Tag: DMG

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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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Is it Addiction or Starvation?

1. Talk Therapy or “Just say no” can’t help a genetic difference.

Talk therapy is also beneficial but can not “cure” a biological difference in metabolism.
  • Looking up the definition of the word “disease” suggests that a genetic difference affecting a body wide receptor system might fit the term “body disease.” “Disease: a disorder of structure or function in a human, animal, or plant, especially one that produces specific signs or symptoms or that affects a specific location and is not simply a direct result of physical injury.” – Oxford Dictionaries (I.1.disease)
Redefining the neurobiological underpinnings and genetic risks of the behavior we call addiction could lead to more targeted help for the sufferers of addiction rather than continuing to treat them primarily by focusing on a discussion of their difficulties with motivation or impulse control.
The Endogenous Cannabinoid System holds answers.
Background information:
  • Endogenous refers to something that can be made internally by our body rather than a chemical that is needed to be obtained from an external source on a daily or semi-regular basis. An example such as oxygen from the air we breathe is needed within every few minutes or cellular damage can start to occur; or trace nutrients such as essential fats or fat soluble vitamins may not be needed as often because they can be stored in the fat and membranes of the body. They may only need to be consumed in the diet every few days or weeks without resulting in negative health effects. The body can store extra vitamin D during summer months that can last most of the winter but does start to run out by springtime.
A person with a metabolic difference due to genetics, chronic illness, or the standard changes associated with aging may need an external source of nutrients that other people of average health would be able to make internally – “endogenously.”
  • Cannabinoids are a type of chemical called phospholipids which are formed from a lipid, a type of fat, and the mineral phosphorus.
I have a genetic difference in my ability to phosphorylate (I.2.wikigenes.BHMT) so that I am unable to make phospholiids endogenously and I have found that having an external source of cannabinoids in my diet every day helps my chronic illness conditions and improves my muscle and nerve control. I am registered as a Medical Marijuana patient in a state where it has been legalized for medical use.
     Some of my symptoms that are relieved by the herbal medicine have been troubling me since I was an infant. I had severe eczema throughout my childhood and severe congestion. Rarely could I breathe through both nostrils and nosebleeds were also common. The enzyme the BHMT gene produces when functioning incorrectly is associated with a risk for vascular problems – ie nosebleeds or easy bruising or spider veins or all of them.
     The protein that the gene normally produces is necessary in Glycerophospholipid biosynthesis, metabolism , and Phospholipid metabolism, (so a double mutation in this gene may make it difficult for me to make phospholipids endogenously), among 17 pathways in all – that is an important enzyme: (I.6.genecards.BHMT) And the CDK-mediated phosphorylation and removal of Cdc6 SuperPath involves 97 other pathways which include a Calcium2+ pathway and a Parkinsons Disease pathway and creatine metabolism (important for muscles) and synthesis of DNA and many other metabolic paths/chains of chemical events : (I.7.genecards.phosphorylation)
  • Phospholipids are found in human breast milk and helps stimulate the infant’s appetite and helps support adequate weight gain. The cannabinoids and phospholipid group perform two main functions – they are flexible and form a significant part of membrane walls, like building blocks or bricks; they can also be released from the membrane and act as messenger chemicals that can activate other systems or be modified slightly to become a different type of messenger chemical called eicosanoids.
  • Eicosanoids include the leukotrienes: Santa Cruz Biotechnology,(I.8.scbt.com)

2. It might be motivating to learn of an underlying cause to cravings.

It might help a person to learn that for a person with a genetic difference, difficulties with motivation or impulse control are likely due to an underlying deficiency of a substance they are missing, which would likely have helped them have better impulse control and to not have cravings for substances.
Someone without the genetic difference would be making the substances internally which would help them have good impulse control and not crave substances.
     Helping the person with substance abuse problems to find approved external sources of the substance (cannabinoids) seems like it would be more helpful and potentially more motivating for them to be able to view themselves as a worthwhile person with special dietary needs rather than as an unmotivated drug addict who just doesn’t try hard enough to change.
     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.

