Before leaving the topic of “getting to know your TRP channels,” I’d like to introduce the vanilloid family. They were among the first TRP channels to be identified with lab techniques. This is all very tiny stuff, difficult to work with compared to a craft or construction project in the full size world we can see without a microscope. It is easy, however, to see when someone is scratching or wincing from pain, so the lab technicians and research scientists are to be commended for their fine eye for microscopic detail.
Vanillin or vanilloid receptors can have a calming effect on the body – baked goods with vanilla have a little extra besides love soothing the body. However some types of TRVP channels can also be stimulated by hot pepper due to its capsaicin content. (G3.99) Capsaicin is the active phytochemical that causes a feeling of “hot” when hot peppers are eaten – because it activated a TRPV channel which activates a nerve to send a signal to the brain that is most likely to be interpreted as “hot” although some people learn to enjoy the feeling, or may be genetically different and experiencing slightly differently than other people who couldn’t imagine eating very hot, hot peppers (G3.100)
The aroma of vanilla can lead to an emotional feeling of comfort even without eating a food containing the phytochemical that can activate the TRPV channels. “Aroma” does involve nerves being activated in response to a chemical in the air that enters the nostrils. Tiny amounts of “vanilla” aroma are entering the nose and physically activating TRPV channels which physically activate nerve signals that tell the brain “something” happened. This time it wouldn’t be as obviously “hot” as the capsaicin though, the vanilla is activating a different TRP channel which would activate a different nerve. If hot peppers had been experienced before the memory of them would be strong enough to remember not to eat them or touch them again. Making “noxious” chemicals, irritants or toxins, is a plant defense mechanism to encourage animals to not eat the plant unless it is ready for the seeds to be spread. A delicious fruit smells delicious when it is ripe and the seeds are ready to be “planted” somewhere other than right where the plant is growing. Some plants make seed pods that catch the wind or have burrs and attach to animal fur as animals walk by, and other plants make delicious fruit or other nutritious seeds to encourage animals to eat them, and carry the seeds elsewhere to be “planted” later (whenever the animal defecates). Nature is amazing.
Vanilla is a delicious smelling seed pod so the plant must want its seeds to be eaten. For delicious history and recipe information see Primer: Vanilla Part One and Two, by Jasmine, a culinary blogger. (G3.102, G3.103)
We learn from previous experiences when to avoid something and when to reach for a second helping. If the brain had experienced home baked cookies in the past, then the scent of them baking any time in the future might set off an expectation of delicious food and activate saliva glands in addition to causing a calm or pleasant emotional response to the aroma of vanilla or a comforting memory from childhood. Aromas can also be tied to emotional responses that were learned in childhood or at any time in a trauma situation. Positive memories associated with an aroma may be triggered by re-experiencing the favorite fragrance or negative memories might also be triggered by a reminder of something associated with the trauma.
Cancer treatments can be so nauseating that patients are counseled to avoid favorite foods during the first few days after the treatment in order to prevent negative associations of nausea being linked to their favorite food. When feeling “under the weather” there is a natural instinct to want to tempt the appetite with a comfort food – but if it is most likely going to be thrown up and the hope is that a few nutrients get absorbed before that happens then a bowl of oatmeal or a entree from an expensive restaurant would be equally unappealing on the way back up and the unusual meal might be more likely to cause memories of the experience. So – the common sense recommendation from dietetics eat the oatmeal while feeling sick or something neutral and save the favorites for later.
TRP channels – what were they again?
Physiology and Pharmacology of the Vanilloid Receptor, (G3.98) Excerpt: “In addition to the contribution of the vanilloid receptor as a target of the neurogenic inflammation underlying different diseases, TRPV1 is gaining interest for the treatment of neuropathic, postoperative and chronic pain and, recently, for the therapy of epithelial disorders [epithelial = skin or membrane]. Thus, for instance, topical capsaicin or resiniferotoxin have been used in postherpetic neuralgia, diabetic neuropathy, postmastectomy pain and arthritis [64,103]. Recently, TRPV1 has been clearly validated as a key target for management of chronic pain in bone cancer . As a result, the development of specific TRPV1 antagonists is a central focus of current drug discovery.” (G3.98)
To review: magnesium is the ion that is needed inside of the cell to power the TRP or ion channel’s ability to stop some chemicals from entering the cell’s interior while allowing other chemicals to enter. Magnesium is the soldier at the gate with the energy to stand sentry all day and night – if present. If there is magnesium deficiency, the sentry with energy to keep the gate shut is gone and any chemical floating around in the fluid outside of the cell that is small enough to fit through the open ion channel is able to flow through the unguarded gates. The capsaicin that can treat pain when used topically is over stimulating the receptors to the point where they are no longer sending any pain signals. When there is a magnesium deficiency then calcium itself can be a cause of pain.
