[71]  Fischer, K.D. and Agrawal, D.K. (2014) Vitamin D Regulating TGF-β Induced Epithelial-Mesenchymal Transition. Respiratory Research, 15, Article 146.
[72]  Isik, S., Ozuguz, U., Tutuncu, Y.A., Akbaba, G., Helvaci, N., Guler, S., et al (2011) Serum Transforming Growth Factor-Beta Levels in Patients with Vitamin D Deficiency. European Journal of Internal Medicine, 23, 93-97.
[73]  Yadav, H., Quijano, C., Kamaraju, A.K., Gavrilova, O., Malek, R., Chen, W., et al. (2011) Vitamin D Supplementation Decreases TGF-β1 Bioavailability. Protection from Obesity and Diabetes by Blockade of TGF-β/Smad3 Signaling. Cell Metabolism, 14, 67-79.
[74]  Yong-Chao, Q., Chen, Y.-L., Pan, Y.-H., Ling, W., Tian, F., Zhang, X.X., et al. (2017) Changes of Transforming Growth Factor Beta 1 in Patients with Type 2 Diabetes and Diabetic Nephropathy: A PRISMA-Compliant Systematic Review and Meta-Analysis. Medicine, 96, e6583.
[75]  Mahmudpour, M., Roozbeh, J., Keshavarz, M., Farrokhi, S. and Nabipour, I. (2020) Angiotensin II Stimulates Canonical TGF-β Signaling Pathway through Angiotensin Type 1 Receptor to Induce Granulation Tissue Contraction. Journal of Molecular Medicine, 93, 289-302.
[76]  Mahmudpour, M., Roozbeh, J., Keshavarz, M., Farrokhi, S.and Nabipour, I. (2020) COVID-19 Cytokine Storm: The Anger of Inflammation. Cytokine, 133, Article ID: 155151.
[77]  Elkahloun, A.G. and Saavedra, J.M. (2020) Candesartan Could Ameliorate the COVID-19 Cytokine Storm. Biomedicine & Pharmacotherapy, 131, Article ID: 110653.
[78]  Sugimoto, J., Romani, A.M., Valentin-Torres, A.M., Luciano, A.A., Ramirez Kitchen, C.M. and Funderburg, N. (2012) Magnesium Decreases Inflammatory Cytokine Production: A Novel Innate Immunomodulatory Mechanism. The Journal of Immunology, 188, 6338-6346.
[79]  Barros-Martins, J., Förster, R. and Bosnjak, B. (2022) NK Cell Dysfunction in Severe COVID-19: TGF-β-Induced Downregulation of Integrin Beta-2 Restricts NK Cell Cytotoxicity. Signal Transduction and Targeted Therapy, 7, Article 32.
[80]  Chambers, P.W. (2022) Long Covid, Short Magnesium. Open Access Library Journal, 9, e8736.
[81]  Lin, J.T., Martin, S.L., Xia, L. and Gorham, J.D. (2005) TGF-β1 Uses Distinct Mechanisms to Inhibit IFN-γ Expression in CD4 T Cells at Priming and at Recall: Differential Involvement of Stat4 and T-bet. The Journal of Immunology, 174, 5950-5958.
[82]  Raga, D., Soliman, D., Samaha, D. and Yassin, A. (2016) Vitamin D Status and Its Modulatory Effect on Interferon Gamma and Interleukin-10 Production by Peripheral Blood Mononuclear Cells in Culture. Cytokine, 85, 5-10.
[83]  Dhanda, A.D., Felmlee, D., Boeira, P., Moodley, P., Tan, H., et al. (2022) Patients with Moderate to Severe COVID-19 Have an Impaired Cytokine Response with an Exhausted and Senescent Immune Phenotype. Immunobiology, 227, Article 152185.
[84]  Nabi-Afjadi, M., Karami, H., Goudarzi, K., et al. (2021) The Effect of Vitamin D, Magnesium and Zinc Supplements on Interferon Signaling Pathways and Their Relationship to Control SARS-CoV-2 Infection. Clinical and Molecular Allergy, 19, Article 21.
[85]  Meng, X., Nikolic-Paterson, D. and Lan, H. (2016) TGF-β: The Master Regulator of Fibrosis. Nature Reviews Nephrology, 12, 325-338.
