And what do osmomechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids have in common?

// 7/1/16 addition: This post is for people suffering from Irritable Bowel Syndrome (IBS) which is not well understood, easy to diagnose or treat, and can be life threatening when more severe symptoms continue long term. The condition can continue for years or be a life long issue that flairs up at times and is less severe at other times.

Dietary tips can be helpful but why some foods seem to trigger symptoms while others don’s has not been well understood either. The common factor underlying why some foods seem to be triggers for many people may be the TRP channels that are found in cells throughout the intestines and actually in most cells of most life forms. //

So what do osmo-mechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids all have in common?

They all may be able to overstimulate Transient Receptor Potential channels (TRP channels) within the gastrointestinal system and cause severe diarrhea in susceptible individuals.

In many cases, the activation mechanism of TRP channels is unclear (Figure 1), but known activators include specific agonists such as mustard oil (TRPA1) and capsaicin (TRPV1), an increase in intracellular Ca2+ (TRPM4, 5), temperature (heat: TRPV1, 2, 3, 4, TRPM4, 5; cold: TRPM8, TRPA1), mechanical or osmotic stress (TRPV4, TRPCs?) and phospholipase C (PLC) activation. TRP channel activity can be further modulated by intracellular phosphatidylinositol phosphates, such as PI(4,5)P2 and membrane potential, but also by inflammatory mediators, cannabinoids and steroids (Nilius, 2007; Rohacs, 2007; Nilius and Voets, 2008).” [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012403/]

The TRP channels are a large group found in many species of life from yeast, to worms, fish and mammels. The agonists/activating chemicals for many of the types of TRP channels have not all been identified as of yet.

One type of TRP channels were formerly called Vanilloid Receptors, and are now called TRPV channels. Vanilloid Receptors were known to be activated by capsaicin found in hot peppers and chili powder. And more recent or less well known research has also found that they can be activated by cannabinoids and steroids, (see the link from the excerpt above), and osmomechanical stress.

Osmo-mechanical stress might be a precursor to edema, excess fluid in the extracellular space; if an organ or cell over fills with fluid it would mechanically be adding physical pressure to the organ or cell — and instead of popping like an overfull water balloon the TRP channels open in response to the physical pressure and let the excess fluid leak out into the extracellular space or into the area surrounding the heart for example. [http://www.ncbi.nlm.nih.gov/books/NBK92821/] Fibrotic heart disease would be adding mechanical stretching stress within the heart. TRP channels are being studied for possible use in preventing fibrotic heart disease. From that research article, we are told that changes in temperature may also activate them:

The activation mechanisms of TRP channel are highly diversified. Some TRP channels appear to be constitutively active, whereas others are activated by Gq-linked receptor activation, oxidative stress, changes of temperature, or an elevation of intracellular Ca2+ [126128]. All the TRP channels appear to be regulated by PIP2 [134137] .” [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874073/]

  • PIP2 = phosphoinositides = phosphatidylinositol phosphates (PIPs) = phosphorylated deriviatives of phosphatidylinositol (PI) [http://www.annualreviews.org/doi/abs/10.1146/annurev.cellbio.21.021704.102317]
  • PIP2 = phosphatidylinositol-4,5-bisphosphate and PI, and phospholipase C (PLC) from the first excerptare involved in cannabinoid metabolism within plasma membranes: [page 9 Kendall et. al., Behavioral Neurobiology of the Endocannabinoid System (Springer, 2009, New York)]

Steroids and hormone D function similarly. And Benicar and curcumin can function similarly to hormone D. And curcumin is a medically active extract from turmeric, a powdered spice that is a main ingredient in curry powder. Turmeric is made from the root of a plant that is biologically very similar to ginger,  which is also a root that is used as a dried spice or  may be used as a chopped vegetable in stir-fry dishes and other foods. Ginger has over 400 active phytochemicals, and one of them might be acting similarly to the curcumin — but that is speculation based on the similarity of symptoms of Irritable Bowel Syndrome that both ginger and curry powder stimulate.

Because — what else do osmomechanical stress, changes of temperature, chili powder, curry powder, ginger, Benicar, hormone D, steroids, and cannabinoids all have in common? — They all may irritate Irritable Bowel Syndrome, (IBS), for some people, along with emotional stress and other things like eating fructose in much quantity (example: from a piece of fruit or fruit juice) or gassy vegetables like cabbage and cruciferous vegetables and beans (gas would be adding mechanical pressure to those TRP channels which might be an over-active culprit in IBS patients).

