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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.

“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/
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Aging biomarker found to be increased in LongCovid, epigenetic changes possible

Evidence of aging, five years on average, was found in survivors of Covid who experienced ongoing illness after an apparent recovery or even only ever having had mild symptoms initially. (1) Other research has found evidence of autoimmune antibodies against certain types of G-protein coupled receptors – need a different post for that.

  • Evidence for Biological Age Acceleration and Telomere 2 Shortening in Covid-19 Survivors. Alessia Mongelli, Carlo Gaetano, Michela Gottardi Zamperla, et al., medRxiv, April 27, 2021, preprint, (1)
  • “The results show a consistent biological age increase in the post-covid population (mean 58,44 DS 14,66 ChronoAge Vs. mean 67,18 DS 10,86 BioAge, P<0,0001), determining a DeltaAge acceleration of 10,45 DS 7,29 years (+5.25 years above range of normality) compared to 3,68 DS 8,17 years for the COVID19-free population (P<0,0001). A significant telomere shortening parallels this finding in the post-COVID19 cohort compared to COVID19-free subjects (post-COVID19 TL: 3,03 DS 2,39 Kb vs. COVID19-free: 10,67 DS 11,69 Kb; P<0,0001).” (1)
  • Additionally, ACE2 expression was decreased in post-COVID19 patients compare to COVID19-free, while DPP-4 did not change. ” (1)

ACE2 receptor expression was expected to be decreased in patients with increased viral load due to the virus destroying the cells with the receptors. Eventually less ACE2 function would be left and patients would exhibit symptoms similar to genetic ACE2 knockout mice – bred to not have ACE 2 receptors in order to see the effect on health. It can provide information about what function something has to see what goes wrong when the animal doesn’t have it.

Also of interest – stopping the virus from entering the ACE2 receptor means that it can’t replicate and go on to infect other cells or people – pomegranate peel may block access: Pomegranate peel – anti-COVID19, may block ACE2 receptor access to the SARS-CoV-2 virus. I ate some pomegranate peel today. *Recipe at the end of this post, more information about pomegranate prep & benefits G13. Pomegranate.

Pomegranate extract reduces inflammation and modulates health and gene transcription.

Pomegranate extract, of the whole fruit or peel is a very potent anti-inflammatory and modulator of health, (6), even epigenetics to some extent – epigenetics effects which genes will be transcribed into proteins by the cell. Pomegranate extract was found to modulate/effect microRNAs which control which mRNA will get transcribed. (2)

“Pomegranate extract intake reversed the surgery-mediated upregulation of various miRNAs and mildly reduced expression of selected miRNAs in tumour tissue compared with normal tissue.” (2)

What is microRNA? — “Noncoding (nc) RNAs also possess a regulatory effect on gene expression. MicroRNAs (miRNAs) are small ncRNAs of 20–22 nt that inhibit gene expression at the posttranscriptional level either by imperfect base-pairing to the mRNA 3′-untranslated regions to repress protein synthesis, or by affecting mRNA stability (reviewed in [23]).” (2)

What is mRNA? — “Messenger RNA (mRNA) molecules carry the coding sequences for protein synthesis and are called transcripts;” (3) Messenger RNA is copied from the double helix strands of DNA that make a gene. The messenger RNA is a single helix – one ladder leg instead of both sides of the spiraling ladder with nucleotide steps, or one side of a zipper.

What is epigenetics? — “The term ‘epigenetics’ refers to modifications in gene expression caused by heritable, but potentially reversible, changes in DNA methylation and chromatin structure. Major epigenetic mechanisms include DNA hyper- and hypomethylation [11], remodelling of the chromatin, modification of histones by histone acetylation and methylation (among others), and noncoding RNAs [12].” (2)

What are methyl donors? — Folate in the bioactive methylated form and methylated B12 are both helpful for providing the methyl groups needed for DNA methylation. The small chemical group added onto genes is like turning the light switch off, that gene is no longer in the ready to be transcribed mode. Choline is another methyl donor in the B vitamin group. See: Methyl Donors & BPA.

