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/

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.
Binge eating disorder for some sufferers may involve a genetic difference in the endogenous cannabinoid system which leaves the person unable to produce the cannabinoids normally and so they are left hungry, starving for the foods that are better sources of cannabinoids naturally.
Chocolate is the richest standard food source that isn’t a controlled substance but it isn’t a low calorie food (hemp oil and hemp seed products are not available in a limited quantity but they are still difficult for farmers to grow in all areas and medical marijuana is still considered a controlled substance at the U.S. federal level.) Less calorie dense foods than chocolate include pomegranate seeds, dark green leafy vegetables and herbs such as oregano and other green leafy herbs. So if binge overeating sounds sadly familiar, consider making an enormous salad and it may be just what your body needs. I use a half a pomegranate worth of seeds on my salad, which is about 1/2 cup of the seeds, and 1 teaspoon each of Italian Seasoning and Basil or Tarragon or some other leafy green herb. The enormous (a full dinner plate size is what I mean) salad might also help sufferers who are trying to resist the urge to over-consume alcohol or a few other addictive substances as well, if an underlying difference is present in their genetic code.

A dinner plate with a soup spoon and regular spoon for size comparison. Salad includes romaine lettuce, cilantro, tarragon, Italian seasoning, carrot, celery, avocado, pomagranite seeds, hemp seed and pumpkin seed kernels, lime juice and hemp oil and sea salt to taste.

The discussion of foods that are good sources of phospholipids or cannabinoids is not to suggest that medical marijuana patients should stop using their medication but simply to point to some food sources that might be available to most people where ever they live. Medical marijuana has significantly more cannabinoids than the foods that I mentioned in the previous paragraph or which will be mentioned later. My own physical symptoms are better helped by use of medical marijuana than by very large salads however the large salads are less expensive and have less effect on my mood. My previous use of the psychiatric medication Olanzapine has changed my withdrawal reaction to the medication and to marijuana significantly. I still have four months supply of the medication Olanzapine and plan to never ever use it again because its physical side effects while using it are very bad and withdrawal from it are much worse, frighteningly worse.
Medical marijuana patients who have never used olanzapine are unlikely to have the negative withdrawal reaction that I now experience within a few hours of my last dose. The strain of medical marijuana or type of synthetic or natural product is also important for any user in order to have a positive mental health reaction. Pure THC or the synthetic version, Dronabinol, can cause increased anxiety. Strains that have a mixture of cannabinoids and terpenes seem to help balance the mental effects in a way that is less likely to cause increased anxiety. Real lemon and lime products that contain the oil is one example of a easily available food substance that provides terpenes which help reduce the anxiety effects of medical marijuana or the synthetic Dronabinol. Terpenes and a link about lemon is included later in this post.
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)
Phospholipids are a combination of a lipid with the mineral phosphorus. They are important for helping make flexible membranes and play a role in immune health and energy metabolism. Phosphorus is also part of molecules used in energy production (ADP & ATP) and genetic structure, DNA and RNA (nucleotides) when combined with proteins or sugars.
  • Food Sources of Phospholipids and other phospho-nutrients: Hemp seed kernels and oil; Artemisia turanica/wormwood leaf; amaranth seed; asparagus; avocado fruit or the inner kernel, dried and powdered; beans/legumes; cardamom seeds and powder; carrots; celery stalks and leaves; cocoa beans and cocoa powder, baker’s chocolate, dark chocolate and to a lesser amount milk chocolate and chocolate syrup; coconut; cumin seed/powder; fennel seed, flax seed, pine nuts; sesame seeds, pumpkin seed kernels, squash seeds; butternut squash and pumpkin; gingko leaf; grapefruit and orange juice with the pulp; Jerusalem artichoke (this is a root vegetable rather than a green artichoke); lettuce, spinach and mustard leaves and other leafy green vegetables and herbs; nuts/peanuts, cashews, walnuts; oats; okra seeds; onion root, leek leaves, garlic;  parsnip root; pomegranate seeds and pomegranate peel extract;rice, white or brown but the bran is the best source; rosemary; sorghum;  sweet potato or yam; buckwheat (a seed botanically that is not wheat and is gluten free); wheat. (G.26)

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. 