3. Genetics of the cannabinoid system and binge eating disorder, alcohol abuse and drug addiction.

“It is important to note that, as with alcohol, marijuana, and heroin, a human genetic variant of the cannabinoid CB1 receptor gene CNR1 has been associated with susceptibility to cocaine and amphetamine dependence (Ballon et al. 2006, Comings et al. 1997; Zhang et al. 2004).”
  • Behavioral Neurobiology of the Endocannabinoid System; Ch.13: Drug Addiction, (page 334, I.9.Searchworks)
Endocannabinoids: The Brain and Body’s Marijuana and Beyond is a reference textbook available online as a pdf. (I.10.Endo.pdf)  It includes information regarding the genetic differences known to be associated with binge eating disorder and other drug addictions affected by rimonabant, a chemical which inhibits the endogenous cannabinoid system. Use of rimonabant affected craving for food/sucrose and alcohol in animal research, and it was found to reduce rewarding effects of morphine/opioids, amphetamine, cocaine and diazepam in other studies.
  • Rimonabant is not in use for drug addictions because it is associated with a significantly increased risk for suicide. This is an important point to note – blocking the endogenous cannabinoid system is associated with a significant risk for suicide.
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?
  • For more information regarding binge eating disorder, drug addiction and rimonabant: See Ch.3: Endocannabinoid Receptor Genetics and Marijuana Use, (p72-73 & 91, I.10.Endo.pdf) and Ch.13: Behavioral Effects of Endocannabinoids, mentions that research with rimonabant has helped show excessive alcohol drinking behavior and development of alcoholism may be related to genetic differences in the CB1 receptors. (p319, I.10.Endo.pdf)
  • Impulse control deficits may involve the cannabinoid system: See Ch.13: Behavioral Effects of Endocannabinoids, (pp325-330, I.10.Endocannabinoids.Full Text.pdf).
  • Schizophrenia may be related to a deficiency in the cannabinoid receptors themselves rather than being due to a deficiency in cannabinoids: See Ch.15, Neuropsychiatry: Schizophrenia, Depression, and Anxiety,; of the book Endocannabinoids: The Brain and Body’s Marijuana and Beyond: (p378, I.10.Endocannabinoids.Full Text.pdf)
More recently a gene has been identified in binge eating disorder, the gene for the cytoplasmic FMR1-interacting protein 2 (CYFIP2). (I.11.sciencedaily) The gene has a number of known variations and has allso been associated with Fragile X, an autism like condition, ADHD, autism, obsessive-compulsive behavior, and Prader-Willi Syndrome.. (I.12.ncbi.FragileX)
     The enzyme the gene CYFIP2 produces when functioning normally is involved in many metabolic pathways in the body including one that plays a role in myelination of nerve cells and one in phospholipid metabolism. (I.13.reuters) (I.14.genecards.CYFIP2)
     So an external source of cannabinoids might help a person with a problem in their CYFIP2 gene to have normal appetite control and also to protect their nerves from multiple sclerosis – which causes degeneration of myelin.  Myelin is similar to the lipid part of some of the phospholipids of the endogenous cannabinoid system. Multiple sclerosis has been associated with social anxiety and eating disorders (I.15.omicsgroup) which are also conditions associated with gene differences in the cannabinoid system. Myelin is made with sphingomyelin which is made of sphingolipids. (I.16.sphingolipids) Easy right? (I.17.mpcfaculty.lipids) Even easier – coconut oil is about 50% phospholipids and is a good source of sphingolipids. (I.18.coconut)
    I don’t know if I have any differences in my CYFIP2 gene; it was not one of the 30 genes that were included in the Nutrigenomic Screening I had done for my personal use for the “purposes of research.” Genetic screening is only used for certain conditions in standard health care currently and some types of health care claims can not be made by practitioners about genetic screening for other conditions – no guarantees in life or lab tests. The screening I had was designed to test genes commonly found to have differences associated with autism. (I.33.Nutrigenomic Screening) (p22, I.34.example of the genetic screening I had)
     I have a genetic difference in my ability to phosphorylate (I.2.wikigenes.BHMT) The gene I have a double malfunction in, BHMT, is also associated with multiple sclerosis except it seems to be with an over activity rather than too little function. Methionine and homocysteine metabolism and vitamin B12 may be involved. (I.19.BMHT.MS) Hypothyroidism may be associated with over expression of this gene: (I.20.wikigenes)
     The enzyme BHMT/1 (Call – T), Betaine-homocysteine methyltransferase (BHMT), in normal health helps produce the amino acids methionine and Dimethylglycine (DMG).
     DMG has been found helpful in ADHD, autism, allergies, alcoholism drug addiction, and chronic fatigue syndrome among other chronic issues. Methionine has been found helpful in treating depression, allergies, alcoholism and schizophrenia among other chronic issues. Since learning of the difference in my genetics I have been taking the two amino acids in a powder form that I add to a glass of water. It doesn’t taste good but it leaves me feeling more energetic and with a more positive mood.
     What it tasted most like was a tart red wine and the nutrient content of red wine does contain free amino acids, so someone with a problem with the BHMT gene may have problems with unidentified cravings that wine seem to help. While I did love red wine, it didn’t love me. It was one of the first triggers for severe migraines that I identified and started avoiding. A painkiller did help with migraine pain somewhat but zero time spent with a migraine is my goal.
     I found based on the information that is available regarding dose, that a half teaspoon of each of the amino acid powders helped my mood without causing such an energy boost that it caused an increased heart rate or prevented me from going to sleep. I tried one teaspoon of each initially and found that it was too much of an energy boost. Both amino acids can act as activating chemicals within the brain.
     I have early symptoms of neuropathy, I would rather prevent multiple sclerosis than to learn more about it first hand. Taking the supplemental methionine may be helping my body do what it needs to do to prevent an autoimmune breakdown of my myelin.

