Glycine - good for our extracellular matrix & for immune protection against viral infection.

The extracellular matrix is very important for our immune defense as white blood cells actively patrol the areas surrounding cells for pathogens to remove, such as virus. Deficiency of glycine may be involved for patients with more severe COVID-19. "Glycine intake as nutritional supplement was very effective against virus infections." (1)

Glycine is an amino acid and is important in the structure of protein chains because it is small in size and can allow folding of the long chain into a three dimensional shape. (See post: Glyphosate & COVID19) It is important within proteins (such as collagen) that help stabilize the gooey gelatin like fluid that supports the areas within our cells and surrounding our cells. There can be a thicker layer immediately surrounding cells which is called a glycocalyx, a term also used to describe the gel coating that surrounds bacteria.

"Biofilms formed by an alginate-overproducing strain of Pseudomonas aeruginosa have a complex structural architecture that allows them to more resist tobramycin than biofilms formed by an isogenic nonmucoid strain. This suggests that an altered structure of biofilms cause increased resistance of pathogens against antibiotics.182 " (9)

It helps protect our cells from bacteria, virus and other pathogens. A stronger extracellular matrix, made possible with daily supplements of 10 grams of glycine, was found to help protect against viral infection. (1)

Glycine is used often in the assembly of collagen proteins. The small glycine molecules help stabilize the triple helix shape of the long column like folded protein. The long sturdy fiber like proteins help add stability and structure to the three dimensional woven mesh of the fluid gelatin like extracellular matrix or cytoplasm within cells.

"Glycine is utilized to synthesize serine, sarcosine, purines, creatine, heme group, glutathione, and collagen. Glycine is a major quantitative component of collagen. In addition, the role of glycine maintaining collagen structure is critical, as glycine residues are required to stabilize the triple helix of the collagen molecule."

The collagen fibers can be chemically stained for viewing on microscope slides. In an image here (7, 8) the collagen fibers are greenish and surround the cells that each have a brownish-black nucleus in the middle.

Extracellular matrix - our glycocalyx - our jelly lining.

We need a healthy extracellular matrix that is not too sticky and dehydrated to prevent easy flow of fluid and cells and not too watery as some solid support is needed. We are almost 70% water but it doesn't seem like it. Magnesium is also essential for the structure of the gelatin like matrix within and surrounding cells. Each atom of magnesium can hold 18 molecules of water in an electrically stabilized cloud of water surrounding the magnesium atom. Sulfates are also essential for the stability of the matrix structure. Monosaccharides, single molecules of sugars, are also an important part of the glycocalyx on cell surfaces. Different types of monosaccarides are combined into surface glycoproteins that tell the immune system information about the cell - whether friend or foe.

Many of the extracellular proteins, such as sialic acid, also carry a negative electrical charge so there is a slight magnetic like repelling against other cells. This is critically important for holding vessel walls open - the negative charge surrounding the interior repels the other wall from collapsing inward. Some food additive emulsifiers may be too effective and also may emulsify our intestinal lining and cause bowel troubles such as diarrhea and discomfort. Gumbo file is a very healthy emulsifier from nature -powdered sassafras leaves - used by indigenous Americans.

• See an early series on the glycocalyx for more about sialic acid/neuraminic acid, for fiber rich foods that are good for our 'jelly lining' see: The Glycocalyx: our jelly filling; more specifics about monosaccharides & food sources is in the post Sugars give energy and structure to life, how they connect together in a complex 'language' is in Glycocompounds: essential sugar building blocks.

"Cells encounter surrounding surfaces first through their glycocalyx and therefore it may substantially contribute to crucial physiological and pathophysiological processes. The glycocalyx is a carbohydrate-enriched sugar coating that covers the surface of many cells, including cancer cells, presumably greatly influencing cellular interactions with their environment at the molecular scale. Its components are glycolipids, glycoproteins and glycosaminoglycans (GAGs). Glycocalyx contains large amounts of chondroitin sulfate (CS), dermatan sulfate, heparan sulfate, sialic acid, and hyaluronic acid, all negatively charged at neutral pH21." (4)

The amino acid Glycine - available in supplements as Dimethylglycine (DMG) and Trimethylglycine (TMG).