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.)

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)

Glyphosate was found in vaccines; and tips for reducing dietary exposure

The nonprofit organization Moms Across America paid to have five types of vaccines tested in an accredited laboratory for the presence of the herbicide glyphosate. The chemical, which was originally patented as an antibiotic and mineral chelator, has never been tested or marketed as an injectable drug. Vaccines are injected directly into the blood stream which bypasses the protection of the gastrointestinal system.

The World Health Organization has advised that glyphosate is a probable carcinogen and it may affect hormones which would make it dangerous potentially for pregnant women and their expected infants:

“Honeycutt continues, “The public must know that their vaccines likely contain glyphosate, a toxic weed killer, which is acknowledged by the EPA as a “reproductive effector” ( i.e.: endocrine disruptor) which “can cause liver and kidney damage” and has been shown to be a neurotoxin. The WHO has deemed glyphosate a probable carcinogen.” – Moms Across America

The MMR II vaccine by the Merck company was found to have the highest level of glyphosate, 25 times more than what was found in the other four types of vaccines that were tested: “had levels up to 25 times higher than the other vaccines, at 2.671ppb.” The MMR II vaccine has been associated with autism as an adverse reaction (possibly due to an encephalitis reaction which then leads to the more extreme brain damage seen in patients with autism).

This supports the theory discussed by Professor Seneff, that glyphosate may be in vaccinations due to the use of animal products in the gelatin based Petri dishes in which the antigens for the vaccinations are grown. The theory suggests that glyphosate is similar enough to the amino acid glycine that it may be being built right into the protein structure of the animals body parts which include the collagen that is used to make gelatin. The glyphosate would be acting like a puzzle piece that kind of fits in one side of the protein but has the wrong shape on the other side of the puzzle piece so no other pieces of the puzzle can be added afterwards. One part of glyphosate would fit well into the protein structure but then another part wouldn’t be able to do what glycine does – which is donate methyl groups – which can help protect against cancer.

Some genetic canaries in the coal mine, such as myself, may have errors in the methylation cycle that disrupt the glycine function without needing any help from glyphosate. While filling my vitamin boxes for a week’s supply I was reminded that one of the supplements I added after getting my genetic methylation cycle results is . . . DMG . . . which is Dimethylglycine. I’ve been taking one of the capsules in the morning and one in the evening — but there is no guidance for how much of it I might need with my particular genetic defect.  My favorite phrase – or least favorite: “More research is needed.” Current information available suggests 2 grams of glycine per day may be a typical amount provided by the diet but ten times that amount may increase health benefits, no toxicity upper limit has been set; https://draxe.com/glycine/

Professor Seneff included tips for how to possibly reduce your exposure to glyphosate and some strategies that have been used on farm animals who were made sick by acute exposure to glyphosate.

Professor Seneff’s slides for her discussion lists”Some Important Nutrients“:

  • Curcumin
  • Garlic
  • Vitamin C
  • Probiotics
  • Methyl tetrahydrofolate – (this is the bioactive form of folic acid)
  • Cobalamin
  • Glutathione
  • Taurine
  • Epsom salt baths  [My how to tips for Epsom salt baths]

She also recommends:

  • Get Grounded” — ie work on general lifestyle and stress reduction strategies;
  • Eat organically grown foods whenever possible;
  • Eat foods containing the mineral manganese; (as glyphosate is a mineral chelator which may limit manganese’s availability for essential functions.) She mentions a few foods and shares an image which appears to include: organic whole grains, seeds, organic tofu and other beans, shellfish, tea, dark green leafy vegetables. This list provides more information — for example cardamom and pumpkin pie spice are sources of manganese:  http://nutritiondata.self.com/foods-000126000000000000000.html
  • Eat foods containing sulfur; (and/or take the Epsom salt baths which would supply magnesium and sulfur.) She mentions a few foods and shares an image which appears to include: beer, cabbage, organic eggs, especially the yolk, crab, shrimp and scallops, cheese, onions, garlic, organic liver, chicken, and something I’m not going to try to guess. Based on this list of the sulfur content of many foods the image may include a picture of dried apricots:  http://apjcn.nhri.org.tw/server/info/books-phds/books/foodfacts/html/data/data5g.html

Professor Seneff speaks very quickly, I may have missed some of her tips for trying to protect yourself from exposure to glyphosate.

She includes information about extracts from common plants that can treat glyphosate poisoning including:

Extracts from common plants such as dandelion, barberry, and burdock can protect from damage, especially if administered prior to exposure.”* (*C Gasnier et al. Journal of Occupational Medicine and Toxicology 2011, 6:3). [https://occup-med.biomedcentral.com/articles/10.1186/1745-6673-6-3]

And cows with glyphosate poisoning have been treated with:

Activated charcoal, bentonite clay, humic and fulvic acids, and sauerkraut juice have been shown to be effective in reducing glyphosate and improving animal health.“** (** H Gerlach et al., J Environ Anal Toxicol 2014, 5:2). [http://www.omicsonline.org/open-access/oral-application-of-charcoal-and-humic-acids-influence-selected-gastrointestinal-microbiota-2161-0525.1000256.pdf]

See the research papers for more detail and a functional medicine professional may be able to help guide individualized treatments with some of the items that are mentioned such as activated charcoal– but seek guidance, professional help is recommended even when using natural treatments.

/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./

Methylation Cycle Defects – in me – genetic screening “for research purposes only”

I purchased an independent genetic analysis which clearly states that it is “For research purposes only. Not for use in diagnostic procedures.” The screening is for informational purposes as there isn’t a physician providing individual care. But that is okay since I enjoy research with an experimental group of N=1 (me).

The genetic screening panel, is self pay, not covered by insurance, and while the company provides free information it also sells nutritional supplements designed to support the special metabolic needs associated with defects in the methylation cycle, which can affect levels of B12 and folate in particular. The screening assessed my genes, (from a finger stick blood sample that I provided by mail), for thirty different gene mutations known to be involved in the methylation cycle, and found — drum roll — eleven mutations in my genes. Four of them are double mutations which I think means that the mutation is on both genes – no normal genes for that protein for me, means that my body has no recipe card to make four types of proteins.

And — drum roll — one of the single gene mutations is on my Vitamin D Receptor gene — specifically of the Fok1 type which has been associated with an increased risk for autoimmune disease.  With a single gene mutation I think roughly half of my Vitamin D Receptors might be normal and half might be three amino-acids longer than normal as described in the following excerpt from a research article about Type 1 Diabetes:

“Variants of the VDR gene have been associated with susceptibility to several autoimmune processes. The roles of the VDR gene polymorphisms depend on their locations (Slattery, 2007). FokI polymorphism is within the DNA binding domain, near the 5′ end, and the rest of the SNPs are in the 3′UTR region within the ligand binding domain. The FokI polymorphism creates an alternative ATG initiation codon in exon 2 leads to a 3 amino-acids longer VDR protein by directly introducing a start codon. A functional impact of this polymorphism on the immune response has been demonstrated (Colin et al., 2000; van Etten et al., 2007). However, VDR gene SNPs influence on VDR expression differ in different populations.” – Elham O. Hamed et. al., “Vitamin D Level and Fok-I Vitamin D Receptor Gene Polymorphism in Egyptian Patients with Type-1 Diabetes,” [http://app.egyptlearn.com/eji/pdf/june2013/1-Elham-Sohag.pdf]

I’m not sure if having an extra “start” codon on half of my Vitamin D Receptors makes them more “startable” / more over active, or whether it would make them less effective. The article suggests the mutation does leave patients more likely to become calcium and vitamin D deficient but it never mentions whether hormone D levels were ever measured or not.

