Magnesium - essential for eighty percent of our body's chemistry.
Magnesium is a trace mineral essential for 80% of body function, (muscular contractions, energy production, removal of infected or precancerous cells, etc). It is used in over 300 enzymes required for metabolism and other chemical reactions in the body such as synthesis of DNA or proteins. (1)
This post is eleven pages long and can be read as a tabbed document: (doc)
Health Conditions linked to Magnesium inadequacy.
Circulatory System: Hypertension, Heart Disease, Stroke, Arrhythmias, Atrial fibrillation, Dyslipedemias.
Metabolic: Diabetes, Metabolic Syndrome.
Respiratory: Asthma, COPD, Other Lung/Respiratory.
Central Nervous System (CNS): Depression, Anxiety, ADHD, Migraine, Pain Relief, Addiction, Sleeplessness, Stress.
Muscle/Skeletal: Low Back Pain, Osteoarthritis, Other musculoskeletal (~ muscle cramps, twitches, other chronic joint pain), Osteoporosis, Sarcopenia.
Immune System/Other: Pre-eclampsia, Kidney disease, Crohn's Disease, Chronic Fatigue Syndrome, Colon inflammatory diseases/IBD, Inflammation, Some Cancers.
(todaysdietitian/Modern Day Human Magnesium Requirements)(Seelig/Rosanoff, 2003)
Calcium/Magnesium ratio within cells affects our health.
When magnesium within cells is lower than normal calcium is allowed to enter in excess. Elevated amounts of calcium within the interior of cells acts as a signal to start different types of activity. Increased calcium to magnesium balance within a cell may cause different actions based on the type of cell.
Elevated calcium to magnesium ratio within cells could cause blood vessels to constrict which would increase blood pressure. Vasoconstriction within the heart could cause a random heart rate (arrthymias). Platelets within the blood would become stickier and more prone to clot which could increase risk of strokes.
Cholesterol and glucose over-production may occur in liver cells. Glucose uptake by muscle and fat cells could decrease. Insulin over-production could occur in pancreas cells. Which could lead to Type 2 Diabetes or Metabolic Syndrome.
(39, 40, 41, 42) (todaysdietitian/Modern Day Human Mg Requirements)
Summary Points:
Magnesium is essential for 80% of body function, (muscular contractions, energy production, removal of infected or precancerous cells, etc), (1),
Adequate protein and phospholipids (ATP-AdenosineTriPhosphate --> energy release --> ADP-AdenosineDiPhosphate) are needed for cells to be able to have a full reserve supply of magnesium. (MgATP, 6, 7, 8) Magnesium is located within cells primarily (greater than 99%, 12), as free ion or in an inactive form on molecules of protein or ATP., which means typical blood based lab tests are not helpful for diagnosing chronically low levels of magnesium. See a previous post for more information, food sources and supplement types, and a free etext reference.
Magnesium adequacy through diet or supplementation may help improve symptoms for patients with migraine headaches, Alzheimer's dementia, hypertension, cardiovascular disease, recovery after a cerebrovascular stroke, and type 2 diabetes mellitus (type 2 DM). (9) Muscle cramps may be due to low magnesium levels (9) or an imbalance with calcium levels.
Magnesium supplementation may also help some types of psychiatric conditions such as anxiety, depression, bipolar disorder, schizophrenia. See: Magnesium and the Brain: The original chill pill, (psychologytoday.com). Mental health problems have been escalating in the U.S. and other developed countries, lack of jobs and increased social isolation and cyberbullying are involved, however magnesium/calcium imbalance are also factors. See: Latest Suicide Data Show the Depth of U.S. Mental Health Crisis, (bloomberg.com).
While you need adequate intake of protein for holding reserve supplies of magnesium within cells, you need adequate magnesium for the body to be able to build new proteins or modify protein structure, and to build more DNA or RNA (which uses the nucleotide ATP), (9, 10, 11, 12, 13, 14, 15) and in ATP hydrolysis (release of the stored energy from glucose metabolism in the Kreb's cycle), (18) and the Kreb's cycle. (7) Magnesium deficiency led to lower levels of ATP within red blood cells and increased amounts of ADP, from a 6:1 ratio of ATP:ADP to 2.5:1 at the lowest magnesium level. (19)
Which means supplementing only magnesium or only protein may not fully help protect against cardiovascular stroke or migraine pain or other symptoms associated with magnesium deficiency such as hypertension and Type 2 Diabetes.