EGCG found in Green tea & Pomegranate Peel may protect length of Telomeres.

Pomegranate peel is also a source of EGCG (more commonly associated with green tea) which has been found protective of telomere length, by inhibiting a telomerase enzyme.

“Epigallocatechin-3-gallate, a major component of green tea polyphenols, downregulated expression of human telomerase reverse transcriptase (hTERT), a major enzyme determining telomere stability, through causing promoter hypomethylation and histone deacetylations, thereby inhibiting proliferation of breast cancer cells [12].” (7)

Polyphenols, alkaloids, triterpenes, and xanthones may be plant nutrients that help inhibit the overactivity of the telomerase enzyme seen in some types of cancer cells. (8) EGCG is a polyphenol. Alkaloids include “morphine, strychnine, atropine, colchicine, ephedrine, quinine, and nicotine.” (11) Triterpenes include sterols (such as vit. D group, 12) and carotenoids (vit A). (9) xanthones are found in the Garcinia, mangosteen fruit. (10) Telomeres are a section of non protein encoding DNA at the end of genes. Telomeres get shorter as we age and longer ones indicate younger metabolic age. Excessive lengthening of telomeres can occur in cancer and that isn’t good either.

The really good news about epigenetic changes – they can be changed back.

“In contrast to irreversible genetic alterations (mutations, deletions, etc.), genes silenced by epigenetic modifications are still intact and can be reactivated [13,14].” (2)

Many genes are turned on or off with the change from night to day/day to night. We do more active energy using work during the day, which produces waste chemicals, and more growth and repair, clean up, at night while we sleep. It is very unhealthy to chronically miss sleep.

Sunlight in the day & blackout curtains at night help immune function with melatonin & sunshine vitamins.

Sunlight in the morning or at some point in the awake hours of the day also helps health.

“People have a feeling of wellbeing when exposed to sunlight. This may be due to the fact that keratinocytes produce β-endorphin when exposed to UV radiation.67 ” (12)

A full spectrum lamp with UVB capability for a half hour of artificial “sun” during winter months or for night shift workers may be more beneficial for health, and mood, than a vitamin D2/D3 supplement. Our bodies make other forms of the vitamin D group of sterols, some water soluble, and other forms of vitamin A are also made. (12, 13)

“Bright light treatment requires a minimum of 2,500 lux to be effective, & the brightness recommended by researchers & clinicians for most people is 10,000 lux – an amount significantly higher than standard indoor lighting.” (14) This reference is recommending no UV in the light treatment, however for the vitamin D and A chemistry UVB is needed and UVA may also have some role in health in moderation.

Seasonal Affective Disorder (SAD) lamps may not provide the UVB, and the UVB intense ones are only meant for 30 minute use or less per day, as sunburn possible, so that type of light wouldn’t treat the SAD problem in the same way as the no UVB lights. (13, 15) The 10,000 lux lamps may be helping patients with Seasonal Affective Disorder (14) by increased beta-endorphins. Serotonin increase is involved in the benefit of Bright Light Therapy (BLT) which was found to be better than placebo in a metareview. (16) Bright Light Therapy was found to reduce cerebral monoamine oxidase A (MAO-A) levels which have a seasonal decrease in healthy controls compared to participants with SAD. Serotonin receptors and transport proteins may also be affected by the light treatment. (17)

Black out curtains at night and covering all little alarm clock lights and other device lights helps our body switch into night-time biology of clean-up and repair. Melatonin is also made at night and lights can reduce the amount that is made. It helps immune function and seems helpful against COVID-19. Melatonin produced in the lungs prevents infection by novel coronavirus. (18)

Lack of niacin, which is needed in increased amounts during infection or inflammation, would lead to overuse of tryptophan instead. Lack of tryptophan would lead to a lack of serotonin and melatonin, both of which are made from tryptophan. (19)

We may need a healthy gut microbiome, to have overall health.