  • The book, “Tell Me What to Eat If I Have Irritable Bowel Syndrome; Nutrition You Can Live With; Including Dozens of Healthful Mouth-Watering Recipes,” by Elaine Mager, M.P.H., R.D., includes dietary advice and other information about Irritable Bowel Syndrome (IBS). (Warning – most of the recipes contain gluten
  • Re corticosteroids and hormone D:  http://www.oapublishinglondon.com/article/1471

Other diseases that are not well understood but which involve edema and excess fluid entering the area between cells include Chronic Obstructive Pulmonary Disease (COPD) and Congestive Heart Failure (CHF).

So a lack of adequate potassium or magnesium might be involved in allowing too much calcium to enter the interior of cells where it can act as a trigger to increase the flow across the TRP channels even more.

A summary:

/Disclaimer: 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./

Pre-eclampsia, Magnesium Deficiency, or Grass Staggers?

Pre-eclampsia is a frequent and life threatening problem for pregnant and postpartum women that can occur prenatally or up to 48 hours after delivery. The primary cause of the syndrome has been unrecognized in the medical field. However, the treatment and prevention of magnesium deficiency has been well understood in the dairy industry and the symptoms of the two conditions are very similar.

We study animals in medical research because it is unethical to experiment on humans. Farmers and vets care for dairy animals because it is ethical and profitable to help maintain their health. What they learn can help us understand other mammals too – such as humans.

Hypomagnesemia, also known as grass staggers, can occur in the pregnant or postpartum cow, but it can also occur in herds feeding on low magnesium fields. Weakness and falls occur in the cattle and they recover when feed is provided that contains adequate magnesium. The best treatment is prevention by providing extra magnesium if the feed has low levels. [1]

Magnesium deficiency can cause leg cramps, constipation, weakness, falling, cardiac arrythmias, edema and hypertension, anemia and poor immune health, ringing in the ears, irritability and headaches, and when severe seizures are possible. [2] I have had some of these symptoms – including the “wobbles” – feeling weak in the legs and almost stumbling. These symptoms are quite similar to those described for pre-eclampsia and at its most severe seizures are also a risk.

Current care for a human with pre-eclampsia might involve calcium channel blocker pharmaceuticals prenatally for controlling hypertension and intravenous doses of magnesium sulfate in the ER or delivery room for preventing or treating eclamptic seizures. Calcium causes muscle fibers to contract and magnesium allows them to relax.

Calcium channel blockers are patent-able pharmaceuticals trying to perform the job nature assigned to magnesium. The movement of potassium and sodium through ion channels in nerve cell membranes is well understood. A similar interaction is known about calcium and magnesium in the contraction of muscle fibers. Magnesium is the main gate keeper inside of the cell; it can prevent entry of calcium. When low on magnesium the muscles may be flooded with calcium and the constant contraction of the muscle fibers can turn into early labor cramps and possibly seizures.

Puffy ankles (edema) means intracellular fluid is leaking out and more calcium channel blockers are necessary, but more magnesium please. The prenatal woman is low in magnesium because she has been using extra to grow a baby – she can’t grow a baby out of pharmaceuticals.

Eight percent of pregnancies may be affected by pre-eclampsia/eclampsia and the current medical recommendation suggests that calcium and aspirin might help. [4] A different source states that the condition is a problem for up to 10% of women in developing nations and affects between 3-5% of pregnancies for women in the USA. [9]  Pregnant people are already told to consume extra calcium in their diets. If that strategy were working then why do eight percent of pregnancies still have pre-eclampsia problems?

Magnesium supplements have been reported to be helpful for preventing leg cramps during pregnancy in one study but results from another study didn’t replicate the results. [5]  A large study has begun based in Brazil that plans to provide the trial group of prenatal participants with two 150 mg magnesium supplements per day throughout the pregnancy in the hopes of preventing pre-eclampsia and reducing the number of infants born prematurely or at a low birth weight. [10] Another study focused on assessing the difference in long term mineral status of patients who had pre-eclampsia prenatally compared to those who didn’t. The results found that long term calcium status was the same which does not support the current theory that calcium deficiency is involved in the condition. [11]

