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:

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/

Vaping and TRP channel activators.

Vaping is a slang term used to describe a method for inhaling tobacco or other herbs without literally burning them with a flame. Electric heating devices turn volatile chemicals within the tobacco or herb into a vapor (gaseous form of the chemical) that can be inhaled. Typically smokers of tobacco don’t draw the smoke of cigarettes or a pipe deeply into the lungs while smokers of marijuana do tend to inhale and hold the smoke. Either type of smoking does create toxins from the act of burning the herb/tobacco leaf.

Electric vaping cartridges heat a liquid mixture that may contain nicotine from tobacco or THC/CBD from marijuana possibly along with other chemicals to help keep the mixture mixed (emulsifying oils such as glycerine) or chemicals that add a flavor and/or odor. The goal of vaping was to reduce the health risks that are linked to carcinogens in tobacco or to the chemicals that are created during burning a substance (too many decorative candles in a poorly ventilated home can also be a health hazard). Unfortunately there have been health problems and even some deaths linked to vaping nicotine or cannabinoid containing vape products.

Health risks have been linked to the glycerine (exogenous lipoid pneumonia (ELP), a type of pneumonia caused by excess fats/lipids in lung cells) (2), however other health problems have also occurred. No one chemical has been found that can be linked to all of the health problems or deaths that have occurred. (1) In addition to the type of pneumonia attributed to the glycerine content, several of the chemicals used to add flavor to vape products have been linked to various negative health symptoms.

Cinnamon contains cinnamaldehyde which has been found to be a health risk in vape products. (7) Risks have also been linked to o-vanillin, found naturally in vanilla, and pentanedione (found in honey). Other potentially harmful chemicals were also a frequent problem when fifty flavored vape products were tested 92% were positive for diacetyl, acetylpropionyl, or acetoin. (9) Glycerine may be harmful as a fatty substance that doesn’t belong in the lungs but may also be acting as modulators or activators of TRPV channels. (glycerine/glycerol) (12) Butter flavorings use 2-3-Pentanedione which has already been associated with lung problems associated with microwave popcorn. (13)

More complex flavors include several flavoring chemicals in combination, and risk may also increase from combinations or increased total quantity of the chemicals used as flavorings. Products available for sale may not be subject to regulation or labeling requirements so what a vape liquid contains may not be available to a consumer or a medical professional.

Natural phytonutrients found in vanilla and cinnamon add fragrance and health benefits, however when inhaled deeply into the lungs they may be overactivating cells due to their ability to open channels through cell membrane walls which allows excess calcium to enter the cell, or through the membranes of mitochondria found within cells. Cinnamaldehyde and vanillin are both TRP channel activators. TRP channels are portals through the cell membrane wall or in the membrane of organelles within the cell such as mitochondria, the main energy producing part of every cell. The TRPA1 channel is a type associated with coughing and mucous production. (8) Ethyl vanillin activates TRPA1 channels (10) and more typically vanillin is known to activate TRPV channels (the V stands for vanilloid). (11)

Vitamin E content in vape mixtures has also been linked with health risks associated with vaping. (4) Vitamin E can act as a preservative against oxidation, or spoilage of the oil content in a mixture, and it may also act as a TRP channel modulator – affecting the ability of other chemicals to open TRP channels. Vitamin E might help keep them closed in some tested conditions. (5) Cannabinoids can also act as TRP channel activators. (6) The non-euphoria producing cannabinoid known as CBD activates TRPV1 channels and the euphoria producing cannabinoid in marijuana known as THC activates the TRPA1 channels. (11)

Normally the fragrance of foods is sensed within the nose. The tongue and the lungs have no scent receptors. The cinnamon smells fragrant in small amounts but sniff a large amount and you may sneeze and your nose will likely start dripping with extra mucous production. Extra mucous production is a protective mechanism to keep potentially harmful or irritating chemicals from being inhaled into the lungs.

