genetics – Effective Self Care info

February 25, 2021

Cannabinoids are made with the BHMT gene (and others).

Cannabinoids are complex molecules we can make when genetically and nutritionally, healthy and nourished. Various genetic differences are known that cause a deficiency in endogenously made cannabinoids – phospholipids. Lack of cannabinoids negatively effects many areas of health throughout the body and brain, the mood and decision making, and appetite, and movement are all affected by cannabinoid availability.

It is discrimination to prevent research from occurring into the medical benefits of cannabis and cannabinoids and to prevent people who need an external source from having access to it. Covid and LongCovid may be increasing the number of people who might benefit from an external source as epigenetic changes or some other effects of the viral infection may be causing dysfunction in normal production of cannabinoids or some other problem.

Cannabinoids and the Cannabinoid receptors perform many functions in the body.

Membranes and growth of tissue is affected directly as building blocks that are part of the membranes, and indirectly as messenger chemicals that help promote and guide growth.

Cannabinoids also have widespread effects on immune function in addition to brain and nerve function. Cannabinoid receptors are found throughout the brain and also on white blood cells, leukocytes. Our immune function also needs endogenous, internally made, cannabinoids, or would benefit from an external source if endogenous cannabinoids were not able to be made normally.

“In human leukocytes the expression of cannabinoid receptor mRNA has been reported to be lower than that found in brain tissue. The message has, however, been detected in all subsets of leukocytes examined. The message levels are greatest in S cells, followed sequentially by natural killer cells (NK), polymorphonuclear neutrophils (PMN), T8 cells, monocytes and T4 cells.” (11)

Leukocytes help us fight viral infections and patrol for other infectious pathogens or precancerous or cancerous cells. Nutrients work together, synergy – increased power together than any on their own. We need magnesium for leukocytes to be able to perform the killing, apoptosis, and we need niacin to help with the safe removal of debris or engulfing of virus or small cells. Cell contents that are spilt into surrounding tissue has to be removed or it causes more inflammatory damage and can lead to death of other cells.

Niacin reduces inflammation for us in some direct ways and indirectly by inhibiting the NF-kB inflammatory pathway. Deficiency may increase neurodegeneration as well as reduce immune function for fighting virus or cancer.

“Reports suggest that deficiency of niacin can increase the risk of neurodegeneration, immunological disorder and inflammation stress [14]. Additionally, niacin exerts its anti-inflammatory effect by suppressing the NF-κB pathway [15].” (18)

The cannabinoid system is also involved in neurotransmitter levels.

“According to previous studies, CB1r [Cannabinoid Receptor type 1] is located in the locus coeruleus (LC) and in the dorsal raphe nucleus (DRN), and it regulates noradrenaline (NA) and serotonin (5HT) release, respectively, by the modulation of GABAergic and glutamatergic terminals (117, 118).” (17)

Problems with the endocannabinoid system can affect mood such as changes in serotonin leading to anxiety or depression. Adequate niacin intake helps preserve our serotonin levels by sparing tryptophan.

“Genetic studies pointed out interesting results regarding the involvement of polymorphisms or epigenetic modifications of CNR1 as susceptibility/risk biomarkers to develop anxiety disorders. Lazary and cols. analyzed the interaction of the promoter regions of the serotonin transporter (5HTT; SLC6A4) and CNR1 genes on anxiety. Specific constellations of CB1r and 5HTT promoters were closely associated with high or low synaptic 5HT concentrations, which could result critically in the vulnerability to experience an anxiety disorder (124). Hay and cols. employed CRISPR/CAS9 technology to disrupt a highly conserved regulatory sequence (ECR1) of the gene encoding CB1r (CNR1).” (17)

Cannabinoid system differences occur in ethnic & gender groups. We may be equal but we are not all the same.

Who has the gene differences may vary with ethnicity. “With 60 DNA samples (120 alleles) for each of the 4 ethnic groups studied, we had 90% power to detect a variant allele with a true population frequency of ≥ 2% [16]. ” “Twenty-five SNPs were observed in BHMT — 17 in AA, 8 in CA, 9 in HCA, and 10 in MA subjects (Table 1 and Fig. 2 upper panel).” (1) Number of cannabinoid receptors has been found to vary based on ethnicity and gender with people of Caucasian background having the most, people with African/black background having slightly fewer, and Asian having significantly fewer than those of people with Caucasian or African ethnicity. (11)

“The relative levels of the 58 kDa CBI protein 1070 E.S. Onaivi et al. from the male volunteers were, 47.4%; 39.0% and 13.6% for the White, Black and Asian blood samples respectively as shown in Fig. 3. The relative levels of the Cl31 protein in the male and female volunteers were 49.6%, 32.2% and 18.2% for the white and black females in comparison to the black male blood samples respectively as shown in Fig. 4. Therefore in both males and females, the cannabinoid receptors appear to vary by gender and ethnicity, for example Fig. 3 show white male > black male > Asian male and Fig. 4 show white female > black female > black male.” (11)

African Americans were found to have variations in the BHMT gene almost twice as often than Caucasian and Mexican-American ethnic groups and Hans Chinese American were least likely (small group study). (1)

The BHMT gene and Endogenous Cannabinoid production & breakdown.