4. Sometimes people are wrong – Nixon was wrong.

“If the good people, in their wisdom, shall see fit to keep me in the background, I have been too familiar with disappointments to be very much chagrined.” – Abraham Lincoln (1809-1894), (p 634, I.23)
Hemp fiber was essential for rope and strong fabric. Thomas Jefferson grew hemp and is said to have smoked it too. It is time to stop being disappointed in loved ones who are likely suffering from a metabolic deficiency that leaves them susceptible to substance abuse or overeating and instead start accepting that they have needs that a person of average health doesn’t have or may not have to the same extent. Many nutrients are needed in a just right amount, not too little or too much.
     Cannabinoids are powerful and can be consumed in excess however it does not have the toxicity and deadliness of many other substances that are abused, including alcohol.
     The American Medical Association has recommended that marijuana be rescheduled as an herb with medicinal benefits. (I.24.AMA resolution) (I.25.veteransformedicalmarijuana)
     Rescheduling marijuana as a medicinal plant would free academic researchers to study its medicinal benefits. As a “Scheduled Substance” currently research studies are only supposed to assess toxicity and rehabilitation areas rather than design experiments assessing the medicinal value. Currently the synthetic form of the main euphoric cannabinoid, THC, is listed at a “safer” level of risk than the marijuana plant itself.
     The synthetic forms can be even more dangerous as they are more concentrated and are in isolation rather than also providing the non-euphoric cannabinoids that are found in most strains of marijuana and which have calming effects. Synthetic THC or THC in excess can cause paranoia and other mood symptoms that would have been unknown to Thomas Jefferson when he enjoyed smoking marijuana that was milder in the amount of THC it likely contained and more likely to be balanced with non-euphoric cannabinoids.
     The problem with black market development of a product is that it is often being designed to maximize the “buzz” or “euphoria” rather than the medicinal or pain killing effects. However, there is not that much “euphoria” felt by the person with chronic illness who is using a larger quantity of marijuana everyday due to an underlying inability to make cannabinoids because a tolerance is built up and they simply need some of the herb or other concentrated sources of cannabinoids every day just to maintain a state of health and function that is a little closer to everyone else’s “normal function“.    

     The person with a chronic need wants an herbal medicine that has a balanced variety of cannabinoids that treats a variety of symptoms, not just the euphoria inducing THC that can lead to overdose symptoms of a racing heart, feeling very chilled, and paranoia or anger combined with extra energy, so manic behavior might be a risk with an overdose reaction. Real lime or lemon juice products that are concentrated rather than being a watery lemonade may help counteract some of the mood changes associated with an overdose of THC. More on lemon oil is included in the next section. 