Horseradish has a very pungent smell and hot pepper simply burns when eaten or when it gets on delicate mucous membranes and eating either will also cause increased mucous production and release – in other words – a runny nose. Horseradish and hot pepper also contain potent TRP channel activators – they are causing mucous to be released. Extra mucous production is normal for your nose, it can just drip or be blown out, but deep within your lungs too much mucous production can cause the lungs to overfill and it may lead to pneumonia or Chronic Obstructive Pulmonary Disease (COPD) also involves lungs that are too full of liquid. COPD patients are recommended to avoid use of e-cigarettes as they may increase the inflammatory response of COPD lung cells (3)

The simplest take home point might be to avoid flavors in vape products altogether – the lungs can’t smell them, neither can your tongue, only your nose can. Unless you are inhaling through your nose, where mucous membranes are designed to prevent entry of toxic chemicals and TRP channel activators, then it would likely be safest to avoid sweetened or flavored vape products and avoiding unregulated products helps reduce the risk of unknown ingredients present in unknown amounts. An article on Healthline includes a long list of specific chemicals found in vape products that may have health risks. The article reviews other known health risks and includes links to the research articles. See: Is Vaping Bad for You? And 12 Other FAQs. (9)

*Vaping is not recommended during pregnancy due to the health hazards that are known, and the many unknowns about the health risks to a developing baby.

Continued:

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.

Things that may overstimulate TRP channels.

For more information and reference list about TRP channels see G3: Relaxation & Stress, and G5: Preeclampsia & TRP Channels.

Reference List

  1. Health Canada, Information Update – Health Canada warns of potential risk of pulmonary illness associated with vaping products, Oct. 11, 2019, hc.media.sc@canada.ca; https://www.newswire.ca/news-releases/information-update-health-canada-warns-of-potential-risk-of-pulmonary-illness-associated-with-vaping-products-867534807.html
  2. Viswam D, Trotter S, Burge PS, Walters GI, Respiratory failure caused by lipoid pneumonia from vaping e-cigarettes. BMJ Publishing Group Limited 2018 http://dx.doi.org/10.1136/bcr-2018-224350 , https://casereports.bmj.com/content/2018/bcr-2018-224350
  3. Heightened response to e-cigarettes in COPD, European Respiratory Society, https://openres.ersjournals.com/content/5/1/00192-2018
  4. Brueck H, Vaping is leading to a spate of lung injuries, comas, and death. Lung experts say oils like vitamin E may be partially to blame. Insider, Sep 19, 2019, https://www.insider.com/why-is-vaping-dangerous-for-your-lun
  5. Nazıroğlu M, Özgül C, Vitamin E modulates oxidative stress and protein kinase C activator (PMA)-induced TRPM2 channel gate in dorsal root ganglion of rats. C. J Bioenerg Biomembr (2013) 45: 541. https://doi.org/10.1007/s10863-013-9524-x https://link.springer.com/article/10.1007/s10863-013-9524-x
  6. Muller C, Morales P, Reggio PH. Cannabinoid Ligands Targeting TRP Channels. Front Mol Neurosci. 2019;11:487. Published 2019 Jan 15. doi:10.3389/fnmol.2018.00487 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340993/
  7. Clapp PW, Lavrich KS, van Heusden CA, et al., Cinnamaldehyde in flavored e-cigarette liquids temporarily suppresses bronchial epithelial cell ciliary motility by dysregulation of mitochondrial function. American Journal of Physiology-Lung Cellular and Molecular PhysiologyVol. 316, No. 3, https://www.physiology.org/doi/abs/10.1152/ajplung.00304.2018?journalCode=ajplung
  8. Geppetti P, Patacchini R, Nassini R, Materazzi S, Cough: The Emerging Role of the TRPA1 Channel. Lung (2010) 188(Suppl 1): 63. https://doi.org/10.1007/s00408-009-9201-3 https://link.springer.com/article/10.1007/s00408-009-9201-3
  9. Is Vaping Bad for You? And 12 Other FAQs, Healthline https://www.healthline.com/health/is-vaping-bad-for-you
  10. Wu SW, Fowler DK, Shaffer FJ, Lindberg JEM, Peters JH. Ethyl Vanillin Activates TRPA1. J Pharmacol Exp Ther. 2017;362(3):368–377. doi:10.1124/jpet.116.239384 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539581/
  11. Premkumar LS. Transient receptor potential channels as targets for phytochemicals. ACS Chem Neurosci. 2014;5(11):1117–1130. doi:10.1021/cn500094a https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240255/
  12. Kahn-Kirby AH, Dantzker JLM, Apicella AJ, et al., Specific Polyunsaturated Fatty Acids Drive TRPV-Dependent Sensory Signaling In Vivo. Cell, Vol 119, Issue 6, 17 Dec. 2004, pp 889-900 https://www.sciencedirect.com/science/article/pii/S0092867404010475#!
  13. CDC – Flavorings-Related Lung Disease: Exposures to Flavoring Chemicals, NIOSH Workplace Safety and Health Topic, https://www.cdc.gov/niosh/topics/flavorings/exposure.html