Additional link 7/14/16, suggests that the Fokl polymorphism may have long and short versions and the long version may cause over activity of the vitamin D receptor and the short version may be under active. And it mentions that defects in the VDR gene may increase risk for hyperparathyroidism, osteoarthritis, cancer and infection risk. Increased intestinal absorption of calcium and increased bone turnover may be a factor in the increased risk for osteoarthritis. Excerpt:

“In a series of 20 fibroblast cell lines of different VDR genotype, the relative transcription efficiency was measured of the endogenous VDR protein which was differing by the genotype at the FokI RFLP (F and f alleles) and the poly(A) stretch with long (L) and short (S) alleles which is acting as a transcription factor for a 1,25-dihydroxyvitamin D3-responsive reporter gene. This study provided evidence for so-called high (of the “FL” genotype) and low (of the “fS” genotype) VDR activity.”

“Indeed, the VDR gene has been found associated with a number of different phenotypes of which, especially, the associations with osteoarthritis, hyperparathyroidism, cancer and infection-susceptibility, so far are supported by several independent and large studies reporting similar associations.” “For example, VDR gene variants can influence calcium metabolism through differential absorption in the intestine and, at the same time, influence bone turnover, while also the occurrence of osteophytosis (as a part of osteoarthritis) can be influenced, together resulting in a net effect on BMD measured at a certain site, at a certain age and in a subject with a certain diet.”

[Uitterlinden A., et. al., Vitamin D receptor gene polymorphisms in relation to Vitamin D related disease states. Journal of Steroid Biochemistry & Molecular Biology 89–90 (2004) 187–193http://web.udl.es/usuaris/e4650869/Morella06/BB/VDR%20related%20diseases.pdf] [via http://questioning-answers.blogspot.com/2015/07/vitamin-d-metabolic-gene-variants-and-risk-for-autism.html]

That is interesting as I’ve had osteoarthritis symptoms in two of my toes for years (there’s an increased risk for dancers and people in other sports to have osteoarthritis develop due to overuse or injury and I had broken two toes as a teen. The toes healed at the time but lost range of motion later in life. I’ve also experienced secondary hyperparathyroidism which was diagnosed more recently and the hormonal imbalance can cause significant mental health symptoms. Maintaining my calcium and magnesium intake in balance  while limiting intake of vitamin D and exposure to excessive sunlight seems to be adequate for helping me to be able to keep my parathyroid hormone level within normal limits without further medication or other treatment.

A different older post has a citation that clarified the roles of vitamin D and hormone D. Vitamin D is actually only associated with a carrier protein that seems to act as an “off” switch and prevents it from activating the Vitamin D Receptor. Any free D that is not carried by the special carrier protein, becomes activated to the hormone. And since there are typically many, many more open Vitamin D Receptors in the body than the supply of active hormone could ever fill, any free D, if there is a deficiency or lack of the carrier protein, is likely to become activated to hormone D and then proceed to activate a Vitamin D Receptor. My lab tests and symptoms have always been worse when I have excess D so I’ve been wondering if I might have a genetic mutation in my D carrier protein gene, but this methylation cycle panel didn’t check that gene.

The four double mutations are in the genes: MTHFRC677T (Call – T), MTRR/A66G (Call – G), BHMT/1 (Call – T), and MAO A/R297R (Call – T).

The seven single mutations are in the genes: SHMT/C1420T (Call – Hetero), MTR/A2756G (Call – Hetero), BHMT/8 (Call – Hetero), CBS/A360A (Call-Hetero), COMT/V158M (Call-Hetero), COMT/H62H (Call-Hetero), as well as the VDR/Fok1 (Call-Hetero) mutation.