The microbes in our intestines may have a larger role in health than we realized because they also impact our epigenetics – we want our good guys to be helping us then.

“Recent research has indicated that the gut microbiota and gut microbial metabolites might be important mediators of the diet–epigenome interaction (previously reviewed in [29–31]).” (2)

Obesity has been found to be related frequently to less beneficial microbiome species. (4) Anxiety can also be linked to microbiome species. (5) “Animal models strongly suggest a role for the gut microbiome in anxiety- and trauma-related disorders. The microbiota–gut–brain (MGB) axis sits at the epicenter of this new approach to mental health. The microbiome plays an important role in the programming of the hypothalamic–pituitary–adrenal (HPA) axis early in life, and stress reactivity over the life span.” (5)

More information about POTS & epigenetic changes:

I go into more detail about epigenetic changes, methyl donors and Postural Orthostatic Tachycardia Syndrome (POTS) – a problem that has been occurring for some Covid survivors and a problem I’ve had symptoms of twice and got better from twice – See: Epigenetic changes may also be involved in Covid19 or LongCovid. I prefer being healthy to being unhealthy and I’m willing to work to get better when I can.

Seasoned Peas and Pistachios, with Pomegranate peel.

Peas with pistachios, with cumin and coriander and a little pomegranate peel (inner pith)..

*Pound of frozen Peas, boil for a few minutes with a cup of Pistachios in water to cover the food – then pour off the water. It may contain oxalates from the pistachios. Add a 1/4 cup of fresh water to the drained food along with a half teaspoon of Cumin, Coriander and Gumbo file; one tablespoon powdered or minced dehydrated Pomegranate Peel (inner pith); and simmer with the peas & pistachios for a minute or two to set the Gumbo file thickener and mix the flavors. Serve the peas hot or cold with a little Apple Cider Vinegar and Salt to taste. Makes about four 3/4 cup servings.