Helping others is a way of life; TRP channels

“Whenever we see something which could be done to bring benefit to others, no matter how small, then we should do it.” — Tai Situ Rinpoche

(SamyeLing.org)

Sometimes getting started is the hardest part.

Notes & links for TRP channel enthusiasts, on chronic pain, gender differences with migraine, IBS/colitis, and the role of magnesium and TRP channels in fetal development:

The condensed version – women are more prone to migraines then men possibly due to a protective effective of testosterone. Estrogen may increase or decrease risk of migraine depending on amounts/balance with progesterone. Either way, magnesium deficiency can increase chronic pain and other TRP channel problems because it is a mineral that helps keep them closed – they are like gates in the cell membrane.

Magnesium deficiency in very early stages of pregnancy or conception can have a negative impact on development of the embryo which can cause problems with physical and/or brain growth which can affect the infant throughout life. Pumpkin seeds has been the short answer I’ve given for years (post) – they are a good source of magnesium and many other nutrients, about one to two ounces, 2-4 tablespoons per day is a healthy serving. Like many things in life too much regularly may not be as healthy. Epsom salt baths are a topical source of magnesium and sulfate which would bypass any problems with digestion making it a good source for people with Irritable Bowel Syndrome or colitis, both of which can be problems linked to overactive TRP channels. (More about magnesium sources.)

Stress can be a cause of overactive TRP channels in addition to the risk of changes occurring during early conception/embryological development.

Other triggers for TRP channels include hot pepper (capsaicin), vitamin D/ and curcumin (a vitamin D analog) a phytonutrient found in turmeric, the yellow spice used in curry powder, ginger, horseradish; volatile chemicals such as formaldehyde, gasoline fumes, cigarette smoke, ammonia; very cold temperatures or very hot temperatures; increased pressure such as might occur during carnival rides or from overeating a large meal or gassy meals with large servings of raw vegetables such as cabbage or broccoli. Cinnamon, mint, vanilla can also activate some types of TRP channels – there is a large variety of TRP channels and they don’t all react to the same triggers and not all types are found in the same organ systems within the body so migraines and bowel troubles may not share the same triggers, but having a place to start can be helpful instead of feeling that everything you eat or do might be a problem.

