Note about notes, an open notebook.

I write about many topics because I am interested in many topics. Health itself is a vast topic – interconnected though. Research silos with specialists focusing on the minutia of one area of study creates disconnect that may prevent seeing the greater whole needed for health.

I like health and haven’t had it consistently since early childhood. Many genetic differences in metabolism is part of my problem I’ve learned which makes it easy for me in some ways to see how important a body function may be in every day life – because I don’t have it. This also means solutions that work for me may not work the same for people with typical genetic metabolism. It may help some people though. Metabolic problems can occur due to illness, older age, or malnutrition.

Learning is teamwork. I study what others have written and make notes so I may more easily find the information that I read again. The internet is a big place, full of wonderful information – finding it again is not always easy. My blogs are my notebook – open access in the hope that it may help lead others to finding useful information for their own purposes.

I like health and current medical system does not focus on prevention or early treatment guidance. You have to be quite sick to prove a need for a diagnosis or treatment and the treatment may just be a medication that makes overall health worse rather than being guidance to correct underlying differences and improve natural function. My approach is the early identification of problems and how to restore natural function. Genetic differences and nutritional needs are my main focus and area of more experience. I am learning, there is a lot to learn.

Based on what I have learned about my body’s differences and chronic issues, paralysis, Alzheimer’s dementia, liver and kidney injury may be in my future – I would rather not have to experience any of those – which means I have to figure out what I may need to do to prevent them – because the focus of western medicine is on treating problems after they are fairly severe and show up on a lab test.

If my notes can help other people or researchers too, on their own path towards learning, bonus.

*mentioned to my sister this morning – I would need a graduate degree (or several) to understand all of this stuff – and then it would still be hard. This is very advanced information – I am not an expert – point is – no one is. Prevention of organ damage in sepsis is not happening across the US with the Covid epidemic – prevention requires early treatment before too much damage and irreversible scar tissue is formed.

The main mechanisms involved in the pathogenic cascade and in the evolution of sepsis are represented by the inflammatory response, immune response, and redox activity, followed by the involvement of cellular defects, which all lead to severe organ dysfunction. Adding to this phenomenon are severe respiratory infections; tissue hypoxia; acute kidney injury (AKI); metabolic imbalances; and, last but not least, derangements of the biological system as a whole. Through the augmentation of the inflammatory status and through the concomitant derangement of several organ functions, a high percentage of critical patients with sepsis develop multiple organ dysfunction syndrome (MODS), and finally death [8,10–12]. ” (1)

However, recent results have proven that cannabinoids are responsible for a decrease in the expression of certain pro-inflammatory cytokines such as IL-6, IL-12, IL-1, IL-2, and TNF-α.” (1)

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 (my notes for further study re last post)

  1. Anca Raluca Dinu, Alexandru Florin Rogobete, Tiberiu Bratu, et al., Cannabis Sativa Revisited—Crosstalk between microRNA Expression, Inflammation, Oxidative Stress, and Endocannabinoid Response System in Critically Ill Patients with Sepsis. Cells 2020, 9, 307; doi:10.3390/cells9020307, 28 January 2020 https://www.dropbox.com/sh/ux0r70xaszbnlj8/AAB4k6QoFRRM-XyKzacCs4-Pa?dl=0Furthermore, a series of important implications on inflammation and the immune system that are induced by the activity of cannabinoid receptors stimulated by the delta-9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD) have been noticed. One of the most important is their ability to reduce the biosynthesis of pro-inflammatory mediators and the modulation of immune mechanisms. Different studies have reported that cannabinoids can reduce oxidative stress at mitochondrial and cellular levels. … we wish to present the possible implications of cannabinoids in the most important biological pathways involved in sepsis, such as inflammation, redox activity, immune system, and epigenetic expression.”
  2. Tafti M, Ghyselinck NB. Functional Implication of the Vitamin A Signaling Pathway in the Brain. Arch Neurol. 2007;64(12):1706–1711. doi:10.1001/archneur.64.12.1706 https://jamanetwork.com/journals/jamaneurology/fullarticle/794818
  3. Kathleen L. McCoy, “Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation”, Mediators of Inflammation, vol. 2016, Article ID 5831315, 18 pages, 2016. https://doi.org/10.1155/2016/5831315 https://www.hindawi.com/journals/mi/2016/5831315/

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.