(I.26.fastcompany)

5. Medical Marijuana helps reduce opioid use, which can save lives.

     We currently have an epidemic of deaths due to opioid medications, prescription and black market drugs. The increase in deaths is due in part to the over prescription of opioid painkillers by the medical community but it is also due to black market substitutes that have been introduced in recent years. One type is particularly potent and is being sold as something else so consumers wouldn’t even know that they were being given a stronger version of an opioid medication than the prescription medication they were told they were purchasing on the black market – key point – don’t buy drugs on the black market because you don’t know what they might contain.
     This likely seems an obvious point which, honestly, even the drug addict knows that but their need is great enough during withdrawal that they may be more likely to take risks.
     Women may be especially at risk for opioid addiction whether it is due to differences in size or physiology is unknown. Addiction to opioids seems to occur for women at lower doses of the medication that were taken for a shorter amount of time than for men who become addicted. Women may be more susceptible to the cravings for the drug. (I.27.jotopr)
     In states with medicinal marijuana sales of painkillers dropped,which would include the opioids. Physicians are not comfortable with the inability to “prescribe” a set dose. “Take two hits and call me in the morning?” was asked in jest or in seriousness by a psychiatry professor, Deepak D’Souza, who also has researched marijuana. (I.28.npr)
     Deaths due to overdoses of opioids have also decreased in those states. (I.29.nbcnews) The cannabinoid and opioid receptor systems may both be involved in the regulation of appetite. Levels of the hormone leptin may be increased in response to CB1 receptors in the hypothalamus. Leptin and other appetite hormones may then “control opioid-regulated feeding…(Verty et al., 2003).” See Ch.13: Behavioral Effects of Endocannabinoids, (p313, I.10.Endocannabinoids.Full Text.pdf).
     Since marijuana use seems to be saving lives and has low toxicity risks, it doesn’t seem like how big a dose is as big a question as how to get a safe reliable supply to more patients in pain. The answer does exist but it is one a physician or psychiatrist is unlikely to like – the dose varies based on the person’s genetics and metabolism, the supply of nutrients available, tolerance, etc.; the answer is “It depends.” But the medication is so safe that worries about “too much” are really unnecessary, except possibly for more concentrated synthetic sources or extracted cannabinoid oil products.
     Signs of “too much” THC or synthetic THC can include a racing heartbeat, which very, very rarely has caused a couple/very few deaths. To the user first experiencing the racing heartbeat of excess THC, it may be frightening and feel like a panic attack. Relax it slows down again and only people with a pre-existing heart condition may be at risk during the time that the heart-rate is rapid.
     So if you have a weak heart – avoid excessive amounts of THC. The rapid heart-rate doesn’t occur at low doses. It may be accompanied a feeling of being chilled, and suddenly needing a jacket. Anxiety or anger may occur with excess THC or synthetic THC or during withdrawal from an excessive amount.
     The aromatic terpenes in citrus oil can have a calming effect if anxiety is a problem after consuming marijuana. Pinene from pistachio nuts may also be helpful, but a glass of lemonade might help the mood more quickly than eating pistachios because they would take longer to digest. (I.26.fastcompany)
     Artificial lemon flavored products wouldn’t help, only real lemon or lime juice products would help calm a mood unsettled by an excess or imbalance of THC. The plant contains many active phytochemicals which can include terpenes and other cannabinoids that are calming to the mood rather than causing euphoria. THC is the only cannabinoid in marijuana that causes euphoria.
     Opioid medications also cause euphoria – so why is one more socially acceptable than the other? Smoking is dirty and smelly and – the easiest way to not overdose.
     Eating products or the concentrated synthetic dose in one single sitting can leave a person feeling symptoms of overdose about one hour later, far too late to stop at half a serving or a small taste to see how you might handle that particular product and/or the strain that was used in it. Different strains of the plant can cause very different symptoms and help different types of symptoms, so the question of “how much” is less significant than which strain to use and the method to use to consume it.
     Smoking provides fairly instant changes to the mood so it is easy to tell if you’re getting more anxious or developing a rapid heart rate. Strains of marijuana can vary a lot, some types may cause the anxiety symptoms, while others would just cause the stereotypical “couchlock” – falling asleep. While setting fire to the couch might be a very real risk, otherwise, no danger other than possibly drooling a little and looking stupid. Looking stupid is better than looking dead from an opioid overdose – in my opinion – and I am a medical marijuana patient who has experienced these symptoms and read research about safe use.