Genetic defects in the methylation cycle of expectant mothers or in the expected infant have been associated with an increased risk for autism developing in the infant later in life. Children with a COMT mutation were at increased risk to develop autism, but I will have to dig through old posts, (1, 2), to find that citation: [4: Schmidt RJ1, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tancredi DJ, Tassone F, Hertz-Picciotto I., Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism., Epidemiology. 2011 Jul;22(4):476-85, [http://www.ncbi.nlm.nih.gov/pubmed/21610500] I didn’t include the specific genetic mutations in the old posts; the article mentioned two for mothers and one for the child. The COMT 427 AA gene in the child turns out to be a slightly different mutation than the COMT mutations reported in my genetic panel, however I do have the double T mutation in my MTHFR 677 gene mentioned in this article as placing expectant mothers at increased risk for having a child with autism. But my CBS mutation is single and also different than the one mentioned in the following excerpt:

Excerpt from the Abstract:

“Significant interaction effects were observed for maternal MTHFR 677 TT, CBS rs234715 GT + TT, and child COMT 472 AA genotypes, with greater risk for autism when mothers did not report taking prenatal vitamins periconceptionally (4.5 [1.4-14.6]; 2.6 [1.2-5.4]; and 7.2 [2.3-22.4], respectively). Greater risk was also observed for children whose mothers had other one-carbon metabolism pathway gene variants and reported no prenatal vitamin intake.”

Excerpt from the article:

“However, children with the COMT 472 AA genotype were at increased risk for autism if their mothers reported having taken periconceptional prenatal supplements (OR = 1.8 [CI = 0.99–3.5]), and were at substantially higher risk if their mothers did not (7.2 [2.3–22.4];”              [4, full text article available]

The four double mutations are in the genes:

  1. MTHFRC677T (Call – T), Methylene tetrahydrofolate reductase, This version of the gene may have less activity than the more typical version of the gene (the T stands for Thymine, the more effective version has a C, cytosine). https://en.wikipedia.org/wiki/Methylenetetrahydrofolate_reductase  It may cause hyperhomocysteinemia especially if levels of folate, B6 and B12 are deficient. [http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/81648] May make deficiency of methylated folate more of a risk and make folic acid supplements not useful.
  2. MTRR/A66G (Call – G), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase or methionine synthase reductase, This mutation may increase risk for elevated levels of homocysteine and may affect folate and vitamin B12 methylation. Levels of B12 might be normal but not functional due to the lack of methylation. [http://mtrra66g.com/] * this site is commercial and recommends a methyl form of B12 however one of my other mutations might be affected negatively by excess methyl donors, see the selfhacked.com link in the #4 “warrior gene” within this list.  [https://ghr.nlm.nih.gov/gene/MTRR] [http://www.ncbi.nlm.nih.gov/gene/4552]
