The Cholinergic System

The cholinergic system is the network of acetylcholine receptors clustered within certain brain regions which the activation of or inhibition of in total affects most of our actions.

More specifically negatively effecting the cholinergic system might cause symptoms of “dry mouth, tachycardia or bradycardia, drowsiness, sedation, and short-term memory loss,” – all potential symptoms that may occur with varying doses of THC, the euphoria causing cannabinoid found in marijuana. (1) Tachycardia is a very rapid heart rate and bradycardia is a very slow rate. Olanzapine, one of the anti-cholinergic medications mentioned in the last post, causes cannabinoid receptors in the prefrontal cortex to be overactive which would cause a similar effect to that of taking a large dose of THC – a cannabinoid that activates cannabinoid receptors in the prefrontal cortex.

What else does the cholinergic system do?

Acetylcholine has been found to have a large role in memory consolidation – forming memories. Low levels can cause memories to be retrieved (possibly significant in Traumatic Brain Injury, TBI, 3) and high levels facilitate the formation of new memories. Low acetylcholine levels might cause symptoms of perseveration, continuing an action repetitively, not being able to stop an action at the typical time. Damage to the medial septum/vertical limb of the diagonal band (MS/VDB) portion of the cholinergic nerve pathways might also cause perseverative behavior. (2)

Acetylcholine levels are involved in the processing of information for considering uncertainty, possibly for helping with decision making.. The new sensory information is compared to past memories, comparing incoming sensory data to stored memory data , (2) for the purpose of identifying danger or dinner – is the shape seen in the distance more like a tiger to run away from or a gazelle to pursue?

Movement involves a couple neurotransmitters for different aspects of an action. The ability to move requires acetylcholine and the motivation to move involves dopamine. (4) Dopamine is known as the reward neurotransmitter while acetylcholine is more of an action one. Should I start running towards the distant figure or away? Is it a dopamine rewarding delicious dinner of gazelle or a fear inducing tiger? Creeping slowly close enough to be able to tell without startling a gazelle or alerting a tiger would be a dopamine motivated and courageous action to take, acetylecholine would be involved in the decision to take the risk and move closer. Noradrenaline, another neurotransmitter, might also be involved in a decision involving the tradeoff between danger and reward. The neurotransmitters work as a team, see the excerpt included later. (2)

The ability to decide to move closer and to do so would be negatively effected by problems with acetylcholine, noradrenaline, or with dopamine.

What does the Dopaminergic System do? – Parkinson’s Disease & Dopamine.

Parkinson’s Disease is a degenerative disease that may involve epigentic changes in DNA, (4) – some are turned on or off with the removal or addition of methyl groups along the length of the DNA molecule.

  • Methyl groups are small, an oxygen and a hydrogen atom, and might also be thought of as a key blocking a door lock so that no other keys can be used to open the door- to activate the DNA for replication into RNA and protein molecules.

Symptoms of Parkinson’s Disease include muscle tremors and difficulty controlling or initiating movements. Walking can be slow and jerky, and hand writing very shaky. The primary degeneration within the brain involves an area that produces dopamine which may then activate dopamine receptors elsewhere in the brain along a dopaminergic network. (2) As the cells that would typically produce dopamine are damaged the body becomes less able to send the dopaminergic nerve signals that would motivate motion. The ‘fight/flight/freeze’ fear response may also be involved, becoming overactive with chronic stress and eventually leaving the body in the ‘freeze’ response. (4)

The problem from having the fight/flight/freeze response in a chronic state of ‘on’ is that it shifts the body into more inflammatory chemical pathways and turns off more restorative toxin removal and growth chemical pathways. One theory about a cause of Parkinson’s Disease (PD) suggests this overactive fear response and resulting underactive detoxification pathways leaves the body with too much of a toxic waste product from dopamine breakdown called dopal, an aldehyde. (4)

PD may result from protective negative feedback loops – the body purposely inhibiting the dopamine producing cells in the brain involved in Parkinson’s Disease in order to stop the increased levels of dopal – or the increasing levels of dopal build up most in the dopamine producing cells and cause their damage or death sooner than in other cells throughout the rest of the body. (4)

Current treatments for Parkinson’s Disease are focused on increasing dopamine levels rather than trying to break down levels of dopal – which may be worsening the degenerative problem overall. (Eckert, thesis 2012, 4) Pesticides may also be a causative factor in PD by causing malfunction of the enzyme (aldehyde dehydrogenase , ALDH) that in normal health would quickly breakdown the toxic dopal aldehyde into less toxic metabolites of the chemical. Some people with Parkinson’s Disease may have a genetic difference making them unable to make a functional form of the enzyme ALDH, so their levels of the aldehyde dopal would be chronically elevated. (4)

Patients with Parkinson’s Disease also tend to have gastrointestinal symptoms and dopamine is also produced in the GI tract. Food sensitivities to other aldehydes can also be common for patients with PD. Perfumes and other chemical scents also contain aldehydes and may also increase symptoms of pain, muscle rigidity, and brain fog (a non-scientific term for cognitive symptoms where thinking may feel fuzzy or clouded compared to normal – I would make a decision if I could get the thought from here to there through this feeling that I’m swimming through molasses, but that seems too exhausting, I will just rest here treading molasses instead). (4)

