G3.6.1.7: TRPV channels – the comfort of vanilla, the heat of capsaicin.

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 [42]. 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.  (G3.117G3.118)

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)


G3.5: Negative stress chemicals may cause symptoms like itching, migraines, pain or IBS.

Our bodies don’t have specific receptors just for sensing “pain.” Pain is a sign that something is wrong in the body and is sensed in a variety of ways. In medical terminology there are two main types of “pain.”

  • Nociceptive pain is associated with physical damage to the body or by sensations of pressure or heat or extreme cold. It might be due to pressure from a cancer tumor. Nociceptive pain might be described as “sharp, aching or throbbing.”
  • Neuropathic pain is caused by physical damage or pressure on nerves. It might also be due to a cancer tumor but one that is pressing on a nerve. Nerve damage can also be due to some nutrient deficiencies such as vitamin B12,  (G3.13), or other “Nutritional imbalance, alcoholism, toxins, infections or auto-immunity.” Neuropathic pain often is described as “a burning or heavy sensation, or numbness along the path of the affected nerve.” (G3.14)

Some types of pain such as migraine headaches may involve both nociceptive pain due to the pressure of inflammation or dilation of blood vessels an neuropathic pain from pressure on nerves by dilated or inflamed blood vessels.

    The next part gets complicated, some background information:

  • Calcitonin is a hormone released by the thyroid that promotes lower blood calcium levels by reducing bone resorption, (G3.15) (Bone resorption: breakdown of the bone and release of minerals, (G3.16)).
  • Calcitonin Gene-Related Peptide 1 and 2 (CGRP 1: (G3.17) and CGRP 2: (G3.18)) cause dilation of blood vessels in the heart and brain and throughout the body. Its prevalence in the Central Nervous System (CNS) also suggests that it may also have a neurotransmitter or neuromodulator role.

CGRP is produced by nerve cells in the brain and throughout the body. The protein has a role in sensations of pain. It is a member of the calcitonin family of proteins and exerts its effects at receptors that are formed from two other types of receptors.

The CGRP protein has two commonly found forms, one helps reduce pain and one helps increase it – luck of the draw. The alpha form of the protein may help reduce pain while the beta form is associated with migraine, temporomandibular joint (TMJ) pain, psoriasis and irritable bowel syndrome (IBS). The beta form is largely produced in keratinocytes found in the epidermis layer of skin. The alpha form is the type produced more within sensory nerves. (G3.19) (Psoriasis is an eczema-like condition believed to be autoimmune in nature.)

After a physical injury like a bump on the shin, inflammation causes an increased output of the Calcitonin Gene-Related Peptide (CGRP) and an inflammatory protein that is called Substance P, possibly for peptide, which is another word for protein. The release of the peptides follows shortly after an inflammatory event and shortly the chemicals are released there is  edema and plasma leakage in the surrounding area. (G3.20) The inflammatory peptides are also released in increased amounts during migraine headaches. (G3.21) The peptides increase the dilation of blood vessels and cause increased leakage from blood vessels (edema) and “degranulation of mast cells.” (G3.19) (G3.21)

Levels of CGRP increase in people who suffer from migraines and a type of prescription medication, called sumatriptan, which has been found helpful to stop migraine pain, has also been found to inhibit the release of CGRP in migraine patients. The medication may be inhibiting the release of CGRP by increasing intracellular levels of calcium. The “cytokine TNF-α” may be involved in migraine pain. (G3.21)

That was the background – the bottom line – magnesium deficiency can make the body more susceptible to the negative effects of CGRP, Substance P and chronic stress. And a chronic stress situation combined with chronic magnesium deficiency may lead to the development of inflammatory conditions like migraines, fibromyalgia, PTSD, or Irritable Bowel Syndrome. The magnesium deficiency associated with the inflammatory peptides CRGP and Substance P may be causing an increase in the level of the cytokine TNF as early as two days after a deficient diet was begun in a research study with lab animals. (G3.22)

So an Epsom salt bath or foot soak may relieve itch by providing the body with a form of magnesium that can be absorbed through the skin bypassing any GI problems that might underlie a chronic magnesium deficiency. It isn’t uncommon to have a diet low in magnesium but it is also not uncommon in the food supply. Problems with poor absorption or increased kidney or bowel loss are common causes of chronic magnesium deficiency.