The BHMT gene encodes an enzyme involved in homocysteine metabolism and the production of amino acids methionine, and dimethylglycine from betaine. (2) The BHMT enzyme is visualized in a graphic of the folded shape, made up of four parts, monomers, coupled into two sets of dimers, figure C: (1.1).

The BHMT enzyme is also involved in about 60% of the glycerophospholipid production pathway (2) which means important cannabinoids may not be able to be made internally and would need to be obtained in the diet or other sources or suffer deficiency symptoms chronically. People with Cystic Fibrosis also can’t make cannabinoids however the fatty acid end of the molecule is what can’t be made normally. The BHMT gene difference would disrupt production of the glycerophosphate end of the larger cannabinoid molecule. PA, PE, PI, and PS production might be reduced or dysfunctional and breakdown of LPC and LPE which might lead to some types of cannabinoids being unavailable and others unable to be broken down and remove normally so excess might collect -unknown by me. (3)

Phospholipids: PA, phosphatidic acid; PE, phosphatidylethanolamine; PC, phosphatidylcholine; PS, phosphatidylserine; PG, phosphatidylglycerol; CL, cardiolipin; PI, phosphatidylinositol. (15)
LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine, (19)

Research in cannabinoid chemistry was limited to toxicity or addiction due to the rescheduling of marijuana by the Nixon administration as nonmedical. Since the differences in function of the endocannabinoid system varies with ethnic group it is somewhat genetic discrimination to as well as racial discrimination to target an ethnic group with a law that wouldn’t affect all ethnic groups equally. Someone unable to make cannabinoids would have more craving and physical need for a rich source of phospholipids or cannabinoids, than a person with normal ability to make cannabinoids and/or a low or normal amount of cannabinoid receptors compared to someone with many of them.

Cannabinoid receptors effect mood, & may be involved in anxiety, depression, and possibly suicide.

Lysophosphatidylcholine, LPC, can cause an increase in calcium flow into cells at an atypical cannabinoid receptor GPR55 (4, 5) which is excitatory. Over activity, excess calcium entry, might be a negative to cell health. During normal activation levels the atypical cannabinoid receptor has anti-depressant effects and may help prevent suicide as the brains of suicide victims have fewer GPR55 receptors than typical. (14)

“This result, plus the observation that GPR55 increases intracellular calcium, suggests that GPR55 activation enhances neuronal excitability. These findings, together with the preferential expression of GPR55 on large-diameter DRG neurons, which can be involved in nociception, particularly in neuropathic or inflammatory pain states (29–31), suggest that GPR55 may have a pronocioceptive [pain increasing] role.” (5)

So overactivity of the GPR55 receptors might be perceived as chronic pain and might affect mood and suicidal ideation. Cannabinoid receptors in the prefrontal cortex (CB1) are also known to be involved with suicide risk from research with people suffering from anorexia (17) or alcoholism and depression. (16)

Cannabinoids also can reduce oxidative stress & inflammation, and may be helpful for preventing or treating neurocognitive degeneration conditions.

Calcium can cause oxidative stress damage and would be increased during times of strenuous activity or infection or other times of increased metabolism. THC can cross the blood brain barrier and can help reduce oxidative stress and may be helpful for treatment of neurocognitive degeneration. It was found to improve glucose use within cells and improve brain function in other ways with no toxicity problems in an animal based study. (12)

“In silico analysis predicted THC to be permeable across the blood-brain-barrier. THC was also predicted to have an oral LD50 and toxicity class values of 482 mg/kg and 4 respectively. These results indicate that C. sativa improves glucose consumption with concomitant suppression of oxidative stress and cholinergic dysfunction, and modulation of purinergic and gluconeogenic activities in brain tissues.” (12)

Personal experience – I have a double BHMT allele – it isn’t something I would recommend trying yourself.