Cancer prevention may also be possible by preventing chronic low levels of magnesium as mutations in DNA may be more likely with inadequate magnesium. Excess calcium or imbalance in vitamin D and calcium/magnesium balance may also be involved in increased cancer risk. (10, 13) Magnesium is used by white blood cells during apoptosis of infected or damaged cells and autophagy, the removal of cells by white blood cells, may help protect against Alzheimer's dementia. Both apoptosis and autophagy are the typical defense against precancerous cells or mismarked cells that may lead to autoimmune reactions. Once cancer is established magnesium supplements would be inadequate alone as a treatment and would also be providing the nutrient to the cancer cells.
Magnesium and calcium are electrolytes - electrically active ions similar to sodium and potassium.
Magnesium is an electrically active trace mineral/metal that is predominantly found within cell fluid and bone matrix. Only about one percent of the body's magnesium is found in the blood plasma fluid, circulating throughout the body within blood vessels, and also through the lymphatic and glymphatic systems. (Gervin 1983, ref) (interstitial fluid) Calcium is chemically electrically active in a similar way to magnesium. Both metals can donate or accept two protons and are chemically written with a +2, while sodium and potassium can donate or accept one proton which would be written as +1.
Sodium and potassium are typically referred to as electrolytes however calcium, magnesium and other electrically active ions are also found in blood plasma and in the fluid around cells, called extracellular fluid or interstitial fluid. The fluid within cells is called intracellular fluid or cytoplasm and it also contains ions/electrolytes. The balance of ions within the different types of fluid varies somewhat however the overall average is similar to the balance of ions in sea water. The total fluid volume is about 60% of our body's weight, of that most is found within cells, 60% intracellular fluid, and of the 40% extracellular fluid, 20% is blood plasma transported in arteries and veins, and 80% is interstitial fluid, transported in the lymphatic system. (Lymphatic fluid, 4) Magnesium would be in greater concentration in the 60% intracellular fluid and calcium would be in greater concentration in the 40% extracellular fluid.
Magnesium powers membrane transport channels - a natural calcium channel blocker.
Within the cells magnesium may be used within enzymes, over 300 require the trace mineral, or may provide their electrical power to cell membrane transport channels which allow certain chemicals to enter the cell while blocking others - when adequate magnesium ions are available to block the channels including some involved in sodium/potassium balance. (16, 18) Magnesium deficiency seemed to decrease the activity of the sodium/potassium channels in an animal based study. It led to increased intracellular sodium levels which could be a mechanism for the increased risk of arrythmias (irregular heart rate) with magnesium deficiency. (17)
Magnesium in muscles and the inner ear (tinnitus).
Magnesium causes relaxation of muscles - blocking entry of calcium into the muscle fiber, and calcium entry causes muscle contractions within smooth muscle fibers (such as the muscle fibers of the gastrointestinal tract) or striated muscle fibers (found in the muscles with voluntary control such as those of the arms and legs, and also in the heart which is not under voluntary control). (31, 32, 33, 34, 35, 36, 37) Magnesium deficiency can be an underlying cause of muscle cramps or twitches (such as a nonstop twitch in the eyelids) (9), and may also be a factor in tinnitus (nonstop or intermittent ringing or buzzing sounds in the ears/ear). (28) Daily supplementation with 532 milligrams of magnesium was found helpful to relieve symptoms of tinnitus in a small clinical trial. (30) Magnesium inhibits glutamate channels which are involved in activating the hair cells of the ear canal. It may also help by helping relax blood vessels to the inner ear and increasing blood flow. (29)
Magnesium is stored within the cell in an inactive form on protein molecules or ATP.
Even within the cells the majority of magnesium stores are not available in the electrically active form. Most of the back-stock of magnesium within cells is stored on proteins or molecules of ATP (the nucleotide involved in the Kreb's cycle production of usable energy {ATP bonds} from glucose). (MgATP, 6, 7, 8)
This means magnesium deficiency can take a long time to be seen because of the extra stored within cells on proteins and ATP and the extra stored within our bone matrix can be slowly released to continue powering the 300+ enzymes and membrane channels in every cell of the body. What happens eventually however is a depletion of the backstock of magnesium on the cellular proteins and ATP and osteoporosis can develop in the bone matrix leaving fragile bones at risk for fractures -- and also cell membranes at risk to an influx of too much calcium, or other excitatory chemicals such as glutamates or aspartic acid/aspartate, leaving brain cells at increased risk from food additives, or dehydration, or ischemic stroke.