6. Resources for help or just someone to talk to:

  • National Helpline: Substance Abuse and Mental Health Services Administration: “SAMHSA’s National Helpline, 1-800-662-HELP (4357), (also known as the Treatment Referral Routing Service), is a free, confidential, 24/7, 365-day-a-year treatment referral and information service (in English and Spanish) for individuals and families facing mental and/or substance use disorders.” (1.30samhsa.org)
  • Rape, Abuse and Incest National Network, RAINN Hotline: 1-800-656-HOPE, (1.31RAINN.)
  • U.S. National Suicide Prevention Hotline: “Call 1-800-273-8255, Available 24 hours everyday.” (1.32.suicidepreventionlifeline.org)

Help is only helpful when you accept it. Recognizing that you need it is the first step.

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.

Links and References:

(I’ll finish this list later, I’ve learned a lazy editing tactic is to skip the footnote numbers until the final draft is complete.)

  1. “Disease,” Oxford Dictionaries (I.1.disease)
  2. “BHMT,” wikigenes.org, http://www.wikigenes.org/e/gene/e/635.html (I.wikigenes.BHMT)
  3. Glycerophospholipid biosynthesis,
  4. metabolism ,
  5. Phospholipid metabolism,
  6. (I.6.genecards.BHMT) [http://www.genecards.org/cgi-bin/carddisp.pl?gene=BHMT] (I.6.genecards.BHMT)
  7. (I.7.genecards.phosphorylation) [http://pathcards.genecards.org/card/cdk-mediated_phosphorylation_and_removal_of_cdc6] (I.genecards.phosphorylation)
  8. “Leukotriene,” (I.8.scbt.com)
  9. Behavioral Neurobiology of the Endocannabinoid System; Ch.13: Drug Addiction, (page 334, I.9.Searchworks)  Behavioral Neurobiology of the Endocannabinoid System, Editors David Kendall and Stephen Alexander (Springer, 2009, Nottingham, U.K.). (I.Searchworks)
  10. Endocannabinoids: The Brain and Body’s Marijuana and Beyond, (CRC Press, 2006, Boca Raton, FL), Chapter Three, Endocannabinoid Receptor Genetics and Marijuana Use, editor and chapter by Emmanuel S. Onaivi, et al., (pages 72-73, 91, and 333), Chapter 15, Neuropsychiatry: Schizophrenia, Depression, and Anxiety, chapter by Ester Fride and Ethan Russo, (page 378), (I.10.Endocannabinoids: FullText pdf)
  11. (I.11.sciencedaily) Genetic risk factor for binge eating discovered. Sciencedaily.com, Oct. 26, 2016,  https://www.sciencedaily.com/releases/2016/10/161026170543.htm (I.sciencedaily)
  12. (I.12.ncbi.FragileX) Sabiha Abekhoukh and Barbara Bardoni, CYFIP family proteins between autism and intellectual disability: links with Fragile X syndrome, Front Cell Neurosci. 2014; 8: 81., ncbi.nlm.nih.gov https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973919/ (I.ncbi.FragileX)
  13. (I.13.reuters) Pathway Maps: G-protein signaling_RAC1 in cellular process, Life Sciences Research, thomsonreuters.com, http://lsresearch.thomsonreuters.com/maps/383 (I.reuters)
  14. (I.14.genecards.CYFIP2) CYFIP2, genecards.org,  http://www.genecards.org/cgi-bin/carddisp.pl?gene=CYFIP2 (I.genecards.CYFIP2)
  15. (I.15.omicsgroup) Shahla Mohamadirizi1*, Vahid Shaygannejad2, Soheila Mohamadirizi3 and Marjan Mohamadirizi4, Eating disorders in a multiple sclerosis clinical population and its association with social anxiety.   https://www.omicsgroup.org/journals/eating-disorders-in-a-multiple-sclerosis-clinical-population-and-its-associationwith-social-anxiety-2376-0389-1000183.php?aid=82623 (I.omicsgroup)
  16. (I.16.sphingolipids)
  17. (I17..mpcfaculty.lipids)