I have experience of a lifetime without typical cannabinoid production and the symptoms that may cause. There is a double allele of my BHMT gene which means I can not make some endocannabinoids and can’t break down others. A double allele means both copies contain the same difference from typical. (post, see # 3 in the first list) So I can’t make the BHMT enzyme at all. I supplement with dimethylglycine and methionine since finding out and it helped. I need to continue daily though as genetic metabolic differences mean lifelong symptoms of deficiency of the nutrients that are affected, or an excess of a chemical metabolite that normally would be broken down sooner so it wouldn’t collect.

Post: Clinical Endocannabinoid Deficiency, (CED), and phospholipids. Excerpt:

Conditions that may involve Clinical Endocannabinoid Deficiency, (CED):

Conditions that may involve a deficiency in cannabinoids chronically may include symptoms of pain, muscle spasms, nerve numbness, mood disorders, movement disorders, digestive and appetite problems, appetite and growth failure in infants or colic, menstrual problems and infertility/miscarriages and hyperemesis prenatally.

Pain/inflammation: Migraines, Fibromyalgia.
Mental health: Anxiety, PTSD, Major Depression, Bipolar disorder, Motion Sickness, The balance of cannabinoids (2-AG ~ noneuphoric CBD and anandamide ~ euphoric THC) is a problem in schizophrenia. There is too much of the anandamide, excess THC can cause schizophrenia like symptoms, and providing CBD may help patients. *See this post for more nutritional deficiencies that cause schizophrenia like symptoms, five or more may be involved, suggesting the problem is a symptom rather than a condition with a single cause – and a single cure: The voices that people with schizophrenia are hearing are probably their own inner thoughts.
Nervous system: Multiple sclerosis, Diabetic Neuropathy, Brachial plexopathy, Causalgia, Phantom limb pain, Glaucoma, Huntington’s, Parkinson’s, Cystic Fibrosis,
Appetite/digestive system: Anorexia & Bulimia, Neonatal Failure to Thrive, infantile Colic, Irritable Bowel Syndrome.
Fertility/reproductive system: Dysmenorrhea, Hyperemesis, repeated miscarriages (Russo 2016), (anandamide is needed for implantation of a fertilized egg in the uterus and development of the placenta to occur normally, too much or too little can disrupt the process, Fonseca 2013), male infertility due to sperm motility problems is associated with low levels of anandamide (AEA) (Amoako 2013), (too much can also negatively affect male or female fertility). *See this post for more details about infertility and phospholipids: (Phospholipid or phosphorylation deficiency: Potential symptoms)
Other food sources of cannabinoids exist in addition to marijuana or hemp however the amount provided is in lower concentrations so you might need a large salad that includes several sources at one meal, and other sources in beverages, supplements, or at other meals.

— Addition to the excerpt – the amount of cannabinoids in medical marijuana is a lot more, and more likely to be obviously helpful, than the amount of phospholipids or cannabinoids found in a few foods and spices. Sadly medical marijuana has been stigmatized and illegal for many decades. Research into medical benefits was prevented with Richard Nixon’s administration rescheduled cannabis as having no medical value. Research was only possible on addiction or toxicity. Marijuana/cannabis not only has medical value, it has been used medicinally or in other ways by humans for thousands of years. Paper and rope made from hemp fiber was also a large industry prior to making cannabis illegal.

Conditions I’ve had symptoms of which might be due to Clinical Endocannabinoid Deficiency.

The conditions/symptoms I’ve had over my life from the above list include: Migraines, Fibromyalgia; Anxiety, PTSD, Major Depression, Bipolar disorder; Anorexia & Bulimia, Irritable Bowel Syndrome; and some nerve/numbness symptoms since childhood – dystonia.

The amount of cannabinoids a human needs if they are unable to make them internally/endogenously is not readily available information due to the lack of research. The amount of medical marijuana that I find necessary to feel nerve flow in my fingers and throughout my body and to have other symptoms improve is quite a bit each day. It adds up in money to buy, and time and stigma to use.

Smoking is frowned upon by society and cannabis use is still treated as if it is just an addiction or even criminal (which it still is at the Federal level), so it frightens some people to even learn that you use it, or have used it recently. Chronic users have adapted a tolerance to it (8), and mentally may be more used to functioning with some than going without. The type of strain is important for the terpenes that provide different aroma also provide different health effects. Some can be calming for anxiety (limonene), and another sleep inducing and pain relieving (myrcene).

Daily use every 2-4 hours is what I find helpful and smoking has benefits for dosing. Edibles take longer to feel an effect and then suddenly can be too much. Inhalation effects are fairly immediate and easy to know then when enough has been absorbed. The forms of cannabinoids that are absorbed may vary too with the different intake routes, and inhalation may be more effective for some types of health problems than edible/intestinal absorption. The healthiest I’ve ever felt was when I combined eating some fresh trim or immature buds everyday or edibles along with some smoked bud.