  3. BHMT/1 (Call – T), Betaine-homocysteine methyltransferase (BHMT),  This enzyme 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. Hypothyroidism may be associated with over expression of this gene: [http://www.wikigenes.org/e/gene/e/635.html] Choline deficiency disease and hyperhomocysteinemia (a heart disease risk factor) may be associated with this gene — (not necessarily with this specific mutation though). The protein that the gene normally produces is necessary in metabolism and in the CDK-mediated phosphorylation and removal of Cdc6 SuperPath: [http://www.genecards.org/cgi-bin/carddisp.pl?gene=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  (so a double mutation in this gene may make it difficult for me to make phospholipids endogenously, but this information is out of my depth, organic chemistry wise): [http://pathcards.genecards.org/card/cdk-mediated_phosphorylation_and_removal_of_cdc6] This double mutation in combination with the single mutation (+/-) in (#3 below) BHMT/8 and (#4 below)CBS/A360A may exacerbate each other’s negative effects on my body, causing an up-regulation of the CBS pathway and also may make it more difficult for me to remove toxic heavy metals from my body – see #4 in the next list for the link.
  4. MAO A/R297R (Call – T). “Monoamine oxidase A (MAO-A) is an enzyme in the brain,” Nick-named “The Warrior Gene” because levels need to be just right because it causes the breakdown of neurotransmitters and too little or too much can cause different symptoms from increased violence to increased anxiety and less aggression. “The G or GG allele indicates higher levels of the enzyme, while the T allele indicates lower levels (T is the ‘risk’ allele). (R)   In females, the G allele was associated with higher outward anger (p = 0.002) and it seems like G allele also causes aggression in males. (R)” The T version of R297R mutation is associated with generalized anxiety disorder (which was one of my earlier “diagnoses” but it was from talk therapy with a MSW so it never really “counted” with psychiatrists that I saw more recently.) “Females with TT reported higher levels of ‘‘angry temperament’’.  Female suicide attempters with TT reported higher ‘‘self-aggression’’” “Women are less likely to have these genes.” “People with the low activity MAO-A gene (2R, 3R) are overall more prone to violence. Specifically, when these people feel very provoked or socially isolated their aggression will come out. People with low MAO-A are more likely to be risk takers.  They are are also more likely to take revenge and use greater force if they get screwed over, but not for small screw overs. Mice with low MAO-A are also more aggressive in general and are more likely to start turf wars. People and mice with low MAO-A are more impulsive and aggressive. People with low MAO-A who are abused as kids show more aggressive behaviour as an adult.” The herbal supplement Gingko biloba, riboflavin (vitamin B2), bio-identical progesterone, and keeping to my circadian rhythm, (keeping a regular day/night wake/sleep cycle instead of pulling all-nighters and then sleeping in), may help me if I have low levels of the enzyme (and excess aggression/anxiety): [http://selfhacked.com/2014/12/07/about-mao-a-and-what-to-do-if-you-have-the-warrior-gene/] Reserpine, a drug based on an herb called Rauwolfia serpentina, or Indian snakeroot or sarpagandha may also help: [http://www.warriorgene.info/] * a commercial site.