Glycine is available as a bulk powder available from protein supplement companies focused on the weight lifting industry. Betaine is the more common name for Trimethylglycine (TMG), it and Dimethylglycine (DMG) are available as supplements in tablets or powders. It may be helpful to have both as they are used for different purposes and are not exactly equivalent. DMG can cross the blood brain barrier so it is helpful when the calming inhibitory effects of glycine are needed within the brain. (2)

"Dimethylglycine (DMG) is an amino acid found naturally in plant and animal cells and in many foods such as beans, cereal grains, and liver. It is used to improve energy, boost the immune system, and to manage seizures and autism. There are some positive reports of DMG efficacy on the immune system." (3)

DMG may be helpful for people with seizure risk - it was found to help some patients but not showing conclusively positive results overall. Some patients may have a genetic difference and need an external supply. (3)

People with a BHMT gene allele (like myself) would need an external source of DMG as the BHMT enzyme is needed to breakdown betaine to DMG. You can see the chemical steps in a graphic here: (6). From a previous post: "DMG has been found helpful in ADHD, autism, allergies, alcoholism, drug addiction, and chronic fatigue syndrome among other chronic issues." See #3. BHMT in this post: Methylation Cycle Defects – in me – genetic screening “for research purposes only” A more recent post goes into further detail about the BHMT enzyme's role in the production and breakdown of endocannabinoids. Cannabinoids are made with the BHMT gene (and others).

I have a double BHMT gene allele - I need an external source of DMG and methionine and it helped my mood immensely. It helps me feel more cheerful as well as more energetic. I take about a half teaspoon of each once or twice a day. A teaspoon at a time was too much energetic, seemed to cause a racing heart rate. The total amount a person needs per day may be more than that. Capsules would be giving a smaller amount, I didn't notice much effect at all from taking a little tablet supplement and the price was significantly larger. A half teaspoon of a powder is about 2.5 grams, a tablet is usually about 500 milligrams, 0.5 grams.

I am not taking enough DMG and I hadn't realized TMG might be helpful too - what I also hadn't realized is TMG is betaine - so I should be taking the DMG form, I get betaine from food and I don't do well with too much of a good source (quinoa). We need about 10 grams of glycine per day from dietary sources, yet the typical diet only provides two grams. "Glycine produced by human metabolism is much lower than the cell’s needs giving a general glycine deficiency of 10 g/day in humans." (1)

People who took ten grams of glycine per day as a supplement had fewer viral infections than the control group. (1) "Glycine intake at the afore-mentioned dose prevents the spread of viruses by strengthening the extracellular matrix barriers against their advance. " (1)

Nutritional supplement, 10 g/day, Glycine, promotes young strong collagen, compared to old weak collagen formed from an un-supplemented diet (~2 gr/day) and our own metabolic pathways (~3 gr/day). Graphic from: "Glycine can prevent and fight virus invasiveness by reinforcing the extracellular matrix" (Meléndez-Hevia, et al., 2021) (1)

Gee, I do want "young, strong collagen" (see above image, (1)) , so I will have my glycine drink four times a day. Breaktime, be right back. I will be so cheerful it may be hard to recognize me. :-)

• My "Cheerful Juice" drink reminds me of red wine without the alcohol, ~ 10 oz water, 1/2 teaspoon DMG, 1/2 tsp methionine; a little of my coffee sweetener mix: Stevia, powdered cardamom, sage and oregano; 2 ounces pomegranate juice. If I had taurine and creatine on hand I would try adding that too, but amino acids are acidic. The beverage is tart and I sip it slowly.

People with a genetic problem with methylation may have problems making a variety of proteins, as well as people with a diet deficient in the methyl donating nutrients folate, B12, betaine, choline, and the amino acid methionine. "Studies that simulated methyl-deficient diets reported disturbances in energy metabolism and protein synthesis in the liver, fatty liver, or muscle disorders." [...] "Hypomethylation has a wide spectrum of effects that include genetic, epigenetic, and metabolic alterations." (5) Someone with a genetic problem with methylation would need to take the bioactive, methylated form of B12 and folate. The standard supplement of folic acid and cyanocobalamin are unmethylated forms and would be not helpful for someone unable to remethylate them.