Smoke toxins are a negative that causes the “dopey” effect of the stereotypical marijuana user. Vaping devices exist that heat the bud to a lower temperature so the burnt toxins are not created, however some of the THC conversion occurs at higher temperatures so symptoms may not be helped as much. The vape oil products may have other negative effects on the lungs due to the oil and flavorings being inhaled into the lungs where it can add to pneumonia risk.

How much THC am I getting throughout a day then? Possibly 40% of whatever was in the marijuana you smoked – a lot is lost when you burn the buds. 8 There is approximately 525 mg in an eighth of good medical grade marijuana with 15% THC. (6) That eighth ounce might cost $45-60. One gram per day of 10% THC marijuana might provide 40% of the 100 mg of THC it contains, if smoked vs made into an edible. A quarter to half of a one gram joint every 2-4 hours might be giving 10-20 milligrams of THC each time. Strains that also provide some CBD are important as the cannabinoids work together to do somethings in the body such as inhibit mast cell activation.

Eighty to hundred milligrams of THC is suggested as possibly feeling like an excessive dose all at once for someone with increased tolerance, while 25-80 range might be the typical preferred dose. (8)

I have not calculated this for myself before so it does bring up an interesting question of whether I’m getting too much, or enough, or not enough – the fact that I felt best while also eating fresh trim and other edibles regularly would suggest to me that it is not enough when only smoking and that I do need quite a bit daily.

The non-euphoric CBD has been found safe for use even at 1500 mg per day, though 20-40 mg might be more typically used. (7)

Dronabinol is a capsule form of a THC like medication and it might be prescribed at a 2.5 mg dose twice per day. That might seem like a lot to a new user and not that big of a dose to someone else, although the lack of CBD may be a problem if anxiety is a side effect.

Tolerance levels can reduce after not using for a while and then build back up again. Doses that would seem intense for a new user would not really affect a long term user. (8) Genetics may play more of a role in these differences too, lack of research leaves some questions unasked.

Genetic differences occur in the number of cannabinoid receptors which can effect tolerance for a concentrated source such as medical marijuana.

There can be genetic differences where a person doesn’t make cannabinoids well and has lots of extra cannabinoid receptors, all wanting/ready for cannabinoid activation – but with none or to little available. They might tolerate and prefer a larger dose of THC. Other people might have normal amounts of cannabinoid production and like a smaller dose or none, might not like it. For me it provides feeling throughout my body in a way that I don’t have otherwise. It helps me for muscle knots or spasms and pain. Mentally it helps me with PTSD and anxiety and prevents mast cell histamine excess and hyperexcitability.

Cannabinoids help with learning & forgetting – reshaping nerve pathways – neural plasticity. Pain signal pathways can also be remade more easily with cannabinoids.

Cannabinoids help with learning and nerve flow, and with forgetting – changing nerve pathways to build new as needed and remove the old as they are not needed (old phone number for example). Neural plasticity – changing nerve pathways and synapses between nerves is a function involving cannabinoids. Pain and movement, appetite and growth, cannabinoids affect many functions of the body and neural plasticity can affect pain pathways too – remembered pain in an amputee’s healed wound, and maybe feelings of the missing limb still being there also.

“The same team noted a baseline fragility of serotonergic systems in migraine and fibromyalgia [89], plus the co-occurrence of primary headache in 97% of 201 fibromyalgia patients. In a later study [67], they supported the concept that both disorders represented a failure of serotonergic analgesia and NMDA-mediated neuronal plasticity.” (9)

Synergy – many nutrients work together to perform any action in the body. Magnesium also helps inhibit excess pain nerve signals.

Pain conditions can be caused by deficiency of nutrients or chemicals that inhibit pain sensing nerves. Magnesium is needed to inhibit them as well as cannabinoids. Migraine pain may be not responsive to opiate pain killers. (9)

“A trigeminovascular system has long been implicated as integral to the pain, inflammation and secondary vascular effects of migraine, linked through the NMDA/glutamate system [49]. Cannabinoid agonists inhibit voltage-gated calcium channels, and activate potassium channels to produce presynaptic inhibition of glutamate release [50], without dissociative effects noted with other NMDA inhibitors, such as ketamine.” (9)

*Having adequate potassium and magnesium in the diet and avoiding excess glutamate in seasonings and other dietary sources can also help avoid migraines – in addition to the cannabinoids or cannabinoid receptor agonists – activators.