A different study focused on the difference in current trace mineral status between patients with pre-eclampsia and those without. Blood levels of copper, zinc, selenium, calcium and magnesium were measured. Copper was the only mineral found to have similar levels between the two groups. The blood level of the other four minerals was significantly lower in women who had pre-eclampsia then in the group without the condition during their pregnancy. [12]

When the body is too low in magnesium then the body will increase hormone levels that cause a drop in calcium levels. Too much calcium and too little magnesium in the blood can cause heart symptoms so there are several ways the body can prevent an imbalance between blood levels of calcium and magnesium. A study that looked at whether magnesium sensitive genes were involved in blood pressure control during pregnancy did find that one was more active in pregnancy compared the non-pregnant group.  The gene TRPM6 was more active in the pregnant group than in women in the control group. [13]

Other research regarding the condition has noted an increased risk among close family members (mothers, daughters, sisters – if one has pre-eclampsia, other close female relatives are statistically more likely to also experience it in their pregnancies.)

A study that measured the vitamin D, hormone D, parathyroid hormone, albumin, and calcium blood levels of postpartum women who had had pre-eclampsia and those wh0 hadn’t during their pregnancies and found no significant difference in any of the levels between the two groups. Both groups had low vitamin D levels but normal levels of hormone D, parathyroid hormone, albumin and calcium. [15]

A study at the University of Benin found a significant correlation between low magnesium and increased prevalence of pre-eclampsia. The study concludes with a clear recommendation that consuming magnesium rich foods during pregnancy may improve the outcome:

“Pre-eclampsia and pre-term birth are associated with hypomagnesemia in pregnancy; hence, magnesium supplementation or magnesium-rich diet consisting of green leafy vegetables, soy milk and legumes may improve outcome.  [14]

A review of research regarding magnesium and prenatal health also concluded with a recommendation for pregnant women to consume adequate magnesium rich foods:

This review provides recommendations for further study and improved testing using measurement of red cell magnesium. Pregnant women should be counseled to increase their intake of magnesium-rich foods such as nuts, seeds, beans, and leafy greens and/or to supplement with magnesium at a safe level. [16]

Magnesium sulfate is used during labor and delivery to help prevent seizures in women with pre-eclampsia/eclampsia. I was told that the large dose feels painfully like fire in the veins. Which makes sense because it is an electrically active ion typically found in large amounts only within cell fluid rather than also freely available within the blood plasma. Some clients were very motivated to eat better if it would help prevent blood pressure problems from reoccurring and reduce the possibility of IV magnesium from being necessary. Simple solutions like pumpkin seeds and the DASH diet may be safer too. The high dose of intravenous magnesium sulfate can lead to cardiac problems and patients who receive the treatment are carefully monitored which takes additional staff time and other medical resources. [6]

Ibuprofen or other non-steroidal anti-inflammatory drugs (NAISDs) may help protect the infant during pregnancy if an infection is also part of the problem underlying pre-eclampsia. The ibuprofen helps reduce an increase in cytokines. The cytokine flood is an inflammatory reaction that may be associated with an increased risk to the infant for mental health problems developing later in life. [7]

Pre-eclampsia can be prevented by eating more magnesium rich foods throughout pregnancy. Beans, nuts, seeds and dark green vegetables are rich in magnesium. Chocolate is a good source, and there is a little magnesium in most foods. Whole grains are also good sources except the phytate content reduces mineral absorption. Shelled pumpkin seed kernels are similar to sunflower seeds in texture but they are greenish in color. Both are good sources of magnesium and other nutrients. Pumpkin seeds are a good vegetarian source of zinc, an essential trace mineral.

Mom and baby need magnesium daily. Having a moderate calcium intake will actually help both nutrients to be more usable to the body, baby, and bones. Frequent use of carbonated drinks, coffee, black tea, and acidic juices can cause the kidneys to waste magnesium. A diet high in meats and dairy products is also acid producing during breakdown and bone stores of magnesium may be used during excretion of the waste products if magnesium isn’t available from the diet. Our kidneys actively save calcium while using magnesium to remove the excess acid or excess calcium. Use of calcium rich OTC drugs like Tums or Rolaids frequently may decrease magnesium.

The intestines may not be absorbing magnesium well. Calcium is rare in nature except in dairy products. Our bodies expect lots of magnesium and not much calcium from our day’s intake. Too much vitamin D, when active, can cause even more calcium absorption in the intestines.

