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Hypercoaguability; TNF alpha & Nrf2

*This post got quite long so I put it in a document form too and added a Table of the medicinal foods/herbs/extracts, there are still more to add: docs.google.com . The table of 700 small molecules that may help reduce TNF-alpha by inhibiting the NF-kB pathway is quite large, so I am working on recreating it in list format – work in progress: docs.gogle.com/list of NF-kB pathway inhibitors.

Localized hyercoaguability & granulomatous sarcoidosis.

People with the autoimmune disease called sarcoidosis may develop increased risk of clotting, hypercoaguability, localized to the areas where the disease process progressed to the granulomatous stage. The reason is not known per the research team, Goljan-Geremek et al., as other typical cardiovascular disease markers were not commonly found in sarcoidosis patients who developed venous thromboembolism (VTE). (1)

The problem of increased coaguability was only seen in patients with Stage II or Stage III granulomatous sarcoidosis and was associated with increased levels of “the proinflammatory cytokine cascade [interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF-α) but not with IL-10 [25].” Interleukin 10 is an anti-inflammatory cytokine with a protective effect while Interleukin 6 and 8 are pro-inflammatory. Better understanding of the mechanism would be helpful as localized hypercoaguability may increase risk of pulmonary embolism or other ischemic strokes. (1)

Calcium excess, magnesium deficiency and hypercoaguability.

Magnesium and calcium balance can be involved in blood clotting risks as excess calcium can lead to blood vessel and soft tissue calcification. Vascular calcium plaques can increase risk of blood clots and excess calcium levels can also be a cause of blood clotting – hypercoaguability. (41) (42) Zinc deficiency is mentioned later in this article as a potential cause of hypercoaguability, however several key nutrients may be deficient or in imbalance during cardiovascular disease. Myocardium tissue changes structure and chemical composition during vascular or heart disease. Magnesium was found to be low while calcium levels were elevated. Vitamin D was low, the active hormone form of vitamin D was not measured. Zinc and selenium levels were found to be low. (44)

Vitamin D is involved in calcium and magnesium balance and is anti-inflammatory due to inhibition of the NF-kB pathway. Low levels of vitamin D have been associated with kidney and cardiovascular disease. (45) Curcumin, an analogue of the active hormone D form (1, 25, dihydroxy D), also inhibits the NF-kB pathway and may also be protective against renal or vascular disease. (See Table 1, 11)

The B vitamins, folate, vitamin B6 and B12, are needed for homocysteine metabolism, elevated levels of which are associated with cardiovascular disease, however reducing levels of homocysteine has not reduced thrombotic risk (clotting). (46) The importance of homocysteine may have more to do with its later chemical conversion to the potent antioxidant glutathione. (47) We make more antioxidants everyday during health than we are ever likely to consume from typical foods. Many medicinal herbs or nutrients help promote the antioxidant promoting Nrf2 pathways and inhibit the inflammatory NF-kB pathway. Vitamin B6 can also inhibit the inflammatory NF-kB pathway. (See Table 1, 11)

The nutrients could be thought of as similar to a baseball team – you might be able to play a game without the shortstop or with someone in left field however trying to play without the pitcher or catcher wouldn’t really work at all.

TNF alpha and the NF-kB Pathway

The mechanism for localized hypercoaguability in granulomatous sarcoidosis may be due to the localized increase in Tumor Necrosis Factor alpha (TNF alpha) and interleukin-6 (IL-6) which can cause “microvascular damage leading to thrombosis,” and “ischemia.” Supplementation with flavonoids can block this from occurring by inhibiting an earlier step in the intracellular pathway by preventing the stimulation of the IKK complex and the translocation of NF-κB into the cell nucleus where the pro-inflammatory cytokines are made. (See Figure 1: 2)

Deficiency in Nrf2 may cause an increase in TNF alpha as the protein inhibits production of the Tumor Necrosis Factor alpha protein by the inhibitory effect internally produced antioxidants (Nitric Oxide or glutathione for example, 11) have on the NFkB pathway. (7) And when levels of TNF alpha are elevated production of more Nrf2 is suppressed by the TNF alpha/NFkB pathway (7), which would then further exacerbate the elevated level of it as the inhibition by the Nrf2 protein would be lacking and the presence of increased levels of TNF alpha and other cytokines increases activity of the NF-kB pathway. (7)