[86]  Frangogiannis, N.G. (2020) Transforming Growth Factor-β in Tissue Fibrosis. Journal of Experimental Medicine, 217, e20190103.
[87]  Woo, J., Koziol-White, C., Panettieri Jr., R. and Judea, J. (2021) TGF-β: The Missing Link in Obesity-Associated Airway Diseases? Current Research in Pharmacology and Drug Discovery, 2, Article 100016.
[88]  Colarusso, C., Maglio, A., Terlizzi, M., Vitale, C., Molino, A., Pinto, A., et al. (2021) Post-COVID-19 Patients Who Develop Lung Fibrotic-Like Changes Have Lower Circulating Levels of IFN-β but Higher Levels of IL-1α and TGF-β. Biomedicines, 9, Article 1931.
[89]  Sutariya, B., Jhonsa, D. and Saraf, M.N. (2016) TGF-β: The Connecting Link between Nephropathy and Fibrosis. Immunopharmacology and Immunotoxicology, 38, 39-49.
[90]  Katwa, L.C., Mendoza, C. and Clements, M. (2022) CVD and COVID-19: Emerging Roles of Cardiac Fibroblasts and Myofibroblasts. Cells, 11, Article 1316.
[91]  Beilfuss, A., Sowa, J., Sydor, S., et al. (2015) Vitamin D Counteracts Fibrogenic TGF-β Signalling in Human Hepatic Stellate Cells both Receptor-Dependently and Independently. Gut, 64, 791-799.
[92]  Li, X.H., Huang, X.P., Pan, L., et al. (2026) Vitamin D Deficiency May Predict a Poorer Outcome of IgA Nephropathy. BMC Nephrology, 17, Article No. 164.
[93]  Luo, X., Deng, Q., Xue, Y., Zhang, T., Wu, Z., Peng, H., et al. (2021) Anti-Fibrosis Effects of Magnesium Lithospermate B in Experimental Pulmonary Fibrosis: By Inhibiting TGF-βRI/Smad Signaling. Molecules, 26, Article 1715.
[94]  Tee, J.K., Peng, F., Tan, Y.L., Yu, B. and Ho, H.K. (2018) Magnesium Isoglycyrrhizinate Ameliorates Fibrosis and Disrupts TGF-β-Mediated SMAD Pathway in Activated Hepatic Stellate Cell Line LX2. Frontiers in Pharmacology, 9, Article 1018.
[95]  Wensveen, F.N., Jelencic, V. and Polic, B. (2018) NKG2D: A Master Regulator of Immune Cell Responsiveness. Frontiers in Immunology, 9, Article 441.
[96]  Iotti, S., Wolf, F., Mazur, A. and Maier, J.A. (2020) The COVID-19 Pandemic: Is There a Role for Magnesium? Hypotheses and Perspectives. Magnesium Research, 33, 1-7.
[97]  Lanier, L.L. (2015) NKG2D Receptor and Its Ligands in Host Defense. Cancer Immunology Research, 3, 75-582.
[98]  Lazarova, M. and Steinle, A. (2019) Impairment of NKG2D-Mediated Tumor Immunity by TGF-β. Frontiers in Immunology, 10, Article 2689.
[99]  Zhang, H.-Y., Liu, Z.-D., Hu, C.-J., Wang, D.-X., Zhang, Y.-B. and Li, Y.-Z. (2011) Up-Regulation of TGF-β1 mRNA Expression in Peripheral Blood Mononuclear Cells of Patients with Chronic Fatigue Syndrome. Journal of the Formosan Medical Association, 110, 701-704.
[100]  Iempridee, T., Das, S., Xu, I. and Mertz, J.E. (2011) Transforming Growth Factor β-Induced Reactivation of Epstein-Barr Virus Involves Multiple Smad-Binding Elements Cooperatively Activating Expression of the Latent-Lytic Switch BZLF1 Gene. American Society for Microbiology Journal of Virology, 85, 7836-7848.
[101]  Xu, J., Ahmad, J., Jones, J.F., Dolcetti, R., Vaccher. E., et al. (2000) Elevated Serum Transforming Growth Factor β1 Levels in Epstein-Barr Virus-Associated Diseases and Their Correlation with Virus-Specific Immunoglobulin A (IgA) and IgM. American Society for Microbiology Journal of Virology, 74, 2443-2446.
