G3.6.1: “Calcium sparklets” and Oxidative Stress

G3.6.1.1: “Calcium sparklet” – a burst of energy from a TRP channel; can be measured but not seen.

Calcium and magnesium are both electrically active ions – ions are atoms of an individual element rather than being a more complex molecule that is made of a combination of several different elements. Water is made of one atom of oxygen and two atoms of hydrogen for example. Calcium and magnesium are both individual elements rather than being molecules. They are both considered to be essential trace minerals that we need in our diet on a regular basis or we would get sick and eventually die without enough of either one. They each have an ionic charge of +2 and can exchange one or two electrons.

Ions can typically donate or receive electricity by sharing or receiving one or two electrons. Sodium and potassium are essential trace minerals with a charge of +1, they can exchange one electron. the energy is in the form of electromagnetic radiation, which is also what make “light., (G3.105), so while our human eyes may be too big to detect the “light” of a microscopic burst of energy from the flow of calcium across a TRP channel – maybe a tiny spark might be visible to that microscopic world.

Magnesium sparklers – a spark of life.

Many people may be more familiar with holiday “magnesium sparklers” than with “calcium sparklets” as the mineral magnesium is flammable and can be used to make Fourth of July sparklers, which are a festive sight during celebrations of the U.S. Independence Day.

 

G3.6.1.2: Calcium sparklets can be caused by high blood sugar – hyperglycemia. (G3.108)

  • Calcium and diabetic vascular dysfunction, Focus on “Elevated Ca2+sparklet activity during acute hyperglycemia and diabetes in cerebral arterial smooth muscle cells: This report is also the first to describe a molecular mechanism by which hyperglycemia produces increased [Ca2+]i in VSM and suggests that this mechanism of Ca2+ sparklet activation may be uniquely initiated by hyperglycemia.” (G3.108)

Calcium sparklets are not a good thing, not in excess at least, they represent an open gate into the interior of the cell, allowing a crowd to enter instead of invited guests only. (G3.106, G3.107, G3.108) Too much energy or other types of chemicals suddenly being available on the interior of a cell can over activate it and even lead to the death of the cell.

Excitotoxins” refers to chemicals that can cause a cell to become overactive if the chemical is allowed to enter the interior of the cell. TRP channels are the gateway that selectively lets in some things and keeps out everything else. If TRP channels aren’t able to do their job properly, then too much of “everything else” is able to rush into the cell and that may be what happens for some people more than others. If the everything else includes MSG from a recent meal or the alternative sweetener aspartame then overactivity of the cell may result.

Calcium itself acts as a messenger chemical that can trigger action when it is on the interior of the cell and can act as an “excitotoxin” and lead to the death of cells. During normal health magnesium is in greater abundance inside of the cell and calcium is found in larger amounts than magnesium in the fluid surrounding the cells and within blood plasma.

The alternative sweetener aspartame, brand name Nutrasweet, or the more concentrated version Neotame may both act as excitotoxins. The food flavoring ingredient monosodium glutamate also may over excite cells. What they have in common is a free amino acid that can act as a signal to the brain cell to tell it to get busy doing whatever it usually does, “just get busy, go, keep going, there’s no “off” here, move it . . .” an excitotoxin is the worse drill sergeant ever, and eventually the cell runs out of nutrients and/or builds up waste products of metabolism, and may even die. That’s a dramatization, but roughly that is the story – “oxidative stress” equals “waste products of metabolism.”

G3.6.1.3: Oxidative Stress > metabolic waste products > “TRPA1 sparklets.”

To return to the excerpt and list from the previous section, the first list of chemicals known to activate TRPA1 channels included waste products of metabolism. Metabolism is the chemical deconstruction of a larger molecule into smaller parts. Enzymes are necessary that are specific to the exact type of chemical transformation. Toxins can collect without enough of the right type of enzyme to metabolize them into smaller chemicals that are safe or can be excreted more easily by the kidneys.

  • The summary and excerpt: The TRPA1 receptor is directly activated by calcium levels inside of the cell, and a variety of toxins or “noxious” (irritating) substances that are produced as a normal part of “oxidative stress” otherwise known as “inflammation” including, “4-hydroxy-2-nonenal, hydrogen peroxide, hypochloride, hydrogen sulphide, 15-delta prostaglandin J2 [2528].” and irritants from the environment or diet can also activate the TRPA1 receptor, *1.mustard oil (allyl isothiocyanate: AITC) [29], *2. cinnamaldehyde [30, 31], *3. allicin [32, 33] and *4. formalin [34]…”. (G3.25) Serotonin and other “Inflammatory mediators, such as bradykinin…[19, 35]” (G3.25) can make the receptors more sensitive which can lead to increased responsiveness of nerve endings – more pain (G3.25) or itch. (G3.24)
  • And a new excerpt about oxidative stress and metabolites that are produced within the body, some would activate TRPA1 channels: “Reactive oxygen species (ROS)”(G3.93) formed from oxidative stress were found to activate the TRPA1 channels in the cerebral arteries but not in other areas of the vascular system, “NOX-induced activation of TRPA1 sparklets and vasodilation required generation of hydrogen peroxide and lipid-peroxidizing hydroxyl radicals as intermediates. 4-Hydroxy-nonenal, a metabolite of lipid peroxidation, also increased TRPA1 sparklet frequency and dilated cerebral arteries.” (G3.93).