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. Alessia Mongelli, Carlo Gaetano, Michela Gottardi Zamperla, et al., Evidence for Biological Age Acceleration and Telomere 2 Shortening in Covid-19 Survivors. medRxiv, April 27, 2021, preprint, https://www.medrxiv.org/content/10.1101/2021.04.23.21255973v1
  2. Clarissa Gerhauser, Impact of dietary gut microbial metabolites on the epigenome. Royal Society, 23 April 2018, https://doi.org/10.1098/rstb.2017.0359 https://royalsocietypublishing.org/doi/10.1098/rstb.2017.0359
  3. Ribosomes, Transcription, and Translation, nature.com/scitable https://www.nature.com/scitable/topicpage/ribosomes-transcription-and-translation-14120660/
  4. Davis CD. The Gut Microbiome and Its Role in Obesity. Nutr Today. 2016;51(4):167-174. doi:10.1097/NT.0000000000000167 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082693/
  5. Stefanie Malan-Muller, Mireia Valles-Colomer, Jeroen Raes, et al., The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders. OMICS J of Integ Biology, Vol 22, 2, 2018, Mary Ann Liebert, Inc. DOI: 10.1089/omi.2017.007 https://www.liebertpub.com/doi/pdfplus/10.1089/omi.2017.0077
  6. Ceci C, Lacal PM, Tentori L, De Martino MG, Miano R, Graziani G. Experimental Evidence of the Antitumor, Antimetastatic and Antiangiogenic Activity of Ellagic Acid. Nutrients. 2018;10(11):1756. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266224/Published 2018 Nov 14. doi:10.3390/nu10111756
  7. Yan Bian, Juntong Wei, Changsheng Zhao and Guorong Li, Natural Polyphenols Targeting Senescence: A Novel Prevention and Therapy Strategy for Cancer. Int J Mol Sci. 2020, 21, 684; https://www.dropbox.com/s/wckq66cgye3yjr4/ijms-21-00684-v3.pdf?dl=0doi:10.3390/ijms21020684
  8. Kumar Ganesan ID and Baojun Xu, Telomerase Inhibitors from Natural Products and Their Anticancer Potential. Int. J. Mol. Sci. 2018, 19, 13; doi:10.3390/ijms19010013 https://www.dropbox.com/s/xjhguj3dnbop6h2/ijms-19-00013.pdf?dl=0
  9. Triterpenes, sciencedirect.com, https://www.sciencedirect.com/topics/chemistry/triterpene
  10. Xanthones, sciencedirect.com, https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/xanthone
  11. Alkaloids, sciencedirect.com, https://www.sciencedirect.com/topics/food-science/alkaloid
  12. Wacker M, Holick MF. Sunlight and Vitamin D: A global perspective for health. Dermatoendocrinol. 2013;5(1):51-108. doi:10.4161/derm.24494 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897598/
  13. CK Eternity, The Truth about Vitamin D Metabolism, Mar 12, 2021, Patreon.com, https://www.patreon.com/posts/truth-about-d-48683534
  14. Bright Light Treatment Research. sunbox.com, https://www.sunbox.com/research/bright-light-treatment-research/
  15. Ezvid Wiki, The 6 Best Vitamin D Lights – 2019, Nov 28, 2018, youtube.com, https://www.youtube.com/watch?v=iqk9hzYC5Mc&feature=youtu.be
  16. Pjrek E, Friedrich M, -E, Cambioli L, Dold M, Jäger F, Komorowski A, Lanzenberger R, Kasper S, Winkler D: The Efficacy of Light Therapy in the Treatment of Seasonal Affective Disorder: A Meta-Analysis of Randomized Controlled Trials. Psychother Psychosom 2020;89:17-24. doi: 10.1159/000502891 https://www.karger.com/Article/Abstract/502891
  17. Spies, M., James, G.M., Vraka, C. et al. Brain monoamine oxidase A in seasonal affective disorder and treatment with bright light therapy. Transl Psychiatry8, 198 (2018). https://doi.org/10.1038/s41398-018-0227-2 https://www.nature.com/articles/s41398-018-0227-2
  18. Elton Alisson, Melatonin produced in the lungs prevents infection by novel coronavirus. Agência FAPESP, Jan 27, 2021 https://www.eurekalert.org/pub_releases/2021-01/fda-mpi012721.php
  19. Dmitry Kats, Tweets & images regarding tryptophan, melatonin, and niacin. “Yes, and melatonin is depleting as a result of tryptophan depleting due to inflammation, and only exclusively sufficient niacin supply can flush this inflammation out to then accordingly restore auxiliary biochem and health” “Funny how melatonin is being pushed through publications in relation to #COVID19, whilst they purposefully censor or “ignore” the inflammatory biochemical mechanism that causes this melatonin deficiency & how sufficient niacin supply nips the inflammation in the bud to restore it” https://twitter.com/NiacinIsHealth/status/1354624867300241408?s=20
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Responsibility – self care first, so able to care for others.

Becoming paralyzed or irrational and hyperexcitable from histamine excess would not allow me to be functional. Self care with genetic differences can be more complex than for standard health. Not becoming paralyzed is a goal of mine. I already have finger numbness problems and dystonia all my life.

Choices are not the same for everyone because we don’t all have the same starting points.

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.

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Starvation or addiction?

Previous post on the topic of genetic differences in the cannabinoid system: Is it Addiction or Starvation?. Excerpt:

Substance abusers likely quit using and relapsed again more times than anyone cares to count. every single time a chronic user runs out of their substance of choice they are “quitting” until they get more. 

Do you blame a hungry person for eating breakfast in the morning? Should a person just “quit eating” if they have an overeating disorder? Answer: No. 

  • Cannabinoids might help some types of eating disorders and some types of drug or alcohol addictions by providing an essential nutrient that the person might not be able to make. 
  • If the body can’t make an important substance or convert substances into active forms then it becomes an essential nutrient – essential for that specific person’s daily diet.