Inside the interior of the cell calcium can activate the cell function and cause it to overwork to the point of cell death similarly to the “excitotoxins” such as glutamate or aspartic acid, both used in the food supply as flavorings – they also excite the tongue’s taste buds. MSG, aspartame and Neotame were included in the list of chemicals that might activate TRPA1 receptors which are associated with several chronic pain and chronic itch conditions.
Calcium signals the cell to overwork, which leads to inflammation and signals of pain. Nerve signals are activated by inflammatory chemicals which are also “pain” signals as perceived by the brain – inflammation hurts because it is activating “pain” nerves. “Inflammation,” “oxidative stress,” and “pain” are all experienced as the same thing to the brain. So if someone at work is annoying you and you just can’t stop thinking about it – you might be physically hurting yourself, consider taking a walk in nature or buying a fern instead. Smelling vanilla scented essential oil products may also provide some comfort.
- The research team suspect that “calcitonin gene related peptide (CGRP)” is involved in producing changes underlying the condition of “pain” and “inflammation” for the condition of arthritis at least. Inflammatory chemicals produced in one area of the body could travel and send nerve signals that led to inflammatory pain symptoms being felt in other areas of the body – so over-thinking can hurt? Read more: New Study Proves that Pain is Not a Symptom of Arthritis, Pain Causes Arthritis. Newsroom, University of Rochester Medical Center, urmc.rochester.edu, Sept. 29, 2008, (G3.109)
However CGRP has also been found to be involved in helping to suppress severity of symptoms in autoimmune diabetes. Providing CGRP therapy in an animal based research study helped reduce oxidative stress chemicals and the damage they can cause to pancreas cells that can eventually lead to developing autoimmune diabetes. (G3.114) Researchers working with human patients who have diabetes theorize that those people with a reduced response to stress are the people who seem to progress to diabetes most quickly. (page 19, G3.115) Chemicals similar to CGRP have also been tested therapeutically for heart disease patients and has been found to have some benefits for reducing hypertension, cardiac hypertrophy, and heart failure. (G3.116)
As a dietitian the question I next ask when I learn about a chemical in the body that seems to promote health is how do we make it for ourselves? How can we better assist patients to make it for themselves rather than being dependent on a daily medication? What does a person need to make CGRP ?
Drumroll – an answer does already exist in medical research – magnesium. Providing magnesium directly to an area of bone with a fracture in need of healing, was found to effectively promote increased bone healing – possibly due to a measured increase in levels of CGRP. (G3.117, G3.118)
So would you rather have a medical professional provide you a daily medication at a profit to the medical system – or be informed of ways to change your diet and lifestyle so that you could make the life saving chemical naturally the way healthy people do, everyday?
Like most things in life – too much CGRP isn’t good either. Genetic differences may be involved in risk for migraine as elevated levels of CGRP have been found in patients with migraines. Attempts to block the chemical Substance P were found to be ineffective but use of CGRP agonists/blockers were found to help patients with migraine. (G3.119)
And sugar is something that is a negative when eaten in excess. Too much sugar in the diet typically also means fewer nutrients are being consumed as refined sugar has no additional B vitamins or magnesium, while a piece of bread or fruit would provide some nutrients in addition to the naturally found sugars. Excess sugar in the bloodstream leads to an increased loss of magnesium by the kidneys because the mineral is necessary in order to remove the excess sugar from the blood and add it to the urinary waste stream. (G3.120) B vitamins are needed in order for the body to be able to break down the molecules of sugar so the stored energy is released. Smaller waste chemicals are produced from the larger sugar molecule that will also need to be excreted by the body as a normal part of metabolism (metabolism is roughly equal to all of the body’s many chemical, energy and digestive cycles). A diet with excess refined sugar has also been associated with heart disease risk. (G3.121)
See a healthcare provider for medical advice, diagnosis or treatment.