Magnesium containing skin creams may reduce leg cramps and other prenatal discomforts. Epsom salt foot soaks or baths can be soothing and nourishing as well.

Herbal teas are very nourishing in general – a few would not be recommended with pregnancy but raspberry leaf tea has been used successfully for generations.

“Raspberry leaves as well as the fruit contain many valuable vitamins needed during pregnancy. As well as containing iron, they are rich in vitamins A, C, B, E, calcium, manganese and magnesium. Magnesium particularly contributes to the strengthening of the uterine muscles.” [18]

The DASH diet was designed for helping prevent or manage high blood pressure rather than for pregnancy but pre-eclampsia can involve high blood pressure and the diet includes more emphasis on magnesium rich foods than the standard diet plans. The DASH diet plan includes a group for beans/nuts/seeds which are all good sources of magnesium. [8]

A prenatal diet plan is primarily different from a standard woman’s diet plan by having one additional dairy serving for extra calcium and the equivalent of one additional mixed snack during the second and third trimesters. During the first trimester calorie needs are similar to standard. Make the additional mixed snack a magnesium rich snack and pre-eclampsia might not become a problem. Corn chips and bean dip, peanut butter toast, or pumpkin seed kernels in a trail mix would all be snacks containing magnesium and other nutrients.

Continuing a diet with more magnesium, zinc, selenium, and adequate calcium intake may also help protect women with a history of pre-eclampsia from experiencing heart disease symptoms later in life. An association has been observed in medical research between a history of having had pre-eclampsia and increased risk of heart disease. [17] The DASH diet was designed to help reduce cardiovascular risks associated with high blood pressure. Continuing to follow the diet plan may help protect against heart disease.

Differences in the TRPM6 gene may underlie both the risk for pre-eclampsia and for heart disease risk. In an animal based study providing adequate magnesium helped protect the animals with differences in the TRPM6 gene. [19] TRPM6 channels are more prevalent in epithelial cells (type of cell that forms the skin and the lining of the GI tract) while TRPM7 channels are common throughout the body. Both types transport magnesium. Evidence suggests the TRPM7 type are involved in hypertension. [20] TRPM7 channels may be more involved in risk of heart attack (myocardial ischemia). [21]

More information about TRP channels is included in this post about Irritable Bowel Syndrome: http://transcendingsquare.com/2016/03/30/and-what-do-osmomechanical-stress-changes-of-temperature-chili-powder-curry-powder-ginger-benicar-hormone-d-steroids-and-cannabinoids-have-in-common/

Which led me to wonder if there is any association between IBS and pre-eclampsia – one study found some co-occurrence that was not statistically significant. There was an increased risk (25-30%) found for miscarriage and having a diagnosis of IBS  and depression/anxiety prior to becoming pregnant (how severe the symptoms was not assessed). [22]

A hypothesis regarding intrauterine pressure and pre-eclampsia mentions that it is associated with cell stress and decreased magnesium levels were noted:

“Jarosz et al. reported that in lab animals exposed to IAH of 25 mmHg, histology of the brain demonstrated evidence of ischemic neuronal cell stress and decreased magnesium levels [73].” [23]

A brief background regarding TRP channels – they act as pressure release valves so that organs leak rather than overfill. As a visual picture think of blowing up a balloon, eventually you have to stop or it will pop. The TRP channels would allow the balloon to leak instead of popping. The channels are located throughout the body and are formed from a large protein or group of proteins that cross the cell membranes. Magnesium is an electrically active mineral that provides the energy required to keep the channels closed and only allow transport of desired chemicals through the channel.

Having too little magnesium available leaves the channels without energy to stay closed and prevent fluid or other chemicals from crossing through the channel. Depending on the difference in pressure fluid and chemicals might rush into the cell from the surrounding fluid (extracellular fluid) or fluid and chemicals might rush out of the cell (intracellular fluid) into the surrounding fluid.

The hypothesis about intrauterine pressure and pre-eclampsia includes background information on the condition but magnesium is only referenced (see the excerpt above), its role in TRP channels was not discussed.