An experimental stage chemoprevention drug beta-naphthoflavone helps protect against lung damage in mice deficient in the ability to make Nrf2. (3) Beta-naphthoflavone is an AhR agonist and antioxidant that is only approved for research purposes in animal studies currently. (4) Nrf2 has a protective role within the lungs as seen in a different animal study with Nrf2 deficient mice (knockout mice genetically deficient in Nrf2 -/- ). (5)

Flavones are a type of Flavonoid

Flavones are in the flavonoid family of phytonutrients. Flavonoids as a group are commonly found in many “fruits, vegetables, barks, stems, roots, flowers, tea, and wine.” (6) There are about 6000 flavonoids known within plants and they frequently are colorful pigments within the flowers or other parts of plants where they protect against UV light damage along with other protective roles. (6)

Therapeutically flavonoids are very beneficial for humans also, as they not only are strong antioxidants they also have “anti-inflammatory, anti-mutagenic and anti-carcinogenic properties,” can “modulate key cellular enzyme function,” and are “potent inhibitors for several enzymes, such as xanthine oxidase (XO), cyclo-oxygenase (COX), lipoxygenase and phosphoinositide 3-kinase, (4–6).” (6) Flavonoids may help protect against Coronary Heart Disease (CHD) and reduce mortality rate due to cardiovascular disease.

Onions and Green Tea – ECGC

Flavones are particularly strong antioxidants within the group of flavonoids and onions and tea are good dietary sources. (6) Green or Black tea are good sources of the flavonoid called Epigallocatechin-3-gallate (EGCG) which is known to inhibit the NF-kB pathway. (11, 12) Green and black tea are from the same type of plant however the processing is different. Green tea is simply dried fresh tea leaves and provides about four times more EGCG than black tea (which does have other healthy phytonutrients too). Patient studies suggest that heart health benefits may occur with use of three to five cups of green tea per day, which would provide about 200-350 milligrams EGCG. Bottled teas and supplements may not provide as much as labels suggest while also costing more than loose leaf tea or boxed tea bags. (17)

Orange Zest – Tangeritin

Flavones may help reduce the risk of upper respiratory infections by stimulating taste receptors that detect bitter flavors which then increase cellular production of Nitric oxide (NO) which has antibacterial effects (lethal to bacteria at higher doses). The outer zest of orange peel is a source of a flavone called tangeritin. (10)

Vinpocetine

Flavones therefore, as flavonoids, may be beneficial for Nrf2 levels by reducing the NF-kB pathway by effects on the IKK complex. (See Figure 1: 2) Steroids and cyclooxygenase inhibitors (COX1 & 2 are inhibited by many common pain relievers) are potent anti-inflammatories that also can have significant side effects. Vinpocetine is an anti-inflammatory derived from an alkaloid which has been found helpful for vascular conditions. It also reduces NF-kB activity by inhibiting the IKK complex. (8) Vinpocetine is available as an over the counter supplement singly or may be included in mixed products, and is not advised for use by pregnant people or women of childbearing age due to a possible increased risk of miscarriage according to a recent warning by the FDA. (9) Excess Nf-kB activity leading to increased levels of TNF alpha can also cause miscarriage (spontaneous abortion/fetal death). (See Figure 1: 2)

Long term steroid use may also increase coagulation risk.

An additional factor in risk for hypercoaguability in autoimmune patients such as those with sarcoidosis may be long term use of glucocorticosteroids or other long term steroid/testosterone use. Long term steroid use has been observed to increase risk of clotting, hypercoaguability, in patients with Inflammatory Bowel Disease, (13), and in bodybuilders using steroids. (14, 15)

Steroids reduce Nf-kB activity within the short term and the increased risk of coagulation for bodybuilders using anabolic-androgenic steroids (AS) is thought to be due to a combination of the strain of lifting heavy weights combined with the AAS causing changes in blood platelets and clotting factors along with impaired ability to break down clots: “AAS are responsible for a number of haemostatic defects, including higher platelet number, enhanced platelet aggregation, increased synthesis of procoagulant factors and impaired fibrinolysis.” (15)

The granulomas found in Stage II or III sarcoidosis are typically found in the lungs but may also develop in other areas of the body including in decreasing order of frequency the: “skin, eyes, musculoskeletal system, nervous system, heart, liver, and kidneys.” (16)

Dehydration

Dehydration can also be a risk factor for increased coagulation – with a lack of water how can the blood flow through any blood vessel or organ as well?

