Phospholipid or phosphorylation deficiency, potential symptoms

Phospholipids are essential within membrane structures within and around cells and form the walls of blood vessels and organs including our largest organ – the skin itself. Phosphorylation is chemical process that is essential for building phospholipids and also critical within mitochondria for releasing energy from molecules of sugar (glucose). Severe problems in the ability to make phospholipids or phosphorylate other chemicals would likely lead to severe symptoms and death.

Symptoms of moderate severity might include infertility for females (implantation of the fertilized egg might not occur normally) and for males (sperm motility may be impaired), however too much of some forms might also impair fertility. Often chemicals within biology have a U shape toxicity, too little or too much can be detrimental to health.

Symptoms associated with genetic problems with phospholipid metabolism have been identified that can be grouped in three main types, symptoms affecting the Central Nervous System (the brain), peripheral neuropathies (numbness beginning with the fingers, hands and feet), and symptoms affecting muscles or cardiovascular health. (1)

Choline deficiency and metabolism is also critical for fertility and other functions including nerve and brain cell communication and energy metabolism. Phosphatidylcholine and acetylcholine are needed as messenger chemicals, for DNA production, and in converting sugar to usable energy. (2) Inadequate choline leads to reduced methylation, and epigenetic changes or DNA breaks may be more likely to occur. Liver cancer may occur due to DNA changes in tumor suppressor genes that normally would repair cancerous changes. Choline is required for folate metabolism. (9) So lack of choline prenatally also increases risk for neural tube defects more typically associated with folate deficiency. Egg yolk and other animal food products contain choline, a vegan diet could include nutritional yeast flakes as a source of choline and vitamin B12 (among other B vitamins and nutrients that may also be found in a variety of vegan foods) or peanuts, (Choline/Linus Pauling Institute), beans, seeds, and some vegetables, (see Table 1, choline food sources).

Adequate amounts of various fatty acids (fats) and other vitamins and minerals are also important for the body to be able to make phospholipids, Vitamin A and E and the B vitamin called folate are necessary in addition to trace metals magnesium and zinc. Polyunsaturated fats including the omega 3 fatty acid DHA are also necessary for optimal phospholipid production. Vegetarian sources of ALA, a potential precursor for DHA, may not be converted to EPA and then to DHA by many people. (3) (Magnesium sources)

Supplementing diets with phospholipids (glycerophospholipids, GPLs, and shingoyelin, SM) has been found beneficial without severe side effects for some health conditions and when used along with some types of medications. Arthritis damage due to inflammation was reduced in an animal study. Cachexia, severe weight loss and muscle breakdown, associated with cancer and other inflammatory conditions, may also be reduced with increased intake of phospholipid sources. Krill oil, a marine source of DHA bound to phospholipids, was found helpful in a study of premenstrual syndrome in comparison to fish oils with DHA as free fatty acids. Use of phospholipid sources along with NSAIDs painkillers found reduced problems with GI side effects associated with the pharmaceuticals (such as aspirin and ibuprofen). Ulcerative colitis sufferers may also benefit from increased intake of phospholipid sources. Use for treatment of cancer, cardiovascular, and cognitive conditions has also been studied. (4)

Problems with health or lifestyle that increase nutrient demands due to oxidative stress or toxin load such as alcoholism, (6), increased physical or emotional stress, or aging might lead to problems in complex metabolic pathways including lipid metabolism. “Aging, heart failure and Barth Syndrome [98]” have been associated with decreased glycerophospholipid (cardiolipin, CL) formation in the inner membrane layer of mitochondria which are the main organelle for providing energy within cells. (5) (Barth Syndrome is a rare genetic condition causing weak muscle development, heart problems, low tolerance for exercise, growth delay, increased risk for infections, mitochondrial deficit in production of tetralinoleoyl-cardiolipin. BarthSyndrome.org/about)

Animal Food Sources of Phospholipids:

  • Egg yolk;
  • Organ meats;
  • Krill oil and other fatty fish or fish derived oils;
  • Bovine milk extracts.
    (4)

Plant Food Sources of Phospholipids and other phospho-nutrients:

