Anti-oxidants and Long-Covid (Mg, Glutamate, Butyrate, etc) – Sept 2022

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Anti-oxidants and Long Covid – Sept 2022

Patrick Chambers, MD preprint
Department of Pathology, Torrance Memorial Medical Center, Torrance, California Email: pwc at gte.net
Open Access Library Journal, 9: ****. https://dx.doi.org/10.4236/***.2022.*****

Long Covid has many symptoms that overlap with

• ME (myalgic encephalomyelitis)/CFS (chronic fatigue syndrome),
• FM (fibromyalgia),
• EBV (Epstein-Barr virus),
• CMV (cytomegalovirus),
• CIRS (chronic inflammatory response syndrome),
• MCAS(mast cell activation syndrome),
• POTS(postural orthostatic tachycardia syndrome), and
• post viral fatigue syndrome.

They all portend a “long haul” with an antioxidant shortfall and elevated Ca:Mg. Oxidative stress is the root cause. Linkage between TGF (transforming growth factor)-, IFN(interferon)-y, the RAS(renin angiotensin system), and the KKS(kallikrein kinin system) is discussed. Technical explanations for the renin aldosterone paradox in POTS, the betrayal of TGF- β, and the commonality of markers for the Warburg effect are offered. The etiology of the common Long Covid symptoms of post exertional malaise, fatigue, and brain fog as well as anosmia, hair loss, and GI symptoms is technically discussed. Ca:Mg is critical to the glutamate/GABA(gamma amino butyric acid) balance. The role of GABA and butyrates from the “good” intestinal bacteria in the gut brain axis and its correlation with chronic fatigue diseases are explored. The crosstalk between the ENS(enteric nervous system) and the ANS(autonomic nervous system) and the role of the vagus in both are emphasized. HRV(heart rate variability), the fifth vital sign, points to an expanded gut-brain-heart/lung axis. A suggested approach to all of these - Long Covid, chronic fatigue diseases, post viral fatigue syndrome, and general health - is presented.

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Conclusion

Long Covid and ME/CFS, FM, EBV, CMV, POTS, MCAS, CIRS, and post viral fatigue syndrome are linked by antioxidant deficiency, elevated TGF-β, and the Warburg effect. “Friendly” butyrate producing intestinal bacteria are in short supply. Butyrates rectify the glutamate-GABA imbalance. These two neurotransmitters determine autonomic tone via the vagus nerve, which reflects general health through the fifth vital sign, HRV. Perhaps the gut-brain axis should be expanded to include two other vital organs under vagal control - the gut-brain-heart/lung axis.
The slowly increasing Ca:Mg in the Western diet incriminates Magnesium deficiency as a central player in the pathogenesis of most chronic fatigue diseases. With age there is a steady progression from parasympathetic to sympathetic tone, from GABAergic to glutamatergic predominance, and from a balanced Ca:Mg to a calcium predominant one, at least on a Western diet.
Improving Ca:Mg starts with knowing what it is. A comprehensive chem panel including serum calcium and Magnesium in an otherwise healthy individual without renal disease or medication should provide this information (104). Addressing excess dietary calcium (Ca:Mg>2.6) first and then increasing Magnesium intake might minimize any laxative effect. But for some, changing religion is easier than adjusting diet.

References (some of them)