Protein deficiency in the diet or increased metabolic need for protein might increase risk of low magnesium levels being available in case of a stroke. If a stroke occurred treating with intravenous magnesium fairly soon can help reduce cell damage and preserve abilities. When the body is well supplied with protein, ATP, and magnesium then the stored magnesium would be available in case of a stroke or physical brain trauma. If protein availability was limited the damage from a stroke might be more severe due to less magnesium being available for release.
Protein-energy malnutrition is a type of malnutrition involving a diet low in protein more than calories. The condition was formerly known as kwashiorkor and was first recognized in tropical infants/children. Severe edema with a bloated abdomen is typical visible symptom. (See image, page 30, 46) When magnesium deficiency is also severe the condition is more likely to result in death and strokes are also more common. The serum magnesium level of children with protein-energy malnutrition was found to be significantly lower than in the control group. Low magnesium in drinking water has been associated with increased risk of cerebrovascular disease or death by stroke. (45)
Incomplete protein in the diet seems to be involved - plant sources of protein do not all contain adequate amounts of all the essential amino acids. Missionary work historically may have increased the risk of Protein-energy malnutrition in recently weaned toddlers due to an educational message that eating insects is wrong - eating a diet with inadequate amounts of essential amino acids is what is wrong. In modern times, unfortunately, children in Africa are now being taught to not catch and eat crickets because they are likely contaminated with the pesticides that are commonly used on farm fields.
The amino acids considered essential for a child's diet include: Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine. The traditional African diet in some areas includes complete protein from peanuts and cowpeas are only low in tryptophan. (46) Millet and sorghum are commonly used grains which are low in tryptophan, lysine, methionine, and threonine. (47) The nutrient content of food insects depends on their stage of growth, however on average they are considered a good source of complete protein - providing a similar ratio of essential amino acids as meat or fish. Food insects are also a good source of essential fatty acids, similar to fish, and provide fiber and trace minerals including "copper, iron, magnesium, manganese, phosphorous, selenium and zinc." (48)
Food insects and breastmilk also have in common N-acetyl glucosamine (within insects it is found in the form of the fiber chitin which is not typically thought of as digestible by humans however the enzyme chitinase has been found in human gastric fluid). (49, p 74, section 6.1.8: 50) Intake of N-acetyl glucosamine may help support a healthy intestinal mucousal lining. Impaired mucous lining of the intestine and reduced amounts of "enterocyte heparan sulfate proteoglycan (HSPG)," and "abnormal sulfated glycosaminoglycan (GAG) metabolism" have been observed in patients with protein-energy malnutrition (kwashiorkor). (49) Providing magnesium sulfate by intramuscular injection helped survival for children with protein-energy malnutrition compared to the control group in a small clinical trial. (51)
Magnesium is needed for vitamin D, CoQ10, and cholesterol production.
Magnesium deficiency can lead to low levels of the inactive and active form of vitamin D. Magnesium supplementation is needed to reverse a type of bone degenerative condition called vitamin D resistant rickets. (20) Supplementing with vitamin D and/or calcium has been popular however the benefits against fracture risk and osteoporosis have been unclear or show little benefit. (22) The need for magnesium supplementation instead of or in addition to vitamin D and calcium supplements is in area worth further study. (21) Magnesium is also involved in earlier steps involved in vitamin D production - biosynthesis of cholesterol (23) from which vitamin D can be formed in the skin when sunshine is available.
Magnesium acts similarly to statin medications and is the natural version of a calcium channel blocker medication. (23) Statins have been prescribed to many people in hopes that chemically inhibiting the production of cholesterol would help protect against heart disease, unfortunately the theory has not been proven effective - while cholesterol levels are reduced in about half the patients using the medication, the lower cholesterol levels have not also been associated with reduced mortality from cardiovasclar risks. For patients without heart failure or renal dialysis or for those over age 75 the use of statin medications helped prevent revascularization and major coronary events in about 20% of research trials that were reviewed. (24)
The cardiovascular benefits of statin medications may be due to the inhibition of an interim step in cholesterol formation - mevalonate. Magnesium would also affect mevalonate formation however in a regulatory way - controlling whether or not the reaction happens rather than only inhibiting it. (23) β-Hydroxy β-methylglutaryl-CoA, (HMG Co A) is converted into mevalonate which then can be converted into cholesterol or the provitamin coenzyme Q10. (26)
Lack of CoQ10 may cause muscle pain and lead to mitochondrial dysfunction.