Metal implants & medical devices can also activate the NF-kB pathway.

Metal supports for broken bones or missing bone pieces and other types of metal medical devices that are implanted within the body can be a source of metal exposure or infectious risk from pathogen growth on the surface of the device. Finishing the surface layer of the metal with a nanoparticle size rough texture has been found to interfere with the ability of bacterial pathogens to grow on the surface in comparison to a typically smooth metal surface. Gradual corrosion of the metal over time may remain a problem though and the metallic ions within the body can cause an increase in inflammatory TNF alpha and interleukin cytokines due to activating the NF-kB pathway.

The increased inflammation can increase osteoporosis risk due to increases in the activity of osteoclasts which absorb bone and decrease activity of osteoblasts which deposit more bone matrix. See Figure 16.4, page 267, Trace Metals and Infectious Disease, (link). Reducing the risk of corrosion of the metal implants is desirable as patients with osteoporosis often require metal supports for repair of fractures and then may be at risk of further inflammatory loss of bone due to the TNF alpha and other cytokines. The presence of a metal medical device could also then be a risk for hypercoaguability and ischemic stroke.

Zinc Deficiency can also lead to increased TNF alpha and IL – 1 beta.

Lack of the essential trace metal zinc as a chronic deficiency may add to inflammation and hypercoaguability risks due to epigenetic changes that promote production of the TNF alpha gene and protein and Interleukin 1 beta. The precise mechanism is not known and also involves redox-dependent mechanisms. Supplementation of zinc may be helpful for patients with inflammatory conditions. (Wessels et al, 2013)   (page 291, Trace Metals and Infectious Disease, link) Acute zinc deficiency in an animal based study was associated with more severe reperfusion-injury after myocardial ischaemia (heart attack) in the animals. (43)

Take Home Points

Patients with sarcoidosis may help reduce their risk for clots and ischemic stroke due to localized hypercoaguability occurring within areas of their bodies where granulomas have formed by:

  • maintaining adequate intake of water or other non-diuretic fluids.
  • avoiding long term use of glucocorticosteroids or anabolic-androgenic steroids.
  • increasing intake of onions, green tea, orange zest, (for flavone content)
  • and increasing intake of other Nrf2 promoting foods (other types of phytonutrients in addition to flavones can help the body increase production of the Nrf2 protein which helps increase production of antioxidants such as glutathione and Nitric oxide. Phytonutrients, foods and beverages that may help are available here: Nrf2 Promoting Foods).
  • Adequate protein intake is important for the body to be able to produce Nrf2 proteins, anticlotting factors, and other proteins essential for fluid balance.
  • Histidine and betaine are amino acids found within protein foods which may help inhibit the NF-kB pathway (11) which leads to increased levels of TNF alpha and interleukins which can cause increased coagulation/increased clotting risk. Betaine is formed from the amino acid glycine with three methyl groups and is also called trimethylglycine (TMG). The grain quinoa is a good source of betaine.
  • Adequate zinc in balance with copper intake is important.
  • Adequate magnesium, in balance with calcium and vitamin D is important. Selenium intake in adequate amounts may also be protective.
  • Phytonutrients and other medicinal chemicals may help reduce the inflammatory pathway. Increasing use of the food sources within the daily diet may be helpful to reduce hypercoaguability risk. Excess use of some of the more potent sources would not be advised as the blood thinning effects may be cumulative. Over 700 small molecules have been identified that inhibit the NF-kB pathway (See Table 1: 11) including: the omega 3 fatty acid DHA found in fatty fish such as salmon and sardines and Fish Oil supplements or bottled Krill or Fish oil; the herbal supplement extracts of kava and licorice; 6-gingerol found in ginger, (500 mg ginger in capsule was found as effective for pain relief as ibuprofen in a post dental surgery pain study, (26), 500-1000 mg per day was found effective for pain relief in a metareview of studies on arthritis pain, (27), Ginger was found to be more effective than ibuprofen for reduction of cytokine production in a cell based study of arthritis, (28), for long term use up to a half teaspoon/2500-3000 mg of ginger would be safe from excessive blood thinning effects, more than that consistently may increase risk of easy bruising or bleeding as it also contains phytocoumarins, (29); anandamide (one of our endogenous cannabinoids, which is chemically similar to the euphoria causing cannabinoid THC found in marijuana; cardamonin found in the spice cardamom; the herb Artemisia vestita – Russian Wormwood; Falcarindol found in carrots; Furonaphthoquinone found in the fruit Crataegus pinnatifida (Chinese Hawthorn); garcinone B, found in green fruit hulls of Garcinia mangostana, (18); Glossogyne tenuifolia extract, an herbal supplement used in traditional Chinese medicine sold as Devil’s Claw Extract in English language herbal supplement; Guggulsterone an extract of the resin, called gugal, of the Mukul myrrh tree which is commonly used in ayurveda traditional health care; Honokiol is an extract from Magnolia bark, seeds and leaves traditionally used in eastern/Asian medicine within herbal teas, (19); Hypoestoxide is used in Nigerian medicine and is isolated from the Hypoestes rosea, a plant native to Africa, (20); Isorhapontigenin an analog of resveratrol found in the Chinese herb Gnetum cleistostachyum; Cortex cinnamomi found in the spice cinnamon, an extract from the bark of the Chinese cassia an evergreen tree used in Korean medicine, (21); cryptotanshinone found in the roots of the Salvia miltiorrhiza Bunge (Danshen) plant used in Chinese medicine, (22); Black Rice Extract used in traditional Eastern medicine; Danshensu, found in Salvia miltiorrhiza, (23); diterpenoids are a group of phytonutrients found in many herbs including rosemary, sage and the medicinal herb Gingko biloba, (24, see Table 11.7, visible in this link , lower left corner, 25); Ent-kaurane diterpenoids isolated from a few plants including the fruit of the coffee bean plant, (30); Evodiamine, an extract from the Chinese herbal medicinal plant Evodia rutaecarpa (31); Fomes fomentarius extract of the fungus known as Tinder Conk mushroom or Hoof Fungus; Fucoidan, a polysaccahride found in many species of brown algae and seaweeds; Gallic acid found in tea leaves, red wine and some red plants such as pomegranate, sumac, red raspberries, strawberries, blackberries, red radish, onions, and other plants, used in Ayurveda traditional health care (see 5.2 Phenolic Acids, 32); Ganoderma lucidum, the Lingzhi mushroom used in traditional Chinese medicine; Garcinol, found in the Garcinia indica plant used traditionally in its native tropical growing region to make a sweet drink from the fruit known as Kokum in India and Mangosteen in English, (33); Ginkgolide B, found in the Chinese medicinal tree Gingko biloba, (34); Glycyrrhizin, a sweet flavored extract of Glycyrrhiza glabra (licorice) root, (35); Halofuginone, derived synthetically from fegrifugine or from quinazolinone alkaloid from the Chinese herb Dichroa febrifuga (Chang Shan) hydrangea in English (36); Hematein, found in logwood,Used as a chemical stain & indicator of metals, changing to different colors in the presence of different metals. (37); Herbal compound 861, an extract from ten herbs used in traditional Chinese medicine, (38); Hydoxyethyl starch, branched amylopectin, Used in intravenous infusions (6%) as a plasma volume expander, may cause increased bleeding risk and long term renal damage, especially in critically ill patients. (39); Hydroxyethylpuerarin, (HEP), extract from the dried root of Puerariae radix, an herb used in Chinese traditional medicine (40); mulberry anthocyanins; . There are 700, not all naturally derived, I will be adding a few more from the list.
    (11)
  • cloricromene, a coumarin derivative (medication used in Western medicine) (11) .