Diabetes pain may also not be helped by opiates unless magnesium is also provided – and providing magnesium in a larger dose helped even more! (10)

Post with phospholipid food sources, and magnesium foods and supplement sources and topical sources: To have optimal Magnesium needs Protein and Phospholipids too.
Post about the many conditions that may involve magnesium deficiency: Magnesium – essential for eighty percent of our body’s chemistry.

Give the body what it needs to function and it functions. Miracle!

Sunshine might be part of the miracle too – vitamin D represents a group of chemicals which may aid us in ways we don’t know yet. Supplementing with one – vitamin D, may not be providing us others that we would have made if sun or full spectrum/UVB containing light is available. (13)

We need cannabinoids too – and some of us genetically can’t make them – since birth, and potentially – epigenetic changes might be occurring that cause dysfunction in a person’s ability to make cannabinoids at some point later in their life. Is that happening in LongCovid survivors? -discussed in the 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

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November 10, 2020

Glyphosate increases histamine, both may be a factor in COVID19

Recent posts include a long one on glyphosate, biofuel, and liver disease and how it may be increasing inflammation in severe COVID19; and two other posts (a, b) are about how an immune allergy type reaction increases histamine and a variety of symptoms, and which may be a factor in LongCovid. Foods and the health of our intestinal microbiome, bacteria and other microbes, can also increase histamine directly or indirectly. Some foods contain histamine and others cause more histamine to be produced. Glyphosate residue may also cause an increase in histamine. (1)

Genetics may be a factor in who is more at risk for having excess histamine. There is an enzyme needed to break down the excess histamine from foods, within the intestinal tract, which some people may not be able to make. It can be purchased as a supplement and taken with meals. Other people may have overactive mast cells which are the type of immune cell that produces histamine throughout the body. (1 , 2)

If the mast cells are overactive, MCAS – Mast Cell Activation Syndrome, symptoms may be more severe than a seasonal allergy type of histamine reaction and may include: “rashes, hives, itching, flushing, fainting, headache, abdominal pain, nausea, vomiting, gastroesophageal reflux disease (GERD), fatigue, chronic pain, trouble breathing and many more.” (2) To complicate trying to figure out if this is a problem for oneself or a patient the overactivity of mast cells may also be associated with other complex conditions that have varied symptoms too, including: “allergies, autism, autoimmune disorders, cancer, diabetes, Ehler-Danlos syndrome, postural orthostatic tachycardia syndrome (POTS), fibromyalgia, Lyme disease, mastocytosis, migraines and obesity.” (2) Add the various symptoms together and a person might have a confusing mixture of “twenty to thirty symptoms” and feel “extremely ill.” (2)

Lab tests frequently are not helpful for many of the conditions or MCAS and it may also be unclear whether a person is having histamine symptoms because of intestinal digestion or microbiome problems or due to overactive mast cells throughout the body. Severity of symptoms may be worse if the problem is related to mast cell activation throughout the body. Treatment approach would also be different. Some people might be helped by use of the digestive histamine enzyme while others wouldn’t need it. Both types, digestive histamine excess and mast cell over activity, would be helped by decreasing histamine containing foods or ones that increase release of histamine from mast cells. Eliminating all histamine from the diet would be impractical if not impossible. Reducing the amount might make a significant difference though in reducing the negative symptoms. More details about identifying the type of problem with lab tests or other clinical indicators and an elimination diet description are available here: westonaprice.org. (2)

Glyphosate as a stimulator of histamine release (1) would create a different list of foods to avoid. See the previous post “a long one on glyphosate,” the list of tips are summarized at the top of the post, so the full length can be skipped if desired.

Over active mast cells may involve cannabinoid deficiency. Mast cells have both Cannabinoid Receptor Type 1 and Type 2 on the cell surface and when activated they cause an inhibition of the mast cell.

“Mast cells contain CB1 and CB2 receptors, which when activated inhibit mast cell release (R). Research shows that cannabinoids can suppress mast cell degranulation. … Our results show that CB1 and CB2 mediate diametrically opposed effects on cAMP levels in mast cells. ” (3, 4)

“We have previously shown that exposure of mast cells to cannabinoids that bind to both CB1 and CB2 cause a net suppression in the proinflammatory responses.” […] “At short time points, ligation of either CB1 or CB2 leads to a suppression of cAMP levels. However, over a longer exposure time course, the cAMP responses that follow ligation of the two receptors are diametrically opposed. These results allow us to draw two conclusions. First, the results imply that CB1 and CB2 receptors are not redundant when co-expressed in mast cells. Secondly, the results suggest that the two receptors couple to distinct signalling pathways that diverge downstream of the Gαi/o proteins to which they are both coupled.” (4) – that may suggest that a short time, small amount of THC & CBD may not help suppress the mast cells, by increasing cAMP sufficiently, a longer exposure, larger dose is needed – and that both the CB1 and CB2 receptor types need to be activated for the suppression of mast cell. CBD activates CB2 receptors and THC activates CB1 receptors.