  • Hemp seed kernels and oil;
  • cocoa beans and cocoa powder, baker’s chocolate, dark chocolate and to a lesser amount milk chocolate and chocolate syrup; beans/legumes;
  • soy lecithin & other soy oil extracts, (4) ;
  • carrots; celery stalks and leaves; parsnip root;
  • coconut;
  • cardamom seeds and powder; cumin seed/powder; fennel seed, flax seed, pine nuts; sesame seeds, pumpkin seed kernels, squash seeds;
  • butternut squash and pumpkin; sweet potato or yam;
  • grapefruit and orange juice with the pulp;
  • Jerusalem artichoke (this is a root vegetable rather than a green artichoke);
  • asparagus; avocado fruit or the inner kernel, dried and powdered; Artemisia turanica/wormwood leaf; lettuce, spinach and mustard leaves and other leafy green vegetables and herbs; rosemary;
    gingko leaf; okra seeds;
  • nuts/peanuts, cashews, walnuts;
  • onion root, leek leaves, garlic; 
  • pomegranate seeds and pomegranate peel extract;
  • amaranth seed; oats; rice, white or brown but the bran is the best source; sorghum;  buckwheat (a seed botanically that is not wheat and is gluten free); wheat. (G.26)   

More information about phospholipids/cannabinoids during implantation of a newly fertilized egg.

During the first few days after conception the level of anandamide, an internally produced cannabinoid, has to be at just the right level for the fertilized egg to successfully implant somewhere along the uterine lining. Too much of the natural cannabinoid, anandamide, or too much of a synthetic or plant derived source of a similar cannabinoid can cause the fertilized egg to fail to implant properly. (7) The uterus and placenta both have above average amounts of Type 1 cannabinoid receptors which are the type more prevalent within the brain and are also found within the developing fetal brain. Type 1 cannabinoid receptors are activated by anandamide which is chemically similar to the euphoric cannabinoid, THC, found in marijuana, so prenatal use of marijuana may be a risk to fetal brain development. (8)

The identification of cannabinoid receptors (CBRs) in the uterus and placenta, and the high densities of CB1Rs, functionally coupled to G protein in prenatal developmental stages throughout the human brain, suggest the involvement of the cannabinoid system in neural development (Mato et al., 2003). It has also been suggested that the high expression of CB1 mRNA in the human fetal limbic structures may render such brain structures more vulnerable to prenatal cannabis exposure (Wang et al., 2003).” (8, Ch. 3, page 91)

This means that too much or too little cannabinoids could cause problems with implantation for a female or might negatively effect the developing fetus. So external sources such as marijuana or chemically similar analogs would be something to avoid using for women during times when conception is desired or might occur (which might be up to four or five days after having unprotected sex as sperm may survive a few days) or prenatally for the safety of the developing fetal brain. However, potentially, if a woman had a genetic defect in her ability to make cannabinoids internally or some other health problem effecting the metabolic pathways, then she might only be able to become pregnant successfully when using an external source of cannabinoids/phospholipids. 

Disclaimer: This information is being 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 care guidance. Please seek an individual health care provider for individualized health care guidance.

References:

  1. Lamari, Foudil & Mochel, F & Sedel, F & Saudubray, Jean-Marie. (2012). Disorders of phospholipids, sphingolipids and fatty acids biosynthesis: Toward a new category of inherited metabolic diseases. Journal of inherited metabolic disease. 36. 10.1007/s10545-012-9509-7.
    (https://www.researchgate.net/publication/229426743_Disorders_of_phospholipids_sphingolipids_and_fatty_acids_biosynthesis_Toward_a_new_category_of_inherited_metabolic_diseases)
  2. Phospholipids and Choline Deficiency, SpringerLink,
    (https://link.springer.com/chapter/10.1007/978-1-4757-1364-0_18)
  3. Gimenez MS, Oliveros LB, Gomez NN. Nutritional deficiencies and phospholipid metabolismInt J Mol Sci. 2011;12(4):2408-33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127125/
  4. Daniela Küllenberg, Lenka A Taylor, Michael Schneider and
    Ulrich Massing, Health effects of dietary phospholipids, Lipids in Health and Disease, 2012 11:3 https://lipidworld.biomedcentral.com/articles/10.1186/1476-511X-11-3
  5. Daisuke Hishikawa, Tomomi Hashidate, Takao Shimizu, and Hideo Shindou, Diversity and function of membrane glycerophospholipids generated by the remodeling pathway in mammalian cells,
    May 2014 The Journal of Lipid Research, 55, 799-807. http://www.jlr.org/content/55/5/799.full
  6. Sozio M, Crabb DW. Alcohol and lipid metabolism. Am J Physiol Endocrinol Metab. 2008;295(1):E10-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493591/
  7. B. C. Paria, et al., Dysregulated Cannabinoid Signaling Disrupts Uterine Receptivity for Embryo Implantation, June 8, 2001 The Journal of Biological Chemistry, 276, 20523-20528.[http://www.jbc.org/content/276/23/20523.full]
  8. Endocannabinoids: The Brain and Body’s Marijuana and Beyond; Edited by E. S. Onaivi, T. Sugiura, and V. Di Marzo, Chapter 15, Neuropsychiatry: Schizophrenia, Depression, and Anxiety, by Ester Fride and Ethan Russo, p 373, Chapter 3 Endocannabinoid Receptor Genetics and Marijuana Use, by E. S. Onaivi, et al., pp 91-92 (CRC Press, Taylor and Francis, 2006) https://www.amazon.com/Endocannabinoids-Brain-Bodys-Marijuana-Beyond/dp/0415300088
  9. Zeisel SH. Dietary choline deficiency causes DNA strand breaks and alters epigenetic marks on DNA and histonesMutat Res. 2011;733(1-2):34-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319504/