Statin medication use may cause muscle and joint pain in some users, possibly due to inhibition of Coenzyme Q10 production. Supplements of CoQ10 (200mg/day) may help reduce the muscle pain symptoms for some patients and could also be protecting against a risk of mitochondrial dysfunction caused by low levels of the the coenzyme. (25)
Mitochondrial dysfunction may be a cause of chronic fatigue - low energy production by mitochondria within cells would leave every function in the body with less energy to perform their jobs. Mitochondrial dysfunction may be involved in many conditions including autism, Alzheimer's disease, muscular dystrophy, Lou Gehrig's disease, diabetes and cancer. (clevelandclinic/mitochondrial diseases)
Magnesium helps protect health, and improve our energy level and mood.
Symptoms of magnesium deficiency are often treated with medications (such as calcium channel blockers or statins) instead of providing magnesium. Other medications commonly used to treat symptoms that might involve magnesium deficiency include: beta blockers, blood thinners, anti-hypertensive medications, insulin or metformin, anti-depressants, anti-anxiety medications, anti-inflammatory medications. (43) (todaysdietitian/Modern Day Human Magnesium Requirements)
Adequate protein and phospholipids are also needed for cells to be able to store extra magnesium in an electrically inactive form and magnesium is needed for their synthesis. This might help explain why supplements of magnesium help some patients more than others. Someone who is more chronically ill or malnourished or who has impaired metabolism may need more complete nutrition support rather than only providing a magnesium supplement. Topical supplements of magnesium may be needed for patients with malabsorption problems or for those who don't seem to be helped by increasing dietary sources.
Excess calcium in proportion to magnesium in the diet or from supplements may also be part of the problem for some patients. (44) The average modern diet can include calcium rich dairy products at each meal and snack. Tofu, beans, almonds, sesame seeds, and dark leafy green vegetables are also good sources of calcium.
Free Continuing Education credit for nutritionists/diet techs:
For any dietitians or diet techs, much of the first reference list is from a free continuing education webinar, register for this: Andrea Rosanoff, PhD, and Stella Lucia Volpe, PhD, RDN, ACSM-CEP, FACSM, Recorded Webinar: Modern Day Human Magnesium Requirements: The RDN's Role, Today's Dietitian, https://ce.todaysdietitian.com/node/69241#group-tabs-node-course-default1 The second list is from the last post from the section about magnesium and hypercoaguability.
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.
References
Workinger JL, Doyle RP, Bortz J. Challenges in the diagnosis of magnesium status. Nutrients. 2018;10(9):1202. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163803/
Gervin CA, Nichols WM, Chvapil M, Wangensteen SL. Zinc transport by the heart lymphatic system after acute myocardial infarction., J Surg Res. 1983 Oct;35(4):340-50. https://www.ncbi.nlm.nih.gov/pubmed/6621029
Niels Fogh-Andersen, Burton M. Altura, Bella T. Altura, and Ole Siggaard-Andersen, Composition of Interstitial Fluid, Clin. Chem. 41/10, 1522-1525 (1995) https://pdfs.semanticscholar.org/6955/f9bc101b8adff35b700906dcf77d683367f0.pdf
Lymphatic Fluid and Immunotherapy, maxwellbioscinces.com, https://maxwellbiosciences.com/articles/uncategorized/lymphatic-fluid-immunotherapy
Differences between blood and lymph, vedantu.com, https://www.vedantu.com/biology/difference-between-blood-and-lymph
Storer AC, Cornish-Bowden A. Concentration of MgATP2- and other ions in solution. Calculation of the true concentrations of species present in mixtures of associating ions. Biochem J. 1976;159(1):1-5. https://pdfs.semanticscholar.org/a85b/95b80f2c0fd41f8a39a7c7768887ee784522.pdf