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 individualized health care guidance. Please see an individual health care provider for individual health care services.

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  • M Wang, W Liu, and T J Webster, Chapter 16: The Promise of Nano metals: Reducing Infection and Increasing Biocompatibility, Trace Metals and Infectious Diseases, Ed. Jerome O Nriagu and Eric P Skaar, Strungmann Forum Reports, (MIT Press, 2015, Cambridge, MA) https://mitpress.mit.edu/books/trace-metals-and-infectious-diseases
  • M L Ackland, J Bornhorst, F V Dedoussis, et al., Chapter 17: Metals in the Environment as Risk Factors for Infectious Diseases, Trace Metals and Infectious Diseases, Ed. Jerome O Nriagu and Eric P Skaar, Strungmann Forum Reports, (MIT Press, 2015, Cambridge, MA) https://mitpress.mit.edu/books/trace-metals-and-infectious-diseases
  • Wessels, I., H. Haase, G. Engelhardt, L. Rink, and P. Uciechowski, 2013. Zinc Deficiency Induces Production of the Pro-Inflammatory Cytokines IL-1beta and TNF alpha in Promyeloid Cells via Epigenetic and Redox-Dependent Mechanisms. J. Nutr. Biochem. 24:289-297. https://www.ncbi.nlm.nih.gov/pubmed/22902331
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Epsom Salt Foot Soaks

*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)



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To have optimal Magnesium needs Protein and Phospholipids too.

Good news and bad news – magnesium in the form of Epsom salt, magnesium sulfate, has been in use medicinally since the seventeenth century and written about in peer reviewed medical journals since the early nineteenth century. (1) That is both the good and bad news – it is helpful, but it still isn’t used for many conditions where it might be needed. It is not patentable as a pharmaceutical medication because it is a natural substance. It or magnesium chloride and some other forms are in use for a few conditions including preeclampsia, migraines, stroke, and traumatic brain injury. Minor athletic injuries may be treated with Epsom salt soaks (3) and some psychiatric care providers may also recommend the treatment. 

A textbook on the topic of magnesium use for medical conditions reviews the mineral’s role in the body during health and chronic illness or when genetic differences in metabolism are present. It is complex metabolically and just taking a supplement doesn’t always get magnesium to the problem area of the body. Magnesium is primarily found within cells, and most is bound to proteins or phospholipids rather than as free ions, in blood plasma or other extracellular fluid and not all forms can cross the blood brain barrier to help with migraines or other brain injuries.(1) Magnesium sulfate and magnesium chloride have been found helpful for those purposes (1) and both can be used topically which can bypass problems with poor absorption in the digestive system. (3)  

Magnesium oxide is a form sometimes used in supplements that has been found to be very poorly absorbed even when the digestive system is in normal health. Only four percent of a dose is likely to be absorbed and the remaining 96% tends to cause loose stools by causing the intestinal muscles to relax too much if the supplement is in a larger dose. (1) Math – a 250 mg supplement of magnesium oxide might only have 10 milligrams absorbed and 240 milligrams pass through in the next bowel movement.  

Magnesium aspartate has been found helpful in some research studies, but the aspartate is an excitatory amino acid that can cause overactivity within brain cells possibly even leading to cell death, so it may not be ideal for people with some conditions such as headaches or brain injury. Other forms of supplements found to typically be well absorbed include magnesium citrate and magnesium glycinate. More recent research is using magnesium threonate as a form that may be more likely to be absorbed through the blood brain barrier. (1) 

Summary points:  

Symptoms of deficiency may include:  

  • Headaches or migraines may be a symptom because magnesium is used within the brain to protect against excess calcium or glutamate entry into brain cells. It is involved in fluid balance so high blood pressure may occur; tiredness and easy weight gain may be symptoms of chronic deficiency as it may cause insulin resistance and is essential within metabolism to turn sugar into a form of usable energy. Muscle cramps are also a common symptom of magnesium deficiency and may include a twitching of the eyelids. Tinnitus, a constant dull ringing sound in the ears, can occur. (1) (2) 

Food sources of magnesium include: 

  • Green leafy vegetables, broccoli, cauliflower, cabbage, sweet potato, squash; fruit, bananas; dark chocolate; beans, tofu; nuts such as cashews & almonds; pumpkin, pomegranate and sesame seeds, tahini; peanuts; brown rice, whole grains; yogurt. (2) 
Magnesium Food Sources and Symptoms of Deficiency.