Brain fog is also a common complaint for people with chronic Candida yeast infections which can be in the GI tract or elsewhere in or on the body. Chronic yeast growth may be involved in risk for Parkinson’s Disease as they generate aldehydes during their growth or decomposition an use up nutrients that the human would need to detoxify aldehydes. (4)

The methylated active form of the B vitamin Folate is needed for detoxification of aldehydes. Someone with a genetic variation that prevents normal methylation could have increased risk for degenerative diseases that involve epigenetic changes which require methyl groups to be added or removed from DNA; and/or be at increased risk for degenerative changes caused by toxin buildup. Folic acid is an unmethylated, not bioactive, form of folate that is used in most supplements and fortified foods instead of folate, the form that would be found naturally occurring in folate rich foods such as beans, peas, and asparagus.

Formaldehyde is a neurotoxin found in smog or smoke and in the diet as a metabolite, produced during aging of the product or during digestion.

Formaldehyde is an aldehyde that is a known toxin. It is a common environmental pollutant in smog or smoke, either from a fire, candle flame, or cigarette. Formaldehye also is released during offgassing of volatile chemicals from vinyl plastic products – i.e. ‘new car smell.’ And it can be found in foods. Formaldehyde is produced chemically during the break down of some food products as they age. Older packages of shelf stable juice can contain a significant amount of formaldehyde. It is also created during the breakdown of the artificial sweeteners called aspartame and Neotame. Aspartame (brand names include Nutrasweet TM or Equal TM) is required to be listed on food labels while Neotame, slightly more concentrated form, is not required to be listed on processed food labels, whether ‘conventional’ or ‘organic’. See a previous post for more guidance about avoiding formaldehyde: Formaldehyde: Heath Risks, Environmental and Dietary Sources, (

Returning to the cholinergic system – part of the neurotoxic effects of formaldehyde is due to it having an inhibitory effect on acetylcholine activity. Increased formaldehyde levels leads to an increase in levels of the enzyme that breaksdown acetylcholine, resulting in less of the neurotransmitter being available for stimulating the acetylcholine receptors of nerve cells. (5)

Neurotransmitters work together as a team.

The neurotransmitters also work together as a team in many ways, so problems with one are likely to negatively affect the other’s functions too. All of them are involved in attention abilities and novelty seeking, (2) : knowing where to pay attention – to see if the distant figure is a tiger or a gazelle, and being able to follow its motion; and in looking for newness such as changes in the environment – or is it a lion in the distance and another one just joined the first?

Other neurotransmitters, or neuromodulators as they are called in the following excerpt, include serotonin and noradrenaline. There are other neurotransmitters that do not also function as neuromodulators and other chemicals that act as neuromodulators but are not also neurotransmitters. Neuromodulators may increase or decrease the likelihood that the activation of nerve cell receptor wil be enough to send a nerve signal from the cell to other nerve cells. A neurotransmitter can directly interact with a matching nerve cell receptor and if the incoming signal is strong enough then cause the cell to send a nerve signal to other nerve cells.

It is difficult to pinpoint a specific function for each neuromodulator. It has been suggested that dopamine is related to positive value, serotonin to risk aversion, noradrenaline to vigilance, and acetylcholine to attentional effort (Krichmar, 2008). Another theory posits that dopamine is related to reward prediction, while serotonin is related to temporal discounting, and that noradrenaline regulates the exploration/exploitation tradeoff, while acetylcholine controls learning rate (Doya, 20022008).”

(Avery, 2017) (2)
  1. Domino E.E. (1999) Cannabinoids and the Cholinergic System. In: Nahas G.G., Sutin K.M., Harvey D., Agurell S., Pace N., Cancro R. (eds) Marihuana and Medicine. Humana Press, Totowa, NJ
  2. Avery MC, Krichmar JL. Neuromodulatory Systems and Their Interactions: A Review of Models, Theories, and Experiments. Front Neural Circuits. 2017;11:108. Published 2017 Dec 22. doi:10.3389/fncir.2017.00108
  3. Sherin JE, Nemeroff CB. Post-traumatic stress disorder: the neurobiological impact of psychological trauma. Dialogues Clin Neurosci. 2011;13(3):263–278.
  4. Dopamine: Aldehyde Poisoning and Parkinson’s Disease, On Thinking Parkinson’s, June 20, 2018,
  5. Zendehdel R, Fazli Z, Mazinani M. Neurotoxicity effect of formaldehyde on occupational exposure and influence of individual susceptibility to some metabolism., Environ Monit Assess. 2016 Nov;188(11):648. Epub 2016 Oct 31. parameters.

Translational medicine – getting research to the patient.

We fundraise for research for cures to disease yet sadly it seems too long for patients living uncomfortably in the present. Seventeen years was an average found in one research study about how long it takes for medical research results to make it into the doctor office and to the patient. Much of the information about magnesium in the last post dates back as far as the 1960s and 70s, that is almost 60 years, not 17. Some discoveries were made by Mildred Seelig, a primary researcher in the role of magnesium in health , and coauthor of one of the books in the reference list (The Magnesium Factor, 38).