Garfinkel L, Garfinkel D. Magnesium regulation of the glycolytic pathway and the enzymes involved. Magnesium. 1985;4(2-3):60-72. https://www.ncbi.nlm.nih.gov/pubmed/2931560
Wilson JE, Chin A. Chelation of divalent cations by ATP, studied by titration calorimetry. Analytical Biochem. 1991;193(1):16-19. https://www.ncbi.nlm.nih.gov/pubmed/1645933
Volpe SL. Magnesium in disease prevention and overall health. Adv Nutr. 2013;4(3):378S383S. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650510/
Abdelgawad IA, El-Mously RH, Saber MM, Mansour OA, Shouman SA. Significance of serum levels of vitamin D and some related minerals in breast cancer patients. Int J Clin Exp Pathol. 2015;8(4):4074-4082. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466982/
Romani AM. Magnesium in health and disease. Met Ions Life Sci. 2013;13:49-79. https://www.ncbi.nlm.nih.gov/pubmed/24470089
Long S, Romani AM. Role of cellular magnesium in human diseases. Austin J Nutr Food Sci. 2014;2(10):1051. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379450/
Rubin H. Central roles of Mg2+ and MgATP2- in the regulation of protein synthesis and cell proliferation: significance for neoplastic transformation. Adv Cancer Res. 2005;93:1-58. https://www.ncbi.nlm.nih.gov/pubmed/15797443
George GA, Heaton FW. Effect of magnesium deficiency on energy metabolism and protein synthesis by liver. Int J Biochem. 1978;9(6):421-425. https://www.sciencedirect.com/science/article/pii/0020711X78900551
Weisinger JR, Bellorin-Font E. Magnesium and phosphorus. Lancet. 1998;352(9125):391-396. https://www.thelancet.com/journals/lancet/article/PIIS0140673697105359/fulltext
Dorup I, Skajaa K, Thybo NK. Oral magnesium supplementation restores the concentrations of magnesium, potassium and sodium-potassium pumps in skeletal muscle of patients receiving diuretic treatment. J Intern Med. 1993;233(2):117-123. https://www.ncbi.nlm.nih.gov/pubmed/8381850
Fischer PW, Giroux A. Effects of dietary magnesium on sodium-potassium pump action in the heart of rats. J Nutr. 1987;117(12):2091-2095. https://www.ncbi.nlm.nih.gov/pubmed/2826728
Fagher B, Sjögren A, Monti M. A microcalorimetric study of the sodium-potassium-pump and thermogenesis in human skeletal muscle. Acta Physiol Scand. 1987;131(3):355-360. https://www.ncbi.nlm.nih.gov/pubmed/2447746
Flatman PW, Lew VL. The magnesium dependence of sodium-pump-mediated sodiumpotassium and sodium-sodium exchange in intact human red cells. J Physiol. 1981;315:421-446. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1249391/
Deng X, Song Y, Manson JE, et al. Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III. BMC Med. 2013;11:187. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765911/
Rosanoff A, Dai Q, Shapses SA. Essential nutrient interactions: does low or suboptimal magnesium status interact with vitamin D and/or calcium status? Adv Nutr. 2016;7(1):25-43. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717874/
Jill Jin, MD, MPH, Vitamin D and Calcium for Preventing Fractures, Guidelines, JAMA Patient Page, JAMA Network, April 17, 2018 https://jamanetwork.com/journals/jama/fullarticle/2678617
Rosanoff A, Seelig MS. Comparison of mechanism and functional effects of magnesium and statin pharmaceuticals. J Am Coll Nutr. 2004;23(5):501S-505S. https://www.ncbi.nlm.nih.gov/pubmed/15466951
Cholesterol Treatment Trialists' Collaboration Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials., The Lancet, Vol 393, Issue 10170, pp407-415, Feb. 02, 2019, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31942-1/fulltext
Deichmann R, Lavie C, Andrews S. Coenzyme q10 and statin-induced mitochondrial dysfunction. Ochsner J. 2010;10(1):16–21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3096178/
Pacanowski MA, Frye RF, Enogieru O, Schofield RS, Zineh I. Plasma Coenzyme Q10 Predicts Lipid-lowering Response to High-Dose Atorvastatin. J Clin Lipidol. 2008;2(4):289–297. doi:10.1016/j.jacl.2008.05.001 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2598393/