“CBD alone without THC maybe ineffective at treating dysfunctional mast cells because THC has a strong binding affinity for both CB1 and CB2 receptors, cannabidiol (CBD) has no particular binding affinity. Instead, many of the therapeutic benefits of CBD are created through indirect actions.” (3)

Edibles or smoke? “However, when it comes to MCAS patients who are more severe, they tend to not tolerate ingesting the Medical Cannabis oil or edibles but may can inhale the actual Organic Medical Cannabis Flower and find great relief from MCAS symptoms.” (3)

More information about mast cells and what they do is included in Mast Cells: MCAS, genetics and solutions. geneticlifehacks.com (1) Viruses can activate mast cells, which then release histamine and other inflammatory cytokines and chemicals. The immune mast cells are also called granulocytes because when activated they release little packets, granules, full of the inflammatory chemicals. Flu virus has been found to activate mast cells and mast cell inhibitors helped reduce lung damage and mortality in severe cases of influenza. Too much inhibition during an active infection might not be helpful though, because the goal is to kill the virus infected cells or other pathogens that can activate mast cells. (1)

What does histamine do?

“Brain histamine promotes wakefulness and orchestrates disparate behaviors and homeostatic functions.” […] “Dysfunctions of the histaminergic system may also contribute to the pathogenesis of multiple sclerosis and its murine model of experimental autoimmune encephalomyelitis,” […] “Histamine neurons send broad projections within the CNS that are organized in functionally distinct circuits impinging on different brain regions.” (5)

Histamine promotes wakefulness, so an excess may lead to insomnia problems, and it affects a lot of varied behaviors and balance of functions throughout the body, disparate – a wide range of behaviors, which suggests why there can be such a wide range of symptoms, and homeostatic – balance of body functions – no longer as able to stay at an even center, too tired, or too excited, too cold or too flushed, numbness or pain – roughly. Too itchy too often.

“Histamine itch and non-histamine itch are mainly mediated by TrpV1 and TrpA1 respectively. In addition, Trp channels can be coupled to cytokine receptors, toll like receptors or may even be directly activated by pruritogens.” (6)

Inflammatory bowel disease (IBD) can involve overactive mast cells and excess histamine activating Trp channels in the intestines, (1), leading to sudden diarrhea and/or pain. “Pruritigens” refers to other chemicals that directly activate Trp channels such as horseradish or Latex that cause itching, (pruritus). Others may cause the bowel symptoms of IBD including cinnamaldehyde from cinnamon, capsaicin from hot pepper, curcumin in turmeric, and other chemicals in spices or herbs like ginger, cloves, and mint. Previous post 1, post 2/webpage G3.5-3.6.2, G5.

Yes, it is not easy to figure out what you can eat if you have Mast Cell Activation Syndrome, or to safely use as skin care products or medications as some of the ingredients might be Trp channel activators.

Medications that may help reduce mast cell activation in the condition of Irritable Bowel Syndrome, similar to Inflammatory bowel disease but less severe, include mast cell stabilizers and “a medication to reduce prostaglandin E2 synthesis (e.g. a COX2 inhibitor) stopped the hypersensitivity in the animal model of IBS. [ref]” (1) Pomegranate peel extract and other antioxidants may act in part through COX2 inhibition. (previous post) Prep tips for pomegranate & the peel: G13.

Mast cell activation may also be involved in autoimmune diseases including Multiple sclerosis, Type 1 Diabetes, and Rheumatoid arthritis. (1) The excessive release of cytokines and inflammatory chemicals can lead to cell damage in surrounding tissue. Mast cells tend to be located within specific tissue areas of the body or along epithelial layers (skin and membrane linings of blood vessels or other tissue), rather than be free moving like some other types of immune white blood cells. (1) Some people may have overactivity in some areas of the body rather than throughout the entire body.