A variety of tips for reducing Substance P levels are included in the article Trichodynia, Pain, and Substance P. Exercise, hobbies that use repetitive motions of the hands such as knitting, and stretching exercises may help reduce excess levels of the inflammatory chemical according to the article on the website drwardbond.com, see the article for more details: (G3.23)

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)


Newborn screening for autism – 3 sets of 5 potential biomarkers

I bought the research study regarding newborn screening for autism and it is exciting but was based on a small number of patients with a diagnosis of autism spectrum disorder (n=16, control group n=32).

  1. Newborn screening for autism: in search of candidate biomarkers. [http://www.ncbi.nlm.nih.gov/pubmed/23547820 ]

The research study evaluated the newborn umbilical cord blood for 90 biomarkers (various types of lab tests), 76 biomarkers were found to have consistant data available for all study subjects,  and three sets of five biomarkers were found to be consistently increased or decreased in the infants who were diagnosed with autism later in life compared to the infants in the control group (the research study only used patients with an autism diagnosis who had been screened and diagnosed by the same physician in order to reduce risk of inconsistent diagnostic standards in the experimental group (n=16).

The three sets of five biomarkers need to be tested with a larger group of children with autism diagnoses to see if the results can be repeated. Feasibly to save money on lab tests all newborns might be screened with the set of five most predictive lab tests and the infants who are positive for those five might then be screened for the second set of five tests or all ten of the other biomarkers. The fifteen biomarkers include calcitonin (increased) and Thyroid Stimulating Hormone (TSH, decreased). Low TSH levels can cause increased calcitonin levels which causes reduced blood calcium levels. Elevated blood levels of calcium may cause an increase in calcitonin and having adequate levels of hormone 1, 25 D may be necessary for keeping calcitonin levels within a normal range. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC442503/]

Vitamin D was not one of the 90 lab tests that were included in this research study, however the sibling study performed in Sweden suggested that low vitamin D at birth is involved but that other factors are also involved because all of the children born to Somalian refugees were found to have low vitamin D so that lab value would not be helpful as a screening test. 2) Swedish Study Suggests Low Vitamin D at Birth May Increase Autism Risk [https://www.autismspeaks.org/science/science-news/swedish-study-suggests-low-vitamin-d-birth-may-increase-autism-risk]

Alpha feto-protein (AFP) is one of the fifteen biomarkers found to be predictive for autism later in life. Levels of AFP have been found to be increased in both the mothers of infants who develop autism later in life and in the infants who develop autism later in life. Buy the research study to find out the other twelve – feasibly a concerned parent (with money and a cooperative physician) might be able to have their newborn’s blood screened for the fifteen biomarkers on their own initiative, right away, rather than waiting for the mainstream medical industry to do further research studies.

— The fact that autism was unknown in Somalia suggests that it is unlikely to be a naturally occurring condition and that it is unlikely to be caused by a lack of anti-autism medicine or by the lack of an anti-autism vaccination, so waiting for the for-profit medical industry to devise a for-profit strategy to prevent autism seems like it might take awhile. Concerned parents should have a right to seek effective care for their children and for themselves.

Autism seems to be a condition that occurs prenatally which leaves the newborn infant with metabolic differences but who otherwise appears normal and then, depending on nutritional and environmental conditions, at around age two to four the child’s development shifts towards symptoms of autism. The goal of newborn screening would be to identify which infants are most at risk for that later shift towards autism so that they might be able to be given additional care in order to prevent the damaging autoimmune like changes to the child’s brain. A few different genetic defects that affect nutrient needs may be involved so a newborn who is identified as high risk for developing autism symptoms later in life might then benefit from being screened for genetic defects in the methylation cycle, or with the vitamin D binding protein, or with hemoglobin metabolism. Infants identified as more at risk for autism later in life may also benefit from being screened for hypothyroidism, iodine deficiency, or an excess of bromide, chloride and fluoride.

In summary, for now, this is complicated but very exciting — we have the information we need in order to help women prevent autism before conception and to help identify which newborns may be more at risk for developing autism symptoms later in life so that we can help give the infants the additional nutritional and environmental support that might help them prevent the longterm autoimmune like brain damage from ever occurring.

Older individuals who already have autism diagnoses may also be helped by additional nutritional and environmental support (reduce their exposure to pollutants and foods or foods additives that their unique metabolism can’t digest as well as average) but a “cure” for the changes that already occurred in the brain may not be possible for children and adults who have already been diagnosed with an autism spectrum disorder. Individualized nutritional support might help reduce negative symptoms and improve quality of life for patients who already have an autism diagnosis.

/Disclosure: 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./