The seven single mutations/polymorphisms are in the genes:

  1. SHMT/C1420T (Call – Hetero), Serine hydroxymethyltransferase, This polymorphism was not found to have an increased risk of Down’s Syndrome (DS) (thought possible because it affects folate) and levels of metabolites of the folate pathway seemed similar between the experimental groups of mothers (had children with DS) and control groups of mothers (did not have children with DS).  A protective role was actually found for this polymorphism (which sounds nicer than mutation, allele is another word for variations of the same gene.) [http://www.ncbi.nlm.nih.gov/pubmed/21687976]
  2. MTR/A2756G (Call – Hetero), methionine synthase gene, This mutation may cause up-regulation of the conversion of homocysteine to methionine which requires and might use up stores of methylated B12. [http://mtra2756g.com/] * a commercial site.
  3. BHMT/8 (Call – Hetero), see #3 above for general information about this gene’s protein.
  4. CBS/A360A (Call-Hetero), “CBS (cystathionine beta synthase) is a gene that converts homocysteine into cystathionine. 
The CBS pathway is the gateway into a number of essential biochemical processes. 
The biochemical pathways that follow and are linked to CBS are Transsulfuration and Glutathionine Synthesis.

 It is essential to address that Glutathione (GSH) is among the most important endogenously-produced antioxidants in every cell of the body. Glutathione activity in cells is critical for normal detoxification and defense mechanisms in every cell.” (I’m suggested to eliminate eggs from my diet — too late, they are already gone, but also cruciferous vegetables, onions and garlic – sad face. but I’m also suggested to avoid excess methyl donors like choline — and coffee is a methyl donor – sad face – it is already gone too, very sad face): “Restriction of supplemental methyl groups is important. We all need methyl groups, but those with active CBS up-regulations 
need to be cautious with how much sulfur and how many methyl groups they are taking in daily.
 This includes common supplements such as: L-methionine, L-cysteine, L-taurine, MSM, Glucosamine,  L-Glycine, DMSO, SAMe, NAC, methylcobalamin, methyl-folate, Betaine HCL, Choline. Restricting Vitamin B6 may also be warranted in CBS up-regulations. P5P (pyridoxal 5 phosphate), however, does not appear to increase CBS activity.” [http://metabolichealing.com/metabolic-gateways-cbs-gene-mutations-glutathione/] *That link is to a clinic. (So when my B6 runs out, I should special order the P5P version — which a pharmaceutical company is trying to patent as a prescription medication, if it can gain the FDA’s approval to make the more biologically active form of an essential nutrient unavailable without a prescription because it would interfere with their potential profits: “How does Medicure think it can get away with this? Its petition states rather candidly: “Pharmaceutical companies developing new drugs must be protected from companies that may seek to market the ingredients in those drugs as dietary supplements. The marketing of such products has the potential to undermine the incentive for the development of new drugs because many people may choose to purchase the supplements rather than the drugs.”” An essential nutrient is not a drug — companies have to tack on a fluoride or bromide or something else that makes the new chemical slightly different in order to be able to patent a chemical within the normal process. Bio-identical nutrients are not usually able to be patent protected – because they are essential, especially for people with metabolic defects in their ability to convert less active forms to the more active form. In my state, the Michigan Consumer Protection Act of 1976 is supposed to protect people from having their disability used against them in business transactions such as buying a supplement or prescription medication. 445.903x: “(x) Taking advantage of the consumer’s inability reasonably to protect his or her interests by reason of disability, illiteracy, or inability to understand the language of an agreement presented by the other party to the transaction who knows or reasonably should know of the consumer’s inability.“, And products aren’t supposed to misrepresented such as calling an essential nutrient a prescription medication: 445.903e: “(e) Representing that goods or services are of a particular standard, quality, or grade, or that goods are of a particular style or model, if they are of another.”  [http://www.legislature.mi.gov/(S(45hcye5dzt3luno152p33nku))/mileg.aspx?page=getobject&objectname=mcl-445-903])
  5. COMT/V158M (Call-Hetero), Catechol-O-Methyltransferase, Variations of this gene may lead to swings in dopamine levels that can cause mood swings. Red and purple foods may not be processed well and also may cause problems in mood swings for some people (like purple berries and red food dye (?) just reading, aghast that I’ve survived this long. Red food dye was one of my earliest migraine triggers.) [http://resqua.com/702188759/what-does-the-comt-gene-mutation-mean] Defects in this gene are associated with ADD/ADHD. [http://www.snpedia.com/index.php/Yasko_Methylation] And with panic disorder. [http://www.genecards.org/cgi-bin/carddisp.pl?gene=COMT]
  6. COMT/H62H (Call-Hetero), see #5 above.
  7. VDR/Fok1 (Call-Hetero). – the gene for the Vitamin D Receptor, see the excerpts within the earlier text of this post. And: “VDR Fok is involved with Blood sugar regulation. VDR mutations oppose COMT mutations in the regulation of dopamine levels. A VDR mutation means that a person is less sensitive to methyl group supplement levels. (Mood swings.) A VDR mutation can result in behaviors opposite to a COMT mutation. See Dr. Roberts comments at http://www.heartfixer.com/AMRI-Nutrigenomics.htm#VDR%20Taq:%20%20Vitamin%20D%20Receptor%20Taq%20Abnormality ” [http://www.snpedia.com/index.php/Yasko_Methylation] Dr. Roberts comments suggest that my normal VDR Taq gene helps balance the COMT +/- genes so that I have reasonable dopamine production but might have increased risk for mood swings. hmmmm

So I went and bought some more wild yam progesterone cream because I had run out a while ago and forgot to buy more and it has helped my mood and other peri-meopausal symptoms in the past. I also bought some Gingko biloba because I have also used that in the past with no problems and mood swings and self-aggression are no fun.

/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./