Regarding COVID19 illness, the cytokine interleukin 6 (IL-6) tends to be present in excess, (8), and it is a mast cell activator. (1) Vitamin C can help inhibit IL-6. (7)

Psychological stress causes mast cells to release their histamine and other chemicals – uh oh, time to think serenely about that. (1)

Tips to worry less – can you do anything about them? If no, try to let them go. Writing worries on notes and putting them in a worry jar is one idea – you did something about it. You can look through your worries later. If yes, plan your time – 1. write down your goals, long term – 5-10 years, mid length, this year, and short term, this day/week/month, and 2. make an action plan, what steps to take today, write a list. 3. Do your plan, cross off your list items. It can feel more organized and good to check off your short term goals, and more peaceful to have a plan. (9)

Regarding the complexity of Mast Cell Activation Syndrome, or histamine from food – writing down your symptoms and daily food, beverages, and other lifestyle issues that standout from your routine can help to start seeing a pattern of which foods or habits might be adding to the problem. Elimination diets are quiet simple to start and need to be followed for a couple weeks to get the body cleared out of the potential problem foods and hopefully start feeling better, whether itchy, headaches, fatigue, brain-fog, or pain, numbness, or other symptoms. Then add only one thing back and see if symptoms return. Symptoms may be fairly immediate, or the next day or two so gradual reintroduction will be easiest to track whether it seems to cause symptoms.

Lab tests and other help and medication may be nice too, if available, but an elimination diet can be done fairly easily and safely. Stick to a variety of foods from the different food groups and read bottles on any supplements or medications to check for ingredients that might also be trigger substances ‘starch’ is usually wheat or corn based unless specifically labeled like tapioca or arrowroot starch. Other post (a) includes links with a food diary and information about elimination diets for histamine issues. Not all people have exactly the same sensitivities and there can be an additive effect, many problem foods on the same day as stress – may become a flare up. Some of the lists vary and some are more restricted than others, but most have similarities in the worst risk foods. Starting with eliminating some of those and seeing if you start feeling better can also be a way to work towards learning what are problem foods for you personally.

Reference List

Mast cells: MCAS, genetics, and solutions, geneticlifehacks.com, https://www.geneticlifehacks.com/mast-cells/
Hidden in Plain Sight: Histamine Problems, westonaprice.org, https://www.westonaprice.org/health-topics/modern-diseases/hidden-in-plain-sight-histamine-problems/
Www.TickedOffMastCell.Org, Medical Cannabis: Mast Cell Activation Syndrome, 10/24/2019, ibcnj.com https://ibcnj.com/medical-cannabis-mast-cell-activation-syndrome/
Small-Howard AL, Shimoda LMN, Adra CN and Turner H, Anti-inflammatory potential of CB1-mediated cAMP elevation in mast cells. Biochem. J. (2005) 388, 465–473 https://anandaenterprises.com.au/wp-content/uploads/2019/12/Anti-inflammatory-Potential-of-CB1-mediated-CAMP-Elevation-in-Mast-Cells.pdf.pdf
Passani MB, Panula P, Lin JS. Histamine in the brain. Front Syst Neurosci. 2014;8:64. Published 2014 Apr 28. doi:10.3389/fnsys.2014.00064 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009418/
Sun S, Dong X. Trp channels and itch. Semin Immunopathol. 2016;38(3):293-307. doi:10.1007/s00281-015-0530-4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798920/
Härtel C, Puzik A, Göpel W, Temming P, Bucsky P, Schultz C: Immunomodulatory Effect of Vitamin C on Intracytoplasmic Cytokine Production in Neonatal Cord Blood Cells. Neonatology 2007;91:54-60. doi: 10.1159/000096972 https://www.karger.com/Article/Abstract/96972#
Grifoni E, Valoriani A, Cei F, et al. Interleukin-6 as prognosticator in patients with COVID-19. J Infect. 2020;81(3):452-482. doi:10.1016/j.jinf.2020.06.008 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278637/
Gerry McCann, How to Manage Your Time Worry Less and Discover more Happiness, youtube.com, https://youtu.be/RgBb4xNrM-s

August 14, 2017August 14, 2017

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.

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.)

“Disease,” Oxford Dictionaries (I.1.disease)
“BHMT,” wikigenes.org, http://www.wikigenes.org/e/gene/e/635.html (I.wikigenes.BHMT)
Glycerophospholipid biosynthesis,
metabolism ,
Phospholipid metabolism,
(I.6.genecards.BHMT) [http://www.genecards.org/cgi-bin/carddisp.pl?gene=BHMT] (I.6.genecards.BHMT)
(I.7.genecards.phosphorylation) [http://pathcards.genecards.org/card/cdk-mediated_phosphorylation_and_removal_of_cdc6] (I.genecards.phosphorylation)
“Leukotriene,” (I.8.scbt.com)
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)
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)
(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)
(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)
(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)
(I.14.genecards.CYFIP2) CYFIP2, genecards.org, http://www.genecards.org/cgi-bin/carddisp.pl?gene=CYFIP2 (I.genecards.CYFIP2)
(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)
(I.16.sphingolipids)
(I17..mpcfaculty.lipids)
(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
(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)
(I.20.wikigenes)
( methionine )
( Dimethylglycine (DMG).
John Bartlett, Familiar Quotations, 14th Ed., 1910, (p 634, I.23)
(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)
(I.25.veteransformedicalmarijuana) AMA Votes to Reschedule Medical Marijuana, VMCA, http://www.veteransformedicalmarijuana.org/node/67 (I.veteransformedicalmarijuana)
(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)
(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)
(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)
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)
National Helpline: Substance Abuse and Mental Health Services Administration: 1-800-662-HELP (4357), (1.30samhsa.org)
Rape, Abuse and Incest National Network, RAINN Hotline: 1-800-656-HOPE, (1.31RAINN.)
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Amy Yasko, Nutrigenomic Testing, Holistic Health International, http://www.holisticheal.com/health-tests/nutrigenomic-testing (I.33.Nutrigenomic Screening)
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)