Mitochondrial Diseases, ClevelandClinic.org, https://my.clevelandclinic.org/health/diseases/15612-mitochondrial-diseases
Tinnitus and Magnesium, tinnitus.org, https://www.tinnitus.org.uk/tinnitus-and-magnesium
Joseph Mercola, MD, Can Magnesium Relieve Your Tinnitus?, Prohealth.com, https://www.prohealth.com/library/can-magnesium-relieve-your-tinnitus-47779
Cevette MJ, Barrs DM, Patel A, et al., Phase 2 study examining magnesium-dependent tinnitus., Int Tinnitus J. 2011;16(2):168-73. https://www.ncbi.nlm.nih.gov/pubmed/22249877
Zhang A, Carella A, Altura BT, Altura BM. Interactions of magnesium and chloride ions on tone and contractility of vascular muscle. Eur J Pharmacol. 1991;203(2):223-235. https://www.ncbi.nlm.nih.gov/pubmed/1800119
Altura BM, Altura BT. Role of magnesium ions in contractility of blood vessels and skeletal muscles. Magnesium Bull. 1981;3(1a):102-114. http://www.magnesium-ges.de/jdownloads/Literatur/Altura/altura_1981_role_of_magnesium_ions_in_contractility_of_blood_vessels_and_skeletal_muscles_444.pdf
Konishi M. Cytoplasmic free concentrations of Ca2+ and Mg2+ in skeletal muscle fibers at rest and during contraction. Jpn J Physiol. 1998;48(6):421-438. https://www.ncbi.nlm.nih.gov/pubmed/10021496
Yang Z, Wang J, Altura BT, Altura BM. Extracellular magnesium deficiency induces contraction of arterial muscle: role of PI3-kinases and MAPK signaling pathways. Pflugers Arch. 2000;439(3):240-247. https://www.ncbi.nlm.nih.gov/pubmed/10650973
Yang ZW, Gebrewold A, Nowakowski M, Altura BT, Altura BM. Mg(2+)-induced endothelium-dependent relaxation of blood vessels and blood pressure lowering: role of NO. Am J Physiol Regul Integr Comp Physiol. 2000;278(3):R628-R639. https://www.physiology.org/doi/full/10.1152/ajpregu.2000.278.3.R628
Yang ZW, Wang J, Zheng T, Altura BT, Altura BM. Low Mg(2+) induces contraction and Ca(2+) rises in cerebral arteries: roles of ca(2+), PKC, and PI3. Am J Physiol Heart Circ Physiol. 2000;279(6):H2898-H2907. https://www.physiology.org/doi/pdf/10.1152/ajpheart.2000.279.6.H2898
Turlapaty PD, Altura BM. Magnesium deficiency produces spasms of coronary arteries: relationship to etiology of sudden death ischemic heart disease. Science. 1980;208(4440):198-200. https://www.ncbi.nlm.nih.gov/pubmed/7361117
Seelig MS, Rosanoff A. The Magnesium Factor. 1st ed. New York, NY: Avery Penguin Group; 2003:278-279; 369-370 https://www.barnesandnoble.com/p/the-magnesium-factor-mildred-seelig/
Resnick L. The cellular ionic basis of hypertension and allied clinical conditions. Prog Cardiovasc Dis. 1999;42(1):1-22. https://www.ncbi.nlm.nih.gov/pubmed/10505490
Resnick LM. Ionic basis of hypertension, insulin resistance, vascular disease, and related disorders. The mechanism of “syndrome X.” Am J Hypertens. 1993;6(4):123S-134S. https://www.ncbi.nlm.nih.gov/pubmed/8507440
Rosanoff A. Nutritional magnesium is associated with metabolic syndrome, cardiovascular disease and its risk factors, and other NCDs: a bibliography. Magnesium Education website. http://www.magnesiumeducation.com/the-mg-hypothesis-of-cardiovascular-disease-abibliography
Rosanoff A, Weaver CM, Rude RK. Suboptimal magnesium status in the United States: are the health consequences underestimated? Nutr Rev. 2012;70(3):153-164. https://www.mgwater.com/articles/Rosanoff/(09)%20Suboptimal%20Magnesium%20Status%20in%20the%20United%20States.pdf
Rosanoff A, Capron E, Barak P, Mathews B, Nielsen FH. Edible plant tissue and soil calcium:magnesium ratios: data too sparse to assess implications for human health. Crop Pasture Sci. 2015;66:1265-1277. http://agris.fao.org/agris-search/search.do?recordID=US201600101821
Rosanoff A. Rising Ca:Mg intake ratio from food in USA Adults: a concern? Magnesium Res. 2010;23(4):S181-S193. https://www.mgwater.com/Ca-Mg.pdf
Karakelleoglu C, Orbak Z, Ozturk F, Kosan C. Hypomagnesaemia as a mortality risk factor in protein-energy malnutrition. J Health Popul Nutr. 2011;29(2):181–182. doi:10.3329/jhpn.v29i2.7863 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126992/