Topical sources of magnesium include:  

    • Epsom salt, magnesium sulfate, can be used in baths or foot-soaks, or in damp poultices placed on other sore body parts. For a bath, about one cup of salt in a half bath, soak for 20 minutes three times a week, no more than 40 minutes to avoid excess absorption.
      Symptoms of excess absorption can include slowing heart rate, an overly relaxed muscles which can cause loose stools, for up to a day if very excessive. (3)
      An advantage of magnesium sulfate includes the sulfate in a form that doesn’t need sunshine exposure to skin in order for the body to be able to transform sulfur found in foods into the bioactive sulfate form. 
  • Magnesium chloride is available for topical use in body lotions & as an oily feeling liquid solution.People with digestive problems may not be absorbing much magnesium from food or supplements. 
Topical sources of Magnesium and bioactive Sulfate.

Supplemental forms of magnesium may include: 

    • Magnesium citrate, Mg glycinate, Mg L-threonate, Mg lysinate, Mg orotate, Mg malate, and Mg taurate are all fairly well absorbed forms and generally don’t cause side effects when taken in smaller amounts a few times a day (200-250 mg) instead of in a large dose (more than 400 mg in a single dose). People using diuretics or with increased sweat or urine losses for other reasons may need extra magnesium intake to make up for increased loss of magnesium in urine or sweat. People with late stage kidney disease may need to avoid excess Mg intake. (1) (4) 
  • Magnesium sulfate can be taken in water in very small amounts (a few crystals, a very tiny amount) (3), & it or Mg chloride may also be available in capsule form.
    Magnesium aspartate is well absorbed but the aspartate is an excitatory amino acid and may cause headaches for some users. 
  • Magnesium oxide is poorly absorbed (~ only 4%) & may cause loose stools for more users than the other forms. (1) 
Supplemental sources of Magnesium.
  • Food Sources of Phospholipids and other phospho-nutrients: Hemp seed kernels and oil; Artemisia turanica/wormwood leaf; amaranth seed; asparagus; avocado fruit or the inner kernel, dried and powdered; beans/legumes; cardamom seeds and powder; carrots; celery stalks and leaves; cocoa beans and cocoa powder, baker’s chocolate, dark chocolate and to a lesser amount milk chocolate and chocolate syrup; coconut; cumin seed/powder; fennel seed, flax seed, pine nuts; sesame seeds, pumpkin seed kernels, squash seeds; butternut squash and pumpkin; gingko leaf; grapefruit and orange juice with the pulp; Jerusalem artichoke (this is a root vegetable rather than a green artichoke); lettuce, spinach and mustard leaves and other leafy green vegetables and herbs; nuts/peanuts, cashews, walnuts; oats; okra seeds; onion root, leek leaves, garlic;  parsnip root; pomegranate seeds and pomegranate peel extract;rice, white or brown but the bran is the best source; rosemary; sorghum;  sweet potato or yam; buckwheat (a seed botanically that is not wheat and is gluten free); wheat. (G.26)   

More information about protein and water needs are available in a post about kidney health: Make every day Kidney Appreciation Day.