[…]

The problem with addiction to some substances or to eating excess food for some cases of over eating disorders is an underlying inability to make the cannabinoids but a remaining need for them and a hunger, an urge for “something,” something that is unknown however. And what people choose to consume in order to try to quench that unknown hunger varies from food and alcohol, to the rest of the drugs that are commonly abused. 

Dietary sources are needed instead. However our food supply has limited sources. Vine ripened produce or lemon oil, rich in aroma, are examples of a food containing cannabinoids or a similar group of aromatic and medicinal phytochemicals called terpenes. Chocolate and the herb rosemary are two other food sources. The spices cardamom, cloves, and nutmeg are also sources. Non-euphoric cannabinoids also exist and may have medicinal benefits depending on the patient’s condition. Copaiba oil is a food grade essential oil that can have non-euphoric cannabinoid content with medicinal benefits.

Wouldn’t it be nicer to tell starving people that they are starving rather than that they are poorly motivated? 

~~~ end of excerpt.

Wouldn’t it be nicer to hand starving people safe foods or supplements of what they need? before chronic degenerative changes occur that can’t be reversed, such as nerve paralysis?

Worse things are also said about people who use marijuana and criminal charges can occur. Reefer madness advertising and other media spread the image of marijuana being something of jazz nightclubs and black men who might be a danger to your women, along with the marijuana that would turn her wild. — It does decrease inhibition and increase sensation so the risks are greater for making reckless mistakes. Caution. Also caution about believing media distortion – it might be for political or corporate profit goals.

The marijuana culture tends to be a sharing one – people who are regular users may relate to each other through a common understanding of the body and mood relief that can occur when you really can’t make your own cannabinoids.

Mental health awareness – we are all more susceptible to reckless decisions/non-decisions, going along with other’s suggestions/ when we are overly hungry, angry, lonely, or tired. (12 step group slogan HALT).

Lessons learned the hard way can help other people avoid similar problems. Sharing strategies that have helped others can help recognize problem situations and pause a moment – HALT – and think twice about making any important decisions until better rested or calm and fed.

Sharing personal stories can help show the real world problems others have had to survive somehow.

I can make reckless mistakes just from being overly stressed, tired, hungry, or lonely. Emotionally vulnerable people are at risk, people with ADHD or on the autism spectrum, or have other social or mental skill deficits can be at risk of being taken advantage of. Survivors of child sex trauma or child abuse may be more at risk of revictimization – grooming behavior means the child is being slowly raised to think something is normal behavior and even enjoyable and a treat to look forward too. What might seem like a reckless mistake may be a combination of limited skills, lack of boundaries, and physical stressors.

Anxiety and stress or fear can be major factors in panicked decision making.

Cannabinoids affect mood as modulators – may increase appetite at low amounts and decrease appetite at large doses. The balance and amount can calm anxiety or PTSD, or an excess or imbalance might cause anxiety or paranoia. CAUTION, is reasonable, especially with the modern more concentrated strains and products.

The anxiety of cannabinoid deficiency can be quite severe, or withdrawal if the person gets withdrawal symptoms, can also be bad in an anxious jittery kind of way. Other users understand and will ‘catch you a buzz,’ knowing you or other people will share their relaxing herb with you on another day.

Reefer Madness was a movie made to instill a negative image in public opinion of the marijuana/cannabis plant. Hemp cannabis plants were also being grown and used extensively as a fiber source for making rope and paper. Paper industry ran newspaper articles and ads that added to the reefer madness narrative.

It certainly deserves some cautions and guidance, especially with the more potent modern medical strains of marijuana. Risks can include the increase in reckless behavior due to reduced inhibition (yes, cannabis was involved in the tattoo decision-making), also perception and memory can be affected. Some things may stand out vividly, important, larger than life, while other things may be a little distant and foggy, indistinct and the memories form similarly. Decision making is also impaired by slowness sometimes, something might be said and in the fogginess you let it go, but then as the words repeat in memory, you realize that you didn’t agree and might have said so if less foggy from marijuana.