“Increased TRPA1 sparklet frequency” (G3.93) can be caused by chemicals that are produced during oxidative stress – which can be caused by emotional or physical reasons. The significance is that it means more calcium or other chemicals could be rushing through the open channel in the membrane wall. Calcium can also be an activating substance as was mentioned in the first summary and excerpt. This is complex chemistry and is just meant to be an introduction to the topic of oxidative stress in relation to conditions of chronic pain and itch. That second excerpt is from an additional list and is about chronic migraine – who are the people who might be more likely to have overactive TRPA1 channels? – quite a few besides those with sensitive skin or pain problems. A more complete list is in the next section but it is likely an incomplete list.

G3.6.1.4: “People with overactive TRPA1 channels” may include people with symptoms of:

  • chronic itch (G3.24);
  • chronic arthritis (G3.25);
  • inflammatory bowel diseases (IBD: ulcerative colitis, Crohn’s disease)” (G3.76);
  • people with an Irritable Bowel Syndrome (IBS) may also have had a history of child trauma, domestic violence or sexual abuse:  “As Leserman and Drossman (2007) note, patients with a history of physical or sexual abuse in childhood, or intimate partner violence, have 1.5 to 2 times the risk of reporting gastrointestinal symptoms or having a functional gastrointestinal disorder.,” (G3.94); and trauma survivors may also have comorbid chronic pain conditions such as fibromyalgia: “Van Houdenhove et al. (in press) found that 64% of patients in a group for FMS or Chronic Fatigue Syndrome had at least one type of either child or adult trauma. More concerning was that 39% of the group reported abuse during childhood and as adults, indicating a lifelong pattern of abuse. Although these findings are somewhat mixed,” (G3.94);
  • a medical hypothesis suggests TRPA1 channels may be involved in many chronic pain and airway conditions and also diabetes: “Furthermore, TRPA1 is also involved in persistent to chronic painful states such as inflammation, neuropathic pain, diabetes, fibromyalgia, bronchitis and emphysema.,” (G3.95);
  • symptoms of “diabetic hypersensitivity” (G3.96)  might feel or sound like: “Don’t touch me it hurts.” Symptoms of mechanical hypersensitivity may feel like being physically over sensitive to any sensation. Any touch may be experienced as “pain” or “itch” instead of being pleasant. Symptoms of hypersensitivity associated with diabetes have been found to respond to TRPA1 channel antagonists – chemical inhibitors – a medicine in other words. (G3.96) Reducing the over activity of the TRPA1 channels would help resolve the underlying problem but overmedicating would be a risk. Too much inhibition, too much of the medication could be dangerous to long-term health as the TRPA1 channels play important functions throughout the body.;
  • chronic migraine,” “cluster headache,” (G3.77); “Reactive oxygen species (ROS)”(G3.93) formed from oxidative stress were found to activate the TRPA1 channels in the cerebral arteries but not in other areas of the vascular system, “NOX-induced activation of TRPA1 sparklets and vasodilation required generation of hydrogen peroxide and lipid-peroxidizing hydroxyl radicals as intermediates. 4-Hydroxy-nonenal, a metabolite of lipid peroxidation, also increased TRPA1 sparklet frequency and dilated cerebral arteries.” (G3.93);
  • preeclampsia may involve overactivity of the TRPA1 channel, it also has mechanico-sensitive properties or other TRP channels  – more research is needed: (G3.78, G3.79, G3.80, G3.81, G3.82, G3.83);
  • chronic respiratory conditions involving “airway inflammation” such as “asthma” or “COPD,” overly dry airways may be a problem causing difficulty with completely emptying the lungs (G3.84);
  • cardiac issues such as Congestive Heart Failure may involve TRPC channels, (G3.85), which are not activated by the food type items on the list below but which are likely to be activated by cannabinoids which are #8 on the list below, (G3.89, G3.90);
  • male infertility due to motility issues in the sperm, (G3.87, G3.88). TRPC channels (G3.89) can be activated by Phospholipase C (G3.90) which suggests they can be activated by other phospholipids as well. So a deficiency or gene difference affecting their production endogenously may be involved in male infertility involving motility. More research is needed. In the meantime formaldehyde is definitely not beneficial for fertility in women or men. There is more research available regarding exposure risks for female reproductive health (G3.91) than for males.(G3.92)

G3.6.1.5: People with overactive TRPA1 channels may be sensitive to:

And now we return to the list from the section on the last page. It is greatly expanded now with more food items and other possible substances that can activate TRPA1 channels and TRPC channels, gathered from the research about the list of conditions that might be at increased risk for overactive TRP channels. The TRP channels are all membrane channels but there are many individual types and several categories. The basic form and function is similar however and is described and illustrated in an article about the TRPC channel and cardiohypertrophy associated with Congestive Heart Failure, which was included in the previous list.  (G3.85)

  1. Mustard:  “mustard oil”, (G3.25); “Isothiocyante derivatives constitute the main pungent ingredients in wasabi (allyl isothiocyanate), yellow mustard (benzyl isothiocyanate), Brussels sprouts (phenylethyl isothiocyanate), nasturtium seeds (isopropyl isothiocyanate) and capers (methyl isothiocyanate). Allyl isothiocyanate is the major active ingredient in mustard oil.” (G3.67); Yellow mustard is the condiment used in many ways in cooking. It is a spice made from a small seed that is dried and powdered. It has medicinal value for a variety of conditions. Mustard oil applied topically as a massage oil is reported to provide relief for pain due to arthritis. (G3.68) Wasabi is a type of horseradish like seasoning used in Japanese cooking.It is a root vegetable that also has many medicinal benefits. (G3.72) Brussel sprouts are a vegetable that look like tiny cabbages and are botanically related to cabbage. They are very healthy in many ways and might be worth trying in smaller quantities, steamed more thoroughly rather than raw or lightly steamed or sauteed.(G3.71) Nasturtium seeds can be pickled and used in cooking similarly to capers. (G3.69) Capers are a pickled product with a peppery taste which resemble peppercorns, however they are made of the springtime buds of the caper plant which are picked when they are the size of peppercorns, and are preserved in a pickling brine. Capers are used in salads or savory dishes. (G3.70)
  2. Cinnamon:  “cinnamaldehyde”, (G3.25); Cinnamon is a spice used in cooking which is made from the inner layer of bark from a plant. It is dried and powdered and used in baking or savory dishes. Medicinally a ½ teaspoon of cinnamon per day has been found helpful for improving blood sugar control. A half teaspoon is a large amount for a single serving but some people enjoy it at breakfast stirred into a bowl of hot cereal. (G3.43, G3.67))
  3. Onion or Garlic:allicin”, (G3.25); (G3.41) To be more precise – the raw garlic contains allicin; baked or roasted garlic would be less likely to still have allicin present. It would likely be similar for onion, raw or lightly sauteed might be a problem while caramelized, baked, or roasted might be tolerable. (G3.67)
  4. Formaldehyde:formalin“, (G3.25); chemically the two are very similar: (G3.42); and formaldehyde is found in the environment and as a metabolite of some alternative sweeteners and other dietary sources. (G3.56) See the next section (which was posted first on this site) for more information on sources and ways to avoid Formaldehyde.
  5. “(Winter-green),” (G3.67); Wintergreen is a natural flavoring herb in the mint family. It is typically used as an essential oil as a flavoring in many foods and other types of products. It has medicinal benefits related to it containing the chemical that acts as the pain killing ingredient of aspirin.(G3.73)
  6. “eugenol (Cloves)” (G3.67); Cloves are used in a traditional holiday decoration to make an aromatic dried ornament from an orange. The tack like cloves are poked into the rind of a fresh orange and then the fruit is allowed to dry and it shrinks and smells good for a long time without spoiling if it was allowed to dry thoroughly. Cloves for use in cooking or baking are ground into a powder and used in baking and also in savory dishes and chutneys. The spice and essential oil also have medicinal benefits. The essential oil has numbing properties and in traditional medicine is applied topically to the gums for relieving the pain of a toothache.(G3.74)
  7. “and gingerol (Ginger).” (G3.67); – a root with medicinal properties and commonly used in cooking as a minced or chopped vegetable and is used in dried and powdered form as a spice in savory and baked dishes and may be served dried and candied and used as a candy or chopped and used in baked goods or chutneys.Ginger has many medicinal benefits and has been found helpful for the relief of arthritis pain when used in a quantity that would be equal to about a half teaspoon of the dried powder. Pregnant women should avoid large quantities of the herb or vegetable or candy as miscarriage may be a risk. (G3.75)
  8. Δ9-tetrahydro-cannabinol (THC) and cannabinol (an oxidation product of THC).” (G3.67); The herb cannabis also known as marijuana has many medicinal benefits and  is the most significant source of THC but some foods also have some cannabinoid content. The topic of food sources of cannabinoids and risks and safe use warnings are discussed in the section I. Addiction or Starvation?. Medicinal benefits are discussed in detail in the textbook Endocannabinoids: The Brain and Body’s Marijuana and Beyond, editor and Chapter Three by Emmanuel S. Onaivi, et al., (CRC Press, 2006, Boca Raton, FL), which is available online as a pdf:  (I.Endocannabinoids: Full Text pdf)

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)

References: 

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