Epsom salt footsoaks

*Why do I keep mentioning magnesium & Epsom salt (magnesium sulfate)? Because many chronic physical and mental issues involve low intracellular levels of magnesium. Lab tests checking blood levels usually would miss the problem because the level in the blood is very low compared to the level in the cell fluid. Magnesium is needed to provide power within membranes to control flow of chemically active ions like calcium and sodium which are found in a larger amount in the blood and less inside of the cells. Too much calcium within cells can cause over-activity of the cell to the point of cell death.

Magnesium supplements as a therapy can be helpful but the research is mixed, it may not be absorbed well by enough of the subjects in research studies to suggest that it isn’t helpful on average – people are individuals though, not group averages. Epsom salt, crystals of magnesium sulfate, is a well absorbed form when used dissolved in water, too much can be harmful as magnesium can slow the heart-rate if levels within the blood stream become elevated. Safe use of Epsom salt baths, foot-soaks, or even dampened compresses held on sore muscles can be inexpensive and effective.

We need more health care that is inexpensive and effective. The planet needs healthy people and less medical waste. Treatment of illness can be costly in time and supplies for the patients and the healthcare team. Preventing worsening of chronic illness or symptoms mental illness improves quality of life for patients, saves time and money and supplies, and reduces the caseload of an overburdened healthcare system. Frequently there is a problem with accessing healthcare specialists or mental health care services, even if payment isn’t a problem.

Epsom salt foot-soaks – might be simpler than a full bath.

Previously I’ve shared an idea about a need for less expensive bathing facilities in urban areas, Public bathing facilities was an option in Rome. Apartments may have only a shower or there might be more tenants sharing space than is feasible to allow enough time for everyone to take turns in one or two bathrooms. The medicinal value of Epsom salt baths may also be difficult for those most in need to be able to enjoy as mobility might be limited. An easily transportable footsoak basin could be brought to a wheelchair or other seating arrangements.

Currently on the market there are various footsoak/pedicure chairs available for the spa market, prices range from $700 to over $2000. Portable heating and bubbling individual foot spa basins are available for home use that range from $40 to over $100. The disadvantages are size, they appear to be fairly small, meant to just cover the foot and the complexity of the shaped basin would make them difficult to clean. Smaller basins would also be easier to spill and difficult to transport from a sink area to a seating area. (example individual foot spa)

Residential facilities with many people who might benefit from the medicinal value of an Epsom salt bath or footsoak would have utility closets designed for easy use of wheeled mop buckets. A utility sink is equipped with a hose for filling buckets and a low rimmed drainage area is built into the floor for easy emptying and cleaning of the buckets. Some wheeled mop buckets have removable wringers to make the whole device easier to clean and may have different colors available to help identify which area the bucket is intended for use. (example color coded mop buckets) If the idea was found effective I imagine a company would be happy to make a product with a different logo on the side of the buckets and sell them without the wringer attachment. The wheeled buckets have handles on the side as well as the top to make emptying them easier.

Simple solutions are most practical for busy workers. In a residential facility diabetic foot care is a regular need to help prevent small sores from going unnoticed by a patient with numbness/neuropathy and then becoming large sores. Gangrenous infections in small sores are a common cause of amputations being needed for diabetic patients. Magnesium and sulfate from the Epsom salt both have healing value for diabetic patients and people with other types of inflammatory illness. Swollen feet may be improved by regular use of topical magnesium treatments.