Paranoia and anxiety can be mental symptoms of excess THC, and/or the imbalance of THC without the calming effects of CBD and terpenes like limonene and pinene. Real lemon or lime juice/oil or citrus peel products may help with an anxiety reaction as they are a good source of limonene.

Whole marijuana products can cause differing effects due to the different terpenes within the plant strain. Myrcene-sleepiness, pain relief; Limonene & pinene – calming, anti-anxiety.

Sleepiness is promoted by the myrcene content of some strains, it also is a terpene with medicinal effects.

“Myrcene, better known as the active sedating principle of hops and lemon grass, is also found in basil, mangos, and its namesake, Myrcia sphaerocarpa, a medicinal shrub from Brazil traditionally used to treat diabetes, diarrhea, dysentery, and hypertension (Ulbricht, 2011). ” (Hartsal, et al.)

Excess THC can cause physical effects that might seem like a panic attack, but which will subside. Limonene, lemon or lime oil products, may help reduce the effects.

Physical symptoms of excess THC can include a racing heart rate which might add to a sense that there is a panic situation or something to fear, as a racing heart rate is also a part of the feeling of fear. Feeling quite cold may also be a symptom of excess THC. Hunger can occur at lower doses of THC along with the ‘munchies’ – eating way more than typical of something sweet or salty or an odd mix of foods. At higher doses of THC the opposite might occur, a lack of appetite and even nausea or vomiting.

Physical symptoms of THC can include increased libido – feeling frisky, relaxing inhibition, slowing reaction time, odd thinking leading to poor decisions – marijuana is a risk for date rape/bad experiences. It doesn’t affect the memory as significantly as a blackout drunk or ‘roofie’ type date rape drug, however it may leave incomplete or distorted memories where some things stand out and others are fuzzy impressions.

With reduced inhibitions and increased risk of impulsive behavior, caution is needed with when and where, and with who you are using medical marijuana products.

You need a safe place, and safe people around, when consuming medical marijuana in quantities that cause changes in perception. “Come on back to my place and share a bowl” – danger, going into someone’s private space may be taken as a yes for anything else that occurs, or if a yes had been said in the past it might be taken as a yes into the future. Sharing a bowl means sharing the marijuana induced reduction in inhibitions – safer to not enter private space, yet illegal substance to many people and not to be used in public view even with the legalization in some states. <shrug> Progress takes time, caution is reasonable, there can be some potential risks to avoid, including personal stupidity.

Blaming everything on use of marijuana is wrong though, personal vulnerabilities are a risk too, mentioned earlier. Hyperthyroidism is also associated with mania, grandiose thinking and reckless sexual activity, and divorce is common. I had stress, fear to a point near panic, and was placed on a new psychiatric medication at one of largest doses – all can affect decision making negatively.

Caution also though with thinking medical marijuana use is an addiction.

Type 1 diabetes patients have a need for insulin because they can’t make it for themselves – some marijuana patients genetically or due to age or other reasons can’t make endocannabinoids for themselves. Paralysis can be a long term risk of deficiency.

One of the modulating functions of cannabinoids is brain cell maintenance – support the continuing growth of frequently used cells and take away growth support for cells that aren’t being used regularly anymore (practice daily the things that you care about).

“Cannabinoids form a singular family of plant-derived compounds (phytocannabinoids), endogenous signaling lipids (endocannabinoids), and synthetic derivatives with multiple biological effects and therapeutic applications in the central and peripheral nervous systems. One of these properties is the regulation of neuronal homeostasis and survival, which is the result of the combination of a myriad of effects addressed to preserve, rescue, repair, and/or replace neurons, and also glial cells against multiple insults that may potentially damage these cells.” (14)