Florence Dunkel, Learning from Sanambele: Role of Food Insects in Village Nutritional Health, Montana State University-Bozeman (a Power Point presentation) http://www.montana.edu/mali/documents/pptsaspdfs/worldHungerDunkelSanambelepresentationsmallpdfvsn.pdf
Sorghum and Millets in Human Nature, fao.org, http://www.fao.org/3/T0818E/T0818E0d.htm
The Contribution of Insects to Food Security, Livelihoods and the Environment, fao.org, http://www.fao.org/3/i3264e/i3264e00.pdf
Beatrice Amadi, Andrew O Fagbemi, Paul Kelly, et al., Reduced production of sulfated glycosaminoglycans occurs in Zambian children with kwashiorkor but not marasmus., The American Journal of Clinical Nutrition, Vol 89, Issue 2, Feb 2009, pp 592–600 https://academic.oup.com/ajcn/article/89/2/592/4596718
Arnold van Huis, Joost Van Itterbeeck, Harmke Klunder, et al., Edible insects: Future prospects for food and feed security, Food and Agriculture Organization of the United Nations, Rome, 2013, FAO.org, http://edepot.wur.nl/258042
Joan L.Caddell, MD., Magnesium in the therapy of protein-caloriemalnutrition of childhood., The Journal of Pediatrics, Vol 66, Issue 2, Feb 1965, pp 392-413, https://www.sciencedirect.com/science/article/abs/pii/S0022347665801974
Article in the lower right hand column of the Science Direct topic page on Albumin Antibody: - it has a thorough description and graphic (Figure 1) about the blood brain barrier and seizures.
N. Marchi, … D. Janigro, in Encyclopedia of Basic Epilepsy Research, 2009, Inflammation: Cerebrovascular Diseases, Seizures, and Epilepsy Seizures; Epilepsy, and the Blood–Brain Barrier, "Systemic pathologies causing BBB failure may be due to hypertension, stroke, blood hyperosmolarity, or systemically mediated inflammatory processes (due to the production of TNF-α, IL-1β, IL-6, histamine, arachidonic acid, or reactive oxygen species)"
"(Figure 1). Investigators have hypothesized that disruption of the BBB will lead to seizures. This prediction is based on the following experimental findings:" https://www.sciencedirect.com/topics/medicine-and-dentistry/albumin-antibody
References from the last post on hypercoaguability and the NF-kB inflammatory pathway.
DiNicolantonio JJ, Liu J, O'Keefe JH. Magnesium for the prevention and treatment of cardiovascular disease. Open Heart. 2018;5(2):e000775. Published 2018 Jul 1. doi:10.1136/openhrt-2018-000775 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045762/
Andrea Rosanoff, PhD, and Stella Lucia Volpe, PhD, RDN, ACSM-CEP, FACSM, Recorded Webinar: Modern Day Human Magnesium Requirements: The RDN's Role, Today's Dietitian, https://ce.todaysdietitian.com/node/69241#group-tabs-node-course-default1
Karen Skene, Sarah K. Walsh, Oronne Okafor, Nadine Godsman, et al., Acute dietary zinc deficiency in rats exacerbates myocardial ischaemia–reperfusion injury through depletion of glutathione., British Journal of Nutrition, Vol 121, Issue 9 14 May 2019 , pp. 961-973, https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/acute-dietary-zinc-deficiency-in-rats-exacerbates-myocardial-ischaemiareperfusion-injury-through-depletion-of-glutathione/15953E00DA3E69629F36F9F6FE5079A8
Karl T. Weber,1,* William B. Weglicki,2 and Robert U. Simpson3 Macro- and micronutrient dyshomeostasis in the adverse structural remodelling of myocardium, Cardiovasc Res. 2009 Feb 15; 81(3): 500–508. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2639130/
Li YC. Vitamin D: roles in renal and cardiovascular protection. Curr Opin Nephrol Hypertens. 2012;21(1):72–79. doi:10.1097/MNH.0b013e32834de4ee https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574163/
Benjamin Senst; Prasanna Tadi; Hajira Basit; Arif Jan., Hypercoaguability, STATPearls, Last Update: April 29, 2019. https://www.ncbi.nlm.nih.gov/books/NBK538251/
Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy--A Review. Nutrients. 2016;8(2):68. Published 2016 Jan 28. doi:10.3390/nu8020068 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772032/