  18. (I.18.coconut) Handbook of Plant-Based Fermented Food and Beverage Technology, Second Edition, edited by Y. H. Hui, E. Özgül Evranuz  CRC Press, May 17, 2012, https://books.google.com/books?id=5fvRBQAAQBAJ&pg=PA669&lpg=PA669&dq=sphingolipids+in+coconut&source=bl&ots=QlgC46XLn8&sig=Y5AiDM4oUTBp9BS3aOKCtWK0Fbk&hl=en&sa=X&ved=0ahUKEwiQuL-wmdbVAhUG7CYKHXZCCxsQ6AEILjAB#v=onepage&q=sphingolipids%20in%20coconut&f=false
  19. (I.19.BMHT.MS) Naveen Kumar Singhal, et al., Changes in Methionine Metabolism and Histone H3 Trimethylation Are Linked to Mitochondrial Defects in Multiple Sclerosis. J of Neuroscience Vol 35, Issue 45, 2015 PAGES: 15170-15186 ISSN: 0270-6474 https://www.researchgate.net/profile/Rohan_Dassanayake2/publication/283710653_Changes_in_Methionine_Metabolism_and_Histone_H3_Trimethylation_Are_Linked_to_Mitochondrial_Defects_in_Multiple_Sclerosis/links/5693c64508aeab58a9a2aaf3.pdf (I.BMHT.MS)
  20. (I.20.wikigenes)
  21. ( methionine )
  22. ( Dimethylglycine (DMG).
  23. John Bartlett, Familiar Quotations, 14th Ed., 1910, (p 634, I.23)
  24. (I.24.AMA resolution) American Medical Association Medical Student Section, Resolution 2, JUne 8, 2008, http://www.oregon.gov/pharmacy/Imports/Marijuana/Public/AMA_MedStudentSectionResolution.pdf (I.AMA resolution)
  25. (I.25.veteransformedicalmarijuana) AMA Votes to Reschedule Medical Marijuana, VMCA, http://www.veteransformedicalmarijuana.org/node/67 (I.veteransformedicalmarijuana)
  26. (I.26.fastcompany) Chris Dannen, Three Beginner Mistakes to Avoid When Eating Cannabis, fastcompany.com Sept. 10, 2014, https://www.fastcompany.com/3035175/three-beginner-mistakes-to-avoid-when-eating-cannabis (I.fastcompany)
  27. (I.27.jotopr) Karen Barth, New Study Shows Women are Hit the Hardest as Opioid Epidemic Sweeps the Country. Jotopr.com, Feb. 27, 2017, https://jotopr.com/new-study-shows-women-are-hit-hardest-as-opioid-epidemic-sweeps-the-country/?utm_source=ReviveOldPost&utm_medium=social&utm_campaign=ReviveOldPost (I.jotopr)
  28. (I.28.npr) Shefali Luthra, After Medical Marijuana Legalized, Medicare Prescriptions Drop for Many Drugs. npr.org, July 6, 2016, http://www.npr.org/sections/health-shots/2016/07/06/484977159/after-medical-marijuana-legalized-medicare-prescriptions-drop-for-many-drugs (I.npr)
  29. Reuters, Legalized Marijuana Could Help Curb the Opioid Epidemic, Study Finds. March 27, 2017,nbcnews.com,  http://www.nbcnews.com/health/health-news/legalized-marijuana-could-help-curb-opioid-epidemic-study-finds-n739301 (I.29.nbcnews)
  30. National Helpline: Substance Abuse and Mental Health Services Administration: 1-800-662-HELP (4357), (1.30samhsa.org)
  31. Rape, Abuse and Incest National Network, RAINN Hotline: 1-800-656-HOPE, (1.31RAINN.)
  32. U.S. National Suicide Prevention Hotline:  1-800-273-8255, (1.32.suicidepreventionlifeline.org)
  33. Amy Yasko, Nutrigenomic Testing, Holistic Health International, http://www.holisticheal.com/health-tests/nutrigenomic-testing (I.33.Nutrigenomic Screening)
  34. Amy Yasko, Methylation Analysis Pathway: John Doe, Neurological Research Institute, http://www.holisticheal.com/media/wysiwyg/John_Doe_MPA_05.19.17.pdf (p22, I.34.example of the genetic screening I had)
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Cheerful Juice; the morning after

My late night serving of Cheerful Juice did help my mood after watching the presidential debate but I wasn’t able to go to sleep very easily afterwards. The full teaspoon dose of the free amino acids glycine and methionine left me not only with the cheerful mood and boost of energy but it also left me slightly jittery feeling with a more rapid heartbeat.

This morning I tried a half teaspoon dose and within just ten minutes I’m feeling more cheerful but without the jittery burst of increased energy.