Ease of use for workers is important as hauling buckets or basins of water around a facility is strenuous and potentially messy and dangerous. A wheeled bucket could be easily moved, used, emptied and sanitized between uses. After a footsoak it would be easy to inspect a patient’s feet for small sores, provide any toenail maintenance that is needed and possibly give a therapeutic massage.

“It is not enough to do your best; you must know what to do, and then do your best.” – W. Edwards Deming

Knowing that Epsom salt baths can be extremely healing is knowledge – proving that it could be feasible to help many people in a budget friendly way is the next step. Patient care requires safety and effectiveness in order to provide a service ethically that will do no harm and which can still fit within a facility’s budget. A study that tracked groups of patients over time could look at direct symptom relief type of criteria and look at overall health statistics – were there fewer health concerns or falls or mood problems in the group receiving weekly, biweekly, or monthly Epsom salt foot-soaks in comparison to the control group who continued to receive standard care? Or a study design might compare the health parameters of the same group of patients over six months without the Epsom salt foot-soaks and then six months during which foot-soaks were provided.

A review of what little scientific research is available regarding topical magnesium concludes that magnesium containing creams have not shown good absorption. Epsom salt soaks do lead to increases in plasma magnesium levels and urinary excretion of magnesium suggesting that the magnesium sulfate salt water solution does get absorbed through the skin, more likely through hair follicles (4) and sweat glands than the full surface of the skin. (1, 2) Absorption through mucous membranes is also likely, so a full bath would probably provide more absorption in less time than a foot and lower leg soak. More research is needed however and preferably with study subjects who have a chronic conditions that suggests they are magnesium deficient because excess magnesium is not needed and can be dangerous. People who are less deficient in the nutrient might not need as long of a soak time before achieving some symptom relief (may be helpful for muscle cramps, headache, anxiety, psoriasis).

Staying overly long in an Epsom salt bath or foot soak could cause relaxing of smooth muscles which can cause watery diarrhea for the next day (like a stomach flu, all day problem), and more severe can cause slowing of the heart rate, bradycardia, — the point being that Epsom salt soaks are medicinal, not just for relaxing or a spa beauty treatment. When more deficient you might stay in longer before noticing more relaxing of muscles or change in heart rate and as weeks of regular soaks continue you may notice that a shorter soak is now adequate. Foot soaks would be less likely to cause excess absorption that can cause diarrhea/slower heart rate, while falling asleep in a bathtub with Epsom salt might. Ten to twenty minutes is a typical recommendation.

A typical bath is about one cup of Epsom salt to a half bathtub of water, soak for twenty minutes, 1-3 times per week. I get muscle cramps and more anxiety when I take one per week instead of two and at a more severe level of colitis like symptoms I needed three per week, and marked it on a calendar so I wouldn’t forget. Substituting a foot-soak, I probably used a half cup of Epsom salt to a large bucket size plastic bin (rather than a short basin) and left my feet and lower legs in the water for about forty minutes, until the water was cool – I was working on a computer while soaking. Chronic illness is unpleasant, improved quality of life is more pleasant.

*This will likely get some revisions/additional links. It is a continuation of the last post on TRP Channels & magnesium. Food and supplement sources of magnesium and the additional need for protein and phospholipids as carriers for intracellular supplies of magnesium is available in a previous post: To have optimal Magnesium needs Protein and Phospholipids too.

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

  1. Gröber U, Werner T, Vormann J, Kisters K. Myth or Reality-Transdermal Magnesium?. Nutrients. 2017;9(8):813. Published 2017 Jul 28. doi:10.3390/nu9080813 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579607/
  2. reference 13 from (1):
    Epsom Salt Council. [(accessed on 1 October 2015)]; Available online: http://www.epsomsaltcouncil.org/wp-content/uploads/2015/10/report_on_absorption_of_magnesium_sulfate.pdf.
  3. various links about magnesium and PTSD or other mood or brain trauma issues https://www.google.com/search?q=PTSD+brain+changes+calcium+magnesium+imbalance&rlz=1C1CHWA_enUS600US600&oq=PTSD+brain+changes+calcium+magnesium+imbalance&aqs=chrome..69i57.13101j0j7&sourceid=chrome&ie=UTF-8
  4. Chandrasekaran NC, Sanchez WY, Mohammed YH, et al., Permeation of topically applied Magnesium ions through human skin is facilitated by hair follicles., Magnes Res. 2016 Jun 1;29(2):35-42.
    https://www.ncbi.nlm.nih.gov/pubmed/27624531 (4)

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/