Emergency guidance suggested having the woman experiencing severe symptoms physically get into a kneeling position or lay horizontally on their left side:

Within the limitations of this analysis, data suggest that IAP may be altered throughout pregnancy by modifying the maternal position (altering the force direction), with the lowest pressure values obtained in knee–chest and left lateral positions. The negative pressure values obtained in the knee–chest position are important, as inversion of the maternal abdomen may provide an easily available and effective emergency intervention for PE, should this hypothesis be confirmed.” [23]

The article doesn’t provide further description of the position. My guess is a position that was recommended at the time I was pregnant for helping prevent breech delivery – get on hands and knees and then lower the chest and head to the floor, and then relax and stay there a while, having a pillow and watching TV is okay. Yes, see here, scroll down the page: [24]

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.

  1. Grass Staggers In Cattle & Sheep, http://www.dairy-direct.co.uk/?p=2868
  2. Magnesium Fact Sheet for Health Professionals, NIH,  https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/
  3. Effects of Antenatal exposure to Magnesium Sulfate on Neuroprotection and Mortality in Preterm Infants :Maged M. Costantine, MD, Steven J. Weiner, MS, Obstet Gynecol. 2009 August; 114(2 Pt 1): 354-364
  4. Magnesium deficiency-induced spasms of umbilical vessels: relation to preeclampsia, hypertension, growth retardation. Pub:Science, 221 (July 22, 1983): pp376(2)Burton M. Altura, Bella T. Altura and Anthony Carella
  5. http://www.webmd.com/vitamins-supplements/ingredientmono-998-magnesium.aspx?activeIngredientId=998&activeIngredientName=magnesium
  6. http://www.webmd.com/baby/tc/pregnancy-and-epilepsy-topic-overview
  7. http://www.saturdayeveningpost.com/2011/09/12/in-the-magazine/health-in-the-magazine/viral-link-mental-illness.html
  8. http://dashdiet.org/default.asp
  9. https://www.nichd.nih.gov/health/topics/preeclampsia/conditioninfo/Pages/risk.aspx
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096428/
  11. https://www.ncbi.nlm.nih.gov/pubmed/24102858
  12. https://www.ncbi.nlm.nih.gov/pubmed/23825993
  13. https://www.ncbi.nlm.nih.gov/pubmed/26104253
  14. Enaruna NO1, Ande A, Okpere EE., Clinical significance of low serum magnesium in pregnant women attending the University of Benin Teaching Hospital. Niger J Clin Pract. 2013 Oct-Dec;16(4):448-53. 
     https://www.ncbi.nlm.nih.gov/pubmed/23974737
  15. https://www.ncbi.nlm.nih.gov/pubmed/24853885
  16. Dalton LM, et al., Magnesium in Pregnancy, Nutr Rev. 2016 Sep;74(9):549-57.  https://www.ncbi.nlm.nih.gov/pubmed/27445320
  17. https://www.ncbi.nlm.nih.gov/pubmed/25721023
  18. Ferguson, Patricia. “Turning over a new leaf for pregnancy: London-based medical herbalist and ‘living food educator’ Patricia Ferguson discusses how raspberry leaves can help pregnancy.(Raspberry leaves).” Royal College of Midwives Journal. Ten Alps Publishing. 2009. HighBeam Research. 16 Feb. 2011 .
  19. https://www.ncbi.nlm.nih.gov/pubmed/27991852
  20. https://www.ncbi.nlm.nih.gov/pubmed/18192217
  21. https://www.ncbi.nlm.nih.gov/pubmed/24445530
  22. http://www.medscape.com/viewarticle/761575
  23. http://www.sciencedirect.com/science/article/pii/S0306987714002722
  24. https://www.glowm.com/section_view/heading/Umbilical%20Cord%20Prolapse%20and%20Other%20Cord%20Emergencies/item/136
  25. edited by Richard A. King, Jerome I. Rotter, Arno G. Motulsky  The Genetic Basis of Common Diseases, page 539 https://books.google.com/books?id=xKC4swxJC1UC&pg=PA539&lpg=PA539&dq=intrauterine+pressure+in+black+women%27s+pelvic+structure&source=bl&ots=M9TWK8OdYd&sig=YRYuD908NTDc-CChVhIDWKE1l6c&hl=en&sa=X&ved=0ahUKEwjA6qicgsbTAhVHxlQKHWyWBigQ6AEIQDAE#v=onepage&q=intrauterine%20pressure%20in%20black%20women’s%20pelvic%20structure&f=false
  26. G. Ghosh, Racial/ethnic differences in pregnancy-related hypertensive disease in nulliparous women,
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171100/