1. The Warburg effect then and now: From cancer to inflammatory diseases https://doi.org/10.1002/bies.201300084
2. Lactate Metabolism and Signaling in Tuberculosis and Cancer: A Comparative Review (2021) https://doi.org/10.3389/fcimb.2021.624607
3. Relevance of the Warburg Effect in Tuberculosis for Host-Directed Therapy (2020) https://doi.org/10.3389/fcimb.2020.576596
4. Transforming growth factor-beta profiles correlate with clinical symptoms and parameters of haemostasis and inflammation in a controlled human malaria infection (2020) https://doi.org/10.1016/i.cyto.2019.154838
5. Etiology of lactic acidosis in malaria (2021) https://doi.org/10.1371/iournal.ppat.1009122
6. The Warburg Effect 97 Years after Its Discovery (2020) https://doi.org/10.3390%2Fcancers12102819
7. Lotz, M., and Zuraw, B.L. (1987) IFN-y Is a Major Regulator of Cl-inhibitor Synthesis by Human Blood Monocytes. The Journal of Immunology, 139, 3382-3387. https://pubmed.ncbi.nlm.nih.gov/3119706/
8. Zuraw BL, Lotz M. Regulation of the hepatic synthesis of Cl inhibitor by the hepatocyte stimulating factors interleukin 6 and interferon gamma. J Biol Chem. 1990 Jul 25;265(21):12664-70. https://doi.org/10.1016/S0021-9258(19)38395-4
9. Long Covid, Short Magnesium https://doi.org/10.4236/oalib.1108736
10. Grassrootshealth Nutrient Research Institute https://www.grassrootshealth.net/blog/lack-Magnesium-worsening-ability-handle-stress/
11. Protein methylation in mitochondria (2022) https://doi.org/10.1016%2Fi.ibc.2022.101791
12. Human METTL20 Methylates Lysine Residues Adjacent to the Recognition Loop of the Electron Transfer Flavoprotein in Mitochondria https: //doi.org/10.1074/ibc.M114.580464
13. Mitochondria and the Future of Medicine: The Key to Understanding Disease, Chronic Illness, Aging, and Life Itself by Lee Know
14. Alternative medical interventions used in the treatment and management of myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia (2010) ttps://doi.org/10.1089/acm.2008.0376
15. A Comparative Study of Antifatigue Effects of Taurine and Vitamin C on Chronic Fatigue Syndrome https://doi.org/10.4236/pp.2022.138023
16. Competition for glutathione precursors between the immune system and the skeletal muscle: pathogenesis of chronic fatigue syndrome https://doi.org/10.1054/mehy.1998.0780
17. Creatine supplementation in fibromyalgia: a randomized, double-blind, placebo-controlled trial https: / /doi.org/10.1002/acr.22020
18. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity in patients with diabetes mellitus type 2 infected with Epstein- Barr virus https://doi.org/10.1371/iournal.pone.0230374
19. Homocysteine Metabolism: Nutritional Modulation and Impact on Health and Disease, chapter 54, Alan L. Miller, ND, Gregory S. Kelly, ND, Jessica Tran, ND https://musculoskeletalkey.com/homocysteine-metabolism-nutritional-modulation-and-impact-on-health-and-disease/.
20. S-adenosylmethionine inhibits methylation via catabolism to adenine (2022) https://doi.org/10.1038/s42003-022-03280-5
21. Understanding D-Ribose and Mitochondrial Function http: //dx.doi.org/10.7575/aiac.abcmed.v. 6n.1p.1
22. Synergistic and antagonistic antioxidant effects in the binary cannabinoids mixtures https://doi.org/10.1016/i.fitote.2021.104992
23. Chronic fatigue syndrome (CFS): Suggestions for a nutritional treatment in the therapeutic approach (2019) https://doi.org/10.1016/ibiopha.2018.10.076
24. Primary renal Magnesium wasting: an unusual clinical picture of exercise-induced symptoms https://doi.org/10.14814/phy2.12773
25. Rising Ca:Mg intake ratio from food in USA Adults: a concern? http://mgwater.com/Ca-Mg.pdf
26. Distinguishing features of Long COVID identified through immune profiling (preprint August 10, 2022) https://doi.org/10.1101/2022.08.09.22278592
27. The Hypocortisolism in Chronic Fatigue Syndrome (ME/CFS) — Artifact or Central Factor? https://phoenixrising.me/myalgic-encephalomyelitis-chronic-fatigue-syndrome-mecfs-research/pharmacogenomics/the-hypocortisolism-in-chronic-fatigue-syndrome-mecfs-artifact-or-central-factor/
28. Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome https://doi.org/10.1093/qimed/hcn123
29. Calcium and Magnesium Sensitivity of the Carotid Baroreceptor Reflex in Cats https://doi.org/10.1161/01.RES.45.6.815
30. Nitric oxide synthase and cGMP-mediated stimulation of renin secretion https://doi.org/10.1152/aipregu.2001.281AR1146
31. Effects of Magnesium on nitric oxide synthase activity in endothelial cells https://doi.org/10.1152/aipcell.1995.269.3.C612
32. Endothelium-Derived Nitric Oxide Supports Renin Cell Recruitment Through the Nitric Oxide-Sensitive Guanylate Cyclase Pathway https: / /doi.org/10.1161/HypertensionAHA. 111.00221
33. Hydrohysteroid Dehydrogenases - Biological Role and Clinical Importance - Review https://doi.org/10.5772/54149
34. 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. https://doi.org/10.1016/i.nurpra.2021.12.016
35. The Many Talents of TGF- β in the Kidney https://doi.org/10.1097%2FMNH.0000000000000490

see all references in the PDF

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See also Long-COVID is now the biggest COVID concern - many studies

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VitaminDWiki - Vitamin D Receptor activation can be increased in many ways - including Butyrate)

Resveratrol,  Omega-3,  Magnesium,  Zinc,   Quercetin,   non-daily Vit D,  Curcumin,   Berberine,  intense exercise, Butyrate   Sulforaphane   Ginger,   Essential oils, etc  Note: The founder of VitaminDWiki uses 10 of the 16 known VDR activators