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. Mast cells: MCAS, genetics, and solutions, geneticlifehacks.com, https://www.geneticlifehacks.com/mast-cells/
  2. Hidden in Plain Sight: Histamine Problems, westonaprice.org, https://www.westonaprice.org/health-topics/modern-diseases/hidden-in-plain-sight-histamine-problems/
  3. Www.TickedOffMastCell.Org, Medical Cannabis: Mast Cell Activation Syndrome, 10/24/2019, ibcnj.com https://ibcnj.com/medical-cannabis-mast-cell-activation-syndrome/
  4. 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
  5. 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/
  6. 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/
  7. 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#
  8. 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/
  9. Gerry McCann, How to Manage Your Time Worry Less and Discover more Happiness, youtube.com, https://youtu.be/RgBb4xNrM-s

Vaping, Part 3: Combined risks – oils and TRP channel activators.

The risks of vaping may be additive, inhaling oils may increase risk of exogenous lipoid pneumonia (ELP), and inhaling TRP channel activators may increase risk of oxidative stress of cells or mitochondria. See part 1 Vaping and TRP Channel Activators, and part 2 Vaping Risks: ELP pneumonia and Oils, for the first two parts of the series.

Inhaling something accidentally is called aspirating and may occur while trying to swallow saliva, food or beverages, or during vomiting, especially for someone with weak muscles as may occur during chronic illness or with aging. Inhaling vape mixtures is purposeful and the original goal was to reduce health risks known to be associated with toxins caused by burning tobacco or an herb. Tobacco also has known carcinogens which would be removed from a product made with only the nicotine such as nicotine gums, lozenges or a nicotine patch.

Nicotine and cannabinoids can have health benefits, while toxins found in smoke can increase oxidative stress and may cause symptoms such as digestive problems, eczema, in addition to respiratory problems such as a chronic cough or bronchitis. Finding a safer way to consume nicotine or cannabinoids would be desirable however vaping may not be the solution, or not yet.

Flavorings that add odor are unnecessary for a product that isn’t inhaled through the nose, but an antioxidant preservative such as vitamin E and emulsifiers* such as glycerine are added to preserve and stabilize the mixture. Safer substitutes might not be available as other substances that preserve and emulsify might affect the lungs negatively also. Air is for inhaling, not emulsifiers. Vitamin E is oil based, antioxidants that are water based are available such as vitamin C, but then how would it stay mixed with an oil based cannabinoid or nicotine which dissolves better in oil or alcohol?

Nicotine can dissolve in water better than cannabinoids (2) and original vaping mixtures were made for nicotine rather than the cannabinoids THC or CBD. Vaping devices are available for powdered herb which heat the herb at a lower temperature than burning it, the problem with that method is that some of the beneficial cannabinoids in some strains of medicinal marijuana are only produced at higher temperatures so the vaped medicine may not provide the full symptom relief that smoking the strain would provide to a patient.

Trying to remove the glycerine from a nicotine vape mixture might not be fully protective against health risks either. The risk may involve a combination of the nicotine and the glycerine, as suggested in an murine based study of e-cigarette chemicals. Chronic exposure to a mixture containing nicotine and propylene glycol** (3 weeks for 20 minutes per day) was found to slow mucociliary clearing while exposure to the propylene glycol did not. Acute exposure (one week for 20 minutes per day) to either mixture did not cause slower mucociliary clearing. The size of particles effects clearance with larger particle size being more likely to remain in the lungs and smaller particles more likely to be exhaled. (4)

Nicotine also can act as a TRP channel activator (3) so the combination of some of the flavoring chemicals or the nicotine and cannabinoids may be opening the cell membrane’s TRP channels and allowing the glycerin or glycol to enter and accumulate to a level that inhibits cell function, causing Exogenous Lipoid Pneumonia or other health problems.