September 19, 2016March 31, 2017

Dimethylglycine (DMG) has one less methyl group than Betaine (TMG)

In the last post I mentioned that I started taking a specific form of an amino acid after I had found out that I have a genetic defect but that I didn’t really know how much might be necessary per day. The difference in my genes affects my ability to convert betaine the common name for trimethylglycine, into a more usable form called dimethylglycine. Betaine has one more methyl group than DMG. It is also called vitamin B15. Methyl groups are important for many things including preventing cancerous changes from occurring in the genetic structure of cells. [1]

What I didn’t know was how much might be necessary for me to take for daily health. A reference suggested that two grams per day is a minimal daily goal but that up to ten grams per day may be more optimal for health – not enough information is available about that however.

Two to ten grams per day is a specific number. I was taking two 100 milligram tablets per day. Two hundred milligrams is 1800 milligrams less than two grams – so I let my fingers doing the walking and found a bulk supply which I will be able to spoon into something liquid and just drink or eat. The switch will also save me a significant amount of money. [2]

The bottle of sixty 100 mg tablets provided 6000 milligrams / 6 grams of DMG at a price of $7.64 which I would use in one month. That seems inexpensive but it only provides 200 mg per day not 2 grams which is 2000 milligrams. At that level of use the bottle would last three days. At 10 grams per day I would need more than one bottle per day. The one kilogram bag supplies 1,000,000 milligrams for $65.96. If I use 2 grams per day the bag will last me 500 days or 100 days if I tried to use 10 grams per day. (2 grams of powder is roughly less than one teaspoon, there’s about 5 grams of liquid in a teaspoon but you would need to know the density/weight/mass of a powder to be able to calculate how many grams of a powder would fit in a teaspoon [3])

The genetic defect is in the gene that produces an enzyme that helps break down betaine/trimethylglyine into dimethylglycine and it is also involved in methionine metabolism but that is a different supplement/different topic. The gene is BHMT/1 (Call – T), and the enzyme it encodes for is Betaine-homocysteine methyltransferase (BHMT). See point #3 in the following post: Methylation Cycle Defects – in me – genetic screening “for research purposes only” . The post includes the link to the company that provides the genetic screening tests ‘for research purposes only’ (in other words: it can not be claimed to be ‘for diagnostic purposes’ legally at this stage of research and federal regulations).

The screening panel was developed to screen for defects that have been found to be more common in patients with autism. It was created by a scientist with a PhD and experience in genetics rather than an MD. The company provides nutritional information and possibly supplements but I haven’t spent enough time looking at the information to provide any review or opinion. I looked up information about my defects (11 out of 30) on my own. My notes are included in the linked post, it is not written as an essay type article with a beginning and end, it is a long list of notes for each defect*/gene allele/anomaly.

*Some gene differences are not negative as the word ‘defect’ suggests; allele is the word used in genetics for all the many known variations of one gene, there can be many slightly different forms with effects that might be good, bad, or cause no difference in health.

Nutrigenomics is an new area of science which specializes in providing individualized dietary counseling based on a person’s specific genetic structure. A person with typical genetic structure wouldn’t need to consider such a high dose of Dimethylglycine.

If the concern however is glyphosate substituting for glycine within proteins, then assuring that the body has a plentiful supply of the right kind of puzzle pieces (glycine) could help the body build more functional proteins, as repair and growth occurs every day. Glycine is an essential amino acid and and is not considered dangerous in isolation to my knowledge. (Aspartic acid and glutamate are also free amino acids and they can e dangerous in quantity to the brain as they can activate cell function and cause overwork to the point of cell death, hence the nickname excitotoxins – they are used in the food supply in a popular artificial sweetener and as a flavoring agent in substances such as MSG.)

/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./