Caution with use of marijuana – and caution thinking that it is just an addiction or the only factor in someone being vulnerable to sexual manipulation. I have made mistakes, change was needed though and the lessons I learned were needed. Dangerous things happened to me, and I am thankful that I learned more caution before worse things might have happened.

Hyperthyroidism and elevated histamine levels can also lead to mental health symptoms that include mania and increased impulsive behavior. There can be other causes too. People who seek out cannabinoids may find that it helps them to feel more stable. Cannabinoids can inhibit the mast cells which when over active can cause elevated histamine, cannabinoids can also cause a release of histamine. Balance of the different types are important. (2) Cancer tissue also can involve changes in metabolism and possibly histamine levels. (1) Cannabinoids can be helpful for preventing and treating cancer.

Cancer may involve an excess of histamine followed by too little histamine in later stages.

Cancer is frequently associated with weight loss and muscle breakdown, a condition called cancer cachexia. A team has hypothesized that histamine excess may involved in early taste, smell and sleep symptoms also seen with cancer, and a loss of appetite, anorexia, and later stages of severe tissue wasting might involve a drop in histamine. (1)

“Aberrant histamine signaling not only triggers energy-consuming processes, but also anorexia. Moreover, since functions such as taste, smell, and sleep are governed by discrete structures of the brain, which are targeted by distinct histaminergic neuron populations even relatively minor symptoms of cachexia, such as sleep disturbances and taste and smell distortions, also might be ascribed to aberrant histamine signaling. In late stage cachexia, the sympathetic tone in skeletal muscle breaks down, which we hypothesize might be caused by a reduction in histamine signaling or by the interference of other cachexia related mechanisms. Histamine signaling thus might delineate distinct stages of cachexia progression, with the early phase marked by a PSNS-mediated increase in histamine signaling, increased sympathetic tone and symptomatic adipose tissue depletion, and the late phase characterized by reduced histamine signaling, decreased sympathetic tone and symptomatic muscle wasting.  ” (1)

Elevated histamine can have an excitatory effect, hyper-excitable to the point of mania or depression and even suicide – whatever the mood, it might be escalated to extremes as histamine normally has a modulating control. Cannabinoids can have an inhibiting, calming effect on the synaptic junctions between nerve cells and inhibit nerve signals, not just mast cells. “Due to their presynaptic/terminal location, cannabinoid receptors can inhibit synaptic transmission and have the potential to regulate neurogenic inflammation.” (3) Someone with mast cell overactivity and histamine excess might be wanting cannabinoids from marijuana because it helps calm them — it might also be helping prevent early stages of cancer cachexia too if histamine excess is a factor in that. Adequate histamine is protective against colorectal cancer. (4)

Histamine and excess mast cells are also involved in pancreatic cancer.

“Recent findings indicate that the activation of granulocytes and macrophages in pancreatitis results in the release of a number of cytokines and inflammatory mediators and an important inflammatory mediator, the mast cell, secretes histamine as well as other chemotactic molecules and inflammation activators (29–31). Mast cells have been implicated in the pathogenesis of pain in other conditions and some have hypothesized that mast cells and histamine secretion play a role in the pain of chronic pancreatitis, which is characterized by mononuclear inflammatory cell infiltration (27,32–34). Interestingly, it has been shown that humans with painful chronic pancreatitis have an increased number of pancreatic mast cells compared to those with painless chronic pancreatitis (27).” (5)

Histamine is a vasodilator, increasing membrane permeability in the brain and other organs of the body.

Histamine also increases vascular permeability in pancreatic inflammation, suggesting it would also affect brain membrane permeability.

“As histamine has been confirmed to be a potent vasodilator, histamine may possibly be an important factor to study in increased vascular permeability in pancreatic inflammation (28,38).” (5)

Yes, histamine does increase permeability of the blood brain barrier: “Histamine is one of the few central nervous system neurotransmitters found to cause consistent blood-brain barrier opening.” (6)

Cannabinoids could be helping inhibit mast cell activation, reducing histamine levels, which would decrease blood brain barrier permeability protecting against entry of more inflammatory chemicals.