So experimental results for my study group, size n=1, suggest that the 2 to 3 gram dose in a single serving may be safer than a dose of approximately 5 grams in one serving. When free amino acids can act as signaling messenger chemicals within the body or brain then they may also be able to act as excitotoxins in larger doses and overexcite cells possibly to the point of cell death.

Moderation is generally healthiest within biological systems. Many chemicals or nutrients can be safe within a moderate range but then be dangerous when there is either too little or too much. My needs for an external source of the free amino acids dimethylglycine (DMG) and methionine are not normal due to my genetic defect in the gene that is needed to make an enzyme involved in breaking down more complex forms of the free amino acids.

More on the gene defect involved in dimethyl glycine and methionine and a link to the genetic screening test I used is found in this post from March 30, 2016, http://transcendingsquare.com/2016/03/30/methylation-cycle-defects-in-me-genetic-screening-for-research-purposes-only/ . That post is a long list of notes rather than being an essay with a beginning and end, see #3, BHMT/1 (Call – T), Betaine-homocysteine methyltransferase (BHMT), for my notes regarding the specific defect and enzyme that prevents me from being able to fully digest protein foods — since birth — better late than never, I tend to say, but it would be nice for other infants and children to not have to suffer there entire lives due to underlying genetic defects that are now able to be screened for and managed with the use of dietary supplements.

Series on glycine:

  1. Glycine is an Amino Acid with Neurotransmitter Roles, 10/15/2016,  http://transcendingsquare.com/2016/10/15/glycine-is-an-amino-acid-with-neurotransmitter-roles/
  2. Cheerful Juice Lives Up to its Name, 10/20/16,  http://transcendingsquare.com/2016/10/20/cheerful-juice-lives-up-to-its-name/

/Disclaimer: This 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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Glycine is an amino acid with neurotransmitter roles

Subtitle: Rebranding and the power of a name: “Essence of Meat-ade” or “Cheerful Juice.”

Sub-subtitle:  Genetic defects in metabolism can affect the entire body due to lack of essential nutrients.

Background: I was found to have eleven of thirty defects in the methylation cycle that were known to be more common in patients with autism spectrum disorder. The screening is not for diagnostic purposes at this stage but is available to consumers interested in the information for their own research purposes (which might include what to feed their child or themselves for better management of autism symptoms – but it is use at your own risk information rather than ‘evidence based’ medical treatment approved for a certain diagnosis).

One of my genetic defects affects my ability to break down betaine into the free amino acids glycine and methionine (roughly, I would have to review the chemistry for the specifics). So armed with this new information I ordered tablets of each amino acid and started taking them each day as supplements. They seemed to help but it wasn’t a dramatic change in how I felt.

A month or two later before reordering more bottles I considered the question of just how much glycine or methionine I might need each day if I had a defect that prevented me from digesting protein and releasing the essential amino acids. When I looked into how much glycine might be needed by the body each day, I didn’t find much research but there was some and the amount suggested was far greater than the amount I was taking in the form of a tablet — 200 milligram tablet compared to two grams of the essential amino acid as a minimum recommendation with up to ten grams being proposed as possibly beneficial. And no toxicity risks were mentioned. Two grams is equivalent to 2000 milligrams or ten of the tablets each day, which would be expensive and a lot of tablets.

Many things that are available as supplements are also available in bulk as a powder that companies might use to make capsules or tablets for the individual consumer to purchase. The amino acids glycine and methionine were available online in a package size that was designed for individual use, possibly being marketed to people interested in body building or weight lifting.

A teaspoon of a powder substance is roughly five grams, depending on the density of the powder. I decided to try one teaspoon of glycine and one teaspoon of methionine per day as that would easily provide two grams and might provide up to five grams per day.

Results: Free essential amino acids are acidic — like lemonade — but taste a little like protein aka meat, so two teaspoons of free amino acids in water tasted VERY BAD. My nickname for the concoction became “Essence of Meat-ade” for the first day or two, however almost immediately after drinking the vile drink my mood became incredibly cheerful and I was suddenly filled with energy. I was amazed — how could a horrible tasting glass of water change my mood? I started looking forward to the drink and while I had started taking it in the evening I gradually switched to taking it earlier in the day and even twice a day occasionally, which would provide about ten grams of the powder.