Health care choices and food policy regulations affect all age groups. Medicating symptoms instead of treating underlying nutrient deficiency or imbalance can be costly, ineffective, and possibly be allowing chronic degeneration to be occuring due to lack of the nutrient. Nutrient deficiency or imbalance might be due to dietary lack, metabolic differences, malabsorption, or increased needs due to illness or some other reason. Adults and children have been experiencing chronic illness at increased rates in the Unites States and other developed and developing nations.

In the U.S. 43% of children had a chronic health issue (from a list of 20 included in the study) – 32 million children. The number increases to 54.1% when “overweight, obesity, or being at risk for developmental delays are included.” The chronic conditions cause special health care needs for 19.2%, 14.2 million of the chilren. (ref)

While sadly Mildred Seelig passed away before she could see her work reach the majority of patients, young and old, her coauthor for The Magnesium Factor, Andrea Rosanoff, PhD , is still alive and working on the use of magnesium topically for healthcare purposes. Hopefully her work will reach the doctor’s office and the patient before another 17, or 60 years have passed.

Not only are many medications prescribed for symptoms of magnesium deficiency instead of educating on magnesium sources, there are many medications that may decrease magnesium levels. See “Drug Interctions” for individual details, the list includes positive or negative effects – increasing or decreasing efficiency of supplements of Magnesium glycinate -as a prescribed ‘drug’ ( glycinate). Many of the anti-cholinergics mentioned in Table 1, (ref), are also on the list of drugs that cause drug interactions with magnesium glycinate – decreasing its effectiveness. Anti-cholinergics have been associated with increased risk of dementia, especially with greater use, or multiple use, (ref) , and with increased risk fr recurrent falls in postmenopausal women. (ref)

Anti-cholinergics may include drugs prescribed as:

  • antidepressants, (Amitriptyline),*
  • antipsychotics, (Olanzapine),*
  • for asthma, (antihistamine- Diphenhydramine),*
  • urinary bladder problems, (urinary antimuscarinic –Flavoxate),*
  • muscle spasms, (skeletal muscle relaxant – Orphenadrine),*
  • and other issues.
  • *Anticholinergic Medications from Table 1 (ref) that are also on the drug interaction list as drugs that may decrease the therapeutic efficacy of Magnesium glycinate if prescribed as a supplement/drug. ( glycinate)

Olanzapine also has a significant risk of causing Type 2 Diabetes and/or excessive weight gain with extended use and withdrawal symptoms may include severe increased anxiety and suicidal or homocidal urges. Type 2 Diabetes and anxiety can be symptoms of chronic magnesium deficiency.

Health is worth the effort – pain is a symptom of a problem and a signal to figure out what to change to stop the pain – by improving the underlying problem. Sometimes change is age related and adjustments might need to include recognizing that metabolism has slowed, less calories is needed but protein becomes more important, and, recovery from illness, injury, or extended effort might take longer – so be more cautious about risk. Sometimes change is needed in the standard of care – to include preventative screening and education when health symptoms are still in early stages, before chronic degeneration or cancerous changes occur.

Translational medicine – 60 years is too long to wait for life-saving information to reach patients, 17 years is too long too.

Sadly it can even take more than a hundred years for research findings to benefit the consumer. The use of aluminum as an anti-caking agent in baking powder is still common in the U.S. food supply and it was strongly recommended to be removed from foods as an anti-caking agent or food preservative as long ago as 1911. (Gies, 1911, page 44, Ch.4, ref)

The U.S. consumer who includes processed convenience foods in their diet may be getting 100 milligrams of aluminum per day or more, with an average estimate between 2 and 25 milligrams. The provisional tolerable weekly intake for aluminum was lowered by the FAO/WHO Expert Committee in 2006 from 7 milligrams per kilogram of body weight (~490 mg/wk for a 70 kg/154 lb person) to 1 milligram per kilogram of body weight. The change was due to findings showing a potential risk to reproductive and nervous system development at lower doses than previously thought. (page 45, Ch.4, ref)

I love delicious and/or convenient food, however I love health more. I also like economical, effective healthcare solutions for myself, my family, and everyone else – because it is also better for the planet. When we use toxins in our food supply or food production those toxins are also getting into the environment and wildlife’s food and water supply. Teamwork – we humans are part of the food chain, not just at the top of it.

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.

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, ( 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, (
  • 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  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.


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  22. Jill Jin, MD, MPH, Vitamin D and Calcium for Preventing Fractures, Guidelines, JAMA Patient Page, JAMA Network, April 17, 2018
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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.

  1. 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)”

References from the last post on hypercoaguability and the NF-kB inflammatory pathway.

  1. 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
  2. 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,
  3. 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,
  4. 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.
  5. Li YC. Vitamin D: roles in renal and cardiovascular protection. Curr Opin Nephrol Hypertens. 2012;21(1):72–79. doi:10.1097/MNH.0b013e32834de4ee
  6. Benjamin Senst; Prasanna Tadi; Hajira Basit; Arif Jan., Hypercoaguability, STATPearls, Last Update: April 29, 2019.
  7. 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