Summary - to fight virus well, we need a healthy extracellular matrix for white blood cells to be able to patrol easily -- and to have that we need adequate glycine in our diet and the genetic ability to digest it to Dimethylglycine (DMG).

• We also need to stay well hydrated, and to have adequate sulfate, magnesium, protein and ATP for magnesium storage, and a wide variety of monosaccharides to make surface glycoproteins that say and do the correct functions as cell surface immune markers.

• Epsom salt soaks may be helpful as a topical source of magnesium and sulfate for people with poor intestinal absorption of magnesium, or sometimes there can be a genetic difference limiting intestinal absorption for the person's whole life.

• Fiber rich plant foods are also needed to support the extracellular matrix - similar to how gelatin is supported by fruit pectin fibers when making jams.

• We can't do much without B vitamins - they are the body's energy providers, essential for our mitochondria. Lack can lead to mitochondria switching to anaerobic glycolysis which may be a risk for later transition to cancer. Methylated forms of folate and B12 are needed by people with certain gene differences. Niacin in a much higher dose than would be available from the diet can help reduce inflammation, (niacin post) and also help preserve tryptophan stores for use to make serotonin and melatonin (see last post).

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

Reference List

1. Enrique Meléndez-Hevia, Patricia de Paz-Lugo, Guillermo Sánchez, Glycine can prevent and fight virus invasiveness by reinforcing the extracellular matrix. J Functional Foods, Vol 76, 2021, 104318, ISSN 1756-4646, https://doi.org/10.1016/j.jff.2020.104318. https://www.sciencedirect.com/science/article/pii/S1756464620305429

2. Is TMG or DMG more effective?, davincilabs.com, https://blog.davincilabs.com/blog/is-tmg-or-dmg-more-effective

3. Dimethylglycine: Purported Uses, mskcc.org https://www.mskcc.org/cancer-care/integrative-medicine/herbs/dimethylglycine

4. Kanyo, N., Kovacs, K.D., Saftics, A. et al. Glycocalyx regulates the strength and kinetics of cancer cell adhesion revealed by biophysical models based on high resolution label-free optical data. Sci Rep10, 22422 (2020). https://doi.org/10.1038/s41598-020-80033-6 https://www.nature.com/articles/s41598-020-80033-6

5. Obeid R. The metabolic burden of methyl donor deficiency with focus on the betaine homocysteine methyltransferase pathway. Nutrients. 2013;5(9):3481-3495. Published 2013 Sep 9. doi:10.3390/nu5093481 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798916/

6. Glycine formation from betaine-trimethylglycine. image https://www.researchgate.net/figure/Glycine-formation-from-betaine-trimethylglycine-BHMT-betaine-homocysteine_fig5_320773132 from Adeva, María & Souto-Adeva, G. & Ameneiros-Rodríguez, E. & Fernández-Fernández, C. & Donapetry-García, C. & Domínguez-Montero, A.. (2018). Insulin resistance and glycine metabolism in humans. Amino Acids. 50. 10.1007/s00726-017-2508-0. https://www.researchgate.net/publication/320773132_Insulin_resistance_and_glycine_metabolism_in_humans

7. Collagen Fiber, sciencedirect.com, https://www.sciencedirect.com/topics/medicine-and-dentistry/collagen-fiber see,

8. Michal Miko, Ivan Varga, Chapter 6 - Histologic Examination of Peripheral Nerves, Editor(s): RS Tubbs, E Rizk, MM. Shoja, M Loukas, N Barbaro, RJ Spinner, Nerves and Nerve Injuries, Academic Press, 2015, Pages 79-89, ISBN 9780124103900, https://doi.org/10.1016/B978-0-12-410390-0.00006-8. https://www.sciencedirect.com/science/article/pii/B9780124103900000068

9. Baral B, Mozafari MR. Strategic Moves of "Superbugs" Against Available Chemical Scaffolds: Signaling, Regulation, and Challenges. ACS Pharmacol Transl Sci. 2020;3(3):373-400. Published 2020 Apr 13. doi:10.1021/acsptsci.0c00005 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296549/