Another reason to investigate glucosamine in connection with Covid-19

As one can read in my prior posts, I think glucosamine (bioavailable in the human diet via fermented shrimp paste) is helping protect the regions that eat it regularly from high Covid-19 mortality burdens. I think it does so via protection of cartilage and via inhibition of interleukin-6 activity. Based on the very low numbers of Covid-19 cases seen in the Indochinese peninsula, I'm beginning to suspect that glucosamine not only lessens symptom severity but might even be helping stop transmission of the virus. A study I cited before about glucosamine indicates that it stops N-glycosylation in a manner similar to tunicamycin.

In DU145 cells glucosamine reduced the N-glycosylation of gp130, decreased IL-6 binding to cells and impaired the phosphorylation of JAK2, SHP2 and STAT3. Glucosamine acts in a very similar manner to tunicamycin, an inhibitor of protein N-glycosylation. Glucosamine-mediated inhibition of N-glycosylation was neither protein- nor cell-specific. Sensitivity of DU145, A2058 and PC-3 cells to glucosamine-induced inhibition of N-glycosylation were well correlated to glucosamine cytotoxicity in these cells.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057579/

An interesting thing about tunicamycin is that it can prevent some coronaviruses from producing any infectious virions.

To examine these possibilities, we analyzed the oligosaccharide moieties of the membrane proteins of the avian coronavirus infectious bronchitis virus. In addition, we determined the effect of inhibiting the glycosylation of these proteins on viral maturation and infectivity. Infectious bronchitis virus virions contain nine proteins. Four of these proteins, GP36, GP31, GP28, and P23, are closely related structurally and appear to be homologous to the E1 proteins of murine coronaviruses. We found that the oligosaccharides of GP31 and GP28 could be removed with endoglycosidase H and that neither of these glycoproteins was detectable in tunicamycin-treated cells. These two results indicated that GP31 and GP28 contain N-linked oligosaccharides. Therefore, O-linked oligosaccharides are not a universal feature of the small coronavirus membrane glycoproteins. Tunicamycin inhibited glycosylation of all of the viral glycoproteins but did not inhibit production of virions by infectious bronchitis virus-infected cells. The virions released by these cells contained only the three non-glycosylated viral proteins P51, P23, and P14. These particles were not infectious. Therefore, it appears that glycosylated infectious bronchitis virus polypeptides are not required for particle formation. However, the viral glycoproteins are apparently indispensible for viral infectivity.

https://pubmed.ncbi.nlm.nih.gov/6294330/

The places that eat fermented shrimp paste the most regularly--Laos, Cambodia, Thailand, and Vietnam--appear to have aspects of their lifestyle that interfere with transmission of Covid-19. Perhaps shrimp paste-provided glucosamine is one of those aspects. Someone with more resources than I have should be investigating this possibility.

A contributory reason to why food supplements and vitamins are too often a waste of money: magnesium stearate

Fat cells secrete an enormously important protein called FABP4 (alternative name is aP2). It is involved in metabolic syndrome, obesity, heart disease, hypertension, diabetes, and cancer. (See https://journals.sagepub.com/doi/full/10.4137/CMC.S17067). When we start releasing stored fat from our fat cells, it goes up. When we fast, it goes up. It appears to me that it stands in the way of weight loss by working together with PPAR-gamma to store lipids (See https://www.biorxiv.org/content/10.1101/2020.01.03.894493v1 and https://pubmed.ncbi.nlm.nih.gov/11872365/). So targeting FABP4 with various compounds has been the subject of much research. 

Many compounds that can inhibit FABP4 naturally occur in various foods, herbs, and spices that often pop up as associated with lower fat gain from hypercaloric and/or high fat diets. These compounds are easy to find for sale online and in vitamin stores. But they usually are sold in capsules that include magnesium stearate, an additive used to improve "flow" and make encapsulation easier. Unfortunately for everyone who finds that they seem to be wasting their money on vitamins, prescription pills, and supplements in pursuit of better health, magnesium stearate is quickly turned into magnesium and oleic acid in their bodies. Oleic acid stimulates FABP4 in the liver (https://www.nature.com/articles/s41388-018-0597-1, Supplemental Figure 3). Magnesium stearate also typically contains some palmitic acid (http://library.njucm.edu.cn/yaodian/ep/EP5.0/16_monographs/monographs_l-p/Magnesium%20stearate.pdf), which increases FABP4 in macrophages (https://pubmed.ncbi.nlm.nih.gov/31363792/). Pill "fillers" aren't the inactive substances that people tend to view them as.