Pregnant women are advised to avoid use of vaped products (and to avoid smoke from tobacco or marijuana). An animal based study did find negative effects on lung alveoli development in newborn animals exposed to e-cigarette vape mixtures for the first ten days of their lives. Reduced weight gain was also noted. The negative effects were seen in the group exposed to nicotine and propylene glycol mixtures rather than the group exposed only to propylene glycol. (6)

If there is a take home point it may be that “Smoking is bad, mmmkay,”*** consider trying the nicotine patch, gum or lozenges, — but avoiding nicotine, smoking, or vaping during pregnancy is advised.

Cannabinoids are needed for fertility for females and males in a U shape curve – too little can cause infertility and too much can cause infertility. CBD is non-euphoria causing and is equivalent to the 2-AG form that is found in greater amounts during normal health than the THC equivalent called anandamide. Neither is recommended currently for use during pregnancy however genetic differences may cause a deficiency. Chocolate and some other legal food sources are available. Non-euphoria producing cannabinoids are the most abundant in plants and are also found in human breast milk and are important for stimulating the infant’s appetite and growth rate. We need cannabinoids in every cell of the body for many functions.. See the post Clinical Endocannabinoid Deficiency, (CED), and Phospholipids, for more information about symptoms or conditions that may be associated with a lack of cannabinoids and a list of legal food sources.

Footnotes:

*Glycerine is a natural emulsifier, helping to keep a water and oil mixture mixed without needing to shake it – picture an oil and vinegar salad dressing that separates into two layers compared to mayonnaise which has egg yolk as the emulsifier to keep the oil and water mixed together. (1)

** Glycerine/glycerin is also known as glycerol and glycols are similar chemically to glycerol. Some forms are more toxic to humans or animals than other forms. They are sweet syrupy liquids and may be consumed by animals if spilled in the form of antifreeze which would be toxic. (5)

*** South Park, paraphrase of a quote by the school guidance counselor Mr. Mackey.

Series:

Disclaimer: This information is provided for educational purposes within the guidelines of Fair Use. It is not intended to provide individual guidance. Please seek a health care provider for individualized health care guidance.

Reference List

  1. Pat Thomas, Read the Label: Emulsifiers, TheEcologist.org, Dec 14, 2008, https://theecologist.org/2008/dec/14/read-label-emulsifiers
  2. Nicotine, Chemistry Encyclopedia, http://www.chemistryexplained.com/Ne-Nu/Nicotine.html
  3. Feng Z, Li W, Ward A, et al. A C. elegans model of nicotine-dependent behavior: regulation by TRP-family channels. Cell. 2006;127(3):621–633. doi:10.1016/j.cell.2006.09.035 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859215/
  4. Laube BL, Afshar-Mohajer N, Koehler K, et al. Acute and chronic in vivo effects of exposure to nicotine and propylene glycol from an E-cigarette on mucociliary clearance in a murine model. Inhal Toxicol. 2017;29(5):197–205. doi:10.1080/08958378.2017.1336585 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553614/
  5. 14.6: Glycols and Glycerol, The Basics of General, Organic, and Biological Chemistry, (Ball DW, et al.) Chemistry LibreTexts, Last Updated, Aug 12, 2019 https://chem.libretexts.org/Bookshelves/Introductory_Chemistry/Book%3A_The_Basics_of_GOB_Chemistry_(Ball_et_al.)/14%3A_Organic_Compounds_of_Oxygen/14.06_Glycols_and_Glycerol
  6. McGrath-Morrow SA, Hayashi M, Aherrera A, et al. The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice. PLoS One. 2015;10:e0118344.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338219/