/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./

  1. Robert Vink, Mihai Nechifor, editors, Magnesium in the Central Nervous System, University of Adelaide Press, 2011, adelaide.edu.au, free ebook pdf, https://www.adelaide.edu.au/press/titles/magnesium/magnesium-ebook.pdf  (1) 
  2. Rachael Link, MS, RD,Top 10 Magnesium-rich Foods, Plus Proven Benefits, DrAxe.com, https://draxe.com/magnesium-deficient-top-10-magnesium-rich-foods-must-eating/ (2) 
  3. Magnesium sulfate (Epsom salt) – Side Effects Dosage, Interactions, everydayhealth.com https://www.everydayhealth.com/drugs/magnesium-sulfate (3) 
  4. Magnesium Types Compared: What is the Best Magnesium for You?, swansonvitamins.com, https://www.swansonvitamins.com/blog/chelsea/magnesium-types-compared  (4) 
  5. 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 (5)
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Sleep and Health

The sleep/wake cycle impacts health in many ways. The hormone melatonin has become more familiar as it now more available over the counter as a supplement that may help with sleep. It may help with getting to sleep – but timing – when it is taken, and how much – not an excess, are important factors, and it may not help with staying asleep. Sleep and wake are very complex processes within the brain and body, with many chemical signals causing activation or inhibition of different areas of the brain which then signal activation or inhibition of body functions. Reviewing all of them is beyond the scope of this post – including just the summary points is my goal.

  • Insomnia seems to be a hyperarousal of the system, both the brain and body remain more metabolically active than within normal sleep causing difficulties falling asleep and then leaving the person lest rested after sleeping because it was never reaching deeper relaxation of the brain’s activity levels. The hyperarousal tends to continue during the day so the person with insomnia may be irritable and not able to concentrate as well but may not feel tired or sleepy as might be expected after missing that many hours of sleep. The risk with ongoing insomnia though is the person is in need of deeper sleep and accidents may be more likely to occur in physical activity or in oversight of details in mental activity, especially when there are multiple demands on attention.
  • The wake/sleep cycle is essential for health for many reasons but the overall point is that different functions of metabolism occur when awake than during sleep, and both are important to overall health. Repair and detoxification, roughly, are the focus of the sleep hours and energy use and activity and learning/creating new connections between brain and nerve cells are the focus of wake hours.
    • Sleep and wake have different specialized genes and proteins for metabolism – what gets made or what gets cleaned up and reused or excreted/detoxified. Wakefulness activates genes that are used in active metabolism, using sugar for energy, and sleep activates genes that are important for using fats for building cell membranes or myelin sheaths around nerve cell connections.
    • Chronic sleeplessness can cause insulin resistance and lead to increased risk for diabetes or metabolic syndrome, whether the sleeplessness was due to inadequate hours of sleep because of a busy schedule, or due to poor sleep quality because of insomnia or other health problems or overuse of caffeine or stimulating lights late at night. More about insulin resistance, Type 2 diabetes and metabolic syndrome is available in a TEDmed video talk about obesity and insulin resistance. A doctor suggests that the approach medical research has taken in looking at obesity as a cause of insulin resistance may be wrong – insulin resistance may lead to obesity. Peter Attia-What If We’re Wrong About Diabetes?, TEDmed.
    • Hypertension, high blood pressure, is also a risk of chronic sleep problems.
    • Add up the problems of reduced myelin sheath production, blood sugar and blood pressure problems, and it is easy to see that long term risks of poor sleep quality may include dementia whether typical forgetfulness type due to loss of connections between brain cells or the loss of brain cells in Alzheimer’s dementia.

Solutions vary depending on the type of sleep problem however general tips for an ideal sleep setting include:

  • A cool room temperature – the body temperature is at its lowest during sleep.
  • Complete darkness – for the pineal gland to make melatonin the use of a light blocking eye mask on long airplane rides may help provide deeper sleep. In the home setting or when traveling cover alarm clock lights or other digital lights during the night and close curtains. Complete light blocking curtains are ideal.
  • Stop using digital screen devices about a half hour to an hour before intended time to try to sleep. Additional tips about electric light: Digital screens are a very bright type of light and blue lens glasses are available for eye protection for anyone who spends many hours per day using laptops or smartphones. The light settings on the device may also offer a dimmer evening setting which may help reduce eyestrain.*
  • Avoid coffee or other caffeine containing stimulants for about four to six hours prior to intended time to try to sleep.
  • Have a regular time to go to sleep and wake up each day. The average person does need about 7 to 8 hours of sleep each night and teenagers and toddlers ideally may need 10 hours of sleep for best cognitive performance and physical health. Lack of sleep for adults seems to negatively affect reasoning and verbal performance more than short term memory. (3)
  • Avoid high fat, hard to digest meals or snacks in the hours prior to intending to try to sleep.
  • A cool compress on the forehead or over the eyes or on top of the head may help relax sooner if insomnia and racing thoughts are a problem or feeling hot and jittery. Reusable gel packs designed for sprained ankles or other sore muscles can be kept in the freezer and then wrapped in a few layers of thin fabric to protect the skin from being overly chilled. The gel pack will eventually lose its coolness but use on the forehead may help slow down the metabolic activity of the brain, which then helps slow down signals to the body to be jittery – 20 to 30 minutes with a cool gel pack may help reach a more relaxed state before the pack is warm. Having several in the freezer could allow you to rotate the warm one with a chilled one if reawakening in the middle of the night is a problem. **
  • If reawakening in the middle of the night is a problem but you are still sleepy, try not to use any bright lights while visiting the bathroom or kitchen, etc. If wide awake, then it is recommended to just get up and do something for a while until feeling sleepy again rather than tossing and turning in bed and getting more anxious or jittery.
  • If reawakening in the middle of the night is consistently happening around 4:00 am then low serotonin levels may be a problem.  (University Health News) Taking the precursor to serotonin, 5HTP or the herbal St John’s Wort, may help provide your body with serotonin.
  • Cognitive Behavioral Therapy for sleep issues has been found to be as or more effective than sleep promoting medications while they are in use, and more effective at long term benefits even after the therapy or medication is no longer in use. Anxiety may be an issue but habits can also affect insomnia, naps and early bed times may disrupt sleep and staying awake during the day, and ideally getting some bright sunshine or full spectrum light during wake hours can help with the body’s 24 hour metabolic patterns. (CBT-I, National Sleep Foundation)

*Modern laptops or smartphones emit bluelight which may inhibit sleep. (1) Wearing blue light blocking glasses in the evening for any screen time may help reduce the effect. It has been found helpful to prevent sleep difficulties to wear them during the three hours prior to trying to go to sleep. The blue light blocking glasses are not needed for use throughout the day however. Eyestrain from a long day working with a light screen may cause dry itchy eyes and eyedrops for moisture and taking occasional breaks may help prevent that problem. Read more: (2).

**The tip about keeping gel packs in the freezer for use as a cold compress for the forehead that I mentioned for insomnia in a previous post (about the glymphatic system within the brain and its potential role in prevention of Alzheimer’s disease ), is something that I have found helpful in the past for migraines. I tried it recently for insomnia after learning in the course about sleep and neurobiology that a “biothermal device” had been found helpful in sleep lab studies for patients with insomnia. (Sleep, Neurobiology, Medicine and Society, coursera.org)

The drawing suggested they had an electric blanket type compress size cooling device that laid over the forehead and slightly over the ear area, so a little bigger than a gel pack designed for sprained ankles. However a gel pack for sprained ankles is already at stores and electric cooling biothermal devices are not yet available to my knowledge. The point – my trial use with a freezer gel pack for insomnia was very helpful at slowing my thoughts and helping my body reach a relaxed state fairly quickly. I didn’t immediately go to sleep but it did seem to help. I’ve tried it several times now and one night got another out of the freezer when I was awake but sleepy in the middle of the night. 

Environmental cues and genetic differences can effect sleep patterns. (Sleep, Neurobiology, Medicine and Society, coursera.org) (How Nature and Nurture Shape the Sleeping Brain, nature.com)

There is more on this topic however this is an overview of the importance of sleep.

/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./

  1. Dustin Eves, Do Computer Screens Emit UV Light? techwalla.com, https://www.techwalla.com/articles/do-computer-screens-emit-uv-light
  2. Do Blue Light Blocking Glasses Really Work? 2018, nymag.com,     http://nymag.com/strategist/article/blue-light-blocking-glasses-work.html
  3. Conor J Wild, Emily S Nichols, Michael E Battista, Bobby Stojanoski, Adrian M Owen; Dissociable effects of self-reported daily sleep duration on high-level cognitive abilities, Sleep, , zsy182, https://doi.org/10.1093/sleep/zsy182