[102]  Chaigne-Delalande, B., Li, F.-Y., O’Connor, G.M., et al. (2013) Mg2 Regulates Cytotoxic Functions of NK and CD8 T Cells in Chronic EBV Infection through NKG2D. Science, 341, 186-191.
[103]  Mirzaei, H. and Faghihloo, E. (2018) Viruses as Key Modulators of the TGF-β Pathway; A Double-Edged Sword Involved in Cancer. Reviews in Medical Virology, 28, e1967.
[104]  Chung, J.Y.F., Chan, M.K.K., Li, J.S.-F., Chan, A.S.-W., Tang, P.C.-T., Leung, K.-T., et al. (2021) TGF-β Signaling: From Tissue Fibrosis to Tumor Microenvironment. International Journal of Molecular Sciences, 22, Article 7575.
[105]  Theoharides, T., Stewart, J.M., Hatziagelaki, E. and Kolaitis, G. (2015) Brain “Fog,” Inflammation and Obesity: Key Aspects of Neuropsychiatric Disorders Improved by Luteolin. Frontiers in Neuroscience, 9, Article 225.
[106]  Weinstock, L.B., Brook, J.B., Walters, A.S., Gorisd, A., Afrine, L.B. and Molderings, G.J. (2021) Mast Cell Activation Syndrome (MCAS) Symptoms Are Prevalent in Long-COVID. International Journal of Infectious Diseases, 112, 217-226.
[107]  Nishio, A., Ishiguro, S. and Miyao, N. (1987) Specific Change of Histamine Metabolism in Acute Magnesium-Deficient Young Rats. Drug-Nutrient Interactions, 5, 89-96.
[108]  Takemoto, S., Yamamoto, A., Tomonaga, S., Funaba, M. and Matsui, T. (2013) Magnesium Deficiency Induces the Emergence of Mast Cells in the Liver of Rats. Journal of Nutritional Science and Vitaminology, 59, 560-563.
[109]  Kaieda, S., Fujimoto, K., Todoroki, K., Abe, Y., Kusukawa, J., Hoshino, T., et al. (2022) Mast Cells Can Produce Transforming Growth Factor Β1 and Promote Tissue Fibrosis during the Development of Sjögren’s Syndrome-Related Sialadenitis. Modern Rheumatology, 32, 761-769.
[110]  Pinto, M.D., Lambert, N., Downs, C.A., Abrahim, H., Hughes, T.D. and Rahmani, A.M. (2022) Antihistamines for Post Acute Sequelae of SARS-CoV-2 Infection. The Journal for Nurse Practitioners, 18, 335-338.
[111]  Johansson, M., Ståhlberg, M., Runold, M., et al. (2021) Long-Haul Post-COVID-19 Symptoms Presenting as a Variant of Postural Orthostatic Tachycardia Syndrome: The Swedish Experience. JACC: Case Reports, 3, 573-580.
[112]  Stewart, J.M., Taneja, I., Glover, J. and Medow, M.S. (2008) Angiotensin II type 1 Receptor Blockade Corrects Cutaneous Nitric Oxide Deficit in Postural Tachycardia Syndrome. American Journal of Physiology-Heart and Circulatory Physiology, 294, H466-H473.
[113]  Wadhwania, R. (2017) Is Vitamin D Deficiency Implicated in Autonomic Dysfunction? Journal of Pediatric Neurosciences, 12, 119-123.
[114]  Hoffman, B. (2021) Hoffman Centre for Integrative and Functional Medicine.
[115]  Shi, Y., Liu, T., Yao, L., et al. (2017) Chronic Vitamin D Deficiency Induces Lung Fibrosis through Activation of the Renin-Angiotensin System. Scientific Reports, 7, Article No. 3312.
[116]  Lanz, T.V., Ding, Z., Ho, P.P., Luo, J., Agrawal, A.N., Srinagesh, H., et al. (2010) Angiotensin II Sustains Brain Inflammation in Mice via TGF-β. The Journal of Clinical Investigation, 120, 2782-2794.
[117]  Krishna, A.R. (2020) Can You Overdose on One-Size-Fits-All Multivitamins?
[118]  Rosanoff, A., Dai, Q. and Shapses, S.A. (2016) Essential Nutrient Interactions: Does Low or Suboptimal Magnesium Status Interact with Vitamin D and/or Calcium Status? Advances in Nutrition, 7, 25-43.


comments powered by Disqus

Contact Us