Interesting hot pepper trivia: “Although both sexes showed sensitivity to capsaicin, males required a four-fold higher dose of capsaicin than females for a similar response (Lu et al., 2009)” (ref 2)

Quotes from an excerpt of ref 1,
(https://www.researchgate.net/figure/Involvement-of-TRP-channels-in-stress-TRPV1-a-member-of-TRP-channel-is-present-in_fig2_234019431) )
Importance of TRP channels in pain:

  • Implications for stress, causal or strong correlation: “altered expression, function and/or regulation of TRPs are key changes which induce patho-physiological conditions like stress, neuropathic pain and cancer.”  
  • “TRPM2 and TRPV4 are involved in oxidative stress- induced cell death of hippocampal neurons (121).” – the hippocampus is an area involved in short term memory and is damaged early in Alzheimer’s disease.
  • “several TRPs can also be activated by estrogen, endrogen, testosterone, cortisol and many other steroids (Table 1)”– so stress could increase TRP channel activity due to inc levels of cortisol. /Speculation: Estrogen mimetics might also be over activating TRP channels./
  • Overactivating TRP channels can also cause IBS symptoms: “over-stimulation of TRPs leads to an influx of excess Ca 2+ which is generally associated with the cell death (126)”
  • “TRPV1 regulates food absorption, emesis, colitis and also regulates the gut – brain axis mainly by responding to endovanilloids and endocannabinoids (132-133).” – colitis is a more severe bowel condition than IBS, has similarities in symptoms though

Re reference 2:
Migraines are 3 times more likely to be a problem for women than men and it may be due to the sex hormone’s ability to activate TRPV1 channels https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102492/ … this info may help with developing more targeted treatments.
“migraineur women exhibited a thicker posterior insula and precuneus cortices compared to male migraineurs & the healthy controls of both sexes (Maleki et al., 2012)”
Testosterone may help protect men from migraines or as severe a migraine if they do have one. It helps modulate activity of TRPM8 channels. Over expression of TRPM8 channels “by a testosterone-mediated mechanism” is seen in prostate cancer.

Re reference 3:
Genetic differences in gene for TRPM8 channels (transient receptor potential melastatin 8) have been identified that are more common in people w migraine sensitivity. They are activated by cold temperatures and/or menthol (mint).

Re reference 4:
TRPM6 & TRPM7 channels and magnesium are known to be critical in embryological development, inc pigmentation/melanin. Mg deficiency during pregnancy can cause significant problems.
TRPM7 & magnesium also critical for dopaminergic cells/Parkinson’s disease. other embryo dev differences w Mg deficiency were seen in the gut & spine (less straight). – a review: TRPM Channels and Magnesium in Early Embryonic Development (4)

TRP channels may become overly active from stress or during fetal development. The symptoms can be difficult to notice a pattern of triggers because the TRP channels have many different ways of being activated. See the G3 excerpt in this document for more details, Child Trauma, Possible Relationship or Chronic Physical Symptoms as an Adult – or for a more condensed version see the graphic below.


“If I had more time, I would have written a shorter letter.” ~ Blaise Pascal

(QuoteInvestigator)
Things that may overstimulate TRP channels.

“Well begun is half done.” – Aristotle

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

References:

  1. Kumar, Ashutosh & Goswami, Luna & Goswami, Chandan. (2013). Importance of TRP channels in pain: Implications for stress. Frontiers in bioscience (Scholar edition). S5. 19-38. https://www.researchgate.net/publication/234019431_Importance_of_TRP_channels_in_pain_Implications_for_stress
  2. Artero-Morales M, González-Rodríguez S, Ferrer-Montiel A. TRP Channels as Potential Targets for Sex-Related Differences in Migraine Pain. Front Mol Biosci. 2018;5:73. Published 2018 Aug 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102492/doi:10.3389/fmolb.2018.00073 Interesting hot pepper trivia: “Although both sexes showed sensitivity to capsaicin, males required a four-fold higher dose of capsaicin than females for a similar response (Lu et al., 2009)
  3. Dussor G, Cao YQ. TRPM8 and Migraine. Headache. 2016;56(9):1406-1417. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335856/
  4. Komiya Y, Runnels LW. TRPM channels and magnesium in early embryonic development. Int J Dev Biol. 2015;59(7-9):281-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685952/