Nutrients work as a team – niacin also is important for reducing vascular inflammation.

Niacin or nicotinic acid is involved in energy production within mitochondria and can help reduce inflammation by turning it into the heat of a skin flushing reaction that is similar to the reddening warmth of an allergy reaction – both involve mast cells and histamine. Plentiful supplies of niacin help the body transform the inflammatory oxidative stress chemicals into more benign forms. Niacin also helps down regulate the production of inflammatory chemicals formed via the Nf-Kb pathway. (7)

Niacin is involved in our ability to burn lipids for warmth or energy in the brown or white adipose tissue (BAT & WAT), (8), mentioned in the cancer cachexia hypothesis as possibly being overactive, adding to unwanted weight loss, and due to an increase in histamine levels. (1)

Activation of the receptor for niacin causes a decrease in breakdown of triglycerides to free fatty acids, which would lead to lower blood lipid levels: “…the orphan G protein-coupled receptor GPR109A has been identified to be a receptor for niacin.” […] “Activation of GPR109A upon binding niacin functions in a G protein-coupled manner to decrease cAMP production, resulting in decreased hormone-sensitive lipase activity and reduced hydrolysis of triglycerides to free fatty acids (11., 12., 13.).” (10)

The warmth of the skin flushing reaction of niacin involves the niacin receptor and the release of chemicals, prostaglandin D2 and E2. “Recent studies have indicated that niacin-induced flushing was mediated by GPR109A through the release of prostaglandin D2 and prostaglandin E2 (14, 15).” (10) Prostaglandins are made from arachidonic acid which can be part of cannabinoid molecules. It is released from the phospholipid end when the cannabinoid is released from the membrane. Elevated levels of arachidonic acid being present can suggest cannabinoid breakdown is also elevated.

“Prostaglandins and thromboxane A2 (TXA2), collectively termed prostanoids, are formed when arachidonic acid (AA), a 20-carbon unsaturated fatty acid, is released from the plasma membrane by phospholipases (PLAs) and metabolized by the sequential actions of prostaglandin G/H synthase, or cyclooxygenase (COX), and respective synthases.” (13)

The niacin receptor, GPR109A, is regulated by G-protein-coupled receptor kinase 2, (GRK2), Gi, and Arrestin3. (10) Cannabinoid receptors are also G-protein coupled receptors.

  • GRK2 also regulates Type 2 Cannabinoid receptors. (11)
  • The arrestin proteins regulate light receiving rhodopsin, a G-protein coupled receptor and may also activate cannabinoid receptors, more needs to be learned. Cancer cell types frequently have increased cannabinoid receptors, yet providing cannabinoids can help treat cancer. (12)
  • Gi are a group of G protein alpha subunits; G proteins are guanine nucleotide-binding proteins which can act as a activating switch inside of cell for other functions, that can be activated from an external receptor, such as niacin activating the G-protein-coupled receptor GPR109A; or anandamide/THC and 2-AG/CBD activating the Cannabinoid Receptors Type 1 or 2; or a photon of light activating a rhodopsin protein.

The body is a complex team of chemicals that somehow work together in a way that allows most of us to walk and talk and function – stopping cancer and fighting virus is part of that daily function.

Lack of niacin may increase risk of cancer as it leads to depletion of NAD+ and dysfunction of the mitochondria’s ability to produce energy by oxidation of glucose. (9) Mitochondria switch to producing energy by fermenting glucose or glutamate without oxygen – a change that is associated with the mitochondria in cancer cells.

Adequate niacin and cannabinoids in balance and magnesium are all involved in the phagocytosis of infected or cancerous cells or other toxic cellular debris or proteins. The nutrients are reused by the cell or detoxified and eventually excreted in a process called by a few names, autophagy and apoptosis, lysosomal engulfment of cellular debris, or phagocytosis – engulfment of a smaller cell.

Is the desire for or use of marijuana an addiction or starvation? It seems to fall into the category of conditionally essential nutrients – essential for health for some conditions – those who can’t make them internally. It might also refer to nutrients that we can make but which we need in such large amounts that some must be obtained from the diet – such as nucleotides.

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

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