- 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.
- The Academy of Nutrition and Dietetics has a service for locating a nutrition counselor near you at the website eatright.org: (eatright.org/find-an-expert)
- G3.98: (97-102 was from a blog posted on Nov 26,, 2011) Angel Messeguer, Rose Planells-Cases, and Anton Ferrer-Montiel, Physiology and Pharmacology of the Vanilloid Receptor, (Curr. Neuropharmacol., 2006 January: 4(1) : 1-15) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430674/ (G3.98)
- G3.99: Makoto Tominaga, Michael J. Caterina, Annika B. Malmberg, et al., The Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli., Neuron, Vol. 21, 531–543, September, 1998 http://www.columbia.edu/cu/biology/courses/w3004/recitation7.pdf (G3.99)
- G3.100: Capsaicin; Neurobiology of Disease 07, Connecticut College, conncoll.edu, https://sites.google.com/a/conncoll.edu/neurobiology-of-disease-07/home/capsaicin (G3.100)
- G3.102: Jasmine, Primer: Vanilla Part One, Confessions of a Cardamom Addict, cardamomaddict.blogspot.com, http://cardamomaddict.blogspot.com/2006/01/primer-vanilla-part-one.html (G3.102)
- G3.103: Jasmine, Primer: Vanilla Part Two, Confessions of a Cardamom Addict, cardamomaddict.blogspot.com, http://cardamomaddict.blogspot.com/2006/01/primer-vanilla-part-two.html (G3.103)
- G3.109: New Study Proves that Pain is Not a Symptom of Arthritis, Pain Causes Arthritis. Newsroom University of Rochester Medical Center, urmc.rochester.edu, Sept. 29, 2008, https://www.urmc.rochester.edu/news/story/2131/new-study-proves-that-pain-is-not-a-symptom-of-arthritis-pain-causes-arthritis.aspx (G3.109)
- G3.114: Sheng Li Xue Bao. Calcitonin gene-related peptide gene therapy suppresses reactive oxygen species in the pancreas and prevents mice from autoimmune diabetes. Acta Physiologica Sinica 2003 Dec 25;55(6):625-32. http://www.actaps.com.cn/paper/200306/pdf/02.pdf (G3.114)
- G3.115: Andrew Curry, The Depression Connection, Diabetes Forecast, May/June 2017, Subscription service, diabetes forecast.org, http://www.diabetesforecast-digital.org/diabetesforecast/may_june_2017?pg=1#pg1 (page 19, G3.115)
- G3.116: Aisah A. Aubdool, Pratish Thakore, Fulye Argunhan, et al., A Novel a-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy, and Heart Failure. Circulation. 2017;136:367-383 http://circ.ahajournals.org/content/136/4/367 (G3.116)
- G3.117: Yifeng Zhang, Jiankun Xu, Ye Chun Ruan, et al., Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats., Nature Medicine, 22, 1160–1169, (2016), http://www.nature.com/nm/journal/v22/n10/full/nm.4162.html (G3.117)
- G3.118: Xiaodan Chen, Magnesium-based implants: Beyond fixators., Journal of Orthopaedic Translation, Volume 10, July 2017, Pages 1-4, sciencedirect.com, http://www.sciencedirect.com/science/article/pii/S2214031X16302820 (G3.118)
- G3.119: Emily Underwood, Feature: Will antibodies finally put an end to migraines?, sciencemag.org, Jan. 7, 2016,
- G3.120: USDHHS, National Institutes of Health, Magnesium – Health Professional Factsheet, ods.od.nh.gov, https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/ (G3.120)
- G3.121: Densie Webb, PhD, RD, Sugar Industry Cover-Up?, Today’s Dietitian, Vol. 19, No. 1, January 2017, pages 20-23, http://www.todaysdietitian.com/newarchives/0117p20.shtml (G3.121)