My mental nickname changed from “Essence of Meat-ade” to “Cheerful Juice,” it helped my mood so much that I loved the stuff no matter how silly my face looked while trying to gulp it down too quickly to taste. I was amazed, and a little sad to consider that I had been without “Cheerful Juice” for my first fifty years of life — but better late than never is a motto of mine. With a double genetic defect I wouldn’t have been able to release glycine or methionine from larger proteins for my entire life — and therefore wouldn’t have had the cheerful effects or boost in energy due to the incomplete digestion of my food.

Why would a bad tasting drink give me a good mood?

I knew the amino acids glutamine and aspartic acid can act as messenger chemicals within the brain so I looked up glycine and methionine and sure enough they both also can act as brain signaling chemicals.

The rest of this information is about glycine’s role as a brain neurotransmitter. It doesn’t cover methionine but it also has roles in brain chemistry.

Glycine is a Neurotransmitter: 

Glycine has inhibitory and excitatory roles in the brain as a neurotransmitter – a type of chemical that can serve as a messenger between brain cells which are called neurons.

“Interestingly, glycine receptors comprised of a1 subunits are efficiently gated by taurine and b-alanine, whereas a2-containing receptors are not (8). The a1 and a2 genes are expressed in the adult and neonatal brain, respectively.”

ie-the type of glycine receptor found within the baby brain is not as well protected as the type found within the adult brain, later in the next paragraph:

“Recently, the expression of a1 and a2 subunits has been shown to be developmentally regulated with a switch from the neonatal a2 subunit (strychnine-insensitive) to the adult a1 form (strychnine-sensitive) at about 2 weeks postnatally in the mouse (8). The timing of this “switch” corresponds with the development of spasticity in the mutant spastic mouse (5), prompting speculation that insufficient expression of the adult isoform may underlie some forms of spasticity.” [1]

Background: Glyphosate is chemically very similar to glycine in that it may be incorporated into proteins but is not functionally the same. A protein containing glyphosate instead of glycine would be dysfunctional. Glycine provides methyl groups which are important for turning strands of DNA on and off, (DNA is the genetic material that acts as recipe cards for making proteins).

If glyphosate is being physically incorporated within body tissues in place of the amino acid glycine, then the role of glycine within early fetal development discussed in the above excerpt might be part of the mechanism for how autism risk may be occurring during the prenatal stage of life.

From a Marketing Perspective: How to sell something that tastes horrible but makes certain people feel great?

From my experience working with special need infants and children I learned that sick children when given a formula they can tolerate will cheerfully start drinking the formula if it  isn’t making them feel sicker — no matter how bad the formula tastes — and some of them are like “Essence of Meat” because they are based on free amino acids that would be easy to digest and wouldn’t have the same allergy risk as the larger and more complex proteins.

So how to market a specialty product? Target the special needs market, and pitch having the genetic screening done first in order to find out who needs the special product — and put the bulk powder in capsules  😉 , I tried to add lemon flavoring to make it more like lemonade but that didn’t change the flavor enough — I’m working on acquiring a taste for it instead.

The genetic screening I had done is “For Research Purposes Only” but it was assembled by a specialist with a PhD and experience in genetics. She is not a medical doctor and no diagnoses are provided however some health information is provided I haven’t reviewed it yet and therefore can not provide any feedback regarding it.

  • The Methylation Cycle genetic screening test: http://www.holisticheal.com/dna-methylation.html
  • My results and my notes regarding the 11 defects, this is a list of notes rather than being in article format, see number three of the double defects for details about the gene BHMT/1 (Call – T), which is for the enzyme Betaine-homocysteine methyltransferase (BHMT): https://effectiveselfcare.info/2016/03/30/methylation-cycle-defects-in-me-genetic-screening-for-research-purposes-only/
  • An excerpt from that post regarding diagnoses that may be helped by use of dimethylglycine (DMG) and methionine as supplements : DMG has been found helpful in ADHD, autism, allergies, alcoholism, drug addiction, and chronic fatigue syndrome among other chronic issues. Methionine has been found helpful in treating depression, allergies, alcoholism and schizophrenia among other chronic issues.

/Disclaimer: This 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./

  1. Steven M. Paul, GABA and Glycine, https://www.acnp.org/g4/GN401000008/Default.htm